Gastrointestinal surgical emergencies in patients treated for hemathological malignancies.

PubMed

Caronna, R; Cardi, M; Arcese, W; Iori, A P; Martelli, M; Catinelli, S; Mangioni, S; Corelli, S; Priore, F; Tarantino, E; Frantellizzi, V; Spera, G; Borrini, F; Chirletti, P

2005-01-01

Upper and lower gastrointestinal symptoms are major and serious complications in patients who undergo chemotherapy for hematological malignancies. Their most frequent causes are acute intestinal graft-versus-host disease (GVHD) after bone marrow transplant, infections, toxicity or preexisting gastrointestinal diseases. Mortality can reach 30-60% of cases. We report 15 cases operated on for abdominal emergencies: 3 severe gastrointestinal bleeding and 12 acute abdomen. We performed 10 bowel resections, one cholecystectomy, one splenectomy, two laparotomy with pancreatic debridement and peritoneal lavage, and one suture of perforated peptic ulcer. Operative mortality was 33.3% (5/15). Deaths have been reported only in the group of patients with acute abdomen. In all cases death was correlated to generalized sepsis related to immunosuppression. We believe that an aggressive approach, consisting of close monitoring and early laparotomy combined with vigorous supportive therapy, should be used when dealing with suspected gastrointestinal complications in patients with hematological malignancies.

Atypical presentation of Legionella pneumonia among patients with underlying cancer: A fifteen-year review.

PubMed

del Castillo, Maria; Lucca, Anabella; Plodkowski, Andrew; Huang, Yao-Ting; Kaplan, Janice; Gilhuley, Kathleen; Babady, N Esther; Seo, Susan K; Kamboj, Mini

2016-01-01

Immunocompromised patients, especially those receiving treatment with corticosteroids and cytotoxic chemotherapy are at increased risk for developing Legionella pneumonia. The aim of this study was to determine clinical and radiographic characteristics of pulmonary infection due to Legionella in persons undergoing treatment for cancer and stem cell transplant (SCT) recipients. Retrospective review of Legionella cases at MSKCC over a fifteen-year study period from January 1999 and December 2013. Cases were identified by review of microbiology records. During the study period, 40 cases of Legionella infection were identified; nine among these were due to non-pneumophila species. Most cases occurred during the summer. The majority [8/9, (89%)] of patients with non-pneumophila infection had underlying hematologic malignancy, compared to 18/31 (58%) with Legionella pneumophila infections. Radiographic findings were varied-nodular infiltrates mimicking invasive fungal infection were seen only among patients with hematologic malignancy and hematopoietic stem cell transplant (SCT) recipients and were frequently associated with non-pneumophila infections (50% vs 16%; P = 0.0594). All cases of nodular Legionella pneumonia were found incidentally or had an indolent clinical course. Legionella should be considered in the differential diagnosis of nodular lung lesions in immunocompromised patients, especially those with hematologic malignancy and SCT recipients. Most cases of nodular disease due to Legionella are associated with non-pneumophila infections. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Fatal Candidemia in a Patient with Acute Lymphoblastic Leukemia

DTIC Science & Technology

2018-02-16

does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ORGANIZATION. 1. REPORT DATE (DO MM-YYYY) 12...Objectives: Describe a case of invasive Candida tropicalis infection as a complication of hematologic n1alignancy Describe the cutaneous...Describe a case of invasive Candida tropicalis infection as a complication of hematologic malignancy Describe the cutaneous manifestations of

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt.

PubMed

Elkady, Abeer; Iijima, Sayuki; Aboulfotuh, Sahar; Mostafa Ali, Elsayed; Sayed, Douaa; Abdel-Aziz, Nashwa M; Ali, Amany M; Murakami, Shuko; Isogawa, Masanori; Tanaka, Yasuhito

2017-03-28

To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA.

Characteristics of escape mutations from occult hepatitis B virus infected patients with hematological malignancies in South Egypt

PubMed Central

Elkady, Abeer; Iijima, Sayuki; Aboulfotuh, Sahar; Mostafa Ali, Elsayed; Sayed, Douaa; Abdel-Aziz, Nashwa M; Ali, Amany M; Murakami, Shuko; Isogawa, Masanori; Tanaka, Yasuhito

2017-01-01

AIM To investigate the prevalence and virological characteristics of occult hepatitis B virus (HBV) infections in patients with hematological malignancies in South Egypt. METHODS Serum samples were collected from 165 patients with hematological malignancies to monitor titers of HBV DNA, hepatitis B surface antigen (HBsAg), and antibodies to HBV core (anti-HBc) and surface antigens. Serum samples negative for HBsAg and positive for anti-HBc were subjected to nucleic acid extraction and HBV DNA detection by real-time polymerase chain reaction. DNA sequences spanning the S region were analyzed in cases with occult HBV infection. In vitro comparative study of constructed 1.24-fold wild type and S protein mutant HBV genotype D clones was further performed. RESULTS HBV DNA was detected in 23 (42.6%) of 54 patients with hematological malignancies who were HBsAg negative, but anti-HBc positive, suggesting the presence of occult HBV infection. The complete HBV genome was retrieved from 6 occult HBV patients, and P120T and S143L were detected in 3 and 2 cases, respectively. Site directed mutagenesis was done to produce 1.24-fold genotype D clones with amino acid mutations T120 and L143. The in vitro analyses revealed that a lower level of extracellular HBsAg was detected by chemiluminescence enzyme immunoassay (CLEIA) with the clone containing T120 mutation, compared with the wild type or the clone with S143L mutation despite the similar levels of extracellular and intracellular HBsAg detected by Western blot. Southern blot experiments showed that the levels of intracellular HBV DNA were not different between these clones. CONCLUSION Occult HBV infection is common in patients with hematological malignancies and associated with P120T and S143L mutations. 120T mutation impairs the detection of HBsAg by CLEIA. PMID:28396718

[Distribution of Pathogenic Bacteria and Its Influence on Expression of BCL-2 and BAX Protein after HSCT in the Patients with Hematological Malignancies].

PubMed

Su, Gui-Ping; Dai, Yan; Huang, Lai-Quan; Jiang, Yi-Zhi; Geng, Liang-Quan; Ding, Kai-Yang; Huang, Dong-Ping

2016-06-01

To investigate the distribution of pathogenic bacteria in the patients with hematologic malignancies received hematopoietic stem cell transplantation (HSCT) and its influence on the expression of BCL-2 and BAX proteins. The clinical data of 64 patients with malignant lymphoma (ML) received auto-HSCT from January 2011 to December 2015 in our hospital were analyzed. On basis of post-treansplant infection, the patients were divided into infection group (36 cases) and non-infection group (28 cases). The distribution of pathogenic bacteria in 2 groups was identified, the T lymphocyte subsets of peripheral blood, expression level of apoptotic proteins and C-reaction protein (CRP) in 2 group were detected. Thirty-six strains of pathogenic bacteria were isolated from 36 case of hematological malignancy after HSCT, including 24 strains of Gram-negative bacteria (66.67%) with predominamce of klebsiella pneumoniae (19.44%). The periperal blood CD4+ (t=2.637, P<0.01), CD4+/CD8+ ratio (t=8.223, P<0.01), BCL-2 protein (t=5.852, P<0.05), BCL-2/BAX ratio (t=14.56, P<0.01) in infection group were significantly lower than those in non-infection group, while CD8+ (t=2.285, P=<0.01), CRP (t=39.71, P<0.01), BAX level in infection group were higher than those in non-infection group. The pearson correcation analysis showed that the CD4+/CD8+ ratio in infection group positively correlated with BCL-2/BAX ratio (t=0.341, P<0.05), while serum CRP level in infection group negatively correlated with BCL-2/BAX ratio (t=-0.362, P<0.05). The pathogenic bacteria infecting ML patients after HSCT were mainly Gram-negative bacteria. The post-transplant infection can promote the expression up-regulation of related inflammatory factors and apoptotic proteins. The pathogens may be involved in cell apoptisis that provides a new strategy to treat the hematologic malignancies.

Two cases of false-positive dengue non-structural protein 1 (NS1) antigen in patients with hematological malignancies and a review of the literature on the use of NS1 for the detection of Dengue infection.

PubMed

Chung, Shimin J; Krishnan, Prabha U; Leo, Yee Sin

2015-02-01

Early diagnosis of dengue has been made easier in recent years owing to the advancement in diagnostic technologies. The rapid non-structural protein 1 (NS1) test strip is widely used in many developed and developing regions at risk of dengue. Despite the relatively high specificity of this test, we recently encountered two cases of false-positive dengue NS1 antigen in patients with underlying hematological malignancies. We reviewed the literature for causes of false-positive dengue NS1. © The American Society of Tropical Medicine and Hygiene.

RS3PE revealing recurrent non-Hodgkin's lymphoma.

PubMed

Gisserot, Olivier; Crémades, Serge; Landais, Cécile; Leyral, Guénaelle; Bernard, Philippe; de Jauréguiberry, Jean-Pierre

2004-09-01

A patient meeting published criteria for remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was found to have a synchronous recurrence of non-Hodgkin's malignant lymphoma. Reported cases of RS3PE associated with hematological malignancies and other forms of cancer are reviewed.

Fluorescence in situ hybridization analyses of hematologic malignancies reveal frequent cytogenetically unrecognized 12p rearrangements.

PubMed

Andreasson, P; Johansson, B; Billström, R; Garwicz, S; Mitelman, F; Höglund, M

1998-03-01

Thirty-two hematologic malignancies--nine with cytogenetically identified 12p abnormalities and 23 with whole or partial losses of chromosome 12--were selected for fluorescence in situ hybridization (FISH) investigations of 12p. These analyses revealed structural 12p changes, such as translocations, deletions, insertions, inversions and amplification, in 20 cases. ETV6 rearrangements were detected in three acute leukemias. One acute undifferentiated leukemia had t(4;12)(q12;p13) as the sole anomaly. The second case, an acute myeloid leukemia (AML), displayed complex abnormalities involving, among others, chromosomes 9 and 12. The third case, also an AML, had an insertion of the distal part of ETV6 into chromosome arm 11q and into multiple ring chromosomes, which also contained chromosome 11 material, resulting in an amplification of a possible fusion gene. The fusion partners in these cases remain to be identified. Thirty-one additional breakpoints on 12p could be characterized in detail. The majority of these breaks were shown to result in interchromosomal rearrangements, possibly indicating the location of hitherto unrecognized genes of importance in the pathogenesis of hematologic malignancies. The FISH analyses disclosed terminal or interstitial 12p deletions in 18 cases. Seven myeloid malignancies showed deletions restricted to a region, including ETV6 and CDKN1B, which has been reported to be frequently lost in leukemias. In four cases, the deletions involved both these genes, whereas two AML displayed loss of CDKN1B but not ETV6, supporting previously reported findings indicating a region of deletion not including this gene. However, one myelodysplastic syndrome lacked one copy of ETV6 but not CDKN1B. Hence, we suggest a minimal region of deletion on 12p located between the ETV6 and CDKN1B genes.

Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort.

PubMed

Teras, Lauren R; Diver, W Ryan; Turner, Michelle C; Krewski, Daniel; Sahar, Liora; Ward, Elizabeth; Gapstur, Susan M

2016-07-01

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer. The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148Bq/m(3)) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74Bq/m(3)) radon levels (HR=1.63, 95% CI:1.23-2.18), and there was evidence of a dose-response relationship (HRcontinuous=1.38, 95% CI:1.15-1.65 per 100Bq/m(3); p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonmelanoma Skin Cancer With Aggressive Subclinical Extension in Immunosuppressed Patients.

PubMed

Song, Silvia Soohyun; Goldenberg, Alina; Ortiz, Arisa; Eimpunth, Sasima; Oganesyan, Gagik; Jiang, Shang I Brian

2016-06-01

Immunosuppression (IS), such as in solid-organ transplant recipients (SOTRs) and patients with human immunodeficiency virus (HIV) or hematologic malignant neoplasms, increases the risk of developing nonmelanoma skin cancers (NMSCs). However, it is unknown whether IS patients are at increased risk of developing NMSCs with aggressive subclinical extensions (NMSC-ASE), which may extend aggressively far beyond conventional surgical margins. To study clinical characteristics of NMSC-ASE among immunocompetent (IC) and various subgroups of IS patients and to suggest a predictive model for NMSC-ASE lesions. A 6-year retrospective review of 2998 NMSC cases between February 26, 2007, and February 17, 2012, at the Dermatologic and Mohs Micrographic Surgery Unit of the University of California, San Diego, Medical Center. Nonmelanoma skin cancers that required at least 3 Mohs micrographic surgery stages with final surgical margins of at least 10 mm were defined as ASE lesions. All cases were categorized into 1 of 2 groups, IS or IC. Immunosuppressed cases were further subcategorized into 3 subgroups: SOTRs and patients with HIV or hematologic malignant neoplasm. The data were analyzed in December 2012. We evaluated the odds ratio of having NMSC-ASE lesions in IS patients (SOTRs, HIV, hematologic malignant neoplasm) compared with IC patients. Other clinical characteristics and preoperative risks were analyzed and compared. Of all 2998 cases, we identified 805 NMSC-ASE cases: 137 IS and 668 IC. Immunosuppressed patients had an odds ratio of 1.94 of having ASE lesions compared with IC patients (95% CI, 1.54-2.44; P < .001). Additionally, the SOTR subgroup was associated with a 2.74 odds of having NSMC-ASE compared with non-SOTRs (95% CI, 2.00-3.76; P < .001), and the presence of hematologic malignant neoplasm was associated with 1.74 times the odds compared with IC patients (95% CI, 1.04-2.90; P = .04). Multivariate analysis found older age (P < .001), lesion locations such as zone 1 (OR, 1.39 [95% CI, 1.04-1.85]; P = .02) or zone 2 (OR, 1.45 [95% CI, 1.08-1.94]; P = .01), and IS status (OR, 1.94 [95% CI, 1.54-2.44]; P < .001) to be significant predictors of ASE. The findings of this study suggest an increased risk for NMSC-ASE lesions in IS patients, especially in SOTRs and those with hematologic malignant neoplasm, but not patients with HIV. Statistically significant predictors of NMSC-ASE lesions such as age, location, and IS status can help physicians choose the most appropriate treatment modalities and optimize surgical planning.

Inpatient rehabilitation improved functional status in asthenic patients with solid and hematologic malignancies.

PubMed

Guo, Ying; Shin, Ki Y; Hainley, Susan; Bruera, Eduardo; Palmer, J Lynn

2011-04-01

The aim of this study was to compare functional outcomes in asthenic patients with hematologic malignancies with those of asthenic patients with solid tumors after inpatient rehabilitation. We hypothesized that asthenic patients with hematologic malignancies are less likely than patients with solid tumors to make functional improvement after rehabilitation. The records of 60 asthenic cancer patients (30 consecutive patients with solid tumors and 30 consecutive patients with hematologic malignancies) who underwent inpatient rehabilitation at a comprehensive cancer center between October 2005 and October 2007 were retrospectively reviewed. Patients with focal neurologic deficits were excluded. All patients admitted to the inpatient rehabilitation unit received 3 hrs of more of therapy per weekday. The main outcomes included total, motor, and cognitive Functional Independence Measure (FIM) scores, hospital and rehabilitation length of stay, and FIM efficiency. The mean total FIM score significantly improved in patients with solid tumors (mean, 15; range, -6 to 38) and in patients with hematologic malignancies (mean, 17; range, -3 to 27); however, between-group differences in FIM scores were not significant (P = 0.31). The solid tumor patients were significantly older than the hematologic malignancy patients (71 ± 11 vs. 64 ± 12 yrs; P = 0.02), but the mean rehabilitation lengths of stay were the same for each group (9.5 days; P = 0.82). The mean FIM efficiency in the hematologic malignancy group was higher than that of the solid tumor group (1.9 vs.1.4; P = 0.049). Asthenic patients with solid tumors or hematologic malignancies could benefit from inpatient rehabilitation and make significant functional gain.

An atypical case of late-onset systemic lupus erythematosus with systemic lymphadenopathy and severe autoimmune thrombocytopenia/neutropenia mimicking malignant lymphoma.

PubMed

Tamaki, Keita; Morishima, Satoko; Nakachi, Sawako; Kitamura, Sakiko; Uchibori, Sachie; Tomori, Shouhei; Hanashiro, Taeko; Shimabukuro, Natsuki; Tedokon, Iori; Morichika, Kazuho; Nishi, Yukiko; Tomoyose, Takeaki; Karube, Kennosuke; Fukushima, Takuya; Masuzaki, Hiroaki

2017-04-01

Here, we report a rare case of systemic lupus erythematosus (SLE) with conspicuous manifestation of hematological abnormalities. At onset, the 52-year-old male patient showed systemic lymphadenopathy and splenomegaly, severe autoimmune thrombocytopenia, and autoimmune neutropenia. Bone marrow examination and lymph node biopsy excluded the possibility of malignant lymphoma. Based on laboratory findings, he was finally diagnosed with combined autoimmune cytopenia coupled with SLE. Atypical clinical manifestations of SLE prompted us to explore the possibility of autoimmune lymphoproliferative syndrome (ALPS). However, we did not detect an increased number of CD4 - /CD8 - , CD3 + , TCRαβ + double-negative T cells in the circulating blood or dysfunctional T cell apoptosis in the Fas/Fas ligand pathway due to mutations in the FAS, FASLG or CASP10 genes. Combined autoimmune cytopenia is a rare clinical entity that in some cases co-occurs with other autoimmune diseases. Given that most SLE patients presenting atypical hematological manifestations at an early stage subsequently exhibit typical systemic manifestations, the present case raises the possibility that initial hematological abnormalities may be signs of unexpected SLE manifestations.

Nutritional status among pediatric cancer patients: a comparison between hematological malignancies and solid tumors.

PubMed

Tah, Pei Chien; Nik Shanita, Safii; Poh, Bee Koon

2012-10-01

This study aimed to compare the nutritional status of pediatric patients with hematological malignancies and solid tumors. A total of 74 pediatric cancer patients were assessed for anthropometric status, biochemical profiles, and dietary intake. The prevalence of undernutrition was higher among patients with solid tumors as reflected in their lower dietary intakes of energy and nutrients compared with patients with hematological malignancies. Adequate dietary intake is important for pediatric cancer patients, but nurses need to pay more attention to the diets of patients with solid tumors as compared with those with hematological malignancies. © 2012, Wiley Periodicals, Inc.

The Critical Role of Inflammation in the Pathogenesis and Progression of Myeloid Malignancies

PubMed Central

Craver, Brianna M.; El Alaoui, Kenza; Scherber, Robyn M.; Fleischman, Angela G.

2018-01-01

Hematopoietic stem cells (HSCs) maintain an organism’s immune system for a lifetime, and derangements in HSC proliferation and differentiation result in hematologic malignancies. Chronic inflammation plays a contributory if not causal role in HSC dysfunction. Inflammation induces HSC exhaustion, which promotes the emergence of mutant clones that may be resistant to an inflammatory microenvironment; this likely promotes the onset of a myeloid hematologic malignancy. Inflammatory cytokines are characteristically high in patients with myeloid malignancies and are linked to disease initiation, symptom burden, disease progression, and worsened prognostic survival. This review will cover our current understanding of the role of inflammation in the initiation, progression, and complications of myeloid hematologic malignancies, drawing from clinical studies as well as murine models. We will also highlight inflammation as a therapeutic target in hematologic malignancies. PMID:29614027

Allogeneic stem cell transplantation for acute myeloid leukemia with del(7q) following untreated chronic lymphocytic leukemia.

PubMed

DeFilipp, Zachariah; Huynh, Donny V; Fazal, Salman; Sahovic, Entezam

2012-01-01

The development of hematologic malignancy in the presence of chronic lymphocytic leukemia (CLL) is rare. We present a case of acute myeloid leukemia (AML) with del(7q) occurring in a patient with a 4-year history of untreated CLL. Application of flow cytometry and immunohistochemistry allowed for characterization of two distinct coexisting malignant cell populations. After undergoing induction and consolidation chemotherapy, the patient achieved complete remission of AML with the persistence of CLL. Allogeneic transplantation was pursued given his unfavorable cytogenetics. Subsequent matched unrelated donor allogeneic stem cell transplantation resulted in full engraftment and complete remission, with no evidence of AML or CLL. Due to a scarcity of reported cases, insight into treatment and prognosis in cases of concurrent AML and CLL is limited. However, prognosis seems dependent on the chemosensitivity of AML. CLL did not have a detrimental effect on treatment or transplant outcome in our case. This is the first reported case of concomitant de novo AML and CLL to undergo allogeneic transplantation. The patient remained in complete hematologic and cytogenetic remission of both malignancies over a year after transplantation.

Immunotherapy in hematologic malignancies: past, present, and future.

PubMed

Im, Annie; Pavletic, Steven Z

2017-04-24

The field of immunotherapy in cancer treatments has been accelerating over recent years and has entered the forefront as a leading area of ongoing research and promising therapies that have changed the treatment landscape for a variety of solid malignancies. Prior to its designation as the Science Breakthrough of the Year in 2013, cancer immunotherapy was active in the treatment of hematologic malignancies. This review provides a broad overview of the past, present, and potential future of immunotherapy in hematologic malignancies.

B-Cell Hematologic Malignancy Vaccination Registry

ClinicalTrials.gov

2017-12-29

Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Waldenstrom Macroglobulinemia; Lymphocytosis; Lymphoma, Non-Hodgkin; B-Cell Chronic Lymphocytic Leukemia; Hematological Malignancies

Residential radon exposure and risk of incident hematologic malignancies in the Cancer Prevention Study-II Nutrition Cohort

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teras, Lauren R., E-mail: lauren.teras@cancer.org; Diver, W. Ryan; Turner, Michelle C.

Dosimetric models show that radon, an established cause of lung cancer, delivers a non-negligible dose of alpha radiation to the bone marrow, as well as to lymphocytes in the tracheobronchial epithelium, and therefore could be related to risk of hematologic cancers. Studies of radon and hematologic cancer risk, however, have produced inconsistent results. To date there is no published prospective, population-based study of residential radon exposure and hematologic malignancy incidence. We used data from the American Cancer Society Cancer Prevention Study-II Nutrition Cohort established in 1992, to examine the association between county-level residential radon exposure and risk of hematologic cancer.more » The analytic cohort included 140,652 participants (66,572 men, 74,080 women) among which 3019 incident hematologic cancer cases (1711 men, 1308 women) were identified during 19 years of follow-up. Cox proportional hazard regression was used to calculate multivariable-adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for radon exposure and hematologic cancer risk. Women living in counties with the highest mean radon concentrations (>148 Bq/m{sup 3}) had a statistically significant higher risk of hematologic cancer compared to those living in counties with the lowest (<74 Bq/m{sup 3}) radon levels (HR=1.63, 95% CI:1.23–2.18), and there was evidence of a dose-response relationship (HR{sub continuous}=1.38, 95% CI:1.15–1.65 per 100 Bq/m{sup 3}; p-trend=0.001). There was no association between county-level radon and hematologic cancer risk among men. The findings of this large, prospective study suggest residential radon may be a risk factor for lymphoid malignancies among women. Further study is needed to confirm these findings. - Highlights: • This is the first prospective, general population study of residential radon and risk of hematologic cancer. • Findings from this study suggest that residential radon exposure may be a risk factor for lymphoid malignancies. • The biologic mechanism for the association between radon exposure and lymphoma risk may be different than for lung cancer. • Confirmation of this association would warrant strengthened public health efforts to mitigate residential radon risks.« less

Decision making in critically ill patients with hematologic malignancy.

PubMed Central

Crawford, S. W.

1991-01-01

Hematologic neoplasms that were previously considered fatal are now potentially curable with techniques such as bone marrow transplantation. Such therapies also carry significant morbidity and mortality. With the increasing application of these therapies, a growing number of physicians are using medical decision making regarding critical care for these patients. The process by which ethical decisions are reached for these critically ill patients may be baffling because of several factors: rapidly evolving treatments, uncertain probabilities of the cure of the malignant disorder, the relatively young age of many of these patients, and the poor prognosis with critical illness. I discuss a process to reach acceptable decisions, providing a case example of the application of the process. This process is derived from the ethical principles that drive decision making in general medicine and attempts to maximize patients' autonomy. It involves a consideration of accurate information regarding the disease process and the prognosis, a clear delineation of the goals of the medical care, and communication with patients. Appropriate, ethical, and consistent decisions regarding the critical care of patients with hematologic malignancy can be reached when these considerations are addressed. PMID:1815387

Early Non Invasive Ventilation and Hematological Malignancies

ClinicalTrials.gov

2018-01-03

Hematological Malignancies; Chronic Hypoxemic Respiratory Failure; Blood And Marrow Transplantation; Malignant Neoplasm of Breast; Malignant Neoplasms of Bone and Articular Cartilage; Malignant Neoplasms of Digestive Organs; Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System; Malignant Neoplasms of Female Genital Organs; Malignant Neoplasms of Ill-defined Secondary and Unspecified Sites; Malignant Neoplasms of Independent (Primary) Multiple Sites; Malignant Neoplasms of Lip Oral Cavity and Pharynx; Malignant Neoplasms of Male Genital Organs; Malignant Neoplasms of Mesothelial and Soft Tissue; Malignant Neoplasms of Respiratory and Intrathoracic Organs; Malignant Neoplasms of Thyroid and Other Endocrine Glands; Malignant Neoplasms of Urinary Tract; Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic

Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy.

PubMed

Malagoli, Carlotta; Fabbi, Sara; Teggi, Sergio; Calzari, Mariagiulia; Poli, Maurizio; Ballotti, Elena; Notari, Barbara; Bruni, Maurizio; Palazzi, Giovanni; Paolucci, Paolo; Vinceti, Marco

2010-03-30

Some epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested. We studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-<0.2, 0.2-<0.4, and > or = 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged <14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects. Relative risk of leukemia associated with antecedent residence in the area with exposure > or = 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies. Though the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation.

Bloodstream infections in patients with hematological malignancies: which is more fatal – cancer or resistant pathogens?

PubMed Central

Gedik, Habip; Şimşek, Funda; Kantürk, Arzu; Yildirmak, Taner; Arica, Deniz; Aydin, Demet; Demirel, Naciye; Yokuş, Osman

2014-01-01

Background The primary objective of this study was to report the incidence of bloodstream infections (BSIs) and clinically or microbiologically proven bacterial or fungal BSIs during neutropenic episodes in patients with hematological malignancies. Methods In this retrospective observational study, all patients in the hematology department older than 14 years who developed febrile neutropenia during chemotherapy for hematological cancers were evaluated. Patients were included if they had experienced at least one neutropenic episode between November 2010 and November 2012 due to chemotherapy in the hematology ward. Results During 282 febrile episodes in 126 patients, 66 (23%) episodes of bacteremia and 24 (8%) episodes of fungemia were recorded in 48 (38%) and 18 (14%) patients, respectively. Gram-negative bacteria caused 74% (n=49) of all bacteremic episodes. Carbapenem-resistant Gram-negative bacteria (n=6) caused 12% and 9% of Gram-negative bacteremia episodes and all bacteremia episodes, respectively. Carbapenem-resistant Gram-negative bacteria included Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=1), and Serratia marcescens (n=1). Culture-proven invasive fungal infection occurred in 24 episodes in 18 cases during the study period, with 15 episodes in ten cases occurring in the first study year and nine episodes in eight cases in the second study year. In 13 of 18 cases (72%) with bloodstream yeast infections, previous azole exposure was recorded. Candida parapsilosis, C. glabrata, and C. albicans isolates were resistant to voriconazole and fluconazole. Conclusion BSIs that occur during febrile neutropenic episodes in hematology patients due to Gram-negative bacteria should be treated initially with non-carbapenem-based antipseudomonal therapy taking into consideration antimicrobial stewardship. Non-azole antifungal drugs, including caspofungin and liposomal amphotericin B, should be preferred as empirical antifungal therapy in the events of possible or probable invasive fungal infections with an absence of pulmonary findings due to increase azole resistance. PMID:25258539

Thromboembolic complications following aminocaproic acid use in patients with hematologic malignancies.

PubMed

Juhl, Rebecca C; Roddy, Julianna V F; Wang, Tzu-Fei; Li, Junan; Elefritz, Jessica L

2018-02-09

Aminocaproic acid is frequently used in patients with hematologic malignancy that present with thrombocytopenia with or without hemorrhage. We conducted a retrospective study to evaluate the safety of aminocaproic acid in 109 patients with hematologic malignancies. Patients were included if aminocaproic acid had been administered for at least 24 hours for the prevention or treatment of thrombocytopenic hemorrhage. Our primary outcome was thromboembolic complications defined as arterial or venous thrombotic events objectively confirmed by imaging studies. Thromboembolic complications occurred in five patients (4.6%) and all were venous thromboses. Other than the underlying malignancy, these patients also had many concurrent risk factors including indwelling central venous catheters, which could have contributed to thromboses. In conclusion, in our population of patients with a variety of hematological malignancies, aminocaproic acid does not appear to be associated with a high incidence of thromboembolic complications.

The relationship between methylenetetrahydrofolate reductase polymorphism and hematological malignancy.

PubMed

Jiang, Ni; Zhu, Xishan; Zhang, Hongmei; Wang, Xiaoli; Zhou, Xinna; Gu, Jiezhun; Chen, Baoan; Ren, Jun

2014-01-01

Methylenetetrahydrofolate reductase (MTHFR) is the key enzyme for folate metabolism. Previous studies suggest a relationship between its single nucleotide polymorphisms (SNP) of C677T and A1298C with a variety of tumor susceptibility including hematological malignancy. SNP frequency distribution in different ethnic populations might lead to differences in disease susceptibility. There has been little research in Chinese people on the MTHFR SNP with the susceptibility of the hematological malignancy. Therefore, this study investigated the relationship between MTHFR SNPs and hematological malignancy in Jiangsu province in China. Gene microarray was used to detect MTHFR C677T and A1298C single nucleotide polymorphism loci on 157 healthy controls and 127 patients from Jiangsu province with hematological malignancies (30 with multiple myeloma, 28 with non-Hodgkin's lymphoma, 22 with acute lymphoblastic leukemia, 40 with acute myeloid leukemia, and seven with chronic myeloid leukemia). The allele frequency of 677T was 41.3% in patients and 33.1% in controls, showed significant difference (chi2 = 4.08, p = 0.043); 677TT genotype with a high susceptibility to hematological malignancy (OR 1.96, 95% CI 1.01 - 4.45, p = 0.041). In subgroup analyses, the genotypes 677TT and 1298CC were associated with significantly increased multiple myeloma risk (TT vs. CC: OR 8.92, 95% CI 1.06 - 75.24, p = 0.006; CC vs. AA: OR = 4.80, 95% CI 1.56 - 14.73, p = 0.044). No associations were found between polymorphisms and susceptibilities to acute lymphoblastic leukemia, acute myeloid leukemia, or non-Hodgkin's lymphoma. MTHFRC677T polymorphisms influence the risk of hematological malignancy among the population in Jiangsu province. Both MTHFR 677TT and MTHFR 1298CC genotypes increase susceptibility to myeloid leukemia.

Exploring Therapeutic Potentials of Baicalin and Its Aglycone Baicalein for Hematological Malignancies

PubMed Central

Chen, Haijun; Gao, Yu; Wu, Jianlei; Chen, Yingyu; Chen, Buyuan; Hu, Jianda; Zhou, Jia

2014-01-01

Despite tremendous advances in the targeted therapy for various types of hematological malignancies with successful improvements in the survival rates, emerging resistance issues are startlingly high and novel therapeutic strategies are urgently needed. In addition, chemoprevention is currently becoming an elusive goal. Plant-derived natural products have garnered considerable attention in recent years due to the potential dual functions as chemotherapeutics and dietary chemoprevention. One of the particularly ubiquitous families is the polyphenolic flavonoids. Among them, baicalin and its aglycone baicalein have been widely investigated in hematological malignancies because both of them exhibit remarkable pharmacological properties. This review focuses on the recent achievements in drug discovery research associated with baicalin and baicalein for hematological malignancy therapies. The promising anticancer activities of these two flavonoids targeting diverse signaling pathways and their potential biological mechanisms in different types of hematological malignancies, as well as the combination strategy with baicalin or baicalein as chemotherapeutic adjuvants for recent therapies in these intractable diseases are discussed. Meanwhile, the biotransformation of baicalin and baicalein and the relevant approaches to improve their bioavailability are also summarized. PMID:25128647

THE DIFFERENTIAL ALGORITHM BETWEEN RHEUMATOLOGIC AND MALIGN DISEASES

PubMed Central

Këpuska, Arbnore Batalli; Spahiju, Lidvana; Bejiq, Ramush; Manqestena, Rufadije; Stavileci, Valbona; Ibraimi, Zana

2016-01-01

Objective: The aim of this study is to determine the differential algorithm between rheumatism and malignant diseases. For every pediatrician, to be warned when attending joint pain and child arthralgia and prevent and treat within time malignant diseases. Methods: Our case presented in Pediatric Clinic, was referred by Regional Hospital of Ferizaj with suspected diagnose of Febris Rheumatica and Arthralgia. The main complaint was joint pain. Initially the patient was admitted at Cardiology and Rheumatology department. Then after examinations was referred to Hemato-Oncology department. Hospitalized during the period from 12.12.2014 to 18.01.2015. Results: Bone marrow biopsy as terminal diagnostic tool reviled severe malignant hematologic disease, which was masked by clinical and lab findings as Febris Rheumatica. Conclusion: Arthralgia as one of child’s often complain, should have a special attention paid to, as it might be a warning sign for a lot of diseases. Steroid treatment should not be used before final diagnose of the disease and before rolling out hematologic etiology with peripheral blood smear. PMID:27147926

Sex chromosome loss and the pseudoautosomal region genes in hematological malignancies

PubMed Central

Weng, Stephanie; Stoner, Samuel A.; Zhang, Dong-Er

2016-01-01

Cytogenetic aberrations, such as chromosomal translocations, aneuploidy, and amplifications, are frequently detected in hematological malignancies. For many of the common autosomal aberrations, the mechanisms underlying their roles in cancer development have been well-characterized. On the contrary, although loss of a sex chromosome is observed in a broad range of hematological malignancies, how it cooperates in disease development is less understood. Nevertheless, it has been postulated that tumor suppressor genes reside on the sex chromosomes. Although the X and Y sex chromosomes are highly divergent, the pseudoautosomal regions are homologous between both chromosomes. Here, we review what is currently known about the pseudoautosomal region genes in the hematological system. Additionally, we discuss implications for haploinsufficiency of critical pseudoautosomal region sex chromosome genes, driven by sex chromosome loss, in promoting hematological malignancies. Because mechanistic studies on disease development rely heavily on murine models, we also discuss the challenges and caveats of existing models, and propose alternatives for examining the involvement of pseudoautosomal region genes and loss of a sex chromosome in vivo. With the widespread detection of loss of a sex chromosome in different hematological malignances, the elucidation of the role of pseudoautosomal region genes in the development and progression of these diseases would be invaluable to the field. PMID:27655702

Bronchoscopic diagnosis of pulmonary infiltrates in granulocytopenic patients with hematologic malignancies: BAL versus PSB and PBAL.

PubMed

Boersma, Wim G; Erjavec, Zoran; van der Werf, Tjip S; de Vries-Hosper, Hilly G; Gouw, Annette S H; Manson, Willem L

2007-02-01

Treatment of patients with hematologic malignancies is often complicated by severe respiratory infections. Bronchoscopy is generally to be used as a diagnostic tool in order to find a causative pathogen. In a prospective study the combination of protected specimen brush (PSB) and protected bronchoalveolar lavage (PBAL) was compared with bronchoalveolar lavage (BAL) for evaluated feasibility and diagnostic yield in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. All specimens from 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) were investigated by cytological examination and various microbiological tests. If clinically relevant and feasible, based on the clinical condition and/or the presence of thrombocytopenia, lung tissue samples were obtained. The majority of the 58 included patients were diagnosed as having acute myeloid leukaemia and developed a severe neutropenia (BAL-group: 27 days; PSB-PBAL group: 30 days). Microbiological and cytological examination of 63 bronchoscopic procedures (35 BAL and 28 PSB-PBAL) yielded causative pathogens in 9 (26%) patients of the BAL-group and 8 (29%) patients of the PSB-PBAL group (PSB and PBAL 4 each). Aspergillus fumigatus was the pathogen most frequently (13%) detected. Using all available examinations including the results of autopsy, a presumptive diagnosis was established in 43% of the patients in the BAL group and 57% of those in the PSB-PBAL group; in these cases microbial aetiology was correctly identified in 67% and 57%, respectively. The complication rate was of these procedures were low, and none of the patients experienced serious complications due to the invasive techniques. Our results showed that modern bronchoscopic techniques such as PSB and PBAL did not yield better diagnostic results compared to BAL in granulocytopenic patients with hematologic malignancies and pulmonary infiltrates. In approximately half of the cases a presumptive diagnosis was made by bronchoscopic procedures.

BCL-2 as therapeutic target for hematological malignancies.

PubMed

Perini, Guilherme Fleury; Ribeiro, Glaciano Nogueira; Pinto Neto, Jorge Vaz; Campos, Laura Tojeiro; Hamerschlak, Nelson

2018-05-11

Disruption of the physiologic balance between cell proliferation and cell death is an important step of cancer development. Increased resistance to apoptosis is a key oncogenic mechanism in several hematological malignancies and, in many cases, especially in lymphoid neoplasias, has been attributed to the upregulation of BCL-2. The BCL-2 protein is the founding member of the BCL-2 family of apoptosis regulators and was the first apoptosis modulator to be associated with cancer. The recognition of the important role played by BCL-2 for cancer development and resistance to treatment made it a relevant target for therapy for many diseases, including solid tumors and hematological neoplasias. Among the different strategies that have been developed to inhibit BCL-2, BH3-mimetics have emerged as a novel class of compounds with favorable results in different clinical settings, including chronic lymphocytic leukemia (CLL). In April 2016, the first inhibitor of BCL-2, venetoclax, was approved by the US Food and Drug Administration for the treatment of patients with CLL who have 17p deletion and had received at least one prior therapy. This review focuses on the relevance of BCL-2 for apoptosis modulation at the mitochondrial level, its potential as therapeutic target for hematological malignancies, and the results obtained with selective inhibitors belonging to the BH3-mimetics, especially venetoclax used in monotherapy or in combination with other agents.

Venetoclax and low-dose cytarabine induced complete remission in a patient with high-risk acute myeloid leukemia: a case report.

PubMed

Liu, Bingshan; Narurkar, Roshni; Hanmantgad, Madhura; Zafar, Wahib; Song, Yongping; Liu, Delong

2018-05-21

Conventional combination therapies have not resulted in considerable progress in the treatment of acute myeloid leukemia (AML). Elderly patients with AML and poor risk factors have grave prognosis. Midostaurin has been recently approved for the treatment of FLT-3-mutated AML. Venetoclax, a BCL-2 inhibitor, has been approved for the treatment of relapsed and/or refractory chronic lymphoid leukemia. Clinical trials on applying venetoclax in combination with cytarabine and other agents to treat various hematological malignancies are currently underway. Here, we present a case of a male patient with poor performance status and who developed AML following allogeneic hematopoietic stem cell transplant for high-risk myelodysplasia. The patient with high risk AML achieved complete response to the combined treatment regimen of low-dose cytarabine and venetoclax. Furthermore, we reviewed current clinical trials on the use of venetoclax for hematological malignancies.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

[Hematologic malignancies in pregnancy].

PubMed

Doubek, R; Petrovová, D; Kalvodová, J; Doubek, M

2009-04-01

To summarize available data concerning hematologic malignancies in pregnancy. Review article. Department of Obstetrics and Gynekology, Fakulty of Medicine, Masaryk University and University Hospital Brno. Compilation of published data from scientific literature. Cancer complicating pregnancy is a rare coexistence. The incidence is approximately 1 in 1,000 pregnancies. The most frequent hematologic malignant tumor is Hodgkin's lymphoma, leukemia is less frequent and myeloproliferative diseases complicating pregnancy are sporadic coexistence. Symptoms of these deseases are often nonspecific and disguised in pregnancy, then the diagnosis can be late. It is imperative that a multidisciplinary team involving hematooncologist and obstetrician (pediatric specialist) care for patient with hematologic malignancies. Cleary, every patient have to know whole prognosis and all risk factors of treatment. Optimum timing of delivery is after 36th week of pregnancy (when chemotherapy is ended more than two weeks ago). We prefer vaginal delivery to caesarean section.

The simultaneous occurrence of multiple myeloma and JAK2 positive myeloproliferative neoplasms - Report on two cases

PubMed Central

Badelita, S; Dobrea, C; Colita, A; Dogaru, M; Dragomir, M; Jardan, C; Coriu, D

2015-01-01

Multiple myeloma and JAK2 positive chronic myeloproliferative neoplasms are hematologic malignancies with a completely different cellular origin. Two cases of simultaneous occurrence of multiple myeloma, one with primary myelofibrosis and another one with essential thrombocythemia are reported in this article. In such cases, an accurate diagnosis requires a molecular testing, including gene sequencing and differential diagnosis of pancytosis associated with splenic amyloidosis. In general, in such cases, of two coexisting malignant hematologic diseases, the treatment of the most aggressive one is recommended. For our two cases, it was decided to start a Velcade based therapy. The main concern was the medullar toxicity, especially when a multiple myeloma was associated with a primary myelofibrosis. Abbreviations:JAK2 = Janus kinase 2 gene, PMF = primary myelofibrosis, MPNs = myeloproliferative neoplasms, ET = essential thrombocythemia, PV = polycythemia vera, MM = multiple myeloma, WBC = white blood cells, Hb = haemoglobin, Ht = haematocrit, Plt = platelets, BMB = bone marrow biopsy, CBC = blood cell count, CT = computerized tomography, LAP = leukocyte alkaline phosphatase, MGUS = monoclonal gammopathy of undetermined significance. PMID:25914740

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals.

PubMed

Hossain, Mohammad Sorowar; Iqbal, Mohd S; Khan, Mohiuddin Ahmed; Rabbani, Mohammad Golam; Khatun, Hazera; Munira, Sirajam; Miah, M Morshed Zaman; Kabir, Amin Lutful; Islam, Naima; Dipta, Tashmim Farhana; Rahman, Farzana; Mottalib, Abdul; Afrose, Salma; Ara, Tasneem; Biswas, Akhil Ranjan; Rahman, Mizanur; Abedin, Akm Mustafa; Rahman, Mahbubur; Yunus, A B M; Niessen, Louis W; Sultana, Tanvira Afroze

2014-06-14

The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the "French American British" classification system. A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n=3468) and 30.8% females (n=1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin's lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country.

Diagnosed hematological malignancies in Bangladesh - a retrospective analysis of over 5000 cases from 10 specialized hospitals

PubMed Central

2014-01-01

Background The global burden from cancer is rising, especially as low-income countries like Bangladesh observe rapid aging. So far, there are no comprehensive descriptions reporting diagnosed cancer group that include hematological malignancies in Bangladesh. Methods This was a multi-center hospital-based retrospective descriptive study of over 5000 confirmed hematological cancer cases in between January 2008 to December 2012. Morphological typing was carried out using the “French American British” classification system. Results A total of 5013 patients aged between 2 to 90 years had been diagnosed with malignant hematological disorders. A 69.2% were males (n = 3468) and 30.8% females (n = 1545), with a male to female ratio of 2.2:1. The overall median age at diagnosis was 42 years. Acute myeloid leukemia was most frequent (28.3%) with a median age of 35 years, followed by chronic myeloid leukemia with 18.2% (median age 40 years), non-Hodgkin lymphoma (16.9%; median age 48 years), acute lymphoblastic leukemia (14.1%; median age 27 years), multiple myeloma (10.5%; median age 55 years), myelodysplastic syndromes (4.5%; median age 57 years) and Hodgkin’s lymphoma (3.9%; median age 36 years). The least common was chronic lymphocytic leukemia (3.7%; median age 60 years). Below the age of 20 years, acute lymphoblastic leukemia was predominant (37.3%), followed by acute myeloid leukemia (34%). Chronic lymphocytic leukemia and multiple myeloma had mostly occurred among older patients, aged 50-over. Conclusions For the first time, our study presents the pattern and distribution of diagnosed hematological cancers in Bangladesh. It shows differences in population distributions as compared to other settings with possibly a lower presence of non-Hodgkin lymphoma. There might be under-reporting of affected women. Further studies are necessary on the epidemiology, genetics and potential environmental risk factors within this rapidly aging country. PMID:24929433

Mold colonization of fiberglass insulation of the air distribution system: effects on patients with hematological malignancies.

PubMed

Takuma, Takahiro; Okada, Kaoru; Yamagata, Akihiro; Shimono, Nobuyuki; Niki, Yoshihito

2011-02-01

We investigated mold colonization of air handling units (AHUs) of heating, ventilating, and air conditioning (HVAC) systems and its effects, including invasive pulmonary mycoses and febrile neutropenia, in patients with hematological malignancies. Sample collection with transparent adhesive tape and culture swabs revealed that AHUs were heavily colonized with molds, including thermotolerant, variously distributed Penicillium spp. Cases of nosocomial invasive pulmonary mycosis were not clustered in specific patient rooms but did occur frequently when the HVAC systems were not in use, prior to intervention (i.e., sealing and disuse of AHUs in private room), and during construction of a new hospital building. Multivariate logistic regression analysis of initial episodes of febrile neutropenia showed that the rate of febrile neutropenia was significantly associated with the duration of neutropenia (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.07-1.27) and with sex (OR: 0.469; CI: 0.239-0.902). An evaluation of private rooms showed that female patients also had a lower rate of fever after intervention (OR: 0.0016; 95% CI: 0.000-0.209). The reduced rate of febrile neutropenia after intervention suggests that mold colonization of AHUs had adverse effects on patients with hematological malignancies.

Mucorales-Specific T Cells in Patients with Hematologic Malignancies.

PubMed

Potenza, Leonardo; Vallerini, Daniela; Barozzi, Patrizia; Riva, Giovanni; Gilioli, Andrea; Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Lewis, Russell E; Luppi, Mario

2016-01-01

Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM.

Risk of hematological malignancies associated with magnetic fields exposure from power lines: a case-control study in two municipalities of northern Italy

PubMed Central

2010-01-01

Background Some epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results have also been yielded and the possibility of bias due to unmeasured confounders has been suggested. Methods We studied this relation in the Modena and Reggio Emilia municipalities of northern Italy, identifying the corridors along high voltage power lines with calculated magnetic field intensity in the 0.1-<0.2, 0.2-<0.4, and ≥ 0.4 microTesla ranges. We identified 64 cases of newly-diagnosed hematological malignancies in children aged <14 within these municipalities from 1986 to 2007, and we sampled four matched controls for each case, collecting information on historical residence and parental socioeconomic status of these subjects. Results Relative risk of leukemia associated with antecedent residence in the area with exposure ≥ 0.1 microTesla was 3.2 (6.7 adjusting for socioeconomic status), but this estimate was statistically very unstable, its 95% confidence interval being 0.4-23.4, and no indication of a dose-response relation emerged. Relative risk for acute lymphoblastic leukemia was 5.3 (95% confidence interval 0.7-43.5), while there was no increased risk for the other hematological malignancies. Conclusions Though the number of exposed children in this study was too low to allow firm conclusions, results were more suggestive of an excess risk of leukemia among exposed children than of a null relation. PMID:20353586

Successful treatment of cerebral aspergillosis: case report of a patient with T-cell large granular lymphocytic leukemia (T-LGL).

PubMed

Turki, Amin T; Rashidi-Alavijeh, Jassin; Dürig, Jan; Gerken, Guido; Rath, Peter-Michael; Witzke, Oliver

2017-12-28

Invasive aspergillosis involving patients with neutropenia or severe immunosuppression, such as patients with hematologic malignancies is associated with high mortality. Patients with T-cell large granular lymphocytic leukemia (T-LGL) on the other hand are considered to be less vulnerable for severe opportunistic fungal infection as their course of disease is chronic and marked by less violent cytopenia then in e.g. Aplastic Anemia. Only neutropenia is regarded as independent risk factor for severe opportunistic infection in T-LGL patients. We report a case of a 53 year old patient with T-LGL, Immune-Thrombocytopenia (ITP) and combined antibody deficiency, who presented with fever and reduced general condition. The patient revealed a complicated infection involving the lungs and later the brain, with the presentation of vomiting and seizures. Broad microbiological testing of blood-, lung- and cerebrospinal fluid samples was inconclusive. In the absence of mycological proof, Aspergillus infection was confirmed by pathological examination of a brain specimen and finally successfully treated with liposomal amphotericin B and voriconazole, adopting a long-term treatment scheme. Beyond typical problems in the clinical practice involving fungal infections and hematologic malignancies, this case of invasive aspergillosis in a patient with T-LGL illustrates caveats in diagnosis, therapy and follow-up. Our data support careful ambulatory monitoring for patients with T-LGL, even in the absence of neutropenia. Especially those patients with combined hematologic malignancies and immune defects are at risk. Long-term treatment adhesion for 12 months with sufficient drug levels was necessary for sustained clearance from infection.

Meeting the challenge of hematologic malignancies in sub-Saharan Africa

PubMed Central

Wood, William A.; Lee, Stephanie J.; Shea, Thomas C.; Naresh, Kikkeri N.; Kazembe, Peter N.; Casper, Corey; Hesseling, Peter B.; Mitsuyasu, Ronald T.

2012-01-01

Cancer is a leading cause of death and disability in sub-Saharan Africa and will eclipse infectious diseases within the next several decades if current trends continue. Hematologic malignancies, including non-Hodgkin lymphoma, leukemia, Hodgkin lymphoma, and multiple myeloma, account for nearly 10% of the overall cancer burden in the region, and the incidence of non-Hodgkin lymphoma and Hodgkin lymphoma is rapidly increasing as a result of HIV. Despite an increasing burden, mechanisms for diagnosing, treating, and palliating malignant hematologic disorders are inadequate. In this review, we describe the scope of the problem, including the impact of endemic infections, such as HIV, Epstein-Barr virus, malaria, and Kaposi sarcoma–associated herpesvirus. We additionally describe current limitations in hematopathology, chemotherapy, radiotherapy, hematopoietic stem cell transplantation, and supportive care and palliation. We review contemporary treatment and outcomes of hematologic malignancies in the region and outline a clinical service and research agenda, which builds on recent global health successes combating HIV and other infectious diseases. Achieving similar progress against hematologic cancers in sub-Saharan Africa will require the sustained collaboration and advocacy of the entire global cancer community. PMID:22461494

Constitutional mismatch repair deficiency syndrome: Do we know it?

PubMed

Ramachandra, C; Challa, Vasu Reddy; Shetty, Rachan

2014-04-01

Constitutional mismatch repair deficiency syndrome is a rare autosomal recessive syndrome caused by homozygous mutations in mismatch repair genes. This is characterized by the childhood onset of brain tumors, colorectal cancers, cutaneous manifestations of neurofibromatosis-1 like café au lait spots, hematological malignancies, and occasionally other rare malignancies. Here, we would like to present a family in which the sibling had glioblastoma, and the present case had acute lymphoblastic lymphoma and colorectal cancer. We would like to present this case because of its rarity and would add to literature.

A Feasibility Study of Virtual Reality Exercise in Elderly Patients with Hematologic Malignancies Receiving Chemotherapy.

PubMed

Tsuda, Kenji; Sudo, Kazuaki; Goto, Goro; Takai, Makiko; Itokawa, Tatsuo; Isshiki, Takahiro; Takei, Naoko; Tanimoto, Tetsuya; Komatsu, Tsunehiko

2016-01-01

Adherence to rehabilitation exercise is much lower in patients with hematologic malignancies (22.5-45.8%) than in patients with solid tumors (60-85%) due to the administration of more intensive chemotherapeutic regimens in the former. Virtual reality exercise can be performed even in a biological clean room and it may improve the adherence rates in elderly patients with hematologic malignancies. Thus, in this pilot study, we aimed to investigate the feasibility and safety of virtual reality exercise intervention using Nintendo Wii Fit in patients with hematologic malignancies receiving chemotherapy. In this feasibility study, 16 hospitalized patients with hematologic malignancies aged ≥60 years performed virtual reality exercise for 20 minutes using the Nintendo Wii Fit once a day, five times a week, from the start of chemotherapy until hospital discharge. The adherence rate, safety, and physical and psychological performances were assessed. The adherence rate for all 16 patients was 66.5%. Nine patients completed the virtual reality exercise intervention with 88 sessions, and the adherence rate was 62.0%. No intervention-related adverse effects >Grade 2, according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, were observed. We noted maintenance of the physical performance (e.g., Barthel index, handgrip strength, knee extension strength, one-leg standing time, and the scores of timed up and go test and Instrumental Activities of Daily Living) and psychosocial performance (e.g., score of hospital anxiety and depression scale). Virtual reality exercise using the Wii Fit may be feasible, safe and efficacious, as demonstrated in our preliminary results, for patients with hematologic malignancies receiving chemotherapy.

Neurological failure in ICU patients with hematological malignancies: A prospective cohort study.

PubMed

Marzorati, Chiara; Mokart, Djamel; Pène, Frederic; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Benoit, Dominique; Citerio, Giuseppe; Azoulay, Elie; Legriel, Stephane

2017-01-01

Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure. Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010-2012). The primary outcome was vital status at hospital discharge. Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status (odds ratio [OR], 3.99; 95%CI, 1.82-9.39; P = 0.0009), non-Hodgkin's lymphoma (OR, 2.60; 95%CI, 1.35-5.15; P = 0.005), shock (OR, 1.95; 95%CI, 1.04-3.72; P = 0.04), and respiratory failure (OR, 2.18; 95%CI, 1.14-4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 (OR, 0.88/point; 95%CI, 0.81-0.95; P = 0.0009) and autologous stem cell transplantation (OR, 0.25; 95%CI, 0.07-0.75; P = 0.02). In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies.

Hemorrhagic pericardial effusion as the debut of acquired hemophilia in a chronic lymphocytic leukemia patient

PubMed Central

Bastida, José María; Cano-Mozo, María Teresa; Lopez-Cadenas, Felix; Vallejo, Victor Eduardo; Merchán, Soraya; Santos-Montón, Cecilia; González-Calle, David; Carrillo, Javier; Martín, Ana Africa; Torres-Hernández, Jose Angel; González, Marcos; Martín-Herrero, Francisco; Pabón, Pedro; González-Porras, Jose Ramon

2017-01-01

Abstract Background: Acquired hemophilia A (AHA) is a rare bleeding disease caused by autoantibodies against factor VIII. Spontaneous bleeding symptoms usually affect the skin and muscle, while pericardial effusion is an extremely rare manifestation. In the elderly, anticoagulant treatment is frequent and bleeding symptoms are usually associated with this. Clinical findings: We report a hemorrhagic pericardial effusion as the AHA debut in a patient with untreated chronic lymphocytic leukemia and anticoagulated with apixaban for atrial fibrillation and chronic arterial ischemia. The patient was treated with recombinant activated factor VII to control the active bleeding and corticosteroids and cyclophosphamide to eradicate the inhibitor. In addition, a briefly review of hematological malignancies associated to acquired hemophilia was performed. Particularities: a) anticoagulant treatment may confuse the suspicion of AHA and its diagnosis; b) hemorrhagic pericardial effusion is an extremely rare presentation; c) bypassing agents raise the risk of thromboembolism; d) hematological malignancies rarely cause AHA (<20% of cases). Conclusion: A multidisciplinary team is needed to diagnose and manage AHA effectively. The use of anticoagulants may lead to the misdiagnosis of clinical symptoms. Chronic lymphocytic leukemia is one of the main causes of hematological malignancies associated. The specific treatment of CLL is still recommended in the event of active disease. PMID:29381944

Targeting MDM4 as a Novel Therapeutic Approach for Hematologic Malignancies.

PubMed

Cao, Lei; Fan, Lei; Xu, Wei; Li, Jian-Yong

2015-01-01

Mouse double minute 4 (MDM4) as a member of MDM family, is an oncogene emerging as an imperative negative regulator of p53. Tumor suppressor protein p53 plays a crucial role in cell cycle arrest, apoptosis and homeostasis. It has been reported that frequent inactivation of p53 was observed in numerous human cancers including hematologic malignancies. MDM4, the newly discovered modulator of p53 protein, is frequently amplified in various solid tumors such as cutaneous melanoma, retinoblastoma and hematological malignances such as chronic lymphocytic leukemia, acute myeloid leukemia and mantle cell lymphoma. Multiple evidences implicate that over-expression of MDM4 is associated with tumor progression and poor prognosis which can be reversed by knockdown of MDM4 expression or restoration of p53 function, and support the rationale for the design of future MDM4-specific therapeutics. This article discusses and focuses on using MDM4 as a novel biomarker as well as a therapeutic target for hematologic malignancies.

Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies.

PubMed

Sun, Chuang; Dotti, Gianpietro; Savoldo, Barbara

2016-06-30

Hematologic malignancies provide a suitable testing environment for cell-based immunotherapies, which were pioneered by the development of allogeneic hematopoietic stem cell transplant. All types of cell-based therapies, from donor lymphocyte infusion to dendritic cell vaccines, and adoptive transfer of tumor-specific cytotoxic T cells and natural killer cells, have been clinically translated for hematologic malignancies. The recent success of chimeric antigen receptor-modified T lymphocytes in B-cell malignancies has stimulated the development of this approach toward other hematologic tumors. Similarly, the remarkable activity of checkpoint inhibitors as single agents has created enthusiasm for potential combinations with other cell-based immune therapies. However, tumor cells continuously develop various strategies to evade their immune-mediated elimination. Meanwhile, the recruitment of immunosuppressive cells and the release of inhibitory factors contribute to the development of a tumor microenvironment that hampers the initiation of effective immune responses or blocks the functions of immune effector cells. Understanding how tumor cells escape from immune attack and favor immunosuppression is essential for the improvement of immune cell-based therapies and the development of rational combination approaches. © 2016 by The American Society of Hematology.

Cutaneous xanthogranulomas, hepatosplenomegaly, anemia, and thrombocytopenia as presenting signs of juvenile myelomonocytic leukemia.

PubMed

Cham, Elaine; Siegel, Dawn; Ruben, Beth S

2010-01-01

The development of xanthogranulomas has been linked to hematologic malignancies in children and adults, based on a number of reports in the literature. In children, a specific association between juvenile xanthogranuloma, neurofibromatosis 1, and juvenile myelomonocytic leukemia has been described. We report a case of a 9-month-old child, without a known diagnosis of neurofibromatosis 1, who presented with hepatosplenomegaly, anemia, thrombocytopenia, and multiple cutaneous nodules, which were confirmed to be juvenile xanthogranulomas upon biopsy. A concurrent work-up showed that the child had juvenile myelomonocytic leukemia. Although cutaneous juvenile xanthogranulomas are benign lesions, in several reported cases they have been shown to herald leukemia. This association between xanthogranulomas and hematologic malignancy is poorly understood. Juvenile xanthogranulomas have a number of morphologic variants and clinical presentations that can be confused with the cutaneous lesions of Langerhans cell histiocytosis and dermatofibroma. Recognition of the broad clinicopathologic spectrum of juvenile xanthogranulomas is critical for proper diagnosis.

Recurrent skin eruption in patient with chronic lymphocytic leukemia and lymphocytic infiltrates of the dermis resembling Sweet's syndrome.

PubMed

Wawrzycki, B; Chodorowska, G; Pietrzak, A; Krasowska, D W; Wąsik, Sz; Dybiec, E; Lotti, T; Hercegova, J

2011-12-01

Sweet's syndrome (acute febrile dermatosis) is characterized by fever, peripheral neutrophil leukocytosis, acute onset of tender erythematous skin lesions (papules, nodules or plaques), and histological findings of a dense infiltrate consisting predominantly of mature neutrophils. Malignancy-associated Sweet's syndrome constitutes approximately 21% of patients, the majority of whom suffer from hematologic disorder. We report the case of patient with chronic lymphocytic leukemia with recurrent eruptions of tender, pseudovesiculated nodules and plaques with good response to corticosteroid therapy, resembling Sweet's syndrome. However, histological examination revealed lymphocytic infiltrate in the dermis, which made impossible to establish diagnosis of acute febrile dermatosis according to diagnostic criteria. Association of the skin eruptions with leukemia was implied by improvement of skin lesions after chemotherapy. We present review of the literature reporting cases with atypical histopathological presentations which preceded classical histological appearances, that were mainly associated with hematological malignancies and discuss them in the context of our patient.

Role of IL-9 and STATs in hematological malignancies (Review).

PubMed

Chen, Na; Wang, Xin

2014-03-01

Although interleukin-9 (IL-9) exhibits pleiotropic functions in the immune system, it remains a well-known cytokine in hematological malignancies. Previous cell culture and animal model studies have revealed that the Janus kinase-signal transducer and activator of transcription signaling pathway, which may be activated by a number of cytokines including IL-9, is critical in hematological malignancies. The current review summarizes the characterization of the biological activities of IL-9, highlights the clearly defined roles of the cytokine, and outlines questions with regard to the functions of IL-9 that require further exploration and their downstream signaling proteins, signal transducers and activators of transcription.

Urine Galactomannan-to-Creatinine Ratio for Detection of Invasive Aspergillosis in Patients with Hematological Malignancies.

PubMed

Reischies, Frederike M J; Raggam, Reinhard B; Prattes, Juergen; Krause, Robert; Eigl, Susanne; List, Agnes; Quehenberger, Franz; Strenger, Volker; Wölfler, Albert; Hoenigl, Martin

2016-03-01

Galactomannan (GM) testing of urine specimens may provide important advantages, compared to serum testing, such as easy noninvasive sample collection. We evaluated a total of 632 serial urine samples from 71 patients with underlying hematological malignancies and found that the urine GM/creatinine ratio, i.e., (urine GM level × 100)/urine creatinine level, which takes urine dilution into account, reliably detected invasive aspergillosis and may be a promising diagnostic tool for patients with hematological malignancies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01576653.). Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Is there an association with constitutional structural chromosomal abnormalities and hematologic neoplastic process? A short review.

PubMed

Panani, Anna D

2009-04-01

The occasional observation of constitutional chromosomal abnormalities in patients with a malignant disease has led to a number of studies on their potential role in cancer development. Investigations of families with hereditary cancers and constitutional chromosomal abnormalities have been key observations leading to the molecular identification of specific genes implicated in tumorigenesis. Large studies have been reported on the incidence of constitutional chromosomal aberrations in patients with hematologic malignancies, but they could not confirm an increased risk for hematologic malignancy among carriers of structural chromosomal changes. However, it is of particular interest that constitutional structural aberrations with breakpoints similar to leukemia-associated specific breakpoints have been reported in patients with hematologic malignancies. Because of insufficient data, it remains still unclear if these aberrations represent random events or are associated with malignancy. There has been a substantial discussion about mechanisms involved in constitutional structural chromosomal changes in the literature. The documentation of more patients with constitutional structural chromosomal changes could be of major importance. Most importantly, the molecular investigation of chromosomal regions involved in rearrangements could give useful information on the genetic events underlying constitutional anomalies, contributing to isolation of genes important in the development of the neoplastic process. Regarding constitutional anomalies in patients with hematologic disorders, a survey of the cytogenetic data of our cytogenetics unit is herein also presented.

Treatment of Febrile Neutropenia and Prophylaxis in Hematologic Malignancies: A Critical Review and Update

PubMed Central

Villafuerte-Gutierrez, Paola; Villalon, Lucia; Losa, Juan E.; Henriquez-Camacho, Cesar

2014-01-01

Febrile neutropenia is one of the most serious complications in patients with haematological malignancies and chemotherapy. A prompt identification of infection and empirical antibiotic therapy can prolong survival. This paper reviews the guidelines about febrile neutropenia in the setting of hematologic malignancies, providing an overview of the definition of fever and neutropenia, and categories of risk assessment, management of infections, and prophylaxis. PMID:25525436

Acute lymphoblastic leukemia and lymphoma in the context of constitutional mismatch repair deficiency syndrome.

PubMed

Ripperger, Tim; Schlegelberger, Brigitte

2016-03-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is one of the rare diseases associated with a high risk of cancer. Causative mutations are found in DNA mismatch repair genes PMS2, MSH6, MSH2 or MLH1 that are well known in the context of Lynch syndrome. CMMRD follows an autosomal recessive inheritance trait and is characterized by childhood brain tumors and hematological malignancies as well as gastrointestinal cancer in the second and third decades of life. There is a high risk of multiple cancers, occurring synchronously and metachronously. In general, the prognosis is poor. About one third of CMMRD patients develop hematological malignancies as primary (sometimes the only) malignancy or as secondary neoplasm. T-cell non-Hodgkin lymphomas, mainly of mediastinal origin, are the most frequent hematological malignancies. Besides malignant diseases, non-neoplastic features are frequently observed, e.g. café-au-lait spots sometimes resembling neurofibromatosis type I, hypopigmented skin lesions, numerous adenomatous polyps, multiple pilomatricomas, or impaired immunoglobulin class switch recombination. Within the present review, we summarize previously published CMMRD patients with at least one hematological malignancy, provide an overview of steps necessary to substantiate the diagnosis of CMMRD, and refer to the recent most relevant literature. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Stop and go: hematopoietic cell transplantation in the era of chimeric antigen receptor T cells and checkpoint inhibitors.

PubMed

Ghosh, Arnab; Politikos, Ioannis; Perales, Miguel-Angel

2017-11-01

For several decades, hematopoietic cell transplantation (HCT) has been considered the standard curative therapy for many patients with hematological malignancies. In addition to the cytotoxic effects of the chemotherapy and radiation used in the conditioning regimen, the benefits of HCT are derived from a reset of the immune system and harnessing the ability of donor T cells to eliminate malignant cells. With the dawn of the era of immunotherapies in the form of checkpoint inhibitors and chimeric antigen receptor (CAR) T cells, the role of HCT has evolved. Immunotherapy with checkpoint inhibitors is increasingly being used for relapsed Hodgkin and non-Hodgkin lymphoma after autologous HCT. Checkpoint inhibitors are also being tested after allogeneic HCT with observable benefits in treating hematological malignancies, but with a potential risk of increased graft versus host disease and transplant-related mortality. Immunotherapy with Cluster of differentiation 19 CAR T cells are powerful options with aggressive B-cell malignancies both for therapy and as induction leading to allogeneic HCT. Although immunotherapies with checkpoint inhibition and CAR T cells are increasingly being used to treat hematological malignancies, HCT remains a standard of care for most of the diseases with the best chance of cure. Combination of these therapies with HCT has the potential to more effectively treat hematological malignancies.

Musculoskeletal Imaging Findings of Hematologic Malignancies.

PubMed

Navarro, Shannon M; Matcuk, George R; Patel, Dakshesh B; Skalski, Matthew; White, Eric A; Tomasian, Anderanik; Schein, Aaron J

2017-01-01

Hematologic malignancies comprise a set of prevalent yet clinically diverse diseases that can affect every organ system. Because blood components originate in bone marrow, it is no surprise that bone marrow is a common location for both primary and metastatic hematologic neoplasms. Findings of hematologic malignancy can be seen with most imaging modalities including radiography, computed tomography (CT), technetium 99m ( 99m Tc) methylene diphosphonate (MDP) bone scanning, fluorine 18 ( 18 F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, and magnetic resonance (MR) imaging. Because of the diversity of imaging appearances and clinical behavior of this spectrum of disease, diagnosis can be challenging, and profound understanding of the underlying pathophysiologic changes and current treatment modalities can be daunting. The appearance of normal bone marrow at MR imaging and FDG PET/CT is also varied due to dynamic compositional changes with normal aging and in response to hematologic demand or treatment, which can lead to false-positive interpretation of imaging studies. In this article, the authors review the normal maturation and imaging appearance of bone marrow. Focusing on lymphoma, leukemia, and multiple myeloma, they present the spectrum of imaging findings of hematologic malignancy affecting the musculoskeletal system and the current imaging tools available to the radiologist. They discuss the imaging findings of posttreatment bone marrow and review commonly used staging systems and consensus recommendations for appropriate imaging for staging, management, and assessment of clinical remission. © RSNA, 2017.

Hematologic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hoogstraten, B.

1986-01-01

The principle aim of this book is to give practical guidelines to the modern treatment of the six important hematologic malignancies. Topics considered include the treatment of the chronic leukemias; acute leukemia in adults; the myeloproliferative disorders: polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis/agnogenic myeloid metaplasia; Hodgkin's Disease; non-Hodgkin's lymphoma; and Multiple Myeloma.

Inonotosis in Patient with Hematologic Malignancy

PubMed Central

Kwon, Mi; Guinea, Jesús; Escribano, Pilar; Jiménez, María del Carmen Martínez; Pulido, Ana; Parra, Verónica; Serrano, David; Gayoso, Jorge; Martín, José Luis Díez; Bouza, Emilio

2018-01-01

We report a lung-invasive fungal disease with possible cutaneous needle tract seeding in a patient with a febrile neutropenia caused by the Basidiomycetes mold Inonotus spp. Although rare, Inonotus spp. should be added to the list of microorganisms causing invasive fungal disease in neutropenic patients with hematologic malignancies. PMID:29260664

The Challenge of Targeting Notch in Hematologic Malignancies

PubMed Central

Hernandez Tejada, Fiorela N.; Galvez Silva, Jorge R.; Zweidler-McKay, Patrick A.

2014-01-01

Notch signaling can play oncogenic and tumor suppressor roles depending on cell type. Hematologic malignancies encompass a wide range of transformed cells, and consequently the roles of Notch are diverse in these diseases. For example Notch is a potent T-cell oncogene, with >50% of T-cell acute lymphoblastic leukemia (T-ALL) cases carry activating mutations in the Notch1 receptor. Targeting Notch signaling in T-ALL with gamma-secretase inhibitors, which prevent Notch receptor activation, has shown pre-clinical activity, and is under evaluation clinically. In contrast, Notch signaling inhibits acute myeloblastic leukemia growth and survival, and although targeting Notch signaling in AML with Notch activators appears to have pre-clinical activity, no Notch agonists are clinically available at this time. As such, despite accumulating evidence about the biology of Notch signaling in different hematologic cancers, which provide compelling clinical promise, we are only beginning to target this pathway clinically, either on or off. In this review, we will summarize the evidence for oncogenic and tumor suppressor roles of Notch in a wide range of leukemias and lymphomas, and describe therapeutic opportunities for now and the future. PMID:24959528

Mucorales-Specific T Cells in Patients with Hematologic Malignancies

PubMed Central

Forghieri, Fabio; Candoni, Anna; Cesaro, Simone; Quadrelli, Chiara; Maertens, Johan; Rossi, Giulio; Morselli, Monica; Codeluppi, Mauro; Mussini, Cristina; Colaci, Elisabetta; Messerotti, Andrea; Paolini, Ambra; Maccaferri, Monica; Fantuzzi, Valeria; Del Giovane, Cinzia; Stefani, Alessandro; Morandi, Uliano; Maffei, Rossana; Marasca, Roberto; Narni, Franco; Fanin, Renato; Comoli, Patrizia; Romani, Luigina; Beauvais, Anne; Viale, Pier Luigi; Latgè, Jean Paul; Luppi, Mario

2016-01-01

Background Invasive mucormycosis (IM) is an emerging life-threatening fungal infection. It is difficult to obtain a definite diagnosis and to initiate timely intervention. Mucorales-specific T cells occur during the course of IM and are involved in the clearance of the infection. We have evaluated the feasibility of detecting Mucorales-specific T cells in hematological patients at risk for IM, and have correlated the detection of such cells with the clinical conditions of the patients. Methods and Findings By using an enzyme linked immunospot assay, the presence of Mucorales-specific T cells in peripheral blood (PB) samples has been investigated at three time points during high-dose chemotherapy for hematologic malignancies. Mucorales-specific T cells producing interferon-γ, interleukin-10 and interleukin-4 were analysed in order to detect a correlation between the immune response and the clinical picture. Twenty-one (10.3%) of 204 patients, accounting for 32 (5.3%) of 598 PB samples, tested positive for Mucorales-specific T cells. Two groups could be identified. Group 1, including 15 patients without signs or symptoms of invasive fungal diseases (IFD), showed a predominance of Mucorales-specific T cells producing interferon-gamma. Group 2 included 6 patients with a clinical picture consistent with invasive fungal disease (IFD): 2 cases of proven IM and 4 cases of possible IFD. The proven patients had significantly higher number of Mucorales-specific T cells producing interleukin-10 and interleukin-4 and higher rates of positive samples by using derived diagnostic cut-offs when compared with the 15 patients without IFD. Conclusions Mucorales-specific T cells can be detected and monitored in patients with hematologic malignancies at risk for IM. Mucorales-specific T cells polarized to the production of T helper type 2 cytokines are associated with proven IM and may be evaluated as a surrogate diagnostic marker for IM. PMID:26871570

Simultaneous presence of two hematological malignancies: chronic lymphocytic leukemia and myelofibrosis in a patient.

PubMed

Palta, Anshu; Garg, Shailja; Chauhan, Sandeep; Varma, Neelam

2011-03-01

Coexistence of chronic lymphocytic leukemia (CLL) with myelofibrosis is a rare association with only isolated case reports in the literature. We report an unusual case of CLL in which the cause of anemia was coexistent myelofibrosis. In a case of CLL presenting with refractory anemia, besides common causes like autoimmune hemolytic anemia and marrow infiltration, other causes like myelofibrosis should be searched for.

Plasma presepsin level is an early diagnostic marker of severe febrile neutropenia in hematologic malignancy patients.

PubMed

Koizumi, Yusuke; Shimizu, Kaoru; Shigeta, Masayo; Okuno, Takafumi; Minamiguchi, Hitoshi; Kito, Katsuyuki; Hodohara, Keiko; Yamagishi, Yuka; Andoh, Akira; Fujiyama, Yoshihide; Mikamo, Hiroshige

2017-01-05

Febrile neutropenia (FN) is a common infectious complication in chemotherapy. The mortality of FN is higher in hematologic malignancy patients, and early diagnostic marker is needed. Presepsin is a prompt and specific marker for bacterial sepsis, but its efficacy in severe febrile neutropenia (FN) is not well confirmed. We tried to clarify whether it is a useful maker for early diagnosis of FN in patients during massive chemotherapy. We measured plasma presepsin levels every 2-3 day in FN cases and evaluated its change during the course of massive chemotherapy. The patients had hematologic malignancy or bone marrow failure, and in all cases, neutropenia was severe during the episode. The baseline levels, onset levels, increase rate at FN onset, and onset / baseline ratio were evaluated for their efficacy of early FN diagnosis. Eleven episodes of bacteremia (six gram negatives and five gram positives) in severe neutropenia were analyzed in detail. While plasma presepsin level was strongly associated to the CRP level (r = 0.61, p < 0.01), it was not associated with the absolute WBC count (r = -0.19, p = 0.19), absolute neutrophil count (r = -0.11, p = 0.41) or absolute monocyte count (r = -0.12, p = 0.40). The average of onset presepsin level was 638 ± 437 pg/mL and the cutoff value (314 pg/mL) has detected FN onset in 9 of 11 cases. The two cases undetected by presepsin were both Bacillus species bacteremia. Plasma presepsin level is a reliable marker of FN even in massive chemotherapy with very low white blood cell counts. Closer monitoring of this molecule could be a help for early diagnosis in FN. But bacteremia caused by Bacillus species was an exception in our study.

The role of telomeres and telomerase in hematologic malignancies and hematopoietic stem cell transplantation

PubMed Central

2014-01-01

Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related factors should be taken into consideration because of their impacts on telomere homeostasis. As activation of telomerase is widespread in tumor cells, it has been employed as a target point in the treatment of neoplastic hematologic disorders. In this review, the characteristics and roles of telomeres and telomerase both in hematologic malignancies and in HSCT will be summarized. The current status of telomerase-targeted therapies utilized in the treatment of hematologic malignancies will also be reviewed. PMID:25139287

Atrial Fibrillation in Hematologic Malignancies, Especially After Autologous Hematopoietic Stem Cell Transplantation: Review of Risk Factors, Current Management, and Future Directions.

PubMed

Mathur, Pankaj; Paydak, Hakan; Thanendrarajan, Sharmilan; van Rhee, Frits

2016-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with significant morbidity and mortality worldwide. In addition to well-established risk factors, cancer has been increasingly associated with the development of AF. Its increased occurrence in those with hematologic malignancies has been attributed to chemotherapeutic agents and autologous hematopoietic stem cell transplantation (AHSCT). Recently, a few studies have attempted to define the etiopathogenesis of AF in hematologic malignancies. The management of AF in these patients is challenging because of the concurrent complicating factors, such as thrombocytopenia, orthostatic hypotension, and cardiac amyloidosis. More studies are needed to define the management of AF, especially rate versus rhythm control and anticoagulation. Arrhythmias, in particular, AF, have been associated with an increased length of stay, increased intensive care unit admissions, and greater cardiovascular mortality. In the present review, we describe AF in patients with hematologic malignancies, the risk factors, especially after AHSCT, and the current management of AF. Copyright © 2016 Elsevier Inc. All rights reserved.

Febuxostat as a Prophylaxis for Tumor Lysis Syndrome in Children with Hematological Malignancies.

PubMed

Kishimoto, Kenji; Kobayashi, Ryoji; Hori, Daiki; Sano, Hirozumi; Suzuki, Daisuke; Kobayashi, Kunihiko

2017-10-01

The aim of the present study was to determine if febuxostat could prevent tumor lysis syndrome (TLS) in children who received induction chemotherapy for hematologic malignancies. A retrospective analysis was performed in 45 pediatric patients with hematological malignancies who received febuxostat (10 mg daily, n=20) or allopurinol (300 mg/m 2 daily, n=25) as a prophylaxis for TLS. A significant decrease of serum uric acid (UA) level was observed in patients with febuxostat over the first 2 days (6.6±3.8 mg/dl vs. 4.5±2.8 mg/dl, p<0.001). The febuxostat group also showed significant reduction of urinary UA/creatinine ratios during the first two days of treatment (0.98±0.85 vs. 0.51±0.26, p=0.010). No significant differences were observed between febuxostat-treated and allopurinol-treated patients regarding the percent change in serum UA level. Febuxostat had a notable effect in reducing serum UA level in children with hematological malignancies. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

PubMed

Bonanad, S; De la Rubia, J; Gironella, M; Pérez Persona, E; González, B; Fernández Lago, C; Arnan, M; Zudaire, M; Hernández Rivas, J A; Soler, A; Marrero, C; Olivier, C; Altés, A; Valcárcel, D; Hernández, M T; Oiartzabal, I; Fernández Ordoño, R; Arnao, M; Esquerra, A; Sarrá, J; González-Barca, E; González, J; Calvo, X; Nomdedeu, M; García Guiñón, A; Ramírez Payer, A; Casado, A; López, S; Durán, M; Marcos, M; Cruz-Jentoft, A J

2015-09-01

The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer

PubMed Central

Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

2018-01-01

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode “XN-BF gating algorithm” to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples. PMID:29425230

Novel flowcytometry-based approach of malignant cell detection in body fluids using an automated hematology analyzer.

PubMed

Ai, Tomohiko; Tabe, Yoko; Takemura, Hiroyuki; Kimura, Konobu; Takahashi, Toshihiro; Yang, Haeun; Tsuchiya, Koji; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Ohsaka, Akimichi

2018-01-01

Morphological microscopic examinations of nucleated cells in body fluid (BF) samples are performed to screen malignancy. However, the morphological differentiation is time-consuming and labor-intensive. This study aimed to develop a new flowcytometry-based gating analysis mode "XN-BF gating algorithm" to detect malignant cells using an automated hematology analyzer, Sysmex XN-1000. XN-BF mode was equipped with WDF white blood cell (WBC) differential channel. We added two algorithms to the WDF channel: Rule 1 detects larger and clumped cell signals compared to the leukocytes, targeting the clustered malignant cells; Rule 2 detects middle sized mononuclear cells containing less granules than neutrophils with similar fluorescence signal to monocytes, targeting hematological malignant cells and solid tumor cells. BF samples that meet, at least, one rule were detected as malignant. To evaluate this novel gating algorithm, 92 various BF samples were collected. Manual microscopic differentiation with the May-Grunwald Giemsa stain and WBC count with hemocytometer were also performed. The performance of these three methods were evaluated by comparing with the cytological diagnosis. The XN-BF gating algorithm achieved sensitivity of 63.0% and specificity of 87.8% with 68.0% for positive predictive value and 85.1% for negative predictive value in detecting malignant-cell positive samples. Manual microscopic WBC differentiation and WBC count demonstrated 70.4% and 66.7% of sensitivities, and 96.9% and 92.3% of specificities, respectively. The XN-BF gating algorithm can be a feasible tool in hematology laboratories for prompt screening of malignant cells in various BF samples.

Neurological failure in ICU patients with hematological malignancies: A prospective cohort study

PubMed Central

Marzorati, Chiara; Mokart, Djamel; Pène, Frederic; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Benoit, Dominique; Citerio, Giuseppe; Azoulay, Elie

2017-01-01

Background Epidemiological studies of neurological complications in patients with hematological malignancies are scant. The objective of the study was to identify determinants of survival in patients with hematological malignancy and neurological failure. Methods Post hoc analysis of a prospective study of adults with hematological malignancies admitted for any reason to one of 17 university or university-affiliated participating ICUs in France and Belgium (2010–2012). The primary outcome was vital status at hospital discharge. Results Of the 1011 patients enrolled initially, 226 (22.4%) had neurological failure. Presenting manifestations were dominated by drowsiness or stupor (65%), coma (32%), weakness (26%), and seizures (19%). Neuroimaging, lumbar puncture, and electroencephalography were performed in 113 (50%), 73 (32%), and 63 (28%) patients, respectively. A neurosurgical biopsy was done in 1 patient. Hospital mortality was 50%. By multivariate analysis, factors independently associated with higher hospital mortality were poor performance status (odds ratio [OR], 3.99; 95%CI, 1.82–9.39; P = 0.0009), non-Hodgkin’s lymphoma (OR, 2.60; 95%CI, 1.35–5.15; P = 0.005), shock (OR, 1.95; 95%CI, 1.04–3.72; P = 0.04), and respiratory failure (OR, 2.18; 95%CI, 1.14–4.25; P = 0.02); and factors independently associated with lower hospital mortality were GCS score on day 1 (OR, 0.88/point; 95%CI, 0.81–0.95; P = 0.0009) and autologous stem cell transplantation (OR, 0.25; 95%CI, 0.07–0.75; P = 0.02). Conclusions In ICU patients with hematological malignancies, neurological failure is common and often fatal. Independent predictors of higher hospital mortality were type of underlying hematological malignancy, poor performance status, hemodynamic and respiratory failures, and severity of consciousness impairment. Knowledge of these risk factors might help to optimize management strategies. PMID:28598990

Eosinophilic folliculitis occurring after stem cell transplant for acute lymphoblastic leukemia: a case report and review.

PubMed

Zitelli, Kristine; Fernandes, Neil; Adams, Brian B

2015-07-01

Eosinophilic folliculitis (EF) comprises classic eosinophilic pustular folliculitis (EPF), human immunodeficiency virus (HIV)-related EF, and infantile EPF subtypes. A fourth proposed subtype describes EF associated with hematologic malignancy. Recently, EF has occurred after bone marrow or stem cell transplantation (SCT). We report a unique case of EF after haploidentical allogeneic SCT for acute lymphoblastic leukemia (ALL) and review the literature for similar cases. A 56-year-old, HIV-negative ALL patient presented with an intensely pruritic papulopustular eruption. He had undergone haploidentical allogeneic SCT 65 days earlier, which he had tolerated well. Histopathology revealed a moderately dense perifollicular and perivascular lymphocytic infiltrate with many eosinophils extending from the superficial dermis to the subcutaneous fat. Fungal stains were negative. These findings were highly consistent with EF. Therapy with a class II topical corticosteroid ointment, oral doxepin, and emollients achieved near-resolution of the lesions within eight weeks. Transition to topical tacrolimus 0.1% ointment applied twice daily to residual lesions yielded complete clearance by 12 weeks with mild post-inflammatory hyperpigmentation. The patient's ALL remains in remission. A fourth proposed subtype of EF is associated with HIV-negative hematologic disease. This subtype is distinguished by a predictable timeframe to presentation and a relatively rapid response to therapy. Although EF is an important consideration in all patients with hematologic malignancy, clinically heightened suspicion is warranted during the 2-3 months after transplant. © 2014 The International Society of Dermatology.

Useful information provided by graphic displays of automated cell counter in hematological malignancies.

PubMed

Gupta, Monica; Chauhan, Kriti; Singhvi, Tanvi; Kumari, Manisha; Grover, Rajesh Kumar

2018-01-21

Automated cell counters have become more and more sophisticated with passing years. The numerical and graphic data both provide useful clues for suspecting a diagnosis especially when the workload is very high. We present our experience of useful information provided by graphic displays of an automated cell counter in hematological malignancies in a cancer hospital where a large number of complete blood count (CBC) requests are received either before or during chemotherapy. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC basophil) and IMI (immature myeloid information) channel scatter plots, and the flaggings generated in various hematological malignancies. The graphic displays have been compiled over a period of 1 year (October 2015-September 2016) from blood samples of various solid and hematological malignancies (approximately 400 per day) received for routine CBC in the laboratory. Approximately 50 000 scattergrams have been analyzed during the study period. The findings were confirmed by peripheral blood smear examination. The scattergram analysis on XE-2100 is very sensitive as well as specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic myeloid leukemia; and chronic lymphoproliferative disorder especially chronic lymphocytic leukemia. It is suggested that the laboratories using the hematology analyzers be aware of graphic display patterns in addition to flaggings generated which provide additional information and give clue toward the diagnosis even before peripheral smear examination. © 2018 Wiley Periodicals, Inc.

Targeting protein-protein interactions in hematologic malignancies: still a challenge or a great opportunity for future therapies?

PubMed Central

Cierpicki, Tomasz; Grembecka, Jolanta

2015-01-01

Summary Over the past several years, there has been an increasing research effort focused on inhibition of protein-protein interactions (PPIs) to develop novel therapeutic approaches for cancer, including hematologic malignancies. These efforts have led to development of small molecule inhibitors of PPIs, some of which already advanced to the stage of clinical trials while others are at different stages of pre-clinical optimization, emphasizing PPIs as an emerging and attractive class of drug targets. Here, we review several examples of recently developed inhibitors of protein-protein interactions highly relevant to hematologic cancers. We address the existing skepticism about feasibility of targeting PPIs and emphasize potential therapeutic benefit from blocking PPIs in hematologic malignancies. We then use these examples to discuss the approaches for successful identification of PPI inhibitors and provide analysis of the protein-protein interfaces, with the goal to address ‘druggability’ of new PPIs relevant to hematology. We discuss lessons learned to improve the success of targeting new protein-protein interactions and evaluate prospects and limits of the research in this field. We conclude that not all PPIs are equally tractable for blocking by small molecules, and detailed analysis of PPI interfaces is critical for selection of those with the highest chance of success. Together, our analysis uncovers patterns that should help to advance drug discovery in hematologic malignancies by successful targeting of new protein-protein interactions. PMID:25510283

Vortex-dislodged cells from bone marrow trephine biopsy yield satisfactory results for flow cytometric immunophenotyping.

PubMed

Bommannan, K; Sachdeva, M U S; Gupta, M; Bose, P; Kumar, N; Sharma, P; Naseem, S; Ahluwalia, J; Das, R; Varma, N

2016-10-01

A good bone marrow (BM) sample is essential in evaluating many hematologic disorders. An unsuccessful BM aspiration (BMA) procedure precludes a successful flow cytometric immunophenotyping (FCI) in most hematologic malignancies. Apart from FCI, most ancillary diagnostic techniques in hematology are less informative. We describe the feasibility of FCI in vortex-dislodged cell preparation obtained from unfixed trephine biopsy (TB) specimens. In pancytopenic patients and dry tap cases, routine diagnostic BMA and TB samples were complemented by additional trephine biopsies. These supplementary cores were immediately transferred into sterile tubes filled with phosphate-buffered saline, vortexed, and centrifuged. The cell pellet obtained was used for flow cytometric immunophenotyping. Of 7955 BMAs performed in 42 months, 34 dry tap cases were eligible for the study. Vortexing rendered a cell pellet in 94% of the cases (32 of 34), and FCI rendered a rapid diagnosis in 100% of the cases (32 of 32) where cell pellets were available. We describe an efficient procedure which could be effectively utilized in resource-limited centers and reduce the frequency of repeat BMA procedures. © 2016 John Wiley & Sons Ltd.

New frontiers in pediatric allogeneic stem cell transplantation

PubMed Central

Talano, Julie-An M.; Pulsipher, Michael A.; Symons, Heather J.; Militano, Olga; Shereck, Evan B.; Giller, Roger H.; Hancock, Laura; Morris, Erin; Cairo, Mitchell S.

2015-01-01

The inaugural meeting of “New Frontiers in Pediatric Allogeneic Stem Cell Transplantation” organized by the Pediatric Blood and Transplant Consortium (PBMTC) was held at the American Society of Pediatric Hematology and Oncology Annual Meeting. This meeting provided an international platform for physicians and investigators active in the research and utilization of pediatric allogeneic stem cell transplantation (AlloSCT) in children and adolescents with malignant and non-malignant disease, to share information and develop future collaborative strategies. The primary objectives of the conference included: 1) to present advances in AlloSCT in pediatric ALL and novel pre- and post-immunotherapy; 2) to highlight new strategies in alternative allogeneic stem cell donor sources for children and adolescents with non-malignant hematological disorders; 3) to discuss timing of immune reconstitution after AlloSCT and methods of facilitating more rapid recovery of immunity; 4) to identify strategies of utilizing AlloSCT in pediatric myeloproliferative disorders (MPD); 5) to develop diagnostic and therapeutic approaches to hematological complications post pediatric AlloSCT; 6) to enhance the understanding of new novel cellular therapeutic approaches to pediatric malignant and non-malignant hematological disorders; and 7) to discuss optimizing drug therapy in pediatric recipients of AlloSCT. This paper will provide a brief overview of the conference. PMID:24820213

Infective and thrombotic complications of central venous catheters in patients with hematological malignancy: prospective evaluation of nontunneled devices.

PubMed

Worth, Leon J; Seymour, John F; Slavin, Monica A

2009-07-01

Central venous catheter (CVC)-related bloodstream infection (CR-BSI) is a significant complication in hematology patients. A range of CVC devices may be used, and risks for the development of complications are not uniform. The objectives of this study were to determine the natural history and rate of CVC-related complications and risk factors for CR-BSI and to compare device-specific complications in a hematology population. An observational cohort of patients with hematologic malignancy was prospectively studied following CVC insertion. Participants were reviewed until a CVC-related complication necessitated device removal, completion of therapy, death, or defined end-of-study date. The National Nosocomial Infection Surveillance definition for CR-BSI was used. Overall and device-specific rates of infective and noninfective complications were calculated and potential risk factors were captured. One hundred six CVCs (75 peripherally inserted central venous catheters [PICCs], 31 nontunneled CVCs) were evaluated in 66 patients, over 2,399 CVC days. Thrombosis occurred in 16 cases (15.1%), exit-site infection in two (1.9%), and CR-BSI in 18 (7.5 per 1,000 CVC days). No significant differences were found when complication rates in PICC and nontunneled devices were compared. An underlying diagnosis of acute myeloid leukemia was negatively associated with CR-BSI (odds ratio (OR) 0.14, p = 0.046), and a previous diagnosis of fungal infection was associated with infection (OR 22.82, p = 0.031). CR-BSI rates in our hematology population are comparable to prior reports. A low rate of exit-site infection and high proportion of thrombotic complications were observed. No significant differences in thrombotic or infective complications were evident when PICC and nontunneled devices were compared. PICC devices are a practical and safe option for management of hematology patients.

Battling the hematological malignancies: the 200 years' war.

PubMed

Lichtman, Marshall A

2008-02-01

The delineation of the hematological malignancies began near the end of the first third of the 19th century with the recognition of the similarity among cases with lymph node tumors and an enlarged spleen (Hodgkin's disease). Descriptions of chronic and acute leukemia and myeloma followed thereafter. In the first years of the 20th century the discovery of x-radiation permitted palliative orthovoltage radiation therapy of Hodgkin's disease. Following World War II, legitimate drug therapy for the hematological malignancies was introduced: nitrogen mustard, adrenocorticotropic hormone and cortisone acetate, and anti-folic acid derivatives, initially aminopterin. Today, about 14 classes of drugs (different mechanisms of action) and >50 individual agents are being used, with others under study. Several examples of agents targeting specific transcription factors or oncoproteins have been introduced. Despite remarkable progress, including the ability to cure acute leukemia in about 70% of children, cure several genetic variants of acute myelogenous leukemia in younger adults, cure some cases of lymphoma in children and younger adults, and induce prolonged remission in many affected persons, the majority of patients face an uncertain outcome and shortened life. Thus, we have much to do in the next several decades. The significant hurdles we must overcome include: the apparent infrequency of an exogenous cause that can be avoided, the exponential increase in incidence rates with age and the dramatic negative effect of aging on the results of treatment, the challenge of one trillion or more disseminated cancer cells among which are a smaller population of cancer stem cells, the profound genetic diversity of the hematological malignancies (apparently hundreds of unique genetic primary lesions), the redundant growth and survival pathways defining the cancer phenotype, the decreasing market for pharmaceutical companies as therapy becomes more specific (fewer target patients) and drug development costs become more expensive, and the significant negative long-term effects of current therapy on both children and adults. These challenges will be gradually overcome, if we (a) develop new models of cooperation among academia, industry, and government, (b) continue the growth of international participation in cancer research (more keen minds to the task), and (c) convince the governments of the world, including that of the U.S., that an investment in minimizing the effects of cancer is as important as defending against other threats to the welfare and longevity of their citizens.

Radioimmunotherapy for treatment of B-cell lymphomas and other hematologic malignancies.

PubMed

Park, Steven I; Press, Oliver W

2007-11-01

Radioimmunotherapy has emerged as one of the most promising treatment options for hematologic malignancies. This review will present the latest information on radioimmunotherapy for treatment of hematologic malignancies in various clinical settings and assess its long-term safety profile. Recent data suggest that radioimmunotherapy with 131I-tositumomab or 90Y-ibritumomab tiuxetan not only induces high response rates but also results in durable remissions in patients with relapsed or refractory indolent non-Hodgkin's lymphomas. Even more notable response rates have been observed when radioimmunotherapy is used as front-line treatment in patients with indolent non-Hodgkin's lymphomas. The use of radioimmunotherapy has been evaluated in the treatment of aggressive lymphomas with promising results, but it remains investigational. Standard doses of radioimmunotherapy given as a conditioning regimen for hematopoietic stem-cell transplant or myeloablative doses of radioimmunotherapy given in conjunction with stem-cell support have yielded encouraging outcomes with durable remissions and a low incidence of treatment-related mortality. The safety and efficacy of radioimmunotherapy has been demonstrated for patients with B-cell lymphomas and other hematologic malignancies in various clinical settings. A number of randomized phase III clinical trials are currently underway to further define radioimmunotherapy's role in the treatment of lymphomas.

Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico.

PubMed

Jaime-Pérez, José Carlos; Chapa-Rodríguez, Adrián; Rodríguez-Martínez, Marisol; Colunga-Pedraza, Perla Rocío; Marfil-Rivera, Luis Javier; Gómez-Almaguer, David

2012-01-01

Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms.

Update on the diagnosis and treatment of Pneumocystis pneumonia.

PubMed

Carmona, Eva M; Limper, Andrew H

2011-02-01

Pneumocystis is an opportunistic fungal pathogen that causes an often-lethal pneumonia in immunocompromised hosts. Although the organism was discovered in the early 1900s, the first cases of Pneumocystis pneumonia in humans were initially recognized in Central Europe after the Second World War in premature and malnourished infants. This unusual lung infection was known as plasma cellular interstitial pneumonitis of the newborn, and was characterized by severe respiratory distress and cyanosis with little or no fever and no pathognomic physical signs. At that time, only anecdotal cases were reported in adults and usually these patients had a baseline malignancy that led to a malnourished state. In the 1960-1970s additional cases were described in adults and children with hematological malignancies, but Pneumocystis pneumonia was still considered a rare disease. However, in the 1980s, with the onset of the HIV epidemic, Pneumocystis prevalence increased dramatically and became widely recognized as an opportunistic infection that caused potentially life-treating pneumonia in patients with impaired immunity. During this time period, prophylaxis against this organism was more generally instituted in high-risk patients. In the 1990s, with widespread use of prophylaxis and the initiation of highly active antiretroviral therapy (HAART) in the treatment of HIV-infected patients, the number of cases in this specific population decreased. However, Pneumocystis pneumonia still remains an important cause of severe pneumonia in patients with HIV infection and is still considered a principal AIDS-defining illness. Despite the decreased number of cases among HIV-infected patients over the past decade, Pneumocystis pneumonia continues to be a serious problem in immunodeficient patients with other immunosuppressive conditions. This is mostly due to increased use of immunosuppressive medications to treat patients with autoimmune diseases, following bone marrow and solid organ transplantation, and in patients with hematological and solid malignancies. Patients with hematologic disorders and solid organ and hematopoietic stem cell transplantation are currently the most vulnerable groups at risk for developing this infection. However, any patient with an impaired immunity, such as those receiving moderate doses of oral steroids for greater than 4 weeks or those receiving other immunosuppressive medications are at also at significant risk.

The Growing Threat of Multidrug-Resistant Gram-Negative Infections in Patients with Hematologic Malignancies

PubMed Central

Baker, Thomas M.; Satlin, Michael J.

2016-01-01

Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts. This review characterizes the epidemiology, risk factors, resistance mechanisms, recommended treatments, and outcomes of the MDR Gram-negative bacteria that commonly cause infections in patients with hematologic malignancies. We also examine infection prevention strategies in hematology patients, such as infection control practices, antimicrobial stewardship, and targeted decolonization. Finally, we assess strategies to improve outcomes of infected patients, including gastrointestinal screening to guide empirical antibiotic therapy, new rapid diagnostic tools for expeditious identification of MDR pathogens, and use of two new antimicrobial agents, ceftolozane/tazobactam and ceftazidime/avibactam. PMID:27339405

Ecthyma gangrenosum mimicking acute invasive fungal sinusitis in an immunocompromised patient.

PubMed

Hekiert, Adrianna M; Cohen, Michael B; Montone, Kathleen T; Palmer, James N; Govindaraj, Satish

2010-06-01

Ecthyma gangrenosum is a rare necrotizing cutaneous infection usually caused by Pseudomonas aeruginosa. We report a case of ecthyma gangrenosum presenting as a sinonasal eschar and mimicking acute invasive fungal sinusitis in an immunocompromised 39-year-old man with a hematologic malignancy. To the best of our knowledge, this represents the first case of ecthyma gangrenosum affecting the sinonasal mucosa to be reported in the literature.

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations.

PubMed

Ebens, Christen L; MacMillan, Margaret L; Wagner, John E

2017-01-01

Hematopoietic cell transplantation for Fanconi Anemia (FA) has improved dramatically over the past 40 years. With an enhanced understanding of the intrinsic DNA-repair defect and pathophysiology of hematopoietic failure and leukemogenesis, sequential changes to conditioning and graft engineering have significantly improved the expectation of survival after allogeneic hematopoietic cell transplantation (alloHCT) with incidence of graft failure decreased from 35% to <10% and acute graft-versus-host disease (GVHD) from >40% to <10%. Today, five-year overall survival exceeds 90% in younger FA patients with bone marrow failure but remains about 50% in those with hematologic malignancy. Areas covered: We review the evolution of alloHCT contributing to decreased rates of transplant related complications; highlight current challenges including poorer outcomes in cases of clonal hematologic disorders, alloHCT impact on endocrine function and intrinsic FA risk of epithelial malignancies; and describe investigational therapies for prevention and treatment of the hematologic manifestations of FA. Expert commentary: Current methods allow for excellent survival following alloHCT for FA associated BMF irrespective of donor hematopoietic cell source. Alternative curative approaches, such as gene therapy, are being explored to eliminate the risks of GVHD and minimize therapy-related adverse effects.

Nonpigmented Metastatic Melanoma in a Two-Year-Old Girl: A Serious Diagnostic Dilemma

PubMed Central

Diniz, Gulden; Tosun Yildirim, Hulya; Yamaci, Selcen

2015-01-01

Although rare, malignant melanoma may occur in children. Childhood melanomas account for only 0.3–3% of all melanomas. In particular the presence of congenital melanocytic nevi is associated with an increased risk of development of melanoma. We herein report a case of malignant melanoma that developed on a giant congenital melanocytic nevus and made a metastasis to the subcutaneous tissue of neck in a two-year-old girl. The patient was hospitalized for differential diagnosis and treatment of cervical mass with a suspicion of hematological malignancy, because the malignant transformation of congenital nevus was not noticed before. In this case, we found out a nonpigmented malignant tumor of pleomorphic cells after the microscopic examination of subcutaneous lesion. Nonpigmented metastatic melanoma was diagnosed by several immunohistochemical and flow cytometric studies. She was offered palliative chemotherapy; however, her parents did not accept treatment. The patient died within 9 months of diagnosis. We emphasized here that the possibility of malignant melanoma in the differential diagnosis of childhood tumors should be kept in mind. PMID:25763285

Risk of hematological malignancies among Chernobyl liquidators

PubMed Central

Kesminiene, Ausrele; Evrard, Anne-Sophie; Ivanov, Viktor K.; Malakhova, Irina V.; Kurtinaitis, Juozas; Stengrevics, Aivars; Tekkel, Mare; Anspaugh, Lynn R.; Bouville, André; Chekin, Sergei; Chumak, Vadim V.; Drozdovitch, Vladimir; Gapanovich, Vladimir; Golovanov, Ivan; Hubert, Phillip; Illichev, Sergei V.; Khait, Svetlana E.; Krjuchkov, Viktor P.; Maceika, Evaldas; Maksyoutov, Marat; Mirkhaidarov, Anatoly K.; Polyakov, Semion; Shchukina, Natalia; Tenet, Vanessa; Tserakhovich, Tatyana I.; Tsykalo, Aleksandr; Tukov, Aleksandr R.; Cardis, Elisabeth

2010-01-01

A case-control study of hematological malignancies was conducted among Chernobyl liquidators (accident recovery workers) from Belarus, Russia and Baltic countries in order to assess the effect of low-to-medium dose protracted radiation exposures on the relative risk of these diseases. The study was nested within cohorts of liquidators who had worked in 1986–87 around the Chernobyl plant. 117 cases (69 leukemia, 34 non-Hodgkin Lymphoma (NHL) and 14 other malignancies of lymphoid and hematopoietic tissue) and 481 matched controls were included in the study. Individual dose to the bone marrow and uncertainties were estimated for each subject. The main analyses were restricted to 70 cases (40 leukemia, 20 NHL and 10 other) and their 287 matched controls with reliable information on work in the Chernobyl area. Most subjects received very low doses (median 13 mGy). For all diagnoses combined, a significantly elevated OR was seen at doses of 200 mGy and above. The Excess Relative Risk (ERR) per 100 mGy was 0.60 (90% confidence interval (CI): −0.02, 2.35). The corresponding estimate for leukemia excluding chronic lymphoid leukemia (CLL) was 0.50 (90%CI −0.38, 5.7). It is slightly higher than, but statistically compatible with, those estimated from a-bomb survivors and recent low dose-rate studies. Although sensitivity analyses showed generally similar results, we cannot rule out the possibility that biases and uncertainties could have led to over or underestimation of the risk in this study. PMID:19138033

Myelodysplastic Syndrome Occurring in a Patient with Gorlin Syndrome.

PubMed

Mull, Jamie L; Madden, Lisa M; Bayliss, Susan J

2016-07-01

We report a case of myelodysplastic syndrome (MDS) occurring in an African American boy with Gorlin syndrome with a novel PTCH1 mutation. Before developing MDS, the patient had been treated with chemotherapy and radiation for a medulloblastoma. He received a bone marrow transplant for the MDS and eventually died of treatment complications. Secondary hematologic malignancies are a known complication of certain chemotherapeutics, although whether a patient with Gorlin syndrome has a greater propensity for the development of such malignancies is unclear. © 2016 Wiley Periodicals, Inc.

Sickle cell crisis leading to extensive necrosis in a low-grade glioma and masquerading high-grade lesion.

PubMed

Agrawal, Amit; Balpande, D N; Khan, A; Vagh, S J; Shukla, Samarth; Chopra, Sumit

2008-01-01

A 9-year-old female child presented with rapid neurological deterioration. Clinical features and imaging findings were suggestive of high-grade malignancy, and hematological investigations were suggestive of sickle cell trait. Histopathology showed features of low-grade malignancy and extensive intratumoral sickling. We hypothesize that the vicious cycle of hypoxia, sickling, thrombosis, ischemia and infarction resulted in the extensive tumor necrosis in the present case causing the initial symptoms and rapid deterioration in the condition of the patient. Copyright 2008 S. Karger AG, Basel.

Eosinophilic dermatosis of hematologic malignancy.

PubMed

Martires, Kathryn; Callahan, Shields; Terushkin, Vitaly; Brinster, Nooshin; Leger, Marie; Soter, Nicholas A

2016-12-15

We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.

Antimicrobial agent prescription patterns for chemotherapy-induced febrile neutropenia in patients with hematological malignancies at Sultan Qaboos University Hospital, Oman.

PubMed

Al Balushi, K A; Balkhair, A; Ali, B H; Al Rawas, N

2013-06-01

The aim of this study was to describe the antimicrobial prescription patterns of patients with hematological malignancies who developed febrile neutropenia (FN) at Sultan Qaboos University Hospital (SQUH) in Oman. This was a retrospective observational study covering a period of 3 years (January 2007-February 2010). FN episodes were studied in patients with hematological malignancies in three different wards at SQUH. A total of 176 FN episodes were analyzed. Overall, 64% of the 107 patients studied experienced at least 2 episodes during the analysis period. Approximately, 69% of the febrile neutropenia episodes had severe neutropenia. The duration of neutropenia was less than 1 week in the majority of the episodes (57%). The mean duration of treatment was approximately 7 days, with no significant difference between specialties or different types of malignancies. Only 34 (19%) episodes had positive cultures, and most of these were from blood samples (30 episodes, 88%). The majority of isolates were gram-negative organisms (63%). The initial empirical treatment included monotherapy (37%), dual therapy (60%) and triple therapy (3%). This study demonstrates that there is a large variation in the antimicrobial treatment of FN episodes in patients with hematological malignancies at SQUH. All chosen drugs were within international guideline recommendations. Copyright © 2013 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

[Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders].

PubMed

Yamane, T; Tanaka, K; Hasuike, T; Hirai, M; Misu, K; Ota, K; Ohira, H; Nakao, Y; Yasui, Y; Inoue, T

1992-08-01

The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.

Secondary malignancy following radiotherapy for thyroid eye disease.

PubMed

Gillis, Christopher C; Chang, Eun Hae; Al-Kharazi, Khalid; Pickles, Tom

2016-01-01

To describe the first case of a secondary meningioma in a patient after radiation treatment for thyroid eye disease (TED). Secondarily to identify any additional cases of secondary malignancy resulting from radiotherapy for thyroid eye disease from our institutional experience. Thyroid eye disease (TED) is a self-limiting auto-immune disorder causing expansion of orbital soft tissue from deposition of glycosaminoglycans and collagen, leading to significant cosmetic and functional morbidity. Established management options for TED include: glucocorticosteroids, orbital radiotherapy, and surgical orbital decompression. Two large series on radiotherapy for TED have been reported without any cases of secondary malignancy. The case of a patient with visual failure, found to have a sphenoid wing meningioma after previous TED radiotherapy is described. We then reviewed 575 patients with at least 3-year follow-up receiving radiotherapy for TED at British Columbia Cancer Agency to identify other possible secondary malignancies. The patient had postoperative improvement in her vision without any identified complications. Three additional cases of hematologic malignancy were identified. The calculated risk in our population of developing a radiation-induced meningioma after TED with at least 3 years of follow-up of is 0.17% (1/575); with hematopoetic malignancies the risk for secondary malignancy is 0.7% (4/575). Our calculated risk for secondary malignancy (0.17%, 0.7%) is similar to the reported theoretical risk published in the literature (0.3-1.2%). There is real risk for the development of a secondary malignancy after radiotherapy treatment of TED and treatment options should include consideration for this potential.

Pattern of hematological malignancies in adolescents and young adults in Bangladesh.

PubMed

Hasan, Md Mahbub; Raheem, Enayetur; Sultana, Tanvira Afroze; Hossain, Mohammad Sorowar

2017-12-01

The adolescent and young adult (AYA) age group (15-39 years) bears distinct characteristics in terms of cancer biology, long-term health and treatment-related complications and psychosocial aspects. The overall scenario of cancer including hematological malignancies (HMs) is largely unknown in Bangladesh, where a significant proportion of people (44% of total population) belong to AYA age group. This study aims to describe the patterns of HM among AYA in the context of Bangladesh METHODS: Two previously published datasets (on hematological malignancies and childhood and adolescent cancer) were merged to construct a comprehensive dataset focusing exclusively on HMs in AYA age group. Univariate descriptive statistics were calculated and bivariate association were tested using Pearson's Chi-square test. A total of 2144 diagnosed HM related cases over a period of 2007-2014 were analyzed. Acute myeloid leukemia (AML) was the most frequent HM (35.1%) in AYAs, which was followed by acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) constituting 22.7% and 20.8%, respectively. Among lymphomas, Non-Hodgkin lymphoma (NHL) constituted 13.9% of all HMs while 4.6% was for Hodgkin's lymphoma (HL). This is the first attempt to provide a glimpse on the pattern and distribution of HMs among AYA in Bangladesh. Future studies are essential to get a better insight on the epidemiology, biology, potential risk factors and treatment outcomes for the AYA age group. Copyright © 2017 Elsevier Ltd. All rights reserved.

Eosinophilic Pustular Folliculitis Post Chemotherapy in a Patient of Non-Hogkins Lymphoma: A Case Report.

PubMed

Bhandare, Prachi C; Ghodge, Rakhi R; Bhobe, Mayur R; Shukla, Pankaj R

2015-01-01

Eosinophilic pustular folliculitis (EPF) was originally described by Ofuji in Japanese patients without any systemic disease. Later it was widely associated with HIV. Lately a large number of hematological malignancies have been associated with EPF. We hereby report an association of non-Hogkins lymphoma with EPF, probably the first in Indian context.

[Fertility preservation in patients with hematological malignancies].

PubMed

Kanda, Yoshinobu

2015-03-01

Antineoplastic chemotherapy and irradiation affect gonadal function and may lead to infertility. Recovery of gonadal function is frequently observed after conventional chemotherapy in young patients with hematological malignancies, but conditioning regimens before hematopoietic stem cell transplantation result in permanent gonadal failure. Cryopreservation of sperm is effective for male patients, but it becomes difficult even after a single cycle of chemotherapy and therefore should be accomplished before starting chemotherapy. Embryo freezing after in vitro fertilization of harvested oocytes is an established method to preserve fertility in female patients. In addition, harvesting and freezing of unfertilized oocytes is also being evaluated in a clinical study. However, collection of good oocytes after chemotherapy is difficult. In addition, oocyte harvesting is an invasive procedure and may be associated with hemorrhage or infectious complications. Ovarian shielding during total body irradiation allows ovary preservation in most female patients, but this cannot be performed in patients with active malignancies. Strategies for gonadal function preservation should be planned before starting treatment for hematological malignancies.

Management of acute perianal sepsis in neutropenic patients with hematological malignancy.

PubMed

Baker, B; Al-Salman, M; Daoud, F

2014-04-01

In neutropenic patients with acute perianal sepsis in the setting of hematological malignancy, the classical clinical features of abscess formation are lacking. Additionally, the role of surgical intervention is not well established. In this review, we discuss the challenges and controversy regarding diagnosis and optimal management when clear surgical guidelines are absent. In the literature, there is great diversity in the surgical approach to these patients, which leads to a high percentage of diagnostic errors, risks of complications, and unnecessary interventions. We review the literature and assess whether surgical intervention produces better outcomes than a non-surgical approach. Studies published on perianal sepsis in neutropenic cancer patients were identified by searching PubMed using the following key words: "perianal sepsis/abscesses, anorectal sepsis/abscess, neutropenia, hematological malignancy, cancer". No randomized or prospective studies on the management of acute perianal sepsis in hematological malignancies were found. The largest retrospective study and most comprehensive clinical data demonstrated that 42% of patients were treated successfully without surgical intervention and without morbidity or mortality related to treatment chosen. Small retrospective studies advocated surgical intervention, while the majority of successes were in a non-operative treatment. It is difficult to formulate a conclusion given the small retrospective series on management of neutropenic patients with hematological malignancies. While there is no evidence mandating a routine surgical approach in this category of patients, non-surgical management including careful follow-up to determine whether the patient's condition is deteriorating or treatment has failed is an acceptable approach in selected patients without pathognomonic features of abscess. Comprehensive and well-designed prospective studies are needed to firmly establish the guidelines of treatment protocols.

DCB - Cancer Immunology, Hematology, and Etiology Research

Cancer.gov

Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

Use of complementary and alternative medicine by patients with hematological diseases experience at a university hospital in northeast Mexico

PubMed Central

Jaime-Pérez, José Carlos; Chapa-Rodríguez, Adrián; Rodríguez-Martínez, Marisol; Colunga-Pedraza, Perla Rocío; Marfil-Rivera, Luis Javier; Gómez-Almaguer, David

2012-01-01

Background Complementary and alternative medicine includes a diverse group of medical and healthcare systems, practices and products not considered part of conventional medicine. Although there is information on unconventional practices in oncological diseases, specific data regarding the use of complementary and alternative medicine by hematology patients is scarce. Objective The aim of this study is to document the prevalence of this modality of unconventional therapy in patients with malignant and benign hematological diseases, particularly children with acute lymphoblastic leukemia. Methods An observational study of adult patients and guardians of children with malignant or benign hematological diseases was carried out by applying a structured questionnaire detailing the use and results of the most prevalent complementary and alternative medicine practices. Results One hundred and twenty patients were included; 104 had malignant and 16 had benign hematological diseases. The use of complementary and alternative medicine was greater in benign diseases but the difference was not statistically significant (64.7% versus 41.7%; p-value = 0.08). Patients and guardians with high school or college educations used these alternative practices more than patients with less schooling (60.7% versus 54.7%; p-value = 0.032). The use of folk remedies was most prevalent followed by herbal preparations and spiritual healing. Sixty-four percent of patients that used these unconventional practices reported improvement in their symptoms and increased capacity to perform daily activities. Conclusion No significant difference was documented between patients with malignant or benign hematological diseases using these alternative practices. The majority of complementary and alternative medicine users reported improvement of the disease or chemotherapy-related symptoms. PMID:23049401

Patients' reflections on communication in the second-opinion hematology-oncology consultation.

PubMed

Goldman, Roberta E; Sullivan, Amy; Back, Anthony L; Alexander, Stewart C; Matsuyama, Robin K; Lee, Stephanie J

2009-07-01

The nature of communication between patients and their second-opinion hematology consultants may be very different in these one-time consultations than for those that are within long-term relationships. This study explored patients' perceptions of their second-opinion hematology-oncology consultation to investigate physician-patient communication in malignant disease at a critical juncture in cancer patients' care and decision-making. In-depth telephone interviews with a subset of 20 patients from a larger study, following their subspecialty hematology consultations. Most patients wanted to contribute to the consultation agenda, but were unable to do so. Patients sought expert and honest advice delivered with empathy, though most did not expect the consultant to directly address their emotions. They wanted the physician to apply his/her knowledge to the specifics of their individual cases, and were disappointed and distrustful when physicians cited only general prognostic statistics. In contrast, physicians' consideration of the unique elements of patients' cases, and demonstrations of empathy and respect made patients' feel positively about the encounter, regardless of the prognosis. Patients provided concrete recommendations for physician and patient behaviors to enhance the consultation. Consideration of these recommendations may result in more effective communication and increased patient satisfaction with medical visits.

[Two Kinds of HLA-mismatched Allogeneic Hematopoictic Stem Cell Transplantation for Treatment of Hematologic Malignancies].

PubMed

Li, Wei-Da; Gao, Zhi-Yong; Yu, Xin-Jian; Lu, Da-Yu; Lu, Dao-Pei

2016-04-01

To investigate the safety and effectiveness of HLA-mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT) combined with related haploidentical bone marrow infusion for treatment of hematologic malignancies and to explore the mathod for reduction of aGVHD incidence and clinical significance. A total of 30 patients with hematologic malignancies (8 cases of AML, 17 AML, 2 MDS and 3 Mix-AL) received related haploidentical and unrelated HLA-mismatched allo-HSCT combined with related haploidentical bone marrow infusion. Among them 20 cases received related haploidentical transplantation of the first donor, 10 cases received unrelated HLA-mismatched treaplantation. The new conditioning regimen for the patients underwent allo-HSCT consisted of fludarabine, busulfan, Me-CCNU and cyclophosphamide. The drugs for GVHD prophylaxis included cyclosporine A and methotrexate, while mycophenolate mofetil and rabbit anti-T-lymphocyte globulin (ATG) were used. All the patients achieved full engraftment. The median time for neutrophils to reach over 0.5 × 10(9)/L was 14 days (8-26 days), while the median time for platelets to reach over 20 × 10(9)/L was 11.5days (10-24 days). The incidence of I-II grade of aGVHD at 100 d was 22.28% (95% CI 9.9%-34.7%), the incidences of II-IV and III-IV grade of aGVHD were 22.7% (95% CI, 10%-35.4%) and 12.7% (95% CI 6.9%-15.5%) respectively. The incidences of I-II and III-IV cGVHD were 13.3% (95% CI, 1.4%- 26.8%) and 3.3 % (95% CI, 0%-12.2%), one case (3.3%) was in extensive cGVHD. DFS and OS of 2 years were 81.1% (95% CI, 66.0%-96.2%) and 68.2% (95% CI 51.0%-85.4%). These data suggest that the incidence of grade II-IV grade of aGVHD in recipients of 2 partially HLA-matched units was lower, co-infusion of haplo-BM and partially matched units in allogeneic transplantation is safe and effective for reducing the incidence of aGVHD and improving the survival in DFS.

Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells.

PubMed

Allegra, Alessandro; Innao, Vanessa; Gerace, Demetrio; Vaddinelli, Doriana; Musolino, Caterina

2016-11-01

Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors. CAR-T treatment has emerged as a promising approach for patients with hematological malignancies, and there are several works reporting clinical trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid leukemia by targeting different antigens. This review reports the history of adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell therapies in development for hematological malignancies. Copyright © 2016 Elsevier Inc. All rights reserved.

Extracellular Vesicles in Hematological Malignancies: From Biology to Therapy

PubMed Central

Caivano, Antonella; La Rocca, Francesco; Laurenzana, Ilaria; Trino, Stefania; De Luca, Luciana; Lamorte, Daniela; Del Vecchio, Luigi; Musto, Pellegrino

2017-01-01

Extracellular vesicles (EVs) are a heterogeneous group of particles, between 15 nanometers and 10 microns in diameter, released by almost all cell types in physiological and pathological conditions, including tumors. EVs have recently emerged as particularly interesting informative vehicles, so that they could be considered a true “cell biopsy”. Indeed, EV cargo, including proteins, lipids, and nucleic acids, generally reflects the nature and status of the origin cells. In some cases, EVs are enriched of peculiar molecular cargo, thus suggesting at least a degree of specific cellular packaging. EVs are identified as important and critical players in intercellular communications in short and long distance interplays. Here, we examine the physiological role of EVs and their activity in cross-talk between bone marrow microenvironment and neoplastic cells in hematological malignancies (HMs). In these diseases, HM EVs can modify tumor and bone marrow microenvironment, making the latter “stronger” in supporting malignancy, inducing drug resistance, and suppressing the immune system. Moreover, EVs are abundant in biologic fluids and protect their molecular cargo against degradation. For these and other “natural” characteristics, EVs could be potential biomarkers in a context of HM liquid biopsy and therapeutic tools. These aspects will be also analyzed in this review. PMID:28574430

Secondary EML4-ALK-positive lung adenocarcinoma in a patient previously treated for acute lymphoblastic leukemia in childhood: a case report.

PubMed

Nakamura, Yoichi; Taniguchi, Hirokazu; Mizoguchi, Kosuke; Ikeda, Takaya; Motoshima, Kohei; Yamaguchi, Hiroyuki; Nagashima, Seiji; Nakatomi, Katsumi; Soda, Manabu; Mano, Hiroyuki; Kohno, Shigeru

2014-06-01

It is widely recognized that the risk of secondary neoplasms increases as childhood cancer survivors progress through adulthood. These are mainly hematological malignancies, and recurrent chromosome translocations are commonly detected in such cases. On the other hand, while secondary epithelial malignancies have sometimes been reported, chromosome translocations in these epithelial malignancies have not. A 33-year-old man who had been diagnosed with acute lymphoblastic leukemia and treated with chemotherapy almost 20 years earlier was diagnosed with lung adenocarcinoma. After chromosomal rearrangement of echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene was detected in this adenocarcinoma, he responded to treatment with crizotinib. It was therefore concluded that this echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene-positive lung adenocarcinoma was a secondary epithelial malignancy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Value of innovation in hematologic malignancies: a systematic review of published cost-effectiveness analyses.

PubMed

Saret, Cayla J; Winn, Aaron N; Shah, Gunjan; Parsons, Susan K; Lin, Pei-Jung; Cohen, Joshua T; Neumann, Peter J

2015-03-19

We analyzed cost-effectiveness studies related to hematologic malignancies from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), focusing on studies of innovative therapies. Studies that met inclusion criteria were categorized by 4 cancer types (chronic myeloid leukemia, chronic lymphocytic leukemia, non-Hodgkin lymphoma, and multiple myeloma) and 9 treatment agents (interferon-α, alemtuzumab, bendamustine, bortezomib, dasatinib, imatinib, lenalidomide, rituximab alone or in combination, and thalidomide). We examined study characteristics and stratified cost-effectiveness ratios by type of cancer, treatment, funder, and year of study publication. Twenty-nine studies published in the years 1996-2012 (including 44 cost-effectiveness ratios) met inclusion criteria, 22 (76%) of which were industry funded. Most ratios fell below $50,000 per quality-adjusted life-years (QALY) (73%) and $100,000/QALY (86%). Industry-funded studies (n = 22) reported a lower median ratio ($26,000/QALY) than others (n = 7; $33,000/QALY), although the difference was not statistically significant. Published data suggest that innovative treatments for hematologic malignancies may provide reasonable value for money. © 2015 by The American Society of Hematology.

Is it intestinal tuberculosis again? Case report.

PubMed

Brat, Kristián; Merta, Zdeněk; Čundrle, Ivan

This case report focuses on an immigrant admitted to the Department of Respiratory Diseases, University Hospital Brno due to suspicion of relapsing intestinal tuberculosis. The patient presented with fever, night sweat, weight loss, diarrhea, and a history of several tuberculosis attacks in the last few years. None of the examinations confirmed the presence of active tuberculosis but raised suspicion of hematological malignancy. Pancytopenia was present in the peripheral blood. However, bone marrow examination and flowcytometry excluded the presence of a hematological malignancy. The results pointed to the possibility of vitamin B12 or folate deficiency that were both confirmed consequently by serum biochemical tests. Cobalamin and folate deficiency were caused by short bowel syndrome that developed after a major intestinal resection that the patient underwent in his past. Combined treatment including vitamins, pancreatic enzymes substitution, antidiarrhoics and spasmolytics was administered. The general health status of the patient improved rapidly with restitution of hematopoiesis, weight gain, and a decrease by 80% in daily number of stools. Clinical appearance of intestinal tuberculosis, short bowel syndrome and of cobalamin and folate deficiency as well as pathophysiology, diagnosis and treatment of these uncommon or even rare diseases are discussed in this case report.Key words: intestinal tuberculosis - pancytopenia - short bowel syndrome - vitamin B12 deficiency.

Translocations in epithelial cancers

PubMed Central

Chad Brenner, J.; Chinnaiyan, Arul M.

2009-01-01

Genomic translocations leading to the expression of chimeric transcripts characterize several hematologic, mesenchymal and epithelial malignancies. While several gene fusions have been linked to essential molecular events in hematologic malignancies, the identification and characterization of recurrent chimeric transcripts in epithelial cancers has been limited. However, the recent discovery of the recurrent gene fusions in prostate cancer has sparked a revitalization of the quest to identify novel rearrangements in epithelial malignancies. Here, the molecular mechanisms of gene fusions that drive several epithelial cancers and the recent technological advances that increase the speed and reliability of recurrent gene fusion discovery are explored. PMID:19406209

‘Trained immunity’: consequences for lymphoid malignancies

PubMed Central

Stevens, Wendy B.C.; Netea, Mihai G.; Kater, Arnon P.; van der Velden, Walter J.F.M.

2016-01-01

In hematological malignancies complex interactions exist between the immune system, microorganisms and malignant cells. On one hand, microorganisms can induce cancer, as illustrated by specific infection-induced lymphoproliferative diseases such as Helicobacter pylori-associated gastric mucosa-associated lymphoid tissue lymphoma. On the other hand, malignant cells create an immunosuppressive environment for their own benefit, but this also results in an increased risk of infections. Disrupted innate immunity contributes to the neoplastic transformation of blood cells by several mechanisms, including the uncontrolled clearance of microbial and autoantigens resulting in chronic immune stimulation and proliferation, chronic inflammation, and defective immune surveillance and anti-cancer immunity. Restoring dysfunction or enhancing responsiveness of the innate immune system might therefore represent a new angle for the prevention and treatment of hematological malignancies, in particular lymphoid malignancies and associated infections. Recently, it has been shown that cells of the innate immune system, such as monocytes/macrophages and natural killer cells, harbor features of immunological memory and display enhanced functionality long-term after stimulation with certain microorganisms and vaccines. These functional changes rely on epigenetic reprogramming and have been termed ‘trained immunity’. In this review the concept of ‘trained immunity’ is discussed in the setting of lymphoid malignancies. Amelioration of infectious complications and hematological disease progression can be envisioned to result from the induction of trained immunity, but future studies are required to prove this exciting new hypothesis. PMID:27903713

Eosinophilic Pustular Folliculitis Post Chemotherapy in a Patient of Non-Hogkins Lymphoma: A Case Report

PubMed Central

Bhandare, Prachi C; Ghodge, Rakhi R; Bhobe, Mayur R; Shukla, Pankaj R

2015-01-01

Eosinophilic pustular folliculitis (EPF) was originally described by Ofuji in Japanese patients without any systemic disease. Later it was widely associated with HIV. Lately a large number of hematological malignancies have been associated with EPF. We hereby report an association of non-Hogkins lymphoma with EPF, probably the first in Indian context. PMID:26538725

Interphase FISH screening for the LCR-mediated common rearrangement of isochromosome 17q in primary myelofibrosis.

PubMed

Bien-Willner, Gabriel A; Stankiewicz, Paweł; Lupski, James R; Northup, Jill K; Velagaleti, Gopalrao V N

2005-08-01

Non-allelic homologous recombination (NAHR) between low-copy repeats (LCRs) has been implicated recently in somatic rearrangements including isochromosome i(17q), which is associated with hematologic malignancies as well as solid tumors. In hematological malignancies, the most common i(17q) breakpoint results from LCR-mediated NAHR, which creates a dicentric chromosome, idic(17)(p11.2). We report an elderly patient who presented with primary myelofibrosis (MF) with myeloid metaplasia (MMM), associated with idic(17)(p11.2) as the sole chromosomal abnormality, making this the first idic(17)(p11.2) myeloproliferative case reported in which the breakpoints are mapped to the breakpoint cluster region in proximal 17p. The rearrangement breakpoint maps to the previously defined LCR cluster, further suggesting that the genomic architecture of proximal 17p may be responsible for the formation of the majority of i(17q) cases. We describe our development of a rapid screening test using interphase FISH to detect idic(17)(p11.2), discuss the potential prognostic value of this molecular diagnostic test, and examine the relevance of LCR-mediated NAHR to common rearrangements in neoplasms. Copyright (c) 2005 Wiley-Liss, Inc.

Clinical Characteristics and Outcomes of Hematologic Malignancy Patients With Positive Clostridium difficile Toxin Immunoassay Versus Polymerase Chain Reaction Test Results.

PubMed

Ziegler, Matthew; Landsburg, Daniel; Pegues, David; Alby, Kevin; Gilmar, Cheryl; Bink, Kristen; Gorman, Theresa; Moore, Amy; Bonhomme, Brittaney; Omorogbe, Jacqueline; Tango, Dana; Tolomeo, Pam; Han, Jennifer H

2018-04-25

In a cohort of inpatients with hematologic malignancy and positive enzyme immunoassay (EIA) or polymerase chain reaction (PCR) Clostridium difficile tests, we found that clinical characteristics and outcomes were similar between these groups. The method of testing is unlikely to predict infection in this population, and PCR-positive results should be treated with concern.Infect Control Hosp Epidemiol 2018;1-4.

[Clinical significance of determination of serum B7-H4 in patients with malignant hematologic diseases].

PubMed

Wang, Xiao-Mei; Hu, Guo-Yan; Liu, Wei; Zheng, Shu-Hua; Lv, Jing; Wang, Hong-Mei; Xu, Jun-Fa

2010-09-01

To study the clinical significance of determination of serum B7-H4 in patients with malignant hematologic diseases. Serum B7-H4 levels were determined in 65 patients with leucemia, 34 patients with lymphoma, 12 patients with multiple myeloma as well as in 50 healthy controls. The serum B7-H4 levels in patients with lymphoma [(38.81+/-10.34) kappag/L] were significantly higher than healthy controls [(31.62+/-9.850) kappag/L] (P<0.01). But there are no significant difference of B7-H4 levels in serum among patients with leucemia, patients with multiple myeloma and healthy controls. These results suggest that the B7-H4 may correlated with lymphoma, but uncorrelated with leucemia and multiple myeloma. Measurement of serum B7-H4 level provide useful information for distinctive diagnosis of different kinds of malignant hematologic diseases.

The Promise of Chimeric Antigen Receptor Engineered T cells in the Treatment of Hematologic Malignancies

PubMed Central

Nagle, Sarah J.; Garfall, Alfred L.; Stadtmauer, Edward A.

2015-01-01

Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor (CAR) T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and acute lymphoblastic leukemia (ALL) have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma (MM), acute myeloid leukemia (AML) and Hodgkin lymphoma (HL). At the same time, the design and production of CAR T cells is being advanced so that this therapy can be more widely utilized. Cytokine release syndrome (CRS) and neurotoxicity are common, but they are treatable and fully reversible. This review will review currently available data as well as future developments and challenges in the field. PMID:26841014

Comparison of survival of adolescents and young adults with hematologic malignancies in Osaka, Japan.

PubMed

Nakata-Yamada, Kayo; Inoue, Masami; Ioka, Akiko; Ito, Yuri; Tabuchi, Takahiro; Miyashiro, Isao; Masaie, Hiroaki; Ishikawa, Jun; Hino, Masayuki; Tsukuma, Hideaki

2016-01-01

The survival gap between adolescents and young adults (AYAs) with hematological malignancies persists in many countries. To determine to what extent it does in Japan, we investigated survival and treatment regimens in 211 Japanese AYAs (15-29 years) in the Osaka Cancer Registry diagnosed during 2001-2005 with hematological malignancies, and compared adolescents (15-19 years) with young adults (20-29 years). AYAs with acute lymphoblastic leukemia (ALL) had a poor 5-year survival (44%), particularly young adults (29% vs. 64% in adolescents, p = 0.01). Additional investigation for patients with ALL revealed that only 19% of young adults were treated with pediatric treatment regimens compared with 45% of adolescents (p = 0.05). Our data indicate that we need to focus on young adults with ALL and to consider establishing appropriate cancer care system and guidelines for them in Japan.

Refeeding Syndrome in Oncology: Report of Four Cases.

PubMed

Windpessl, Martin; Mayrbaeurl, Beate; Baldinger, Christian; Tiefenthaller, Gernot; Prischl, Friedrich C; Wallner, Manfred; Thaler, Josef

2017-02-01

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality.

Refeeding Syndrome in Oncology: Report of Four Cases

PubMed Central

Windpessl, Martin; Mayrbaeurl, Beate; Baldinger, Christian; Tiefenthaller, Gernot; Prischl, Friedrich C.; Wallner, Manfred; Thaler, Josef

2017-01-01

The term refeeding syndrome (RFS) refers to the metabolic perturbations and its attendant complications in subjects who are refed after fasting. The syndrome is characterized by profound shifts of electrolytes and fluids. Its consequences are widespread and sometimes fatal. Patients with malignancies are especially vulnerable due to the presence of multiple comorbidities. We report the course of four patients with malignant or hematological disorders who developed RFS while being treated for their underlying illness. All physicians caring for susceptible patients should be cognizant of the risks of refeeding and treat RFS appropriately to reduce patient morbidity as well as mortality. PMID:28983382

Acute Leukemia and Concurrent Mediastinal Germ Cell Tumor: Case Report and Literature Review.

PubMed

Maese, Luke; Li, K David; Xu, Xinjie; Afify, Zeinab; Paxton, Christian N; Putnam, Angelica

2017-04-01

There is a known association of primary nonseminomatous mediastinal germ cell tumors (NSMGCT) and hematologic malignancy in younger males not linked to treatment. When combined these two rare entities convey a very poor prognosis. Here we report a 16-year-old male with an anterior mediastinal mass diagnosed as a malignant germ cell tumor based on elevation of serologic markers. He was found to have acute leukemia with megakaryocytic differentiation several days later. We focus our report on the pathologic findings, including a review of the literature, and a novel molecular analysis of the germ cell tumor.

Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies

PubMed Central

Eide, Christopher A.; Kaempf, Andy; Khanna, Vishesh; Savage, Samantha L.; Rofelty, Angela; English, Isabel; Ho, Hibery; Pandya, Ravi; Bolosky, William J.; Poon, Hoifung; Deininger, Michael W.; Collins, Robert; Swords, Ronan T.; Watts, Justin; Pollyea, Daniel A.; Medeiros, Bruno C.; Traer, Elie; Tognon, Cristina E.; Mori, Motomi; Druker, Brian J.; Tyner, Jeffrey W.

2017-01-01

Translating the genetic and epigenetic heterogeneity underlying human cancers into therapeutic strategies is an ongoing challenge. Large-scale sequencing efforts have uncovered a spectrum of mutations in many hematologic malignancies, including acute myeloid leukemia (AML), suggesting that combinations of agents will be required to treat these diseases effectively. Combinatorial approaches will also be critical for combating the emergence of genetically heterogeneous subclones, rescue signals in the microenvironment, and tumor-intrinsic feedback pathways that all contribute to disease relapse. To identify novel and effective drug combinations, we performed ex vivo sensitivity profiling of 122 primary patient samples from a variety of hematologic malignancies against a panel of 48 drug combinations. The combinations were designed as drug pairs that target nonoverlapping biological pathways and comprise drugs from different classes, preferably with Food and Drug Administration approval. A combination ratio (CR) was derived for each drug pair, and CRs were evaluated with respect to diagnostic categories as well as against genetic, cytogenetic, and cellular phenotypes of specimens from the two largest disease categories: AML and chronic lymphocytic leukemia (CLL). Nearly all tested combinations involving a BCL2 inhibitor showed additional benefit in patients with myeloid malignancies, whereas select combinations involving PI3K, CSF1R, or bromodomain inhibitors showed preferential benefit in lymphoid malignancies. Expanded analyses of patients with AML and CLL revealed specific patterns of ex vivo drug combination efficacy that were associated with select genetic, cytogenetic, and phenotypic disease subsets, warranting further evaluation. These findings highlight the heuristic value of an integrated functional genomic approach to the identification of novel treatment strategies for hematologic malignancies. PMID:28784769

Paraneoplastic itch: an expert position statement from the Special Interest Group (SIG) of the International Forum on the Study of Itch (IFSI).

PubMed

Weisshaar, Elke; Weiss, Melanie; Mettang, Thomas; Yosipovitch, Gil; Zylicz, Zbigniew

2015-03-01

In clinical practice, the term "paraneoplastic itch" is used to describe itch in patients with cancer. Patients with hematological or solid tumor malignancies can be affected. In general, paraneoplastic itch is considered a rare disorder. However, paraneoplastic itch in hematological malignancies such as polycythemia vera and lymphoma are relatively frequent while other forms of paraneoplastic itch are in fact extremely rare. The true frequency of this symptom is unclear, epidemiological data in this field are limited. Itch in malignant disease may additionally impair patients' quality of life. A population-based cohort study showed that chronic itch without concomitant skin changes is a risk factor for having undiagnosed hematologic and bile duct malignancies. Paraneoplastic itch is rather resistant to treatment. In 2012, an interdisciplinary interest group of physicians and researchers was founded, aiming to generate a clear definition of paraneoplastic itch. In this paper we briefly review the current knowledge and aim to define what can be summarized under the term "paraneoplastic itch".

Fludarabine Based Conditioning for Allogeneic Transplantation for Advanced Hematologic Malignancies

ClinicalTrials.gov

2017-10-25

Acute Myeloid Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Multiple Myeloma; Lymphocytic Leukemia; Myeloproliferative Disorder; Polycythemia Vera; Myelofibrosis; Aplastic Anemia

T-Cell Depleted Allogeneic Stem Cell Transplantation for Patients With Hematologic Malignancies

ClinicalTrials.gov

2016-10-07

Acute Myelogenous Leukemia; Lymphoid Leukemia; Chronic Myelogenous Leukemia; Malignant Lymphoma; Hodgkin's Disease; Chronic Lymphocytic Leukemia; Myeloproliferative Disorder; Anemia, Aplastic; Myelodysplastic Syndromes

Increased adenosine triphosphate production by peripheral blood CD4+ cells in patients with hematologic malignancies treated with stem cell mobilization agents.

PubMed

Manga, Kiran; Serban, Geo; Schwartz, Joseph; Slotky, Ronit; Patel, Nita; Fan, Jianshe; Bai, Xiaolin; Chari, Ajai; Savage, David; Suciu-Foca, Nicole; Colovai, Adriana I

2010-07-01

Hematopoietic stem cell (HSC) transplantation is an important therapeutic option for patients with hematologic malignancies. To explore the immunomodulatory effects of HSC mobilization agents, we studied the function and phenotype of CD4(+) T cells from 16 adult patients with hematologic malignancies undergoing HSC mobilization treatment for autologous transplantation. Immune cell function was determined using the Immuknow (Cylex) assay by measuring the amount of adenosine triphosphate (ATP) produced by CD4(+) cells from whole blood. ATP activity measured in G-CSF-treated patients was significantly higher than that measured in healthy individuals or "nonmobilized" patients. In patients treated with G-CSF, CD4(+) T cells were predominantly CD25(low)FOXP3(low), consistent with an activated phenotype. However, T-cell depletion did not abrogate ATP production in blood samples from G-CSF-treated patients, indicating that CD4(+) myeloid cells contributed to the increased ATP levels observed in these patients. There was a significant correlation between ATP activity and patient survival, suggesting that efficient activation of CD4(+) cells during mobilization treatment predicts a low risk of disease relapse. Monitoring immune cell reactivity using the Immuknow assay may assist in the clinical management of patients with hematologic malignancies and optimization of HSC mobilization protocols. Copyright 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Application and assessment of Chinese arsenic drugs in treating malignant hematopathy in China.

PubMed

Hu, Xiao-mei; Liu, Feng; Ma, Rou

2010-08-01

Chinese arsenic drugs have been applied in Chinese medicine for several centuries. Beginning from 1970s, arsenic containing drugs have been generally used for the treatment of malignant hematologic diseases including acute promyelocytic leukemia, myelodysplastic syndrome, and multiple myeloma. No matter what ingredients of arsenic drugs were applied, either arsenic trioxide, arsenic disulfide, or arsenic containing Chinese herbal compositions including Qinghuang Powder and Realgar-Indigo naturalis formula, they all provided the distinct approaches for the management of malignant hematologic diseases, and good clinical efficacy was obtained with mild adverse reactions. Moreover, the mechanisms of action have been continually elucidated.

Cytogenetics and fluorescence in-situ hybridization in detection of hematological malignancies.

PubMed

Frenny, V J; Antonella, Z; Luisa, A; Shah, A D; Sheth, J J; Rocchi, M

2003-01-01

The technique of Fluorescence In-Situ Hybridization (FISH), a hybrid of cytogenetics and molecular biology has increased the resolution and application of cytogenetics in various neoplastic processes. In various types of leukemias, primary investigation by conventional cytogenetic [CC] technique followed by FISH has increased our understanding of the abnormal clonal formation involving different gene region. Present study is aimed to use different kinds of in-house FISH probes in various hematological malignancies and its correlation with conventional cytogenetic finding. Cytogenetic study was carried out in 360 patients either from peripheral blood or from bone marrow cells suspected for various types of leukemias. Four of 360 cases were further selected for FISH study by using different types of in-house probes, such as BAC [Bacterial Artificial Chromosome], PAC [Phague Artificial Chromosome], alphoid, PCP [Partial Chromosome Paint] and WCP [Whole Chromosome paint]. The results confirmed breakpoints of inversion 16 and del 16 in case 2 and 3 respectively. Whereas, case 1 did not confirm the cytogenetic findings of t(15;17) by PML/RARa fusion signals as multiple cell lines were involved in the patients. PCP and WCP were helpful in the identification of the marker chromosome in case 1. Telomeric and centromeric probes confirmed the cytogenetic findings of t(5;7) in case 4. We observe from this study that, in addition to the conventional cytogenetic study, FISH study provide further confirmation of chromosomal rearrangements. This facilitates our understanding of the neoplastic process more precisely for the better prognostication of the patient.

S-1 induced secondary acute erythroid leukemia with a chromosome inv(12)(p13;q13)

PubMed Central

Matsumoto, Kensuke; Kitanaka, Akira; Uemura, Makiko; Waki, Fusako; Fukumoto, Tetsuya; Ohnishi, Hiroaki; Kubota, Yoshitsugu; Ishida, Toshihiko

2011-01-01

Adjuvant chemotherapy by S-1 following gastrectomy is considered standard treatment in Japan. Analysis of follow-up data have proved the efficacy of S-1 administration, and that hematological adverse events were relatively rare. Pyrimidine anti-metabolites, including S-1, have shown relatively lower risks for secondary hematological malignancies in comparison to alkylating agents and topoisomerase-II inhibitors. We here report a case of therapy-related leukemia after S-1 administration. A patient who had received S-1as the sole adjuvant chemotherapy was diagnosed with acute erythroid leukemia. To the best of our knowledge, our patient represents the first report of S-1 induced acute leukemia. PMID:22147971

The European Hematology Association Roadmap for European Hematology Research: a consensus document.

PubMed

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

2016-02-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap.The EHA Roadmap identifies nine 'sections' in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders.The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. Copyright© Ferrata Storti Foundation.

The European Hematology Association Roadmap for European Hematology Research: a consensus document

PubMed Central

Engert, Andreas; Balduini, Carlo; Brand, Anneke; Coiffier, Bertrand; Cordonnier, Catherine; Döhner, Hartmut; de Wit, Thom Duyvené; Eichinger, Sabine; Fibbe, Willem; Green, Tony; de Haas, Fleur; Iolascon, Achille; Jaffredo, Thierry; Rodeghiero, Francesco; Salles, Gilles; Schuringa, Jan Jacob

2016-01-01

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine ‘sections’ in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients. PMID:26819058

Epidemiological and mycological characteristics of candidemia in patients with hematological malignancies attending a tertiary-care center in India.

PubMed

Dewan, Eshani; Biswas, Debasis; Kakati, Barnali; Verma, S K; Kotwal, Aarti; Oberoi, Aroma

2015-09-01

We undertook the present study to ascertain the contributing risk factors and explore the epidemiological and mycological characteristics of opportunistic candidemia among patients with hematological malignancies. Observational cross-sectional study in a tertiary care center. Consecutive patients with hematological malignancies reporting to the collaborating medical and pediatric units with a febrile episode were recruited and screened for candidemia by blood culture. Recovered Candida isolates were speciated and antifungal susceptibility testing was performed as per Clinical and Laboratory Standards Institute guideline (CLSI) guidelines M44-A. Further analysis was done for potential risk factors and compared between culture positive and negative patients. Of 150 patients recruited, the majority (n=27) were between 51 and 60 years and the male to female ratio was 1.63:1. Fifteen patients (10%) were culture positive. The culture positivity was significantly higher in acute lymphocytic leukemia (ALL) than in non-ALL patients (p=0.03). There was significant association of candidaemia with leucopenia, chemotherapeutic drugs, corticosteroids and presence of indwelling devices. Duration of disease (p=0.032) and duration of hospitalization (p=0.003) were significantly prolonged in culture positive patients. C. tropicalis was the commonest isolate (46.67%), with non- Candida albicans outnumbering C. albicans in all categories of hematological malignancies (2.75:1). All isolates of C. albicans were uniformly sensitive to all the azoles, but only 50% were sensitive to amphotericin B and none to nystatin and flucytosine. This observational study identifies ALL and chronic lymphocytic leukemia (CLL) as the forms of hematological malignancy predominantly associated with candidemia; specifies risk factors and chemotherapeutic agents predisposing patients towards its occurrence; reports a preponderance of C. tropicalis among the causative agents and finds voriconazole to be the most effective antifungal agent against the recovered isolates. This information could assist in tailoring prophylactic and therapeutic antifungal practices for this infection, according to local epidemiological and mycological characteristics. Copyright © 2015. Published by Elsevier B.V.

Copy neutral loss of heterozygosity: a novel chromosomal lesion in myeloid malignancies

PubMed Central

O'Keefe, Christine; McDevitt, Michael A.

2010-01-01

Single nucleotide polymorphism arrays (SNP-A) have recently been widely applied as a powerful karyotyping tool in numerous translational cancer studies. SNP-A complements traditional metaphase cytogenetics with the unique ability to delineate a previously hidden chromosomal defect, copy neutral loss of heterozygosity (CN-LOH). Emerging data demonstrate that selected hematologic malignancies exhibit abundant CN-LOH, often in the setting of a normal metaphase karyotype and no previously identified clonal marker. In this review, we explore emerging biologic and clinical features of CN-LOH relevant to hematologic malignancies. In myeloid malignancies, CN-LOH has been associated with the duplication of oncogenic mutations with concomitant loss of the normal allele. Examples include JAK2, MPL, c-KIT, and FLT3. More recent investigations have focused on evaluation of candidate genes contained in common CN-LOH and deletion regions and have led to the discovery of tumor suppressor genes, including c-CBL and family members, as well as TET2. Investigations into the underlying mechanisms generating CN-LOH have great promise for elucidating general cancer mechanisms. We anticipate that further detailed characterization of CN-LOH lesions will probably facilitate our discovery of a more complete set of pathogenic molecular lesions, disease and prognosis markers, and better understanding of the initiation and progression of hematologic malignancies. PMID:20107230

Ewing's Sarcoma as a Second Malignancy in Long-Term Survivors of Childhood Hematologic Malignancies.

PubMed

Wolpert, Fabian; Grotzer, Michael A; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth; Bode-Lesniewska, Beata

2016-01-01

Modern multimodal treatment has significantly increased survival for patients affected by hematologic malignancies, especially in childhood. Following remission, however, the risk of developing a further malignancy is an important issue. The long-term estimated risk of developing a sarcoma as a secondary malignancy is increased severalfold in comparison to the general population. Ewing's sarcoma family encompasses a group of highly aggressive, undifferentiated, intra- and extraosseous, mesenchymal tumors, caused by several types of translocations usually involving the EWSR1 gene. Translocation associated sarcomas, such as Ewing sarcoma, are only rarely encountered as therapy associated secondary tumors. We describe the clinical course and management of three patients from a single institution with Ewing's sarcoma that followed successfully treated lymphoblastic T-cell leukemia or non-Hodgkin lymphoma. The literature on secondary Ewing's sarcoma is summarized and possible pathogenic mechanisms are critically discussed.

Critical methodological factors in diagnosing minimal residual disease in hematological malignancies using quantitative PCR.

PubMed

Nyvold, Charlotte Guldborg

2015-05-01

Hematological malignancies are a heterogeneous group of cancers with respect to both presentation and prognosis, and many subtypes are nowadays associated with aberrations that make up excellent molecular targets for the quantification of minimal residual disease. The quantitative PCR methodology is outstanding in terms of sensitivity, specificity and reproducibility and thus an excellent choice for minimal residual disease assessment. However, the methodology still has pitfalls that should be carefully considered when the technique is integrated in a clinical setting.

[Hematological malignancy: management of anemia and leukopenia by primary care physicians].

PubMed

Burnand, J; Waeber, G; Duchosal, M A

2009-10-28

In hematological malignancies, the occurrence of anemia is very common and can have significant consequences on daily life. Treatment includes essentially red blood cell transfusions. The prescription of erythropoietic agents and/or iron is exceptionnal and often not registered in Switzerland. The onset of neutropenia is also frequently encountered and in some situations may require the prescription of myeloid growth factors. The purpose of this article is to focus on the current recommendations of these two issues for practitioners.

The challenging aspects of managing adolescents and young adults with Hodgkin's lymphoma.

PubMed

Jachimowicz, Ron D; Engert, Andreas

2014-01-01

Cancer in the adolescent and young adult (AYA) is the second leading cause of nonaccidental death with hematological malignancies spiking during this period. Treatment of AYAs with hematological malignancies usually follows either pediatric or adult protocols with sufficient information lacking on subgroup analyses regarding course and outcome. In this review we will outline up-to-date treatment possibilities for AYAs diagnosed with Hodgkin's lymphoma. Early and late toxicities will be addressed and future directions of research suggested. © 2014 S. Karger AG, Basel.

(1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies.

PubMed

Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

2016-04-19

Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1-3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77-510) vs. 50 (30-125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68-0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe.

(1, 3)-β-D-glucan assay for diagnosing invasive fungal infections in critically ill patients with hematological malignancies

PubMed Central

Azoulay, Elie; Guigue, Nicolas; Darmon, Michael; Mokart, Djamel; Lemiale, Virginie; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Bretagne, Stéphane; Lebert, Christine; Meert, Anne-Pascale; Benoit, Dominique; Pene, Frédéric

2016-01-01

Invasive fungal infections (IFIs) are life-threatening complications of hematological malignancies that must be diagnosed early to allow effective treatment. Few data are available on the performance of serum (1–3)-β-D-glucan (BG) assays for diagnosing IFI in patients with hematological malignancies admitted to the intensive care unit (ICU). In this study, 737 consecutive patients with hematological malignancies admitted to 17 ICUs routinely underwent a BG assay at ICU admission. IFIs were diagnosed using standard criteria applied by three independent specialists. Among the 737 patients, 439 (60%) required mechanical ventilation and 273 (37%) died before hospital discharge. Factors known to alter BG concentrations were identified in most patients. IFIs were documented in 78 (10.6%) patients (invasive pulmonary aspergillosis, n = 54; Pneumocystis jirovecii pneumonia, n = 13; candidemia, n = 13; and fusarium infections, n = 3). BG concentrations (pg/mL) were higher in patients with than without IFI (144 (77–510) vs. 50 (30–125), < 0.0001). With 80 pg/mL as the cutoff, sensitivity was 72%, specificity 65%, and area-under-the-curve 0.74 (0.68–0.79). Assuming a prevalence of 10%, the negative and positive predictive values were 94% and 21%. By multivariable analysis, factors independently associated with BG > 80 pg/mL were IFI, admission SOFA score, autologous bone-marrow or hematopoietic stem-cell transplantation, and microbiologically documented bacterial infection. In conclusion, in unselected critically ill hematology patients with factors known to affect serum BG, this biomarker showed only moderate diagnostic performance and rarely detected IFI. However, the negative predictive value was high. Studies are needed to assess whether a negative BG test indicates that antifungal de-escalation is safe. PMID:26910891

Acute respiratory failure in patients with hematological malignancies: outcomes according to initial ventilation strategy. A groupe de recherche respiratoire en réanimation onco-hématologique (Grrr-OH) study.

PubMed

Lemiale, Virginie; Resche-Rigon, Matthieu; Mokart, Djamel; Pène, Frederic; Rabbat, Antoine; Kouatchet, Achille; Vincent, François; Bruneel, Fabrice; Nyunga, Martine; Lebert, Christine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Chevret, Sylvie; Azoulay, Elie

2015-12-01

In patients with hematological malignancies and acute respiratory failure (ARF), noninvasive ventilation was associated with a decreased mortality in older studies. However, mortality of intubated patients decreased in the last years. In this study, we assess outcomes in those patients according to the initial ventilation strategy. We performed a post hoc analysis of a prospective multicentre study of critically ill hematology patients, in 17 intensive care units in France and Belgium. Patients with hematological malignancies admitted for ARF in 2010 and 2011 and who were not intubated at admission were included in the study. A propensity score-based approach was used to assess the impact of NIV compared to oxygen only on hospital mortality. Among 1011 patients admitted to ICU during the study period, 380 met inclusion criteria. Underlying diseases included lymphoid (n = 162, 42.6 %) or myeloid (n = 141, 37.1 %) diseases. ARF etiologies were pulmonary infections (n = 161, 43 %), malignant infiltration (n = 65, 17 %) or cardiac pulmonary edema (n = 40, 10 %). Mechanical ventilation was ultimately needed in 94 (24.7 %) patients, within 3 [2-5] days of ICU admission. Hospital mortality was 32 % (123 deaths). At ICU admission, 142 patients received first-line noninvasive ventilation (NIV), whereas 238 received oxygen only. Fifty-five patients in each group (NIV or oxygen only) were matched according the propensity score. NIV was not associated with decreased hospital mortality [OR 1.5 (0.62-3.65)]. In hematology patients with acute respiratory failure, initial treatment with NIV did not improve survival compared to oxygen only. gov number NCT 01172132.

The incidence of ototoxicity in child malignancy cases that received carboplatin therapy with otoacoustic emission (OAE) examination

NASA Astrophysics Data System (ADS)

Wibowo, J. K.; Zizlavsky, S.; Suwento, R.; Sjakti, H. A.; Prihartono, J.

2017-08-01

Malignancy is a significant public health problem, both globally and in Indonesia. Chemotherapy is one of the modality in malignancy cases. Carboplatin (cis-diammine-cyclobutanedi-carboxylato platinum) is a second-generation platinum compound that has often been used in the management of cases of malignancies. On the other hand, side effects of cytotoxic drugs need to be considered, especially ototoxic effects. Ototoxicity is dysfunction and damage to the structure of the inner ear that has been caused by drugs or other certain chemicals. The aim of this study is to assess ototoxic effects due to the influence of carboplatin in the cases of children with malignancy. This study uses a serial cross-sectional design to evaluate otoacoustic emission (OAE) signal-to-noise ratio (SNR) change as a result of ototoxic effects and risk factors due to the use of ototoxic carboplatin in the Division of Hematology-Oncology of the Department of Pediatrics at Cipto Mangunkusumo General Hospital in Jakarta, where two of 52 studies’ subjects experienced ototoxicity. In the group were receiving chemotherapy, two (5%) of the 40 subjects has experienced ototoxic events characterized by SNR values less than six, whereas SNR values were not less than six in the group that had not received chemotherapy. Risk factors such as gender, age, carboplatin dose, and cycles of chemotherapy did not have a statistically significant relationship to ototoxity.

Endothelial Cell-Specific Molecule-1 in Critically Ill Patients With Hematologic Malignancy.

PubMed

Zafrani, Lara; Resche-Rigon, Matthieu; De Freitas Caires, Nathalie; Gaudet, Alexandre; Mathieu, Daniel; Parmentier-Decrucq, Erika; Lemiale, Virginie; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Vincent, François; N'yunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Darmon, Michael; Azoulay, Elie

2018-03-01

To assess whether serum concentration of endothelial cell-specific molecule-1 (Endocan) at ICU admission is associated with the use of ICU resources and outcomes in critically ill hematology patients. Prospective multicenter cohort study. Seventeen ICUs in France and Belgium. Seven hundred forty-four consecutive critically ill hematology patients; 72 critically ill septic patients without hematologic malignancy; 276 healthy subjects. None. Median total endocan concentrations were 4.46 (2.7-7.8) ng/mL. Endocan concentrations were higher in patients who had received chemotherapy before ICU admission (4.7 [2.8-8.1] ng/mL vs. 3.7 [2.5-6.3] ng/mL [p = 0.002]). In patients with acute respiratory failure, endocan levels were increased in patients with drug-induced pulmonary toxicity compared with other etiologies (p = 0.038). Total endocan levels higher than 4.46 ng/mL were associated with a higher cumulative probability of renal replacement therapy requirement (p = 0.006), a higher requirement of mechanical ventilation (p = 0.01) and a higher requirement of vasopressors throughout ICU stay (p < 0.0001). By multivariate analysis, total endocan levels at admission were independently associated with ICU mortality (odds ratios, 1.39; 95% CI, 1.06-1.83; p = 0.018). The predictive value of endocan peptide fragments of 14 kDa in terms of mortality and life-sustaining therapies requirement was inferior to that of total endocan. Endocan levels were higher in critically ill hematology patients compared with healthy subjects (p < 0.0001) but lower than endocan values in critically ill septic patients without hematologic malignancy (p = 0.005) CONCLUSIONS:: Serum concentrations of endocan at admission are associated with the use of ICU resources and mortality in critically ill hematology patients. Studies to risk-stratify patients in the emergency department or in the hematology wards based on endocan concentrations to identify those likely to benefit from early ICU management are warranted.

Utility of CRISPR/Cas9 systems in hematology research.

PubMed

Lucas, Daniel; O'Leary, Heather A; Ebert, Benjamin L; Cowan, Chad A; Tremblay, Cedric S

2017-10-01

Since the end of the 20th century, novel approaches have emerged to manipulate experimental models of hematological disorders so that they more accurately mirror what is observed in the clinical setting. Despite these technological advances, the characterization of crucial genes for benign or malignant hematological disorders remains challenging, given the dynamic nature of the hematopoietic system and the genetic heterogeneity of these disorders. To overcome this limitation, genome-editing technologies have been developed to manipulate the genome specifically via deletion, insertion, or modification of targeted loci. These technologies have progressed swiftly, allowing their common use to investigate genetic function in experimental hematology. Among them, homologous-recombination-mediated targeting technologies have facilitated the manipulation of specific loci by generating knock-out and knock-in models. Despite promoting significant advances in our understanding of the molecular mechanisms involved in hematology, these inefficient, time-consuming, and labor-intensive approaches did not permit the development of cellular or animal models, recapitulating the complexity of hematological disorders. On October 26, 2016, Drs. Ben Ebert and Chad Cowan shared their knowledge of and experience with the utilization of CRISPR for models of myeloid malignancy, disease, and novel therapeutics in an International Society for Experimental Hematology webinar titled "Utility of CRISPR/Cas9 Systems in Hematology Research." Here, we provide an overview of the topics they covered, including their insights into the novel applications of the technique and its strengths and limitations. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

Hematology: ATG and Newton's third law of motion.

PubMed

Brunstein, Claudio G

2010-01-01

Patients with hematological malignancies have a risk of developing graft-versus-host disease (GVHD) following allogeneic hematopoietic stem-cell transplantation. The addition of ATG to prophylaxis regimens decreases the incidence of GVHD without compromising overall survival in these patients.

Antiminor Histocompatibility Complex (MiHA) T Cells for Patients With Relapsed Hematologic Malignancies Following Matched HSCT (Guided Lymphocyte Immunopeptide Derived Expansion)

ClinicalTrials.gov

2017-12-04

Hematologic Cancer; Relapse Leukemia; Relapsed Adult ALL; Relapsed Adult AML; Relapsed CLL; Relapsed Non Hodgkin Lymphoma; Relapsed Hodgkin's Lymphoma; Relapsed Myelodysplastic Syndromes; Relapsed Multiple Myeloma

Nutritionally Variant Streptococci Bacteremia in Cancer Patients: A Retrospective Study, 1999–2014

PubMed Central

Yacoub, Abraham T.; Krishnan, Jayasree; Acevedo, Ileana M.; Halliday, Joseph; Greene, John N.

2015-01-01

Background Nutritionally variant Streptococci (NVS), Abiotrophia and Granulicatella are implicated in causing endocarditis and blood stream infections more frequently than other sites of infection. Neutropenia and mucositis are the most common predisposing factors for infection with other pathogens in cancer patients. In this study, we investigated the clinical characteristics of NVS bacteremia in cancer patients and identified risk factors and outcomes associated with these infections. Materials and Methods We retrospectively reviewed all cases of NVS bacteremia occurring from June 1999 to April 2014 at H. Lee Moffitt Cancer Center and Research Institute. The computerized epidemiology report provided by the microbiology laboratory identified thirteen cancer patients with NVS bacteremia. We collected data regarding baseline demographics and clinical characteristics such as age, sex, underlying malignancy, neutropenic status, duration of neutropenia, treatment, and outcome. Results Thirteen patients were identified with positive NVS blood stream infection. Ten patients (77%) had hematologic malignancies, including chronic lymphocytic leukemia (CLL)(1), multiple myeloma (MM)(1), acute myelogenous leukemia (AML)(4), and non-Hodgkin’s lymphoma (NHL)(4). The non-hematologic malignancies included esophageal cancer(2) and bladder cancer (1). Conclusion NVS should be considered as a possible agent of bacteremia in cancer patients with neutropenia and a breach in oral, gastrointestinal and genitourinary mucosa (gingivitis/mucositis). PMID:25960858

Incidence and survival of hematological cancers among adults ages ≥75 years.

PubMed

Krok-Schoen, Jessica L; Fisher, James L; Stephens, Julie A; Mims, Alice; Ayyappan, Sabarish; Woyach, Jennifer A; Rosko, Ashley E

2018-04-13

Evaluating population-based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one- and five-year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010-2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One- and five-year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007-2013, with follow-up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one- and five-year relative survival rates were observed among adults with CLL ages 75-84 years (1 year: 91.8% (95% CI = 91.8-90.8)) and 5 years: 76.5% (95% CI = 74.2-78.6)). The lowest one- and five-year survival rates were observed among adults with AML ages 75-84 (1 year: 18.2% (95% CI = 74.2-78.6) and 5 years: 2.7% (95% CI = 2.0-3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Nanotechnology applications in hematological malignancies (Review).

PubMed

Samir, Ahmed; Elgamal, Basma M; Gabr, Hala; Sabaawy, Hatem E

2015-09-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up.

Nanotechnology applications in hematological malignancies (Review)

PubMed Central

SAMIR, AHMED; ELGAMAL, BASMA M; GABR, HALA; SABAAWY, HATEM E

2015-01-01

A major limitation to current cancer therapies is the development of therapy-related side-effects and dose limiting complications. Moreover, a better understanding of the biology of cancer cells and the mechanisms of resistance to therapy is rapidly developing. The translation of advanced knowledge and discoveries achieved at the molecular level must be supported by advanced diagnostic, therapeutic and delivery technologies to translate these discoveries into useful tools that are essential in achieving progress in the war against cancer. Nanotechnology can play an essential role in this aspect providing a transforming technology that can translate the basic and clinical findings into novel diagnostic, therapeutic and preventive tools useful in different types of cancer. Hematological malignancies represent a specific class of cancer, which attracts special attention in the applications of nanotechnology for cancer diagnosis and treatment. The aim of the present review is to elucidate the emerging applications of nanotechnology in cancer management and describe the potentials of nanotechnology in changing the key fundamental aspects of hematological malignancy diagnosis, treatment and follow-up. PMID:26134389

Applications of Gene Editing Technologies to Cellular Therapies.

PubMed

Rein, Lindsay A M; Yang, Haeyoon; Chao, Nelson J

2018-03-27

Hematologic malignancies are characterized by genetic heterogeneity, making classic gene therapy with a goal of correcting 1 genetic defect ineffective in many of these diseases. Despite initial tribulations, gene therapy, as a field, has grown by leaps and bounds with the recent development of gene editing techniques including zinc finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR) sequences and CRISPR-associated protein-9 (Cas9) nuclease or CRISPR/Cas9. These novel technologies have been applied to efficiently and specifically modify genetic information in target and effector cells. In particular, CRISPR/Cas9 technology has been applied to various hematologic malignancies and has also been used to modify and improve chimeric antigen receptor-modified T cells for the purpose of providing effective cellular therapies. Although gene editing is in its infancy in malignant hematologic diseases, there is much room for growth and application in the future. Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Evaluation of matrix metalloproteinases (MMP)-2 and MMP-9 activity in serum and biochemical and hematological parameters in spontaneous canine cutaneous tumors before and after surgical treatment.

PubMed

Fathipour, Vahid; Khaki, Zohreh; Nassiri, Seyyed Mehdi

2018-01-01

Recently, matrix metalloproteinases (MMP), in particular the gelatinases MMP-2 and MMP-9, generally considered as tumor markers for clinical applications. A longitudinal 2-years follow-up survey was performed on dogs with cutaneous tumor. Serum samples were obtained from 22 dogs with different cutaneous tumors and 22 health dogs at the time of surgery and one month, three months and one year after surgery. Gelatin zymography, hematological and biochemical assessment were performed for all serum samples. The serum alkaline phosphatase activity in dogs with malignant tumors was significantly higher than that in dogs with benign tumors and control cases. Latent forms of MMP-2 and MMP-9 were detected in all of the tumor cases. Gelatin zymography showed active form of MMP-9 in 12 cases (three benign and nine malignant tumors) and active form of MMP-2 in one fibrosarcoma case. Serum activity of active-MMP-9 and total MMP-9 was significantly higher in dogs with cutaneous tumors than those in controls. Tumor cases had higher serum activity of active-MMP-9 rather than controls. MMPs and alkaline phosphatase activities in serum were decreased significantly after surgery. Only one case with perianal gland adenoma showed recurrence of tumor four months after surgery in which active form of MMP-9 had identified one month before recurrence. According to the findings, it will be useful to measure ALP, MMP-2 and MMP-9 activities in the serum of dogs with cutaneous tumor for determination of tumor behavior before surgical treatment.

Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

PubMed

Kikushige, Yoshikane; Miyamoto, Toshihiro

2015-11-01

Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

Survival From Childhood Hematological Malignancies in Denmark: Is Survival Related to Family Characteristics?

PubMed

Erdmann, Friederike; Winther, Jeanette Falck; Dalton, Susanne Oksbjerg; Lightfoot, Tracy; Zeeb, Hajo; Simony, Sofie Bay; Deltour, Isabelle; Ferro, Gilles; Bautz, Andrea; Schmiegelow, Kjeld; Schüz, Joachim

2016-06-01

Due to diverse findings as to the role of family factors for childhood cancer survival even within Europe, we explored a nationwide, register-based cohort of Danish children with hematological malignancies. All children born between 1973 and 2006 and diagnosed with a hematological malignancy before the age of 20 years (N = 1,819) were followed until 10 years from diagnosis. Kaplan-Meier curves and Cox proportional hazards models estimating hazard ratios (HR) and 95% confidence intervals (CI) were used to assess the impact of family characteristics on overall survival in children with hematological malignancies. Having siblings and increasing birth order were associated with reduced survival from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Associations with AML were strongest and statistically significant. HRs of 1.62 (CI 0.85; 3.09) and 5.76 (CI 2.01; 16.51) were observed for the fourth or later born children with ALL (N = 41) and AML (N = 9), respectively. Children with older parents showed a tendency toward inferior ALL survival, while for AML young maternal age was related to poorer survival. Based on small numbers, a trend toward poorer survival from non-Hodgkin lymphoma was observed for children having siblings and for children of younger parents. Further research is warranted to gain further knowledge on the impact of family factors on childhood cancer survival in other populations and to elaborate potential underlying mechanisms and pathways of those survival inequalities. © 2016 Wiley Periodicals, Inc.

Urgent Chemotherapy in Sepsis-Like Shock Related to Hematologic Malignancies.

PubMed

Cherruault, Marlène; Le Goff, Marielle; Tamburini, Jérôme; Pène, Frédéric

2018-05-01

Hematologic malignancies may result in multiple organ involvement including pulmonary and renal dysfunctions, and the less common acute circulatory failure. We herein addressed the outcome of patients with sepsis-like shock related to aggressive hematologic malignancies. A 10-year (2007-2016) monocenter retrospective study. A medical ICU in a tertiary care center. Patients with circulatory shock requiring vasopressors and who subsequently received chemotherapy. Shock was presumably related to the underlying malignancy after ruling out an ongoing or new-onset infectious process. The extent and time course of organ failures was assessed by a modified Sequential Organ Failure Assessment score devoid of the platelet component. None. Seventeen patients were included, including 13 with non-Hodgkin lymphoma, two with hyperleukocytic acute myeloid leukemia, and two with "Human Herpes virus 8"-associated multicentric Castleman's disease. The following associated conditions prompted urgent administration of chemotherapy: tumor lysis syndrome (n = 10), hemophagocytic lymphohistiocytosis (n = 3), compressive bulky tumor (n = 3), pulmonary involvement (n = 3), and disseminated intravascular coagulation (n = 1). Following the initiation of chemotherapy, a number of patients died rapidly from untractable multiple organ failure. In contrast, chemotherapy led to a fast and dramatic improvement in organ failures in early survivors, as shown by the decrease in the modified Sequential Organ Failure Assessment score. However, the overall outcome was poor since only four and three patients could be discharged alive from the ICU and the hospital, and three and two patients remained alive at 6 months and 1 year. Multiple organ dysfunction syndrome related to hematologic malignancies is associated with a dismal outcome. A chemotherapy trial may provide a fast prognostic assessment of the reversibility of organ failure.

Surgical lung biopsy in patients with hematological malignancy or hematopoietic stem cell transplantation and unexplained pulmonary infiltrates: improved outcome with specific diagnosis.

PubMed

Zihlif, Mamoon; Khanchandani, Geeta; Ahmed, Huma P; Soubani, Ayman O

2005-02-01

Using a retrospective review of medical records, we sought the findings of surgical lung biopsy (SLB) in patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) and unexplained pulmonary infiltrates and to determine the impact of this procedure on management and outcome of these patients. Sixty-two patients who underwent SLB were evaluated; 31 patients had underlying hematological malignancy and 31 patients were HSCT recipients; 58% of whom underwent allogeneic HSCT. Thirty-three patients (53%) had focal infiltrates on chest CT scan while 29 (47%) had diffuse infiltrates. Thirteen patients were mechanically ventilated prior to SLB, and 27 (43%) were neutropenic. There were 66 diagnoses in the 62 patients, 44 (67%) were specific and 22 (33%) were nonspecific. The most common specific diagnoses were infection (29%), malignancy (27%), and inflammatory conditions (11%). Aspergillosis was the most common diagnosis of all biopsies (21%). SLB led to a change in therapy in 40% of patients and was associated with complications in 7 patients (11%). Specific diagnosis was more likely to lead to a change in therapy (48% vs. 27%, P = 0.06) and was associated with a lower mortality when compared to a nonspecific finding (30% vs. 59%, P = 0.02). Nonspecific diagnosis, on the other hand, was seen more in patients on mechanical ventilation prior to SLB compared to those off mechanical ventilation (69% vs. 27%, P = 0.02). SLB provides a specific diagnosis in the majority of patients with hematologic malignancy or HSCT recipients and unexplained pulmonary infiltrates. Specific diagnosis is more likely to lead to a change in therapy and is associated with a better outcome. Copyright 2005 Wiley-Liss, Inc.

[Acute hybrid leukemia. Review of the literature and presentation of a case].

PubMed

Guzzini, F; Angelopoulos, N; Banfi, L; Coppetti, D; Ceppi, M; Camerone, G

1990-03-01

In the last years, the development of immunophenotypic and molecular analyses allowed to recognize several cases of hybrid acute leukemia (AL), whose blast cell display both lymphoid and myeloid features. Hybrid, or mixed-lineage, AL seems to have distinct clinical manifestations and hematological findings, and is mainly characterized by resistance to chemotherapy and poor prognosis. We report on a patient with AL, which showed a very rapid switch from the lymphoblastic phenotype exhibited at presentation to a myelomonoblastic one, appeared at first relapse, and lastly progressed to an undifferentiated leukemia in the terminal phase. Together with this morphologic and cytochemical evolution, leukemic cells expressed, besides the primary early-B antigens, new immunological markers related to T-lymphocytic and myeloid lineages. Based on this observation and current understanding of the ontogenesis of hematologic malignancies, we discuss biological mechanisms which are likely to underlie hybrid leukemia.

The Association of Age With Clinical Presentation and Comorbidities of Pyoderma Gangrenosum.

PubMed

Ashchyan, Hovik J; Butler, Daniel C; Nelson, Caroline A; Noe, Megan H; Tsiaras, William G; Lockwood, Stephen J; James, William D; Micheletti, Robert G; Rosenbach, Misha; Mostaghimi, Arash

2018-04-01

Pyoderma gangrenosum is an inflammatory neutrophilic dermatosis. Current knowledge of this rare disease is limited owing to a lack of validated diagnostic criteria and large population studies. To evaluate the association of age with the clinical presentation and comorbidities of pyoderma gangrenosum. This was a multicenter retrospective cohort study performed at tertiary academic referral centers in urban settings. Adults (≥18 years) who were evaluated and diagnosed as having pyoderma gangrenosum at the Brigham and Women's and Massachusetts General Hospitals from 2000 to 2015 and the University of Pennsylvania Health System from 2006 to 2016 were included. Patient demographics, clinical features, medical comorbidities, and treatment. Of the 356 validated cases of pyoderma gangrenosum included in the study, 267 (75%) were women and 284 (84.8%) were white. The mean (SD) age at presentation was 51.6 (17.7) years. Pathergy was recorded in 100 patients (28.1%). A total of 238 patients (66.9%) had associated medical comorbidities: inflammatory bowel disease in 146 patients (41.0%); inflammatory arthritis in 73 patients (20.5%); solid organ malignant neoplasms in 23 patients (6.5%); hematologic malignant neoplasms in 21 patients (5.9%); and hematologic disorders, specifically monoclonal gammopathy of undetermined significance, myelodysplastic syndrome, and polycythemia vera in 17 patients (4.8%). When stratified by age, pathergy was more common in patients 65 years or older (36.3% vs 24.3%; P = .02). Inflammatory bowel disease was the only medical comorbidity that was more common in patients younger than 65 years (47.7% vs 26.6%; P < .001), while a number of medical comorbidities were more common in those 65 years or older, including rheumatoid arthritis (13.3% vs 6.2%; P = .03), ankylosing spondylitis (1.8% vs 0%; P = .04), solid organ malignant neoplasms (13.3% vs 3.3%; P < .001), hematologic malignant neoplasms (9.7% vs 4.1%; P = .04), and the aforementioned hematologic disorders (10.6% vs 2.1%; P < .001). Although clinical presentation in this large cohort was similar between different age groups, disease associations varied by age. The findings of this study may allow for a more focused, age-specific evaluation of patients with pyoderma gangrenosum.

Symptomatic Hypercalcemia in a Patient with B-cell Chronic Lymphocytic Leukemia - A Case Report and Review of the Literature.

PubMed

Koutroumpakis, Efstratios; Lobe, Montgomery; McCarthy, Lezah; Mehdi, Syed

Hypercalcemia due to malignancy is well described in the literature and a common paraneoplastic finding in certain solid tumors. Hematologic malignancies, however, are less frequently associated with hypercalcemia with the exception of myelomas and T-cell lymphomas. This case report describes a patient with B-cell chronic lymphocytic leukemia (B-CLL) who developed symptomatic hypercalcemia. None of the pathogenetic mechanisms of malignancy-associated hypercalcemia already described in the literature could explain the pathogenesis of hypercalcemia in our patient. Calcium levels were normalized after initial treatment and remained within normal limits following treatment of the underlying B-CLL. The follow-up period was 26 months. The normalization of calcium levels was closely associated with the drop in the absolute lymphocyte count. Symptomatic hypercalcemia in B-CLL is exceedingly rare and only documented a few times in the literature. Hypercalcemia, in the present case, was not caused by any of the mechanisms already described in the literature and responded well to treatment of the underlying B-CLL. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Irradiated Donor Cells Following Stem Cell Transplant in Controlling Cancer in Patients With Hematologic Malignancies

ClinicalTrials.gov

2018-05-16

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia in Remission; Hematopoietic Cell Transplantation Recipient; JAK2 Gene Mutation; Loss of Chromosome 17p; Mantle Cell Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; RAS Family Gene Mutation; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hematologic Malignancy; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome; TP53 Gene Mutation

Distribution and features of hematological malignancies in Eastern Morocco: a retrospective multicenter study over 5 years.

PubMed

Elidrissi Errahhali, Mounia; Elidrissi Errahhali, Manal; Boulouiz, Redouane; Ouarzane, Meryem; Bellaoui, Mohammed

2016-02-25

Hematological malignancies (HM) are a public health problem. The pattern and distribution of diagnosed hematological cancers vary depending on age, sex, geography, and ethnicity suggesting the involvement of genetic and environmental factors for the development of these diseases. To our knowledge, there is no published report on HM in the case of Eastern Morocco. In this report we present for the first time the overall pattern of HM for this region. Retrospective descriptive study of patients diagnosed with HM between January 2008 and December 2012 in three centres in Eastern Morocco providing cancer diagnosis, treatment or palliative care services. The FAB (French-American-British) classification system has been taken into account in the analysis of myeloid and lymphoid neoplasms. In this study, a total of 660 cases of HM were registered between January 2008 and December 2012. Overall, 6075 cases of cancers all sites combined were registered during this study period, indicating that HM account for around 10.9 % (660/6075) of all cancers recorded. Among the 660 registered cases of HM, 53 % were males and 47 % were females, with a male to female ratio of 1.1. Thus, overall, men are slightly more affected with HM than women. By contrast, a female predominance was observed in the case of Hodgkin's lymphoma (HL), myeloproliferative neoplasms (MPN), acute myeloid leukemia (AML) and the myelodysplastic syndrome (MDS). HM occur at a relatively young age, with an overall median age at diagnosis of 54 years. Non-Hodgkin's lymphoma (NHL) was the most common HM accounting for 29.7 % of all HM, followed by HL, MPN, multiple myelomas (MM), chronic lymphocytic leukemia (CLL), AML, MDS, acute lymphoblastic leukemia (ALL), and Waldenström macroglobulinemia (WM). The majority of HM cases have been observed among patients aged 60 years and over (40.4 % of HM). Among this age group, NHL was the most common HM. In adolescents, HL was the most frequent HM. This study provided for the first time the pattern and distribution of HM in Eastern Morocco. Our findings justify the need to establish a regional cancer registry as a first step in blood cancer control in Eastern Morocco.

Lymphoepithelioma-Like Carcinoma of the Breast Mimicking Granulomatous Mastitis- Case Report and Review of the Literature

PubMed

Abouelfad, Dalia M; Yassen, Noha N; Amin, Hebat Allah A; Shabana, Marwa E

2017-07-27

Lymphoepithelioma-like carcinoma (LELC) of the breast is an exceedingly rare variant of mammary cancer. To our knowledge, only twenty - one cases have been reported in the literature. Diagnosis of this type of mammary carcinoma may be challenging, owing to its rarity and the histopathological similarity to common inflammatory and malignant lesions of the breast mainly granulomatous mastitis, medullary carcinoma, pleomorphic lobular carcinoma, lymphoma and other hematological malignancies. Our case is the 22nd case of lymphoepithelioma-like carcinoma reported in the breast, presenting with a palpable tender mass in a post-menopausal female. Her clinical picture had been mistaken for inflammatory disease. We present our case, with its detailed clinical history, radiological findings, histopathological and immune-histochemical findings along with a review of the literature. Highlighting this type of tumors may help in appropriate diagnosis. Moreover, studying the behavior of these rare neoplasms is essential to expedite treatment for this tumor type. Creative Commons Attribution License

Hematological consequences of a FANCG founder mutation in Black South African patients with Fanconi anemia.

PubMed

Feben, Candice; Kromberg, Jennifer; Wainwright, Rosalind; Stones, David; Poole, Janet; Haw, Tabitha; Krause, Amanda

2015-03-01

Fanconi anemia (FA) is a rare disorder of DNA repair, associated with various somatic abnormalities but characterized by hematological disease that manifests as bone marrow aplasia and malignancy. The mainstay of treatment, in developed nations, is hematopoietic stem cell transplantation (HSCT) with subsequent surveillance for solid organ and non-hematological malignancies. In South Africa, FA in the Black population is caused by a homozygous deletion mutation in the FANCG gene in more than 80% of cases. Many affected patients are not diagnosed until late in the disease course when severe cytopenia and bone marrow aplasia are already present. Most patients are not eligible for HSCT at this late stage of the disease, even when it is available in the state health care system. In this study, the hematological presentation and disease progression in 30 Black South African patients with FA, confirmed to have the FANCG founder mutation, were evaluated and compared to those described in other FA cohorts. Our results showed that patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with FA of heterogeneous genotype. Further, the incidence of myelodysplastic syndrome is similar to that which has been previously described in other FA cohorts. Although severe cytopenia at presentation may be predicted by a higher number of somatic anomalies, the recognition of the physical FA phenotype in Black South African patients is challenging and may not be useful in expediting referral of suspected FA patients for tertiary level investigations and care. Given the late but severe hematological presentation of FA in Black South African patients, an investigative strategy is needed for earlier recognition of affected individuals to allow for possible HSCT and management of bone marrow disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies. PMID:27605883

Aspirin Is Associated with Improved Survival in Severely Thrombocytopenic Cancer Patients with Acute Myocardial Infarction.

PubMed

Feher, Attila; Kampaktsis, Polydoros N; Parameswaran, Rekha; Stein, Eytan M; Steingart, Richard; Gupta, Dipti

2017-02-01

Patients with hematologic malignancies are at risk for severe thrombocytopenia (sTP). The risk and benefit of aspirin are not known in thrombocytopenic cancer patients experiencing acute myocardial infarction (AMI). Medical records of patients with hematologic malignancies diagnosed with AMI at Memorial Sloan Kettering Cancer Center during 2005-2014 were reviewed. sTP was defined as a platelet count <50,000 cells per µL within 7 days of AMI. Of 118 patients with hematologic malignancies who had AMI, 58 (49%) had sTP. Twenty-five patients (43%) with sTP received aspirin as a treatment for AMI. Compared with patients without sTP with AMI, patients with sTP with AMI were less likely to receive aspirin (83% vs. 43%; p  = .0001) and thienopyridine treatment (27% vs. 3%; p  = .0005). During median follow-up of 3.7 years after AMI, survival was lower in patients with sTP than in those with no sTP (23% vs. 50% at 1 year; log rank p  = .003). Patients with sTP who received aspirin for AMI had improved survival compared with those who did not (92% vs. 70% at 7 days, 72% vs. 33% at 30 days, and 32% vs. 13% at 1 year; log rank p  = .008). In multivariate regression models, aspirin use was associated with improved 30-day survival both in the overall patient cohort and in sTP patients. No fatal bleeding events occurred. Major bleeding was not associated with sTP or aspirin use. Treatment of AMI with aspirin in patients with hematologic malignancies and sTP is associated with improved survival without increase in major bleeding. The Oncologist 2017;22:213-221 Implications for Practice: In patients with hematologic malignancies and acute myocardial infarction with severe thrombocytopenia (platelet count < 50,000 cells/µL), guideline-recommended medical therapy is often withheld because of the fear of major bleeding. In this study, aspirin therapy was associated with improved survival without an increase in major bleeding in this high-risk patient cohort. © AlphaMed Press 2017.

[Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in hematological malignancy patients].

PubMed

Motohashi, Shinya; Hori, Katsuhito; Ono, Takaaki; Ohnishi, Kazunori; Kawakami, Junichi

2012-01-01

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.

Marriage, employment, and health insurance in adult survivors of childhood cancer.

PubMed

Crom, Deborah B; Lensing, Shelly Y; Rai, Shesh N; Snider, Mark A; Cash, Darlene K; Hudson, Melissa M

2007-09-01

Adult survivors of childhood cancer are at risk for disease- and therapy-related morbidity, which can adversely impact marriage and employment status, the ability to obtain health insurance, and access to health care. Our aim was to identify factors associated with survivors' attainment of these outcomes. We surveyed 1,437 childhood cancer survivors who were >18 years old and >10 years past diagnosis. We compared our cohort's data to normative data in the Medical Expenditure Panel Survey and the U.S. Census Bureau's Current Population Surveys. Respondents were stratified by hematologic malignancies, central nervous system tumors, or other solid tumors and by whether they had received radiation therapy. Most respondents were survivors of hematologic malignancies (71%), white (91%), and working full-time (62%); 43% were married. Compared with age- and sex-adjusted national averages, only survivors of hematologic malignancies who received radiation were significantly less likely to be married (44 vs. 52%). Full-time employment among survivors was lower than national norms, except among survivors of hematologic malignancies who had not received radiation therapy. The rates of coverage of health insurance, especially public insurance, were higher in all diagnostic groups than in the general population. While difficulty obtaining health care was rarely reported, current unemployment and a lack of insurance were associated with difficulty in obtaining health care (P < 0.05 and P < 0.001, respectively). CONCLUSIONS/IMPLICATIONS FOR CANCER SURVIVORS: Subgroups of cancer survivors do experience long-term differences in functional outcomes that should be addressed early. Survivors who are unmarried, unemployed, and uninsured experience difficulty accessing health care needed to address long-term health concerns.

Bioequivalence & Food Effect Study in Patients With Solid Tumor or Hematologic Malignancies

ClinicalTrials.gov

2018-04-30

Hematological Neoplasms; Non-Hodgkin's Lymphoma; Hodgkin's Lymphoma; Lymphoma; Multiple Myeloma; Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndromes; Neoplasms; Melanoma; Breast Cancer; Metastatic Breast Cancer; Non-Small Cell Lung Cancer; Small Cell Lung Cancer; Renal Cell Carcinoma; Glioblastoma Multiforme; Osteosarcoma; Sarcoma; Thyroid Cancer; Genitourinary

Multifactorial neutropenia in a patient with acute promyelocytic leukemia and associated large granular lymphocyte expansion: A case report.

PubMed

Reda, Gianluigi; Fattizzo, Bruno; Cassin, Ramona; Flospergher, Elena; Orofino, Nicola; Gianelli, Umberto; Barcellini, Wilma; Cortelezzi, Agostino

2017-03-01

Neutropenia in the setting of acute hematological malignancies may impact disease prognosis, thus affecting therapy dose intensity. This is often due to chemotherapy-induced aplasia as well as to the disease itself. However, chronic neutropenia deserves further investigation, as the management of reversible concomitant causes may avoid treatment delay. The present study describes a case of an acute promyelocytic leukemia patient with chronic severe neutropenia of multifactorial origin, including acute leukemia itself, chemotherapy, autoimmune activation with anti-platelets and anti-neutrophil antibodies positivity, and the rare association of large granular lymphocyte (LGL) expansion. As neutropenia may challenge the diagnosis and treatment of acute malignancies, clinicians and hematopathologists must discuss the differential diagnosis in order to avoid misdiagnosing and undertreating concomitant diseases. In particular, LGL chronic expansion and autoimmunity should be considered.

Generalized palisaded neutrophilic and granulomatous dermatitis-a cutaneous manifestation of chronic myelomonocytic leukemia? A clinical, histopathological, and molecular study of 3 cases.

PubMed

Federmann, Birgit; Bonzheim, Irina; Yazdi, Amir S; Schmidt, Janine; Fend, Falko; Metzler, Gisela

2017-06-01

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is characterized by erythematous papules or plaques on trunk or limbs and is frequently associated with rheumatologic, autoimmune, or hematologic malignancies. Histopathology shows interstitial granulomas composed of epitheloid histiocytes in the reticular dermis with surrounding foci of collagen degeneration and variable neutrophilic inflammation. We report 3 cases of generalized PNGD associated with chronic myelomonocytic leukemia (CMML), a myelodysplastic/myeloproliferative neoplasm, which may show a variety of cutaneous manifestations. SRSF2 P95 hotspot mutations, found in 40%-50% of CMML cases, were retrospectively detected in skin and bone marrow biopsies of all 3 patients, in 1 of them already 5 years before CMML diagnosis. Generalized PNGD may represent a type of cutaneous manifestation of CMML. Because diagnosis of CMML is frequently difficult in cases with isolated persistent monocytosis and minimal dysplasia in the bone marrow, patients with a generalized PNGD should be evaluated for the presence of hematologic disorders including CMML, ideally supported by mutational analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

The impact of oral herpes simplex virus infection and candidiasis on chemotherapy-induced oral mucositis among patients with hematological malignancies.

PubMed

Chen, Y-K; Hou, H-A; Chow, J-M; Chen, Y-C; Hsueh, P-R; Tien, H-F

2011-06-01

The aim of this study was to evaluate the influences of oral candidiasis and herpes simplex virus 1 (HSV-1) infections in chemotherapy-induced oral mucositis (OM). The medical records of 424 consecutive patients with hematological malignancies who had received chemotherapy at a medical center in Taiwan from January 2006 to November 2007 were retrospectively reviewed. The results of swab cultures of fungus and HSV-1 for OM were correlated with associated clinical features. Younger age, myeloid malignancies, and disease status other than complete remission before chemotherapy were significantly correlated with the development of OM. Risks of fever (p < 0.001) and bacteremia were higher in patients with OM. Among 467 episodes of OM with both swab cultures available, 221 were non-infection (47.3%) and 246 were related to either fungal infections, HSV-1 infections, or both (52.7%); of the 246 episodes, 102 were associated with fungal infections alone (21.8%), 98 with HSV-1 infections alone (21%), and 46 with both infections (9.9%). Patients who had received antifungal agents prior to OM occurrence tended to have HSV-1 infection (p < 0.001). Our results suggest that Candida albicans and HSV-1 play an important role in chemotherapy-induced OM in patients with hematological malignancies.

Usefulness of bronchoalveolar lavage and flow cytometry in patients with hematological malignancies and respiratory failure.

PubMed

Ferrà, Christelle; Xicoy, Blanca; Castillo, Nerea; Morgades, Mireia; Juncà, Jordi; Andreo, Felipe; Millá, Fuensanta; Feliu, Evarist; Ribera, Josep-María

2017-04-07

Strategies to improve the efficiency of bronchoalveolar lavage (BAL) are needed. We conducted a study to establish the diagnostic value of BAL in patients with hematological malignancies and pulmonary infiltrates. The correlation of cytologic and flow cytometric study of BAL with the microbiological findings and the clinical evolution was determined. Seventy BAL were performed and flow cytometric study was analyzed in 23 of them. Fifty-three patients did not present any adverse event attributable to BAL. Anti-infectious therapy was modified in 64 (91%) patients. T lymphocyte count >0.3×10 9 /l in peripheral blood was associated with longer OS at 3 years (53 vs. 22%, p=.009). Higher CD4 (>20/μL) and CD8 (>35/μL) lymphocyte counts in the BAL were associated with a longer OS at 3 years: 82 vs. 21% (p=.030) and 80 vs. 23% (p=.059). Our study confirms the clinical value of BAL for treatment decision making in patients with hematological malignancies and acute respiratory failure. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

A New Sandwich ELISA for Quantification of Thymidine Kinase 1 Protein Levels in Sera from Dogs with Different Malignancies Can Aid in Disease Management

PubMed Central

Jagarlamudi, Kiran Kumar; Moreau, Laura; Westberg, Sara; Rönnberg, Henrik; Eriksson, Staffan

2015-01-01

Thymidine kinase 1 (TK1) is a DNA precursor enzyme whose expression is closely correlated with cell proliferation and cell turnover. Sensitive serum TK1 activity assays have been used for monitoring and prognosis of hematological malignancies in both humans and dogs. Here we describe the development of a specific sandwich TK1-ELISA for the quantification of TK1 protein levels in sera from dogs with different malignancies. A combination of rabbit polyclonal anti-dog TK1 antibody and a mouse monoclonal anti-human TK1 antibody was used. Different concentrations of recombinant canine TK1 was used as standard. Clinical evaluation of the ELISA was done by using sera from 42 healthy dogs, 43 dogs with hematological tumors and 55 with solid tumors. An established [3H]-dThd phosphorylation assay was used to determine the TK1 activity levels in the same sera. The mean TK1 activities in dogs with hematological tumors were significantly higher than those found in healthy dogs. In agreement with earlier studies, no significant difference was observed in serum TK1 activities between healthy dogs and dogs with solid tumors. However, the mean TK1 protein levels determined by new TK1-ELISA were significantly higher not only in hematological tumors but also in solid tumors compared to healthy dogs (mean ± SD = 1.30 ± 1.16, 0.67 ± 0.55 and 0.27± 0.10 ng/mL, respectively). Moreover, TK1-ELISA had significantly higher ability to distinguish lymphoma cases from healthy based on receiver operating characteristic analyses (area under the curve, AUC, of 0.96) to that of the activity assay (AUC, 0.84). Furthermore, fluctuations in TK1 protein levels during the course of chemotherapy in dogs with lymphoma closely associated with clinical outcome. Overall, the TK1-ELISA showed significant linear correlation with the TK1 activity assay (r s = 0.6, p<0.0001). Thus, the new TK1-ELISA has sufficient sensitivity and specificity for routine clinical use in veterinary oncology. PMID:26366881

Predictors of and Trends in High-Intensity End-of-Life Care Among Children With Cancer: A Population-Based Study Using Health Services Data.

PubMed

Kassam, Alisha; Sutradhar, Rinku; Widger, Kimberley; Rapoport, Adam; Pole, Jason D; Nelson, Katherine; Wolfe, Joanne; Earle, Craig C; Gupta, Sumit

2017-01-10

Purpose Children with cancer often receive high-intensity (HI) medical care at the end-of-life (EOL). Previous studies have been limited to single centers or lacked detailed clinical data. We determined predictors of and trends in HI-EOL care by linking population-based clinical and health-services databases. Methods A retrospective decedent cohort of patients with childhood cancer who died between 2000 and 2012 in Ontario, Canada, was assembled using a provincial cancer registry and linked to population-based health-care data. Based on previous studies, the primary composite measure of HI-EOL care comprised any of the following: intravenous chemotherapy < 14 days from death; more than one emergency department visit; and more than one hospitalization or intensive care unit admission < 30 days from death. Secondary measures included those same individual measures and measures of the most invasive (MI) EOL care (eg, mechanical ventilation < 14 days from death). We determined predictors of outcomes with appropriate regression models. Sensitivity analysis was restricted to cases of cancer-related mortality, excluding treatment-related mortality (TRM) cases. Results The study included 815 patients; of these, 331 (40.6%) experienced HI-EOL care. Those with hematologic malignancies were at highest risk (odds ratio, 2.5; 95% CI, 1.8 to 3.6; P < .001). Patients with hematologic cancers and those who died after 2004 were more likely to experience the MI-EOL care (eg, intensive care unit, mechanical ventilation, odds ratios from 2.0 to 5.1). Excluding cases of TRM did not substantively change the results. Conclusion Ontario children with cancer continue to experience HI-EOL care. Patients with hematologic malignancies are at highest risk even when excluding TRM. Of concern, rates of the MI-EOL care have increased over time despite increased palliative care access. Linking health services and clinical data allows monitoring of population trends in EOL care and identifies high-risk populations for future interventions.

Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors-Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).

PubMed

Rieger, C T; Liss, B; Mellinghoff, S; Buchheidt, D; Cornely, O A; Egerer, G; Heinz, W J; Hentrich, M; Maschmeyer, G; Mayer, K; Sandherr, M; Silling, G; Ullmann, A; Vehreschild, M J G T; von Lilienfeld-Toal, M; Wolf, H H; Lehners, N

2018-06-01

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.

Successful management of chronic disseminated candidiasis in hematologic patients treated with high-dose liposomal amphotericin B: a retrospective study of the SEIFEM registry.

PubMed

Della Pepa, Roberta; Picardi, M; Sorà, F; Stamouli, M; Busca, A; Candoni, A; Delia, M; Fanci, R; Perriello, V; Zancanella, M; Nosari, A; Salutari, P; Marchesi, F; Pane, F; Pagano, L

2016-09-01

Chronic disseminated candidiasis (CDC) is a complication of Candida infection in immunocompromised patients, involving the liver and spleen, and rarely other organs. The aim of the study is to identify the best antifungal drug for hematologic immunocompromised patients with CDC. In this multicentric retrospective study, the charts of 20 patients with CDC following cytotoxic agent protocols for hematological malignancies, diagnosed from 2003 to 2013, were analyzed. The response to systemic antifungal therapy within 90 days from CDC diagnosis and the possible delay in chemotherapy plan, due to the infection, were evaluated. Six patients were treated with high-dose (HD; 5 mg/kg/daily) liposomal amphotericin B (L-AmB), whereas three received standard-dose (SD) L-AmB (3 mg/kg/daily). Azoles were given to six patients; the remaining five were treated with echinocandins. All patients treated with HD L-AmB (6/6-100 %) achieved complete resolution of CDC; one of them had to interrupt the chemotherapy program for the infection. In the SD L-AmB group, treatment failed in the 100 % of cases and one patient had to delay chemotherapy for the infection. Of the six patients who received azoles, two achieved complete resolution of the infection, four experienced treatment failure, and only three performed chemotherapy as planned. Echinocandins treatment resulted in complete resolution of the infection in 2/5 cases, partial response in 2/5 cases, and failure in one case. In this group, 3/5 patients completed chemotherapy as planned. This study shows that HD L-AmB was particularly effective against CDC in hematologic patients, allowing most patients to continue cytotoxic agent program.

Safety Profile of Anticancer and Immune-Modulating Biotech Drugs Used in a Real World Setting in Campania Region (Italy): BIO-Cam Observational Study

PubMed Central

Scavone, Cristina; Sportiello, Liberata; Sullo, Maria G.; Ferrajolo, Carmen; Ruggiero, Rosanna; Sessa, Maurizio; Berrino, Pasquale M.; di Mauro, Gabriella; Berrino, Liberato; Rossi, Francesco; Rafaniello, Concetta; Capuano, Annalisa; Valentini, G.

2017-01-01

Objectives: To investigate the occurrence of adverse events (AEs) in naïve patients receiving biotech drugs. Design: A prospective observational study. Setting: Onco-hematology, Hepato-gastroenterology, Rheumatology, Dermatology, and Neurology Units in Campania Region (Italy). Participants: 775 patients (53.81% female) with mean age 56.0 (SD 15.2). The mean follow-up/patient was 3.48 (95% confidence interval 3.13–3.84). Main outcome measures: We collected all AEs associated to biotech drugs, including serious infections and malignancies. Serious AEs were defined according to the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, clinical safety data management: definitions and standards for expedited reporting E2A guideline. Results: The majority of the study population was enrolled in Onco-hematology and Rheumatology Units and the most common diagnosis were hematological malignancies, followed by rheumatoid arthritis, colorectal cancer, breast cancer, and psoriatic arthritis. The most commonly prescribed biotech drugs were rituximab, bevacizumab, infliximab, trastuzumab, adalimumab, and cetuximab. Out of 775 patients, 320 experienced at least one AE. Most of patients experienced AEs to cetuximab therapy, rituximab and trastuzumab. Comparing female and male population, our findings highlighted a statistically significant difference in terms of AEs for adalimumab (35.90% vs. 7.41%, p < 0.001) and etanercept (27.59% vs. 10.00%, p = 0.023). Considering all biotech drugs, we observed a peak for all AEs occurrence at follow-up 91–180 days category. Bevacizumab, brentuximab, rituximab, trastuzumab and cetuximab were more commonly associated to serious adverse events; most of these were possibly related to biotech drugs, according to causality assessment. Three cases of serious infections occurred. Conclusions: The results of our study demonstrated that the majority of AEs were not serious and expected. Few cases of serious infections occurred, while no case of malignancy did. Overall, the safety profile of biotech drugs used in our population was similar to those observed in pivotal trials. Notwithstanding the positive results of our study, some safety concerns still remain unresolved. In order to collect more effectiveness and safety data on biotech drugs, the collection and analysis of real world data should be endorsed as well as the management of post-authorization studies. PMID:28932193

How I treat influenza in patients with hematologic malignancies

PubMed Central

Casper, Corey; Englund, Janet

2010-01-01

The 2009 H1N1 influenza pandemic has heightened the interest of clinicians for options in the prevention and management of influenza virus infection in immunocompromised patients. Even before the emergence of the novel 2009 H1N1 strain, influenza disease was a serious complication in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplantation. Here we review the clinical manifestations of seasonal and 2009 H1N1 influenza and discuss current diagnosis, antiviral treatment, and prophylaxis options. We also summarize infection control and vaccination strategies for patients, family members, and caregivers. PMID:20009037

Recent Concise Viewpoints of Chronic Active Epstein-Barr Virus Infection.

PubMed

Okano, Motohiko

2015-01-01

Chronic active Epstein-Barr virus infection (CAEBV) is characterized mainly by prolonged or intermittent fever, lymphadenopathy and hepatosplenomegaly without definite underlying diseases at the diagnosis. Patients with CAEBV also may have various life-threatening conditions including hematological, neurological, pulmonary, cardiac, digestive tract, ocular and/or dermal disorders. Additionally, during the course of illness, they often develop hematological malignancies such as T cell, NK cell or B cell lymphoproliferative disorder (LPD) and/or lymphoma. No causative pathogenetic mechanisms have been sufficiently clarified, and additionally no promising efficacious treatment was demonstrated except for the hematopoietic stem cell transplantation (HSCT) in cases who develop T cell or NK cell LPD or lymphoma. This minireview outlines the recent development for the comprehensive viewpoints of CAEBV mainly regarding to virological, immunological, pathological and therapeutical progresses.

Current status of sperm banking for young cancer patients in Japanese nationwide survey.

PubMed

Yumura, Yasushi; Tsujimura, Akira; Okada, Hiroshi; Ota, Kuniaki; Kitazawa, Masahumi; Suzuki, Tatsuya; Kakinuma, Tosiyuki; Takae, Seido; Suzuki, Nao; Iwamoto, Teruaki

2018-02-02

This study aimed to ascertain the current status of Japanese sperm banking for young cancer patients. During 2015, we mailed the directors of 695 institutes where sperm cryopreservation might be performed with questionnaires requesting information on the number of patients, age, precryopreservation chemotherapy, semen analyses results and diagnoses, cryopreservation success rate, and causes of unsuccessful cryopreservation. Of these 695 institutes, 92 had cryopreserved sperm before chemotherapy within the study period. In all, 820 cancer patients (237 testicular, 383 hematological, 46 bone and soft tissue, 20 brain, and 134 other malignancy) consulted the responding institutes for sperm cryopreservation. Except for testicular tumor, the number of patients whose sperm was preserved before cancer treatment was low compared to that of young cancer patients. Approximately 20% of patients with malignancies other than testicular tumor underwent chemotherapy before cryopreservation. The success rate of cryopreservation in hematological malignancy was 82.5%, significantly lower than that of both the testicular cancer (93.6%) and other malignancy groups (95.6%) (P < 0.05). The primary reasons for preservation failure were azoospermia and poor semen quality. Patients with hematological malignancies had a higher rate of unsuccessful cryopreservation compared to those in other groups, possibly due to the large number of patients requesting sperm cryopreservation after chemotherapy induction. In Japan, information regarding sperm banking prior to cancer treatment appears to be lacking. Information regarding sperm preservation before chemotherapy should be provided to all Japanese oncologists.

Correlation of sociodemographic and clinical parameters with depression and distress in patients with hematologic malignancies.

PubMed

Shreders, Amanda J; Niazi, Shehzad K; Hodge, David O; Chimato, Nicolette T; Kureti, Megha; Kirla, Navya; Agrawal, Ankit; Swaika, Abhisek; Gustetic, Elaine; Foster, Renee; Nelson, Kimberly A; Jani, Prachi; Chanan-Khan, Asher A; Ailawadhi, Sikander

2018-03-01

A quarter of cancer patients struggle with distress or depression during their illness. Multiple organizations including the National Comprehensive Cancer Network recommend universal screening for distress and depression. Herein, we describe a universal screening program in patients with hematologic malignancies and factors associated with distress and depression. Between December 2013 and February 2015, patients with hematologic malignancies took the Patient Health Questionnaire 9 (PHQ-9) and Distress Thermometer (DT) prior to receiving their first outpatient parenteral chemotherapy. Patient demographic information as well as information regarding visit burden and baseline use of psychiatric medications were recorded. A PHQ-9 score of ≥ 9 and a DT score ≥ 4 suggested a high risk of major depression and distress. Intergroup comparisons of categorical and continuous variables were performed via chi-square and Wilcoxon rank-sum tests. Multivariate models were constructed using the stepwise selection technique using all potential variables. Two hundred forty-six patients with a median age at diagnosis 65 years (range 18-94 years) were included. In the multivariate analysis, a PHQ-9 score ≥ 9 was associated with living alone (P = 0.007), positive PHQ-2 (P = 0.003), and high Charlson comorbidity index (CCI; P = 0.02), while a DT score ≥ 4 was associated with being married (P = 0.03) and female (P = 0.03). There was no other association with high scores on either questionnaire. Patients with hematologic malignancies often have prolonged treatment and surveillance. We identified subpopulations within this group who may be at high risk of developing distress and depression and who should be aggressively screened even when universal screening programs are not available.

c-Src activation through a TrkA and c-Src interaction is essential for cell proliferation and hematological malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Min Soo; Kim, Gyoung Mi; Choi, Yun-Jeong

2013-11-15

Highlights: •TrkA was mainly present in other types of leukemia including AML. •TrkA enhances the survival of leukemia by activation of PI3K/Akt pathway. •TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1. •TrkA acted as a key regulator of leukemogenesis and survival through c-Src activation. -- Abstract: Although the kinase receptor TrkA may play an important role in acute myeloid leukemia (AML), its involvement in other types of leukemia has not been reported. Furthermore, how it contributes to leukemogenesis is unknown. Here, we describe a molecular network that is important for TrkA function in leukemogenesis. We found that TrkAmore » is frequently overexpressed in other types of leukemia such as acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), and myelodysplastic syndrome (MDS) including AML. In addition, TrkA was overexpressed in patients with MDS or secondary AML evolving from MDS. TrkA induced significant hematological malignancies by inducing PLK-1 and Twist-1, and enhanced survival and proliferation of leukemia, which was correlated with activation of the phosphatidylinositol 3-kinase/Akt/mTOR pathway. Moreover, endogenous TrkA associated with c-Src complexes was detected in leukemia. Suppression of c-Src activation by TrkA resulted in markedly decreased expression of PLK-1 and Twist-1 via suppressed activation of Akt/mTOR cascades. These data suggest that TrkA plays a key role in leukemogenesis and reveal an unexpected physiological role for TrkA in the pathogenesis of leukemia. These data have important implications for understanding various hematological malignancies.« less

Hematological Toxicity After Robotic Stereotactic Body Radiosurgery for Treatment of Metastatic Gynecologic Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kunos, Charles A., E-mail: charles.kunos@UHhospitals.org; Debernardo, Robert; Radivoyevitch, Tomas

Purpose: To evaluate hematological toxicity after robotic stereotactic body radiosurgery (SBRT) for treatment of women with metastatic abdominopelvic gynecologic malignancies. Methods and Materials: A total of 61 women with stage IV gynecologic malignancies treated with abdominopelvic SBRT were analyzed after ablative radiation (2400 cGy/3 divided consecutive daily doses) delivered by a robotic-armed Cyberknife SBRT system. Abdominopelvic bone marrow was identified using computed tomography-guided contouring. Fatigue and hematologic toxicities were graded by retrospective assignment of common toxicity criteria for adverse events (version 4.0). Bone marrow volume receiving 1000 cGy (V10) was tested for association with post-therapy (median 32 days [25%-75% quartile,more » 28-45 days]) white- or red-cell counts, hemoglobin levels, and platelet counts as marrow toxicity surrogates. Results: In all, 61 women undergoing abdominopelvic SBRT had a median bone marrow V10 of 2% (25%-75% quartile: 0%-8%). Fifty-seven (93%) of 61 women had received at least 1 pre-SBRT marrow-taxing chemotherapy regimen for metastatic disease. Bone marrow V10 did not associate with hematological adverse events. In all, 15 grade 2 (25%) and 2 grade 3 (3%) fatigue symptoms were self-reported among the 61 women within the first 10 days post-therapy, with fatigue resolved spontaneously in all 17 women by 30 days post-therapy. Neutropenia was not observed. Three (5%) women had a grade 1 drop in hemoglobin level to <10.0 g/dL. Single grade 1, 2, and 3 thrombocytopenias were documented in 3 women. Conclusions: Abdominopelvic SBRT provided ablative radiation dose to cancer targets without increased bone marrow toxicity. Abdominopelvic SBRT for metastatic gynecologic malignancies warrants further study.« less

A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.

PubMed

Miyao, Kotaro; Sawa, Masashi; Kurata, Mio; Suzuki, Ritsuro; Sakemura, Reona; Sakai, Toshiyasu; Kato, Tomonori; Sahashi, Satomi; Tsushita, Natsuko; Ozawa, Yukiyasu; Tsuzuki, Motohiro; Kohno, Akio; Adachi, Tatsuya; Watanabe, Keisuke; Ohbayashi, Kaneyuki; Inagaki, Yuichiro; Atsuta, Yoshiko; Emi, Nobuhiko

2017-01-01

Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.

Laparoscopic splenectomy: a single center experience. Unusual cases and expanded inclusion criteria for laparoscopic approach.

PubMed

Marte, Gianpaolo; Scuderi, Vincenzo; Rocca, Aldo; Surfaro, Giuseppe; Migliaccio, Carla; Ceriello, Antonio

2013-06-01

Laparoscopic splenectomy (LS) is nowadays considered as the gold standard for most hematological diseases where splenectomy is necessary, but many questions still remain. The aim of this study was to analyze our 5-years experiences consisting of 48 consecutive LS cases in order to assess the optimal approach and the feasibility of the procedure also in malignant diseases and unusual cases such as a primary spleen lymphoma, a big splenic artery aneurism, or a spleen infarct due to a huge pancreatic pseudo-cyst. Forty-eight consecutive patients underwent LS from January 2006 to January 2011 with at least 1-year follow-up. Clinical data and immediate outcome were retrospectively recorded; age, diagnosis, operation time, perioperative transfusion requirement, conversion rate, accessory incision, hospital stay, and complications were analyzed. We had 14 cases of malignant splenic disease, the most frequent malignant diagnosis was non-Hodgkin's lymphoma (12/14, 85.7 %). Splenomegaly (interpole diameter (ID) >20 cm) was observed in 12 cases (25 %) and massive splenomegaly (ID >25 cm) in 3 cases (6.25 %). Conversion to laparotomy occurred in two patients (4.16 %), both associated to uncontrollable bleeding in patients with splenomegaly. Mean operative time was 138 ± 22 min. Mean hospital stay was 4.5 days. Postoperative morbidity rate was 8.8 % for the benign group and 35.7 % in the malignant group. Mortality occurred in 1/48 patients (2.08 %), as a result of overwhelming post-splenectomy infection (OPSI). LS can be performed safely for malignant splenic disease and splenomegaly without any statistically significant increase of morbidity and mortality rate. Conversion rate is increased for massive splenomegaly. LS should be considered as the preferential approach even in patients with malignant disease, splenomegaly, or unusual cases. Massive splenomegaly should be considered as relative contraindication to LS even at experienced centers.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

PubMed

Dănciulescu Miulescu, R; Carşote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-09-15

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations

PubMed Central

Dănciulescu Miulescu, R; Carșote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-01-01

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves’ disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug’s withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy. PMID:24155785

Respiratory syncytial virus infection in infants with acute leukemia: a retrospective survey of the Japanese Pediatric Leukemia/Lymphoma Study Group.

PubMed

Hatanaka, Michiki; Miyamura, Takako; Koh, Katsuyoshi; Taga, Takashi; Tawa, Akio; Hasegawa, Daisuke; Kajihara, Ryosuke; Adachi, Souichi; Ishii, Eiichi; Tomizawa, Daisuke

2015-12-01

Respiratory syncytial virus (RSV) can cause life-threatening complications of lower respiratory tract infection (LRTI) in young children with malignancies, but reports remain limited. We performed a retrospective nationwide survey to clarify the current status of RSV disease among infants with hematological malignancies. Clinical course, treatment, and outcome of patients with hematological malignancies who suffered from RSV infections at the age of <24 months during anti-tumor therapy from April 2006 to March 2009 were investigated by sending a questionnaire to all member institutions of the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG). Twelve patients with acute leukemia were identified as having experienced RSV disease. The primary diseases were acute myeloid leukemia (n = 8) and acute lymphoblastic leukemia (n = 4). RSV infection occurred pre- or during induction therapy (n = 8) and during consolidation therapy (n = 4). Eight patients developed LRTI, four of whom had severe pneumonia or acute respiratory distress syndrome; these four patients died despite receiving intensive care. In our survey, the prognosis of RSV disease in pediatric hematological malignancies was poor, and progression of LRTI in particular was associated with high mortality. In the absence of RSV-specific therapy, effective prevention and treatment strategies for severe RSV disease must be investigated.

SEIFEM 2017: from real life to an agreement on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant disorders.

PubMed

Busca, Alessandro; Cesaro, Simone; Teofili, Luciana; Delia, Mario; Cattaneo, Chiara; Criscuolo, Marianna; Marchesi, Francesco; Fracchiolla, Nicola Stefano; Valentini, Caterina Giovanna; Farina, Francesca; Di Blasi, Roberta; Prezioso, Lucia; Spolzino, Angelica; Candoni, Anna; Del Principe, Maria Ilaria; Verga, Luisa; Nosari, Annamaria; Aversa, Franco; Pagano, Livio

2018-02-01

The rapid spread of severe infections mainly due to resistant pathogens, justifies the search for therapies aiming to restore immune functions severely compromised in patients with hematologic malignancies. Areas covered: The present review summarizes the current knowledge on the role of granulocyte transfusions and colony-stimulating factors as treatment strategy for hematologic patients with serious infectious complications. In addition, a survey among 21 hematologic centers, to evaluate the clinical practice for the use of G-CSF originator and biosimilars was performed. Expert commentary: Granulocyte transfusions with a target dose of at least 1.5-3 × 10 8 cells/kg, may be considered as an approach to bridge the gap between marrow suppression and recovery of granulocytes. G-CSF shortens the period of neutropenia, the hospitalization, the use of antibiotics and the rate of febrile neutropenia (FN) in adult and pediatric patients with non-Hodgkin lymphoma, and in adults with acute myeloid leukemia where these advantages nevertheless, did not translate into a clinical benefit. G-CSF biosimilar showed equivalence or non-inferiority to filgrastim. There are no data supporting the use of GM-CSF, eltrombopag and erythropoietin for preventing or treating infectious complications in patients with hematologic disorders.

Long non-coding RNAs in B-cell malignancies: a comprehensive overview

PubMed Central

Taiana, Elisa; Neri, Antonino

2017-01-01

B-cell malignancies constitute a large part of hematological neoplasias. They represent a heterogeneous group of diseases, including Hodgkin's lymphoma, most non-Hodgkin's lymphomas (NHL), some leukemias and myelomas. B-cell malignancies reflect defined stages of normal B-cell differentiation and this represents the major basis for their classification. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts longer than 200 nucleotides, for which many recent studies have demonstrated a function in regulating gene expression, cell biology and carcinogenesis. Deregulated expression levels of lncRNAs have been observed in various types of cancers including hematological malignancies. The involvement of lncRNAs in cancer initiation and progression and their attractive features both as biomarker and for therapeutic research are becoming increasingly evident. In this review, we summarize the recent literature to highlight the status of the knowledge of lncRNAs role in normal B-cell development and in the pathogenesis of B-cell tumors. PMID:28947998

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE); a rare association with phyllodes tumour of breast.

PubMed

Sarkar, R N; Phaujdar, Sibaji; Banerjee, Siwalik; Siddhanta, Sattik; De, Dibyendu; Bhattachary, Kuntal; Pal, Hare Krishna

2012-04-01

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare entity mainly found in elderly males. It is characterized by pitting edema mainly of dorsum of both hands giving a "boxing glove hand" appearance; rarely involving feet also, acute in onset, negative rheumatoid factor and a good response to low dose corticosteroid therapy. Clinically it almost resembles a case of polymyalgia rheumatica, late onset rheumatoid arthritis or other seronegative spondyloarthropathy.Though there are multiple underlying factors causing this rare entity but it has very close associations with many malignancies.So far its association with solid tumours and hematological malignancies has been reported. Phyllodes tumour of breast shows wide spectrum of activity from a benign condition to a locally aggressive and sometimes metastatic tumour.One fourth of the cases recur after definitive treatment.Our case represent an unusual association with recurrent phyllodes tumour of breast with RS3PE.

Viral Pneumonia in Patients with Hematologic Malignancy or Hematopoietic Stem Cell Transplantation.

PubMed

Vakil, Erik; Evans, Scott E

2017-03-01

Viral pneumonias in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation cause significant morbidity and mortality. Advances in diagnostic techniques have enabled rapid identification of respiratory viral pathogens from upper and lower respiratory tract samples. Lymphopenia, myeloablative and T-cell depleting chemotherapy, graft-versus-host disease, and other factors increase the risk of developing life-threatening viral pneumonia. Chest imaging is often nonspecific but may aid in diagnoses. Bronchoscopy with bronchoalveolar lavage is recommended in those at high risk for viral pneumonia who have new infiltrates on chest imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

The quality of life of hematological malignancy patients with major depressive disorder or subsyndromal depression.

PubMed

Rezaei, Omid; Sharifian, Ramezan-Ali; Soleimani, Mehdi; Jahanian, Amirabbas

2012-01-01

The purpose of the present study was to compare the quality of life of hematological malignancy patients with major depressive disorder or subsyndromal depression. Sample consisted of 93 hematological malignancy patients recruited from oncology ward of Valieasr hospital for Imam Khomeini complex hospital at Tehran through purposeful sampling. Participants were divided into three groups through diagnostic interview based on DSM-IV-TR criteria and the Beck Depression Inventory-2 (BDI-II): Major depressive disorder (MDD) (n = 41; 44.1%); subsyndromal depression (SSD) (n = 23; 24.7%), and without depression (WD) (n = 29; 31.2%). Participants completed the short-form health survey (SF-36) as a measure of the quality of life. We carried out an analysis of covariance to examine the collected data. Findings showed that there was not a significant difference between patients with MDD and SSD based on measure of quality of life. But patients with MDD and SSD showed significantly worse quality of life than patients with WD. This finding highlights the clinical importance of subsyndromal depressive symptoms and casts doubt on the clinical utility of separation between MDD and subsyndromal depression in terms of important clinical outcomes.

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies.

PubMed

Antun, Ana G; Gleason, Shannon; Arellano, Martha; Langston, Amelia A; McLemore, Morgan L; Gaddh, Manila; el Rassi, Fuad; Bernal-Mizrachi, Leon; Galipeau, Jacques; Heffner, Leonard T; Winton, Elliott F; Khoury, Hanna J

2013-11-01

Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients. The antifibrinolytic agent epsilon aminocaproic acid (EACA) was administered to 44 chronically (median duration, 273 days) and severely (platelet count, 8 × 10(9)/L; range, 1 × 10(9)/L-19 × 10(9)/L) thrombocytopenic patients with hematological malignancies. Prophylactic EACA at a dose of 1 g twice daily was orally administered for a median duration of 47 days (range, 7 days-209 days) until the platelet count recovered to > 30; × 10(9) /L. Platelets were only transfused if bleeding occurred. While receiving EACA, 59% of the patients did not bleed, 25% had 19 episodes of spontaneously resolving minor bleeding that did not require platelet transfusion, and 16% received a median of 4 platelet transfusions (range, 1 transfusion-8 transfusions) for 1 major traumatic and 9 spontaneous grade 2 to grade 3 bleeding (based on the World Health Organization classification of idiopathic thrombocytopenic purpura). No EACA toxicities were noted, and venous thromboses were not observed. EACA is well tolerated and is associated with a low risk of major bleeding in patients with hematological malignancies who are experiencing chronic severe thrombocytopenia. © 2013 American Cancer Society.

Nucleophosmin: a versatile molecule associated with hematological malignancies.

PubMed

Naoe, Tomoki; Suzuki, Tatsuya; Kiyoi, Hitoshi; Urano, Takeshi

2006-10-01

Nucleophosmin (NPM) is a nucleolar phosphoprotein that plays multiple roles in ribosome assembly and transport, cytoplasmic-nuclear trafficking, centrosome duplication and regulation of p53. In hematological malignancies, the NPM1 gene is frequently involved in chromosomal translocation, mutation and deletion. The NPM1 gene on 5q35 is translocated with the anaplastic lymphoma kinase (ALK) gene in anaplastic large cell lymphoma with t(2;5). The MLF1 and RARA genes are fused with NPM1 in myelodysplastic syndrome and acute myeloid leukemia (AML) with t(3;5) and acute promyelocytic leukemia with t(5;17), respectively. In each fused protein, the N-terminal NPM portion is associated with oligomerization of a partner protein leading to altered signal transduction or transcription. Recently, mutations of exon 12 have been found in a significant proportion of de novo AML, especially in those with a normal karyotype. Mutant NPM is localized aberrantly in the cytoplasm, but the molecular mechanisms for leukemia remain to be studied. Studies of knock-out mice have revealed new aspects regarding NPM1 as a tumor-suppressor gene. This review focuses on the clinical significance of the NPM1 gene in hematological malignancies and newly discovered roles of NPM associated with oncogenesis.

Notch signaling: its roles and therapeutic potential in hematological malignancies

PubMed Central

Gu, Yisu

2016-01-01

Notch is a highly conserved signaling system that allows neighboring cells to communicate, thereby controlling their differentiation, proliferation and apoptosis, with the outcome of its activation being highly dependent on signal strength and cell type. As such, there is growing evidence that disturbances in physiological Notch signaling contribute to cancer development and growth through various mechanisms. Notch was first reported to contribute to tumorigenesis in the early 90s, through identification of the involvement of the Notch1 gene in the chromosomal translocation t(7;9)(q34;q34.3), found in a small subset of T-cell acute lymphoblastic leukemia. Since then, Notch mutations and aberrant Notch signaling have been reported in numerous other precursor and mature hematological malignancies, of both myeloid and lymphoid origin, as well as many epithelial tumor types. Of note, Notch has been reported to have both oncogenic and tumor suppressor roles, dependent on the cancer cell type. In this review, we will first give a general description of the Notch signaling pathway, and its physiologic role in hematopoiesis. Next, we will review the role of aberrant Notch signaling in several hematological malignancies. Finally, we will discuss current and potential future therapeutic approaches targeting this pathway. PMID:26934331

Patterns of Cancer in Kurdistan - Results of Eight Years Cancer Registration in Sulaymaniyah Province-Kurdistan-Iraq.

PubMed

Khoshnaw, Najmaddin; Mohammed, Hazha A; Abdullah, Dana A

2015-01-01

Cancer has become a major health problem associated with high mortality worldwide, especially in developing countries. The aim of our study was to evaluate the incidence rates of different types of cancer in Sulaymaniyah from January-2006 to January-2014. The data were compared with those reported for other middle east countries. This retrospective study depended on data collected from Hiwa hospital cancer registry unit, death records and histopathology reports in all Sulaymaniyah teaching hospitals, using international classification of diseases. A total of 8,031 cases were registered during the eight year period, the annual incidence rate in all age groups rose from 38 to 61.7 cases/100,000 population/year, with averages over 50 in males and 50.7 in females. The male to female ratio in all age groups were 0.98, while in the pediatric age group it was 1.33. The hematological malignancies in all age groups accounted for 20% but in the pediatric group around half of all cancer cases. Pediatric cancers were occluding 7% of total cancers with rates of 10.3 in boys and 8.7 in girls. The commonest malignancies by primary site were leukemia, lymphoma, brain, kidney and bone. In males in all age groups they were lung, leukaemia, lymphoma, colorectal, prostate, bladder, brain, stomach, carcinoma of unknown primary (CUP) and skin, while in females they were breast, leukaemia, lymphoma, colorectal, ovary, lung, brain, CUP, and stomach. Most cancers were increased with increasing age except breast cancer where decrease was noted in older ages. High mortality rates were found with leukemia, lung, lymphoma, colorectal, breast and stomach cancers. We here found an increase in annual cancer incidence rates across the period of study, because of increase of cancer with age and higher rates of hematological malignancies. Our study is valuable for Kurdistan and Iraq because it provides more accurate data about the exact patterns of cancer and mortality in our region.

Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita.

PubMed

Parchand, Swapnil; Barwad, Adarsh

2017-01-01

Cytomegalovirus (CMV) retinitis is an opportunistic infection commonly seen in disorders that affect the immune system of the body such as acquired immunodeficiency syndrome and hematological malignancies such as leukemia/lymphoma or organ transplantation. The occurrence of CMV retinitis in the absence of such condition should be thoroughly investigated, as it is a strong indicator of poor immune competence. We here report an interesting case of CMV retinitis as a presenting feature of rare multisystem disorde r "Dyskeratosis congenita."

Constitutional Trisomy 8 Mosaicism with Persistent Macrocytosis.

PubMed

Altıner, Şule; Kutlay, Nüket Y; İlhan, Osman

2016-01-01

Constitutional trisomy 8 mosaicism (CT8M) is a rare chromosomal abnormality. The phenotype varies from normal features to severe malformations. CT8M increases the risk of developing leukemia and myelodysplastic syndrome. As CT8M is very rare, its diagnosis can easily be overlooked, especially in cases with mild phenotypes. Here, we report the diagnostic process of a 40-year-old female patient with CT8M and discuss the importance of follow-up in monitoring for hematological malignancies. © 2016 S. Karger AG, Basel.

Acquired factor VII deficiency associated with acute myeloid leukemia.

PubMed

Anoun, Soumaya; Lamchahab, Mouna; Oukkache, Bouchra; Qachouh, Maryam; Benchekroun, Said; Quessar, Asmaa

2015-04-01

Isolated acquired factor VII deficiency is a rare coagulopathy. It has been reported in 31 patients with malignancy, sepsis, postoperatively, aplastic anemia, and during bone marrow transplantation. We discuss, through a new case of acquired factor VII deficiency, the characteristics of this disease when it is associated with acute myeloid leukemia. Acquired factor VII deficiency in hematological diseases can be caused by intensive chemotherapy, infections, or hepatic dysfunction. The best treatment in developing countries remains corticosteroids associated with plasma exchange, frozen plasma, and antibiotics.

Prototheca wickerhamii algaemia presenting as cholestatic hepatitis in a patient with systemic lupus erythematosus: A case report and literature review

PubMed Central

Min, Zaw; Moser, Stephen A.; Pappas, Peter G.

2012-01-01

Human protothecal infection is uncommon and could be localized or systemic disease. Disseminated Prototheca algaemia tends to occur in immunocompromised patients (solid organ transplants, hematological malignancies) with high mortality. Diagnosis could be missed or delayed due to unusual clinical presentation and/or under-recognition of characteristic microscopic features of Prototheca species. Combined approach that includes removal of source of infection and intravenous amphotericin B provides the best chance of cure. PMID:24432207

Invasive Fungal Infections in Patients with Hematological Malignancies: Emergence of Resistant Pathogens and New Antifungal Therapies

PubMed Central

Gamaletsou, Maria N.; Walsh, Thomas J.; Sipsas, Nikolaos V.

2018-01-01

Invasive fungal infections caused by drug-resistant organisms are an emerging threat to heavily immunosuppressed patients with hematological malignancies. Modern early antifungal treatment strategies, such as prophylaxis and empirical and preemptive therapy, result in long-term exposure to antifungal agents, which is a major driving force for the development of resistance. The extended use of central venous catheters, the nonlinear pharmacokinetics of certain antifungal agents, neutropenia, other forms of intense immunosuppression, and drug toxicities are other contributing factors. The widespread use of agricultural and industrial fungicides with similar chemical structures and mechanisms of action has resulted in the development of environmental reservoirs for some drug-resistant fungi, especially azole-resistant Aspergillus species, which have been reported from four continents. The majority of resistant strains have the mutation TR34/L98H, a finding suggesting that the source of resistance is the environment. The global emergence of new fungal pathogens with inherent resistance, such as Candida auris, is a new public health threat. The most common mechanism of antifungal drug resistance is the induction of efflux pumps, which decrease intracellular drug concentrations. Overexpression, depletion, and alteration of the drug target are other mechanisms of resistance. Mutations in the ERG11 gene alter the protein structure of C-demethylase, reducing the efficacy of antifungal triazoles. Candida species become echinocandin-resistant by mutations in FKS genes. A shift in the epidemiology of Candida towards resistant non-albicans Candida spp. has emerged among patients with hematological malignancies. There is no definite association between antifungal resistance, as defined by elevated minimum inhibitory concentrations, and clinical outcomes in this population. Detection of genes or mutations conferring resistance with the use of molecular methods may offer better predictive values in certain cases. Treatment options for resistant fungal infections are limited and new drugs with novel mechanisms of actions are needed. Prevention of resistance through antifungal stewardship programs is of paramount importance. PMID:29391334

Palifermin in the management of mucositis in hematological malignancies: current evidences and future perspectives.

PubMed

Niscola, Pasquale; Scaramucci, Laura; Giovannini, Marco; Ales, Micaela; Bondanini, Francesco; Cupelli, Luca; Dentamaro, Teresa; Lamanda, Michela; Natale, Giuseppina; Palumbo, Roberto; Romani, Claudio; Tendas, Andrea; Tolu, Barbara; Violo, Leano; de Fabritiis, Paolo

2009-10-01

In the management of hematological malignancies, chemotherapy-induced mucositis is an increasingly recognized problem, leading to potentially severe clinical complications, treatment delays, increased costs and impairment of patient's quality of life. Many forms of cytotoxic treatments given in this setting may induce several degrees of mucositis. In particular, conditioning therapy with hematopoietic stem cell transplantation (HSCT) induces a disruption of the mucosal barrier function throughout the entire gastrointestinal tract facilitating the spreading of bacteria and endotoxin with subsequent increased risk of septicemia and, in the allogeneic setting, a worsening of Graft Versus Host Disease (GVHD). To review the role of palifermin and of other existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology in the setting of hematological malignancies. We searched for palifermin and mucositis of any region of the gastrointestinal tract using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are highly required. In this regard, palifermin (recombinant human keratinocyte growth factor) has been demonstrated to reduce the severity and the duration of oral mucositis and to significantly improve several treatment outcomes in patients submitted to autologous HSCT; data are insufficient to recommend its use in the non-autologous HSCT settings, although interesting properties of this agent deserves other investigations in order to explore other possible indications.

Acute lymphoblastic leukemia mimicking Wilms tumor at presentation.

PubMed

Singh, Amitabh; Mandal, Anirban; Guru, Vijay; Seth, Rachna

2016-09-01

Acute lymphoblastic leukemia (ALL), the commonest malignancy of childhood, is known to manifest with a myriad of atypical presentations. Nephromegaly is a rare presentation of childhood ALL with hepatic mass being even rarer. We present a 3 year-old child with unilateral renal mass and hepatic mass lesion with normal blood counts, initially suspected to have metastatic Wilms tumor based on clinical, radiological and WT1 positivity on immunocytochemistry of renal mass. He was later diagnosed as ALL with peripheral blood flowcytometry and bone marrow examination. Renomegaly at presentation of acute leukemia is not necessarily due to leukemic infiltration and rarely leads to renal impairment. The radiological differential of such a renal mass includes both benign and malignant entities including metastasis. Over-expression of WT1 mRNA has been found in a number of solid tumors and hematological malignancies and is far from being diagnostic of Wilms tumor. Again, a small number of children with acute leukemia may have a deceptively normal complete blood count at presentation. Though, initial all (clinical, radiological, hematological, and immunocytological) parameters pointed towards a diagnosis of Wilms tumor in our case, the subsequent development of thrombocytopenia and lymphocytic leukocytosis prompted further investigation and final diagnosis of ALL. WT1 positivity is a known phenomenon in childhood ALL and undifferentiated lymphoblasts may be positive for WT1 and negative for Leucocyte common antigen. Acute leukemia with renal and hepatic mass with normal blood counts at presentation is a diagnostic challenge.

Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome.

PubMed

Alegría-Landa, Victoria; Rodríguez-Pinilla, Socorro María; Santos-Briz, Angel; Rodríguez-Peralto, José Luis; Alegre, Victor; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

2017-07-01

Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

Study of MGUS, Smoldering Myeloma, Early MDS and CLL to Assess Molecular Events of Progression and Clinical Outcome

ClinicalTrials.gov

2017-08-25

Monoclonal Gammopathy of Undetermined Significance (MGUS); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic-Myeloproliferative Diseases; Hematological Malignancies; B-cell Malignancy, Low-grade; Myelodysplastic Syndrome With Low-grade Lesions; IgG Monoclonal Gammopathy of Uncertain Significance; Smoldering Multiple Myeloma; Waldenstrom Macroglobulinemia

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse

PubMed Central

Kenderian, Saad S.; Porter, David L.; Gill, Saar

2016-01-01

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option in most hematological malignancies. As a form of immunotherapy, allogeneic HCT offers the potential for durable remissions but is limited by transplant related morbidity and mortality due to organ toxicity, infection and graft versus host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematological malignancies. Clinical trials will now need to address the relative roles of CART cells and HCT in the context of transplant-eligible patients. In this review we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT. PMID:27638367

A polyclonal outbreak of bloodstream infections by Enterococcus faecium in patients with hematologic malignancies.

PubMed

Alatorre-Fernández, Pamela; Mayoral-Terán, Claudia; Velázquez-Acosta, Consuelo; Franco-Rodríguez, Cecilia; Flores-Moreno, Karen; Cevallos, Miguel Ángel; López-Vidal, Yolanda; Volkow-Fernández, Patricia

2017-03-01

Enterococcus faecium causes bloodstream infection (BSI) in patients with hematologic malignancies (HMs). We studied the clinical features and outcomes of patients with HM with vancomycin-sensitive E faecium (VSE) and vancomycin-resistant E faecium (VRE) BSI and determined the genetic relatedness of isolates and circumstances associated with the upsurge of E faecium BSI. Case-control study of patients with HM and E faecium-positive blood culture from January 2008-December 2012; cases were patients with VRE and controls were VSE isolates. The strains were tested for Van genes by polymerase chain reaction amplification and we performed pulsed-field gel electrophoresis to determine genetic relatedness. Fifty-eight episodes of E faecium BSI occurred: 35 sensitive and 23 resistant to vancomycin. Mortality was 46% and 57%, attributable 17% and 40%, respectively. Early stage HM was associated with VSE (P = .044), whereas an episode of BSI within the 3 months before the event (P = .039), prophylactic antibiotics (P = .013), and vancomycin therapy during the previous 3 months (P = .001) was associated with VRE. The VanA gene was identified in 97% of isolates studied. E faecium isolates were not clonal. E faecium BSI was associated with high mortality. This outbreak of VRE was not clonal; it was associated with antibiotic-use pressure and highly myelosuppressive chemotherapy. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances

PubMed Central

McLaughlin, Lauren; Cruz, C. Russell; Bollard, Catherine M.

2015-01-01

Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

Type I insulin-like growth factor receptor signaling in hematological malignancies

PubMed Central

Vishwamitra, Deeksha; George, Suraj Konnath; Shi, Ping; Kaseb, Ahmed O.; Amin, Hesham M.

2017-01-01

The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma. PMID:27661006

Measuring symptoms as a critical component of drug development and evaluation in hematological diseases

PubMed Central

Williams, Loretta A; Yucel, Emre; Cortes, Jorge E; Cleeland, Charles S

2014-01-01

With the rapid development of new therapies for patients with hematological malignancies, there is an increasing need for patient report of symptom status during all phases of drug testing. The patient’s perspective on new treatments reflects treatment tolerability as well as symptom benefit, and may assist patients and clinicians in choosing treatments. Inclusion of patient-reported outcomes, more common in solid-tumor than hematological trials, provides early information about symptoms to guide decisions about appropriate dosing and supportive care needs. We provide a historical overview of the use of patient-reported outcomes and symptom assessment in solid-tumor and hematological drug development, and offer recommendations about methodological issues in the monitoring of symptoms in the drug development process in hematological clinical trials. PMID:24910769

Synchronous Occurrence of Chronic Myeloid Leukemia and Mantle Cell Lymphoma

PubMed Central

Li, Ying; Gray, Brian Allen; May, William Stratford

2017-01-01

Chronic myeloid leukemia (CML) and mantle cell lymphoma (MCL) are hematologic malignancies that originate from different oligopotent progenitor stem cells, namely, common myeloid and lymphoid progenitor cells, respectively. Although blastic transformation of CML can occur in the lymphoid lineage and CML has been related to non-Hodgkin lymphoma on transformation, to our knowledge, de novo and synchronous occurrence of CML and MCL has not been reported. Herein, we report the first case of synchronous CML and MCL in an otherwise healthy 38-year-old man. Potential etiologies and pathological relationships between the two malignancies are explored, including the possibility that the downstream effects of BCR-ABL may link it to an overexpression of cyclin D1, which is inherent to the etiology of MCL. PMID:28270940

[A case of fulminant hepatic failure secondary to hepatic metastasis of small cell lung carcinoma].

PubMed

Hwang, Young Tae; Shin, Jung Woo; Lee, Jun Ho; Hwang, Dae Sung; Eum, Jun Bum; Choi, Hye Jeong; Park, Neung Hwa

2007-12-01

Although liver metastasis is commonly found in cancer patients, fulminant hepatic failure secondary to diffuse cancer infiltration into the liver is rare. Liver metastasis-induced fulminant hepatic failure has been reported in patients with primary cancer of the gastrointestinal tract, breast and uroepithelium, and in patients with melanoma and hematologic malignancy. Small cell lung cancer is so highly invasive that hepatic metastasis is common, but rapid progression to fulminant hepatic failure is extremely rare. We report here on a case of a patient who died because of rapid progression to fulminant hepatic failure as a result of hepatic metastasis of small cell lung carcinoma.

Ethical considerations in genomic testing for hematologic disorders.

PubMed

Marron, Jonathan M; Joffe, Steven

2017-07-27

As our technological capacities improve, genomic testing is increasingly integrating into patient care. The field of clinical hematology is no exception. Genomic testing carries great promise, but several ethical issues must be considered whenever such testing is performed. This review addresses these ethical considerations, including issues surrounding informed consent and the uncertainty of the results of genomic testing; the challenge of incidental findings; and possible inequities in access to and benefit from such testing. Genomic testing is likely to transform the practice of both benign and malignant hematology, but clinicians must carefully consider these core ethical issues in order to make the most of this exciting and evolving technology. © 2017 by The American Society of Hematology.

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

[Assessment of Work Engagement in Patients with Hematological Malignancies: Psychometric Properties of the German Version of the Utrecht Work Engagement Scale 9 (UWES-9)].

PubMed

Sautier, L P; Scherwath, A; Weis, J; Sarkar, S; Bosbach, M; Schendel, M; Ladehoff, N; Koch, U; Mehnert, A

2015-10-01

Our purpose was the psychometric evaluation of the German version of the Utrecht Work Engagement Scale-9 (UWES-9), a self-assessment tool measuring work-related resources consisting of 9 items. Based on a sample of 179 patients with hematological malignancies in in-patient and rehabilitative oncological settings, we tested the dimensional structure by confirmatory and explorative factor analysis. We further evaluated reliability, item characteristics, and construct validity of the UWES-9. The confirmatory factor analysis showed acceptable fit for both a 1-dimensional factor structure and the original 3-factor model. Based on an explorative principal component analysis, we were able to replicate the 1-dimensional factor accounting for 67% of the total variance and showing very high internal consistency (α=0.94) and high factor loads (0.73-0.88). The construct validity was further supported by significant positive correlations between work engagement and meaning of work, corporate feeling, commitment to the workplace, and job satisfaction. The German version of the UWES-9 shows good psychometric qualities in measuring dedication to work in patients with hematological malignancies in in-patient and rehabilitative oncological settings. © Georg Thieme Verlag KG Stuttgart · New York.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?

PubMed

Hamaker, M E; Stauder, R; van Munster, B C

2014-03-01

Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population.

Self-regulatory fatigue in hematologic malignancies: impact on quality of life, coping, and adherence to medical recommendations.

PubMed

Solberg Nes, Lise; Ehlers, Shawna L; Patten, Christi A; Gastineau, Dennis A

2013-03-01

Hematopoietic stem cell transplantation (HSCT) is an intensive cancer therapy entailing numerous physical, emotional, cognitive, and practical challenges. Patients' ability to adjust and cope with such challenges may depend on their ability to exert control over cognitive, emotional, and behavioral processes, that is, ability to self-regulate. Self-regulatory capacity is a limited resource that can be depleted or fatigued (i.e., "self-regulatory fatigue"), particularly in the context of stressful life events such as cancer diagnosis and treatment. This is one of the first studies to examine self-regulatory fatigue in a cancer population. The current study aimed to (1) extract items for a specific scale of self-regulatory capacity and (2) examine the impact of such capacity on adaptation in patients with hematologic malignancies preparing for HSCT. Factor analysis of four existing scales gauging psychological adjustment and well-being in 314 patients preparing for HSCT (63% male and 89% Caucasian) identified 23 items (α = 0.85) related to self-regulatory control or fatigue. This measure was then examined using existing clinical data obtained from 178 patients (57% male and 91% Caucasian) undergoing treatment for hematologic malignancies in relationship to quality of life, coping, and self-reported adherence to physicians' recommendations. Controlling for pain severity, physical fatigue, and depression, self-regulatory fatigue scores were incrementally associated with decreased quality of life, use of avoidance coping strategies, and decreased adherence to physicians' recommendations. These results emphasize the potential role of self-regulatory capacity in coping with and adjusting to hematologic cancers and future research is warranted.

On-going clinical trials for elderly patients with a hematological malignancy: are we addressing the right end points?†

PubMed Central

Hamaker, M. E.; Stauder, R.; van Munster, B. C.

2014-01-01

Background Cancer societies and research cooperative groups worldwide have urged for the development of cancer trials that will address those outcome measures that are most relevant to older patients. We set out to determine the characteristics and study objectives of current clinical trials in hematological patients. Method The United States National Institutes of Health clinical trial registry was searched on 1 July 2013, for currently recruiting phase I, II or III clinical trials in hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results In the 1207 clinical trials included in this overview, patient-centered outcome measures such as quality of life, health care utilization and functional capacity were only incorporated in a small number of trials (8%, 4% and 0.7% of trials, respectively). Even in trials developed exclusively for older patients, the primary focus lies on standard end points such as toxicity, efficacy and survival, while patient-centered outcome measures are included in less than one-fifth of studies. Conclusion Currently on-going clinical trials in hematological malignancies are unlikely to significantly improve our knowledge of the optimal treatment of older patients as those outcome measures that are of primary importance to this patient population are still included in only a minority of studies. As a scientific community, we cannot continue to simply acknowledge this issue, but must all participate in taking the necessary steps to enable the delivery of evidence-based, tailor-made and patient-focused cancer care to our rapidly growing elderly patient population. PMID:24458474

Lifestyle factors and risk of leukemia and non-Hodgkin's lymphoma: a case-control study.

PubMed

Parodi, Stefano; Santi, Irene; Marani, Enza; Casella, Claudia; Puppo, Antonella; Garrone, Elsa; Fontana, Vincenzo; Stagnaro, Emanuele

2016-03-01

Risk factors for leukemia and lymphomas in adults are largely unknown. This study was aimed at evaluating the association between lifestyle factors and the risk of hematological malignancies in an adult population. Data were drawn from a population-based case-control study carried out in Italy and included 294 cases (199 lymphoid and 95 myeloid) and 279 controls. Analyses were performed using standard multivariable logistic regression. Hair dye use for at least 15 years was associated with a higher risk of lymphoid malignancies among females (OR 2.3, 95 % CI 1.0-4.9, p = 0.036, test for trend). Furthermore, a protective effect of a moderate to heavy tea consumption on the risk of myeloid malignancies was observed (OR 0.4, 95 % CI 0.2-0.9, p = 0.017). No association was found for the use of alcoholic beverages and tobacco smoking. Our results confirm the potential carcinogenic effect of prolonged hair dye use observed in previous investigations. The excess risk could be explained by exposure to a higher concentration of toxic compounds in hair products used in the past. The protective effect of regular tea consumption observed in an area with a very high prevalence of black tea consumers deserves further investigation.

Comparison of DNA Microarray, Loop-Mediated Isothermal Amplification (LAMP) and Real-Time PCR with DNA Sequencing for Identification of Fusarium spp. Obtained from Patients with Hematologic Malignancies.

PubMed

de Souza, Marcela; Matsuzawa, Tetsuhiro; Sakai, Kanae; Muraosa, Yasunori; Lyra, Luzia; Busso-Lopes, Ariane Fidelis; Levin, Anna Sara Shafferman; Schreiber, Angélica Zaninelli; Mikami, Yuzuru; Gonoi, Tohoru; Kamei, Katsuhiko; Moretti, Maria Luiza; Trabasso, Plínio

2017-08-01

The performance of three molecular biology techniques, i.e., DNA microarray, loop-mediated isothermal amplification (LAMP), and real-time PCR were compared with DNA sequencing for properly identification of 20 isolates of Fusarium spp. obtained from blood stream as etiologic agent of invasive infections in patients with hematologic malignancies. DNA microarray, LAMP and real-time PCR identified 16 (80%) out of 20 samples as Fusarium solani species complex (FSSC) and four (20%) as Fusarium spp. The agreement among the techniques was 100%. LAMP exhibited 100% specificity, while DNA microarray, LAMP and real-time PCR showed 100% sensitivity. The three techniques had 100% agreement with DNA sequencing. Sixteen isolates were identified as FSSC by sequencing, being five Fusarium keratoplasticum, nine Fusarium petroliphilum and two Fusarium solani. On the other hand, sequencing identified four isolates as Fusarium non-solani species complex (FNSSC), being three isolates as Fusarium napiforme and one isolate as Fusarium oxysporum. Finally, LAMP proved to be faster and more accessible than DNA microarray and real-time PCR, since it does not require a thermocycler. Therefore, LAMP signalizes as emerging and promising methodology to be used in routine identification of Fusarium spp. among cases of invasive fungal infections.

A review of molecular mechanisms of the anti-leukemic effects of phenolic compounds in honey.

PubMed

Abubakar, Murtala B; Abdullah, Wan Zaidah; Sulaiman, Siti Amrah; Suen, Ang Boon

2012-11-15

Hematologic malignancies constitute about 9% of all new cases of cancers as reported via the GLOBOCAN series by International Agency for Research on Cancer (IARC) in 2008. So far, the conventional therapeutic and surgical approaches to cancer therapy have not been able to curtail the rising incidence of cancers, including hematological malignancies, worldwide. The last decade has witnessed great research interest in biological activities of phenolic compounds that include anticancer, anti-oxidation and anti-inflammation, among other things. A large number of anticancer agents combat cancer through cell cycle arrest, induction of apoptosis and differentiation, as well as through inhibition of cell growth and proliferation, or a combination of two or more of these mechanisms. Various phenolic compounds from different sources have been reported to be promising anticancer agents by acting through one of these mechanisms. Honey, which has a long history of human consumption both for medicinal and nutritional uses, contains a variety of phenolic compounds such as flavonoids, phenolic acids, coumarins and tannins. This paper presents a review on the molecular mechanisms of the anti-leukemic activity of various phenolic compounds on cell cycle, cell growth and proliferation and apoptosis, and it advocates that more studies should be conducted to determine the potential role of honey in both chemoprevention and chemotherapy in leukemia.

Secondary thrombotic microangiopathy in two patients with Philadelphia-positive hematological malignancies treated with imatinib mesylate.

PubMed

Ojeda-Uribe, Mario; Merieau, Sylvain; Guillon, Marie; Aujoulat, Olivier; Hinschberger, Olivier; Eisenmann, Jean-Claude; Kenizou, David; Debliquis, Agathe; Veyradier, Agnès; Chantrel, François

2016-04-01

Drug-mediated thrombotic microangiopathy may cause life-threatening medical emergencies. Novel targeted therapies have dramatically changed the prognosis of a number of oncological diseases. Tyrosine kinase inhibitors of the Breakpoint Cluster Region-Abelson (BCR-ABL) oncoprotein are used in patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Imatinib mesylate, which was the first anti-BCR-ABL tyrosine kinase inhibitor, has demonstrated a high tolerance profile and efficacy in these patients for many years. Good results have also been observed in patients with gastrointestinal stromal tumors. In this study, we describe two patients with Philadelphia chromosome-positive hematological malignancies who presented with secondary thrombotic microangiopathy that was most likely linked to the use of imatinib. Other potential causes of thrombotic microangiopathy were discarded, and the predisposing role of some comorbidities and potential short or long-term drug-drug interactions was assessed. The clinical and biological data were more indicative of atypical secondary hemolytic uremic syndrome in one of the cases and of secondary thrombotic microangiopathy with renal and cardiac impairment in the other, which is also categorized as secondary hemolytic uremic syndrome. The outcome was favorable after imatinib discontinuation and the treatment of severe cardiac and renal failures. © The Author(s) 2015.

Hematology oncology practice in the Asia-Pacific APHCON survey results from the 6th international hematologic malignancies conference: bridging the gap 2015, Beijing, China.

PubMed

Huang, Xiao Jun; Liu, Kaiyan; Ritchie, David; Andersson, Borje; Lu, Jin; Hou, Jian; Burguera, Adolfo de la Fuente; Wang, JianXiang; Yeoh, Allen; Yan, Chenhua; Zhou, Daobin; Tan, Daryl; Kim, Dong Wook; Wu, Depei; Shpall, Elizabeth; Kornblau, Stephen; Neelapu, Sattava; Hongeng, Suradej; Li, Jianyong; Hu, Jiong; Zhang, Lian Sheng; Wang, Michael; Malhotra, Pankaj; Jiang, Qian; Qin, Yazhen; Wong, Raymond; Champlin, Richard; Hagemeister, Frederick; Westin, Jason; Iyer, Swaminathan; Mathews, Vikram; Wang, Yu; Hu, Yu; Xiao, Zhijian; Shao, Zonghong; Orlowski, Robert Z; Chim, Chor Sang; Mulligan, Stephen; Sanz, Miguel; Ozawa, Keiya; Parmar, Simrit; Issaragrisil, Surapol

2017-06-20

This report serves as a snapshot of the state-of-knowledge in the Asia Pacific (APAC) Hematology Oncology community, and establishes a baseline for longitudinal investigations to follow changes in best practices over time. The objective of this study was to understand the approach to hematologic diseases, common standards of care and best practices, issues that remain controversial or debated, and educational or resource gaps that warrant attention. We used mobile application to disseminate and distribute questionnaires to delegates during the 6th international hematologic malignancies conference hosted by the APAC Hematology Consortium at Beijing, China. User responses were collected in an anonymous fashion. We report survey results in two ways: the overall responses, and responses as stratified between Chinese physicians and "Other" represented nationalities. Overall geographical concordance in survey responses was positive and strong. Perhaps more interesting than instances of absolute agreement, these data provide a unique opportunity to identify topics in which physician knowledge or opinions diverge. We assigned questions from all modules to broad categories of: patient information; diagnosis; treatment preference; transplantation; and general knowledge/opinion. On average, we observed a geographic difference of 15% for any particular answer choice, and this was fairly constant across survey modules. These results reveal utility and need for widespread and ongoing initiatives to assess knowledge and provide evidence-based education in real time. The data will be made more valuable by longitudinal participation, such that we can monitor changes in the state of the art over time.

A phase 1b trial of the combination of the antiangiogenic agent sunitinib and radiation therapy for patients with primary and metastatic central nervous system malignancies.

PubMed

Wuthrick, Evan J; Kamrava, Mitchell; Curran, Walter J; Werner-Wasik, Maria; Camphausen, Kevin A; Hyslop, Terry; Axelrod, Rita; Andrews, David W; Glass, Jon; Machtay, Mitchell; Dicker, Adam P

2011-12-15

In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies. Eligible patients had CNS malignancies that required a (minimum) 2-week course of RT. Sunitinib (37.5 mg) was administered daily for the duration of RT with optional treatment extension of 1 month. Urine was collected at 3 time points for correlative biomarker studies. The primary endpoint was acute toxicity defined according to Common Toxicity Criteria version 3. Fifteen patients were enrolled (12 with CNS metastasis and 3 with primary tumors). RT doses ranged from 14 Gray (Gy) to 70 Gy (1.8-3.5 Gy per fraction). Acute toxicities included hematologic, nausea, hyperglycemia, fatigue, hypocalcemia, and diarrhea. Six patients (40%) developed grade ≤ 2 toxicities. Grade 3 toxicities occurred in 7 patients (47%) and included hematologic toxicity, fatigue, deep vein thrombosis, dysphasia, hyperglycemia, and hyponatremia. No grade 3 through 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events attributed to disease progression occurred. The median follow-up was 34.2 months. Two patients (13%) achieved a partial response, 9 patients (60%) had stable disease, and 2 patients (13%) patients had progressive disease. The 6-month progression-free survival rate for patients who had brain metastasis was 58%. Grade 3 hematologic toxicity was correlated with greater changes in vascular endothelial growth factor levels changes between baseline and the completion of RT. Continuous 37.5-mg sunitinib combined with RT in patients who had CNS malignancies yielded acceptable toxicities and adverse events. The current results indicated that changes in urine vascular endothelial growth factor levels are associated with hematologic toxicity, and this association should be analyzed in a larger cohort. The feasibility, safety, and early response results warrant a phase 2 trial. Copyright © 2011 American Cancer Society.

Bronchoalveolar lavage in malignancy.

PubMed

Poletti, Venerino; Poletti, Giovanni; Murer, Bruno; Saragoni, Luca; Chilosi, Marco

2007-10-01

Bronchoalveolar lavage is a useful diagnostic tool in diffuse or disseminated lung malignancies that do not involve the bronchial structures visible by endoscopy. The neoplastic histotype and the intraparenchymal neoplastic growth pattern are good predictors for diagnostic yield; adenocarcinoma, and tumors with lymphangitic or lepidic growth patterns are more easily diagnosed by bronchoalveolar lavage; in these cases the diagnostic yield reported is higher than 80%. In hematologic malignancies the diagnostic yield is quite good in secondary diffuse indolent B cell lymphomas and in primary B cell lymphomas of mucosa-associated lymphoid tissue (MALT) type but low in Hodgkin disease. Morphological analysis may be implemented by immunocytochemical or molecular tests to identify the cell lineage and the presence of monoclonality. Disorders in which bronchioloalveolar cell hyperplasia/dysplasia is a significant morphological component may have cytological features in bronchoalveolar lavage fluid that mimic lung neoplasms: acute respiratory distress syndrome (ARDS), acute interstitial pneumonitis (AIP), and acute exacerbation of idiopathic pulmonary fibrosis are the most important clinical entities in this group.

Spinal bone marrow necrosis with vertebral compression fracture: differentiation of BMN from AVN.

PubMed

Nix, J S; Fitzgerald, R T; Samant, R S; Harrison, M; Angtuaco, E J

2014-09-01

Bone marrow necrosis (BMN) is a rare malignancy-associated hematologic disorder characterized by necrosis of myeloid and stromal marrow elements with preservation of cortical bone. Overlap between the imaging appearances of BMN and avascular necrosis (AVN) raises the potential for diagnostic confusion. We report a case of BMN presenting with a traumatic multi-level vertebral body collapse, and finding that may potentially confound distinction between the two entities. We discuss important pathophysiologic, clinical, and radiologic differences between BMN and AVN with emphasis on features important in the differential diagnosis.

Experience with protective isolation for infection prevention in the compromised host.

PubMed

Nagao, T

1986-01-01

Ten years of experience with protective isolation of compromised patients was analyzed. The total number of patients was 191 including 116 patients with leukemia. Isolation could significantly prevent exogenous infections such as pneumonia, and prophylactic antibiotic regimens consisting of vancomycin and other nonabsorbable antibiotics could reduce the onset of endogenous infections such as sepsis. Elimination of serious and fatal infections by isolation together with prophylactic antibiotics increased the chances of remission or long-term survival for cases of hematological malignancies, solid tumor and bone marrow transplantation.

Stem Cell Transplantation as Immunotherapy for Hematologic Malignancies

ClinicalTrials.gov

2009-01-28

Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndrome; Paroxysmal Nocturnal Hemoglobinuria; Hodgkin's Lymphoma; Non-Hodgkin Lymphoma

Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

ClinicalTrials.gov

2011-12-07

Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition; Small Intestine Cancer

[Fungemia due to Trichosporon asahii in a patient with hematological malignancy].

PubMed

Odero, Valle; Galán-Sánchez, Fátima; García-Agudo, Lidia; García-Tapia, Ana M; Guerrero-Lozano, Inmaculada; Rodríguez-Iglesias, Manuel A

2015-01-01

Trichosporonosis is an opportunistic infection caused by the genus Trichosporon. The majority of cases of invasive trichosporonosis occurs in immunocompromised individuals. We describe a case of disseminated infection by Trichosporon asahii in a hematology patient. A 52-year-old man diagnosed with acute lymphoblastic leukemia developed a febrile episode during the third cycle of the induction chemotherapy. The blood cultures were positive after 24h incubation, showing elongated structures compatible with fungal elements in the Gram stain. The identification of the fungus as Trichosporon asahii was carried out by the assimilation of compounds of carbon and the amplification and sequencing of the D1/D2 domain and the internal transcribed spacer of the ribosomal DNA. The fungus was also isolated from the pustular lesions that the patient had in the chest. After treatment with amphotericin B, the patient progressed satisfactorily. Trichosporon asahii is an emergent pathogen in immunosupressed patients and its presence should not be considered as colonization, as there is risk of invasive infection. Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

Rare malignant pediatric tumors registered in the German Childhood Cancer Registry 2001-2010.

PubMed

Brecht, Ines B; Bremensdorfer, Claudia; Schneider, Dominik T; Frühwald, Michael C; Offenmüller, Sonja; Mertens, Rolf; Vorwerk, Peter; Koscielniak, Ewa; Bielack, Stefan S; Benesch, Martin; Hero, Barbara; Graf, Norbert; von Schweinitz, Dietrich; Kaatsch, Peter

2014-07-01

The German Childhood Cancer Registry (GCCR) annually registers approximately 2,000 children diagnosed with a malignant disease (completeness of registration >95%). While most pediatric cancer patients are diagnosed and treated according to standardized cooperative protocols of the German Society for Pediatric Oncology and Hematology (GPOH), patients with rare tumors are at risk of not being integrated in the network including trials and reference centers. A retrospective analysis of all rare extracranial solid tumors reported to the GCCR 2001-2010 (age <18 years) was undertaken using a combination of the International Classification of Childhood Cancer (ICCC-3) and the International Classification of Diseases-Oncology (ICD-O-3). Tumors accounting for <0.3% of all malignancies were defined as rare (approx. 6 cases/year and registered malignancy). According to this definition 1,189 rare extracranial solid tumors (18.2% of all malignant extracranial solid tumors) were registered, among these 232 patients (19.5% of rare tumor cases), were not included in preexisting GPOH studies/registries. Within 10 years, the number of registered non-GPOH-trial patients with a rare tumor increased. Though most of the GCCR-registered patients with rare malignant tumors are treated within GPOH trials, there is a considerable number of patients that have been diagnosed and treated outside the structures of the GPOH. These patients should be reported to the recently founded German Pediatric Rare Tumor Registry (STEP). Active data accrual and the development of appropriate structures will allow for better registration and improvement of medical care in these patients. © 2014 Wiley Periodicals, Inc.

Clinical manifestations and management of four children with Pearson syndrome.

PubMed

Tumino, Manuela; Meli, Concetta; Farruggia, Piero; La Spina, Milena; Faraci, Maura; Castana, Cinzia; Di Raimondo, Vincenzo; Alfano, Marivana; Pittalà, Annarita; Lo Nigro, Luca; Russo, Giovanna; Di Cataldo, Andrea

2011-12-01

Pearson marrow-pancreas syndrome is a fatal disorder mostly diagnosed during infancy and caused by mutations of mitochondrial DNA. We hereby report on four children affected by Pearson syndrome with hematological disorders at onset. The disease was fatal to three of them and the fourth one, who received hematopoietic stem cell transplantation, died of secondary malignancy. In this latter patient transplantation corrected hematological and non-hematological issues like metabolic acidosis, and we therefore argue that it could be considered as a useful option in an early stage of the disease. Copyright © 2011 Wiley Periodicals, Inc.

Decreased complement mediated binding of antibody//sup 3/-dsDNA immune complexes to the red blood cells of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, R.P.; Horgan, C.; Buschbacher, R.

1983-06-01

The complement mediated binding of prepared antibody//sup 3/H-dsDNA immune complexes to the red blood cells obtained from a number of patient populations has been investigated. Patients with solid tumors have binding activity similar to that seen in a normal group of individuals. However, a significant fraction of patients with systemic lupus erythematosus, rheumatoid arthritis, and hematologic malignancies have lowered binding activity compared with normal subjects. Quantitative studies indicate the lowered activity probably arises due to a decrease in complement receptors on the respective red blood cells. The potential importance and implications of these findings are briefly discussed.

Targeting BET bromodomain proteins in solid tumors

PubMed Central

Sahai, Vaibhav; Redig, Amanda J.; Collier, Katharine A.; Eckerdt, Frank D.; Munshi, Hidayatullah G.

2016-01-01

There is increasing interest in inhibitors targeting BET (bromodomain and extra-terminal) proteins because of the association between this family of proteins and cancer progression. BET inhibitors were initially shown to have efficacy in hematologic malignancies; however, a number of studies have now shown that BET inhibitors can also block progression of non-hematologic malignancies. In this Review, we summarize the efficacy of BET inhibitors in select solid tumors; evaluate the role of BET proteins in mediating resistance to current targeted therapies; and consider potential toxicities of BET inhibitors. We also evaluate recently characterized mechanisms of resistance to BET inhibitors; summarize ongoing clinical trials with these inhibitors; and discuss potential future roles of BET inhibitors in patients with solid tumors. PMID:27283767

[From conventional cytogenetics to microarrays. Fifty years of Philadelphia chromosome].

PubMed

Hernández, Jesús M; Granada, Isabel; Solé, Francesc

2011-07-23

In 1960 Ph-chromosome was found associated with the presence of chronic myelogenous leukemia. In these 50 years an increasing number of cytogenetic abnormalities have been found associated with hematological malignancies. The presence of these abnormalities is not only important for the diagnosis of the patient, but it also contributes to the prognosis of patients with leukemia or lymphoma. For this reason the WHO classification of hematological disease has included these studies for the correct characterization of leukemias and lymphomas. In addition, the use of FISH and micromatrix methodologies have refined the genetic lesions present in these malignancies. The cytogenetic changes observed also provide further information in relation to the therapy. Copyright © 2010 Elsevier España, S.L. All rights reserved.

Li-Fraumeni syndrome presenting as mucosal melanoma: Case report and treatment considerations.

PubMed

Klein, Jonah D; Kupferman, Michael E

2017-02-01

Li-Fraumeni syndrome (LFS) is a familial cancer predisposition associated with a germline mutation in TP53. Patients with LFS are at risk of developing malignancies and require comprehensive screening. We describe an index case of LFS presenting with mucosal melanoma. A 21-year-old woman presented with a left maxillary mucosal lesion and a left neck mass. Biopsies revealed metastatic mucosal melanoma, which is a pathology previously unreported in LFS families. Genetic testing revealed LFS, with a germline TP53 mutation, and pedigree analysis identified 9 first-degree and second-degree relatives with hematologic malignancies. The patient underwent a maxillectomy and left neck dissection, followed by adjuvant radiotherapy. At 30-month follow-up, there was no evidence of local, regional, or distant failure, nor did she develop a second primary tumor. This represents the first reported case of LFS associated with mucosal melanoma. Treatment considerations, specifically the risks of adjuvant therapy in LFS, are discussed. © 2016 Wiley Periodicals, Inc. Head Neck 39: E20-E22, 2017. © 2016 Wiley Periodicals, Inc.

Multiple Myeloma and Epidural Spinal Cord Compression : Case Presentation and a Spine Surgeon's Perspective

PubMed Central

Ha, Kee-Yong; Kim, Hyun-Woo

2013-01-01

Multiple myeloma, a multicentric hematological malignancy, is the most common primary tumor of the spine. As epidural myeloma causing spinal cord compression is a rare condition, its therapeutic approach and clinical results have been reported to be diverse, and no clear guidelines for therapeutic decision have been established. Three patients presented with progressive paraplegia and sensory disturbance. Image and serological studies revealed multiple myeloma and spinal cord compression caused by epidural myeloma. Emergency radiotherapy and steroid therapy were performed in all three cases. However, their clinical courses and results were distinctly different. Following review of our cases and the related literature, we suggest a systematic therapeutic approach for these patients to achieve better clinical results. PMID:24175035

Transthoracic ultrasonography for the immunocompromised patient. A pilot project that introduces transthoracic ultrasonography for the follow-up of hematological patients in Romania.

PubMed

Frinc, Ioana; Ilies, Petru; Zaharie, Florin; Dima, Delia; Tanase, Alina; Petrov, Ljubomir; Irimie, Alexandru; Berce, Cristian; Lisencu, Cosmin; Berindan-Neagoe, Ioana; Tomuleasa, Ciprian; Bojan, Anca

2017-06-01

In the past decade, there has been significant progress in clinical hematology with the discovery of targeted molecules and thus the achievement of both hematologic and molecular responses. Nevertheless, chemotherapy remains the treatment of choice for many types of hematological malignancies. Aggressive chemotherapy leads to immunosuppression, accompanied by a high rate of infections and an increased rate of treatment-related mortality. Invasive fungal infections as well as more common bacterial and viral infections are frequent in immunocompromised patients as they are difficult to diagnose and treat. Pleuropulmonary infections in immunocompromised patients are diagnosed using clinical examination, imaging and laboratory tests. Many laboratory tests are run for several days before a final result is given and are expensive. Computer tomography is a reliable technique, but it is encumbered by high irradiation and high cost, and can assess lesions larger than 1 cm. Transthoracic ultrasound is a modern method, used in the diagnostic algorithm of pleuropulmonary pathology. It allows the diagnosis of small lesions, can be performed at the patients' bedside, with acceptable costs and no irradiation. A fast, informed and accurate medical decision is essential for a favorable outcome in immunosuppressed patients with an adjacent infection. In the current case series we present the implementation of a new protocol for the follow-up of immunocompromised patients using transthoracic ultrasonography, of great potential use in the clinic.

Current anti-myeloma therapies in renal manifestations of monoclonal light chain-associated Fanconi syndrome: a retrospective series of 49 patients.

PubMed

Vignon, M; Javaugue, V; Alexander, M P; El-Karoui, K; Karras, A; Roos-Weil, D; Royer, B; Asli, B; Knebelmann, B; Touchard, G; Jaccard, A; Arnulf, B; Bridoux, F; Leung, N; Fermand, J P

2017-01-01

We retrospectively reviewed 49 patients with light chain (LC) Fanconi syndrome (FS). Patients presented with chronic kidney disease (median estimated glomerular filtration rate (eGFR) of 33 ml/min/1.73 m 2 ) and tubular proteinuria. All patients tested had elevated fractional excretion of phosphate, uric acid, generalized aminoaciduria and/or normoglycemic glycosuria. Thirty-eight patients had monoclonal gammopathy of renal significance and eleven patients had an overt hematological malignancy. The monoclonal LC isotype was kappa in 46/49 cases. Kidney biopsy in 39 patients showed various proximal tubular lesions and characteristic LC intracytoplasmic crystalline inclusions in 24 patients. Forty-two patients received chemotherapy. Patients with plasma cell proliferation (n=38) received bortezomib-based regimens (n=11), immunomodulatory agents (n=7) or alkylating agents (n=6). High-dose melphalan (HDM) followed by autologous stem cell transplantation was performed in 14 patients. Hematological response was obtained in 90% of evaluable patients, assessed on serum free light chains (FLC). GFR remained stable as long as hematological response was maintained and declined when serum FLC level rebounded. Improvement in proximal tubule function occurred in 13 patients. In patients with LC-associated FS, chemotherapy using HDM and/or new generation anti-myeloma agents can stabilize renal function and improve proximal tubule function. Serum FLC should be used to assess the hematological response, related to renal outcome.

Barriers to the Collaboration Between Hematologists and Palliative Care Teams on Relapse or Refractory Leukemia and Malignant Lymphoma Patients' Care: A Qualitative Study.

PubMed

Morikawa, Miharu; Shirai, Yuki; Ochiai, Ryota; Miyagawa, Kiyoshi

2016-12-01

Palliative care service (PCS) has been shown to be utilized less in patients with leukemia and malignant lymphoma than in those with solid tumors. Previous studies have suggested hematologists' limited awareness of PCS as one of the reason for low PCS referral in hematology. However, little is known about such an awareness and potential barriers to collaboration between hematologists and PCS. The present study aimed to assess ematologists and palliative care specialists' perception about the roles of the hospital-based palliative care team (HPCT) and the barriers to collaboration between hematologists and palliative care teams on relapse or refractory leukemia and malignant lymphoma patients' care MATERIALS AND METHODS: A qualitative study was conducted using semistructured interviews with hematologists and palliative care specialists recruited from a hospital that provides hematology and palliative care by the HPCT. Data were evaluated via content analysis. The study included 11 hematologists and 10 palliative care specialists. Our results revealed that they shared many common perceptions about the roles and expectations of the HPCT. Additionally, 7 categories of barriers to collaboration were identified, including not feeling the need to refer, the difficulty in referral timing, the lack of aggressive approach, the negative image of the HPCT, the need for hematologic malignancy-oriented management, the lack of communication, and others. We have identified hematologists' and palliative care specialists' perceptions of the HPCT's roles and the barriers to their collaboration. A better understanding of such barriers may lead to effective collaboration between hematologists and the HPCT. © The Author(s) 2015.

Quest: A New Approach to Molecular Staging of Tumors

DTIC Science & Technology

2004-08-01

121). Germline heterozygous inactivating mutations in MLH1 cause inefficient DNA mismatch repair, with the consequent increase in mutation frequency and... MLH1 heterozygous first cousins each produced two children with NFI disease and hematological malignancies (120, 121). The parents had no signs of NFl...Ozdag, H., Tuncer, M., Gurgey, A., Uzunalimoglu, 0., Cetinkaya, H., Tanyeli, A., Erken, E., Ozturk, M. Human MLH1 deficiency predisposes to hematological

Chimeric Antigen Receptor T Cells and Hematopoietic Cell Transplantation: How Not to Put the CART Before the Horse.

PubMed

Kenderian, Saad S; Porter, David L; Gill, Saar

2017-02-01

Hematopoietic cell transplantation (HCT) remains an important and potentially curative option for most hematologic malignancies. As a form of immunotherapy, allogeneic HCT (allo-HCT) offers the potential for durable remissions but is limited by transplantation- related morbidity and mortality owing to organ toxicity, infection, and graft-versus-host disease. The recent positive outcomes of chimeric antigen receptor T (CART) cell therapy in B cell malignancies may herald a paradigm shift in the management of these disorders and perhaps other hematologic malignancies as well. Clinical trials are now needed to address the relative roles of CART cells and HCT in the context of transplantation-eligible patients. In this review, we summarize the state of the art of the development of CART cell therapy for leukemia, lymphoma, and myeloma and discuss our perspective of how CART cell therapy can be applied in the context of HCT. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Spectrum of De Novo Cancers and Predictors in Liver Transplantation: Analysis of the Scientific Registry of Transplant Recipients Database.

PubMed

Zhou, Jie; Hu, Zhenhua; Zhang, Qijun; Li, Zhiwei; Xiang, Jie; Yan, Sheng; Wu, Jian; Zhang, Min; Zheng, Shusen

2016-01-01

De novo malignancies occur after liver transplantation because of immunosuppression and improved long-term survival. But the spectrums and associated risk factors remain unclear. To describe the overall pattern of de novo cancers in liver transplant recipients. Data from Scientific Registry of Transplant Recipients from October 1987 to December 2009 were analyzed. The spectrum of de novo cancer was analyzed and logistic-regression was used to identify predictors of do novo malignancies. Among 89,036 liver transplant recipients, 6,834 recipients developed 9,717 post-transplant malignancies. We focused on non-skin malignancies. A total of 3,845 recipients suffered from 4,854 de novo non-skin malignancies, including 1,098 de novo hematological malignancies, 38 donor-related cases, and 3,718 de novo solid-organ malignancies. Liver transplant recipients had more than 11 times elevated cancer risk compared with the general population. The long-term overall survival was better for recipients without de novo cancer. Multivariate analysis indicated that HCV, alcoholic liver disease, autoimmune liver disease, nonalcoholic steatohepatitis, re-transplantation, combined transplantation, hepatocellular carcinoma, immunosuppression regime of cellcept, cyclosporine, sirolimus, steroids and tacrolimus were independent predictors for the development of solid malignancies after liver transplantation. De novo cancer risk was elevated in liver transplant recipients. Multiple factors including age, gender, underlying liver disease and immunosuppression were associated with the development of de novo cancer. This is useful in guiding recipient selection as well as post-transplant surveillance and prevention.

Role of Non Receptor Tyrosine Kinases in Hematological Malignances and its Targeting by Natural Products.

PubMed

Siveen, Kodappully S; Prabhu, Kirti S; Achkar, Iman W; Kuttikrishnan, Shilpa; Shyam, Sunitha; Khan, Abdul Q; Merhi, Maysaloun; Dermime, Said; Uddin, Shahab

2018-02-19

Tyrosine kinases belong to a family of enzymes that mediate the movement of the phosphate group to tyrosine residues of target protein, thus transmitting signals from the cell surface to cytoplasmic proteins and the nucleus to regulate physiological processes. Non-receptor tyrosine kinases (NRTK) are a sub-group of tyrosine kinases, which can relay intracellular signals originating from extracellular receptor. NRTKs can regulate a huge array of cellular functions such as cell survival, division/propagation and adhesion, gene expression, immune response, etc. NRTKs exhibit considerable variability in their structural make up, having a shared kinase domain and commonly possessing many other domains such as SH2, SH3 which are protein-protein interacting domains. Recent studies show that NRTKs are mutated in several hematological malignancies, including lymphomas, leukemias and myelomas, leading to aberrant activation. It can be due to point mutations which are intragenic changes or by fusion of genes leading to chromosome translocation. Mutations that lead to constitutive kinase activity result in the formation of oncogenes, such as Abl, Fes, Src, etc. Therefore, specific kinase inhibitors have been sought after to target mutated kinases. A number of compounds have since been discovered, which have shown to inhibit the activity of NRTKs, which are remarkably well tolerated. This review covers the role of various NRTKs in the development of hematological cancers, including their deregulation, genetic alterations, aberrant activation and associated mutations. In addition, it also looks at the recent advances in the development of novel natural compounds that can target NRTKs and perhaps in combination with other forms of therapy can show great promise for the treatment of hematological malignancies.

Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologique (Grrr-OH) study.

PubMed

Contejean, Adrien; Lemiale, Virginie; Resche-Rigon, Matthieu; Mokart, Djamel; Pène, Frédéric; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Perez, Pierre; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Darmon, Michael; Jourdain, Mercé; Renault, Anne; Schlemmer, Benoît; Azoulay, Elie

2016-12-01

Acute respiratory failure (ARF) is the most frequent complication in patients with hematological malignancies and is associated with high morbidity and mortality. ARF etiologies are numerous, and despite extensive diagnostic workflow, some patients remain with undetermined ARF etiology. This is a post-hoc study of a prospective multicenter cohort performed on 1011 critically ill hematological patients. Relationship between ARF etiology and hospital mortality was assessed using a multivariable regression model adjusting for confounders. This study included 604 patients with ARF. All patients underwent noninvasive diagnostic tests, and a bronchoscopy and bronchoalveolar lavage (BAL) was performed in 155 (25.6%). Definite diagnoses were classified into four exclusive etiological categories: pneumonia (44.4%), non-infectious diagnoses (32.6%), opportunistic infection (10.1%) and undetermined (12.9%), with corresponding hospital mortality rates of 40, 35, 55 and 59%, respectively. Overall hospital mortality was 42%. By multivariable analysis, factors associated with hospital mortality were invasive pulmonary aspergillosis (OR 7.57 (95% CI 3.06-21.62); p < 0.005), use of invasive mechanical ventilation (OR 1.65 (95% CI 1.07-2.55); p = 0.02), a SOFA score >7 (OR 3.32 (95% CI 2.15-5.15); p < 0.005) and an undetermined ARF etiology (OR 2.92 (95% CI 1.71-5.07); p < 0.005). In patients with hematological malignancies and ARF, up to 13% remain with undetermined ARF etiology despite comprehensive diagnostic workup. Undetermined ARF etiology is independently associated with hospital mortality. Studies to guide second-line diagnostic strategies are warranted. ClinicalTrials.Gov NCT01172132.

Exclusion of Older Patients From Ongoing Clinical Trials for Hematological Malignancies: An Evaluation of the National Institutes of Health Clinical Trial Registry

PubMed Central

Stauder, Reinhard; van Munster, Barbara C.

2014-01-01

Introduction. Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. Methods. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Results. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Conclusion. Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. PMID:25170014

Exclusion of older patients from ongoing clinical trials for hematological malignancies: an evaluation of the National Institutes of Health Clinical Trial Registry.

PubMed

Hamaker, Marije E; Stauder, Reinhard; van Munster, Barbara C

2014-10-01

Cancer societies, research cooperatives, and countless publications have urged the development of clinical trials that facilitate the inclusion of older patients and those with comorbidities. We set out to determine the characteristics of currently recruiting clinical trials with hematological patients to assess their inclusion and exclusion of elderly patients. The NIH clinical trial registry was searched on July 1, 2013, for currently recruiting phase I, II or III clinical trials with hematological malignancies. Trial characteristics and study objectives were extracted from the registry website. Although 5% of 1,207 included trials focused exclusively on elderly or unfit patients, 69% explicitly or implicitly excluded older patients. Exclusion based on age was seen in 27% of trials, exclusion based on performance status was seen in 16%, and exclusion based on stringent organ function restrictions was noted in 51%. One-third of the studies that excluded older patients based on age allowed inclusion of younger patients with poor performance status; 8% did not place any restrictions on organ function. Over time, there was a shift from exclusion based on age (p value for trend <.001) toward exclusion based on organ function (p = .2). Industry-sponsored studies were least likely to exclude older patients (p < .001). Notably, 27% of currently recruiting clinical trials for hematological malignancies use age-based exclusion criteria. Although physiological reserves diminish with age, the heterogeneity of the elderly population does not legitimize exclusion based on chronological age alone. Investigators should critically review whether sufficient justification exists for every exclusion criterion before incorporating it in trial protocols. ©AlphaMed Press.

Twenty years of the Italian Fanconi Anemia Registry: where we stand and what remains to be learned.

PubMed

Risitano, Antonio M; Marotta, Serena; Calzone, Rita; Grimaldi, Francesco; Zatterale, Adriana

2016-03-01

The natural history of Fanconi anemia remains hard to establish because of its rarity and its heterogeneous clinical presentation; since 1994, the Italian Fanconi Anemia Registry has collected clinical, epidemiological and genetic data of Italian Fanconi Anemia patients. This registry includes 180 patients with a confirmed diagnosis of Fanconi anemia who have either been enrolled prospectively, at diagnosis, or later on. After enrollment, follow-up data were periodically collected to assess the clinical course, possible complications and long-term survival; the median follow up was 15.6 years. The main goal of the study was to describe the natural history of Fanconi anemia, focusing on the following variables: family history, disease presentation, development of hematological manifestations, development of malignancies, occurrence of hematopoietic stem cell transplantation and survival. Typical morphological and/or hematological abnormalities and/or growth retardation were the most common manifestations at diagnosis; the majority of patients (77%) exhibited hematological abnormalities at the initial presentation, and almost all (96%) eventually developed hematological manifestations. More than half of the patients (57%) underwent a bone-marrow transplant. The occurrence of cancer was quite rare at diagnosis, whereas the cumulative incidence of malignancies at 10, 20 and 30 years was 5%, 8% and 22%, respectively, for hematological cancers and 1%, 15% and 32%, respectively, for solid tumors. Overall survival at 10, 20 and 30 years were 88%, 56% and 37%, respectively; the main causes of death were cancer, complications of the hematological presentation and complications of transplantation. These data clearly confirm the detrimental outcome of Fanconi anemia, with no major improvement in the past decades. Copyright© Ferrata Storti Foundation.

Oceans of opportunity: exploring vertebrate hematopoiesis in zebrafish.

PubMed

Carroll, Kelli J; North, Trista E

2014-08-01

Exploitation of the zebrafish model in hematology research has surged in recent years, becoming one of the most useful and tractable systems for understanding regulation of hematopoietic development, homeostasis, and malignancy. Despite the evolutionary distance between zebrafish and humans, remarkable genetic and phenotypic conservation in the hematopoietic system has enabled significant advancements in our understanding of blood stem and progenitor cell biology. The strengths of zebrafish in hematology research lie in the ability to perform real-time in vivo observations of hematopoietic stem, progenitor, and effector cell emergence, expansion, and function, as well as the ease with which novel genetic and chemical modifiers of specific hematopoietic processes or cell types can be identified and characterized. Further, myriad transgenic lines have been developed including fluorescent reporter systems to aid in the visualization and quantification of specified cell types of interest and cell-lineage relationships, as well as effector lines that can be used to implement a wide range of experimental manipulations. As our understanding of the complex nature of blood stem and progenitor cell biology during development, in response to infection or injury, or in the setting of hematologic malignancy continues to deepen, zebrafish will remain essential for exploring the spatiotemporal organization and integration of these fundamental processes, as well as the identification of efficacious small molecule modifiers of hematopoietic activity. In this review, we discuss the biology of the zebrafish hematopoietic system, including similarities and differences from mammals, and highlight important tools currently utilized in zebrafish embryos and adults to enhance our understanding of vertebrate hematology, with emphasis on findings that have impacted our understanding of the onset or treatment of human hematologic disorders and disease. Copyright © 2014 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Bacteremia due to carbapenem-resistant Enterobacteriaceae in neutropenic patients with hematologic malignancies.

PubMed

Satlin, Michael J; Cohen, Nina; Ma, Kevin C; Gedrimaite, Zivile; Soave, Rosemary; Askin, Gülce; Chen, Liang; Kreiswirth, Barry N; Walsh, Thomas J; Seo, Susan K

2016-10-01

To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior β-lactam/β-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08). CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE-active agents and improve outcomes in this vulnerable population. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

[Polymyositis and essential thrombocytopenia. A case report].

PubMed

Auzary, C; Lhote, F; Buoncuore, A; Casassus, P; Piquet, V; Babinet, P

2000-11-01

The occurrence of polymyositis (PM) correlates with an increased risk of solid tumor. Among hematologic malignancies that are sporadically associated with PM or dermatopolymyositis (DM), lymphoma and chronic lymphoid leukemia are the most frequent. The association between PM and myeloproliferative disorders remains exceptional. We describe the simultaneous revelation of a PM and an essential thrombocytemia (ET). The sensitivity of the PM to corticosteroids was noteworthy and allowed a quick and definitive control of clinical and biological inflammation. Despite the efficiency of a cytostatic agent upon the thrombocytemia, the patient died after numerous thrombotic and hemorrhagic complications of ET. This is the first published case of such an association between PM and TE. The paraneoplastic significance of the PM is discussed.

A Macro View of MicroRNAs: The Discovery of MicroRNAs and Their Role in Hematopoiesis and Hematologic Disease

PubMed Central

Weiss, Cary N.; Ito, Keisuke

2017-01-01

MicroRNAs (miRNAs) are a class of endogenously encoded ~22 nucleotide, noncoding, single-stranded RNAs that contribute to development, body planning, stem cell differentiation, and tissue identity through posttranscriptional regulation and degradation of transcripts. Given their importance, it is predictable that dysregulation of miRNAs, which target a wide variety of transcripts, can result in malignant transformation. In this review, we explore the discovery of miRNAs, their mechanism of action, and the tools that aid in their discovery and study. Strikingly, many of the studies that have expanded our understanding of the contributions of miRNAs to normal physiology and in the development of diseases have come from studies in the hematopoietic system and hematologic malignancies, with some of the earliest identified functions for mammalian miRNAs coming from observations made in leukemias. So, with a special focus on the hematologic system, we will discuss how miRNAs contribute to differentiation of stem cells and how dysregulation of miRNAs contributes to the development of malignancy, by providing examples of specific miRNAs that function as oncogenes or tumor suppressors, as well as of defects in miRNA processing. Finally, we will discuss the promise of miRNA-based therapeutics and challenges for the future study of disease-causing miRNAs. PMID:28838543

Single-unit umbilical cord blood transplantation from unrelated donors in patients with hematological malignancy using busulfan, thiotepa, fludarabine and ATG as myeloablative conditioning regimen.

PubMed

Sanz, J; Boluda, J C H; Martín, C; González, M; Ferrá, C; Serrano, D; de Heredia, C D; Barrenetxea, C; Martinez, A M; Solano, C; Sanz, M A; Sanz, G F

2012-10-01

Attempts to optimize outcomes in cord blood transplantation (CBT) by using new conditioning regimens and standardization of cord blood unit selection are warranted. In all, 88 patients (18 children and 70 adults) with hematological malignancy from nine Spanish institutions underwent a single-unit CBT after an i.v. BU-based myeloablative conditioning regimen. All evaluable patients except one engrafted. The overall cumulative incidence (CI) of myeloid engraftment was 94% at a median time of 19 days. In multivariate analysis, nonadvanced disease stage was the only factor with a favorable impact on myeloid engraftment. The CI of acute GVHD grades II-IV and chronic extensive GVHD were 24% each. The CI of nonrelapse mortality at 100 days, 180 days and 5 years was 14, 23 and 44%, respectively. The 5-year CI of relapse was 18%, whereas disease-free survival (DFS) was 46%, 39% and 11% for patients transplanted in early, intermediate and advanced stages of the disease, respectively. Our study shows high rates of engraftment with fast neutrophil recovery in patients undergoing single-unit CBT using a BU-based conditioning regimen. Long-term DFS can be achieved in a substantial number of patients with high-risk hematological malignancies, particularly when transplanted in an early stage of the disease.

Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies

ClinicalTrials.gov

2017-12-03

Sickle Cell Disease; Transfusion Dependent Alpha- or Beta- Thalassemia; Diamond Blackfan Anemia; Paroxysmal Nocturnal Hemoglobinuria; Glanzmann Thrombasthenia; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Non-Malignant Hematologic Disorders

Care of cancer patients at the end of life in a German university hospital: A retrospective observational study from 2014.

PubMed

Dasch, Burkhard; Kalies, Helen; Feddersen, Berend; Ruderer, Caecilie; Hiddemann, Wolfgang; Bausewein, Claudia

2017-01-01

Cancer care including aggressive treatment procedures during the last phase of life in patients with incurable cancer has increasingly come under scrutiny, while integrating specialist palliative care at an early stage is regarded as indication for high quality end-of-life patient care. To describe the demographic and clinical characteristics and the medical care provided at the end of life of cancer patients who died in a German university hospital. Retrospective cross-sectional study on the basis of anonymized hospital data for cancer patients who died in the Munich University Hospital in 2014. Descriptive analysis and multivariate logistic regression analyses for factors influencing the administration of aggressive treatment procedures at the end of life. Overall, 532 cancer patients died. Mean age was 66.8 years, 58.5% were men. 110/532 (20.7%) decedents had hematologic malignancies and 422/532 (79.3%) a solid tumor. Patients underwent the following medical interventions in the last 7/30 days: chemotherapy (7.7%/38.3%), radiotherapy (2.6%/6.4%), resuscitation (8.5%/10.5%), surgery (15.2%/31.0%), renal replacement therapy (12.0%/16.9%), blood transfusions (21.2%/39.5%), CT scan (33.8%/60.9%). In comparison to patients with solid tumors, patients with hematologic malignancies were more likely to die in intensive care (25.4% vs. 49.1%; p = 0.001), and were also more likely to receive blood transfusions (OR 2.21; 95% CI, 1.36 to 3.58; p = 0.001) and renal replacement therapy (OR 2.65; 95% CI, 1.49 to 4.70; p = 0.001) in the last 7 days of life. Contact with the hospital palliative care team had been initiated in 161/532 patients (30.3%). In 87/161 cases (54.0%), the contact was initiated within the last week of the patient's life. Overambitious treatments are still reality at the end of life in cancer patients in hospital but patients with solid tumors and hematologic malignancies have to be differentiated. More efforts are necessary for the timely inclusion of specialist palliative care.

Care of cancer patients at the end of life in a German university hospital: A retrospective observational study from 2014

PubMed Central

Dasch, Burkhard; Kalies, Helen; Feddersen, Berend; Ruderer, Caecilie; Hiddemann, Wolfgang; Bausewein, Claudia

2017-01-01

Background Cancer care including aggressive treatment procedures during the last phase of life in patients with incurable cancer has increasingly come under scrutiny, while integrating specialist palliative care at an early stage is regarded as indication for high quality end-of-life patient care. Aim To describe the demographic and clinical characteristics and the medical care provided at the end of life of cancer patients who died in a German university hospital. Methods Retrospective cross-sectional study on the basis of anonymized hospital data for cancer patients who died in the Munich University Hospital in 2014. Descriptive analysis and multivariate logistic regression analyses for factors influencing the administration of aggressive treatment procedures at the end of life. Results Overall, 532 cancer patients died. Mean age was 66.8 years, 58.5% were men. 110/532 (20.7%) decedents had hematologic malignancies and 422/532 (79.3%) a solid tumor. Patients underwent the following medical interventions in the last 7/30 days: chemotherapy (7.7%/38.3%), radiotherapy (2.6%/6.4%), resuscitation (8.5%/10.5%), surgery (15.2%/31.0%), renal replacement therapy (12.0%/16.9%), blood transfusions (21.2%/39.5%), CT scan (33.8%/60.9%). In comparison to patients with solid tumors, patients with hematologic malignancies were more likely to die in intensive care (25.4% vs. 49.1%; p = 0.001), and were also more likely to receive blood transfusions (OR 2.21; 95% CI, 1.36 to 3.58; p = 0.001) and renal replacement therapy (OR 2.65; 95% CI, 1.49 to 4.70; p = 0.001) in the last 7 days of life. Contact with the hospital palliative care team had been initiated in 161/532 patients (30.3%). In 87/161 cases (54.0%), the contact was initiated within the last week of the patient’s life. Conclusions Overambitious treatments are still reality at the end of life in cancer patients in hospital but patients with solid tumors and hematologic malignancies have to be differentiated. More efforts are necessary for the timely inclusion of specialist palliative care. PMID:28384214

A Study of CDX-1127 (Varlilumab) in Patients With Select Solid Tumor Types or Hematologic Cancers

ClinicalTrials.gov

2018-01-29

CD27 Expressing B-cell Malignancies for Example Hodgkin's Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Marginal Zone B Cell Lymphoma); Any T-cell Malignancy; Solid Tumors (Metastatic Melanoma, Renal (Clear) Cell Carcinoma; Hormone-refractory Prostate Adenocarcinoma, Ovarian Cancer; Colorectal Adenocarcinoma, Non-small Cell Lung Cancer); Burkett's Lymphoma; Primary Lymphoma of the Central Nervous System

Reduced Intensity Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

ClinicalTrials.gov

2018-05-10

Acute Myeloid Leukemia; Acute Myeloid Leukemia in Remission; Aplastic Anemia; Chronic Myelomonocytic Leukemia; Hodgkin Lymphoma; Indolent Non-Hodgkin Lymphoma; Malignant Neoplasm; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Plasma Cell Myeloma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.

PubMed

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D'Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-05-29

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

A novel antibody–drug conjugate targeting SAIL for the treatment of hematologic malignancies

PubMed Central

Kim, S Y; Theunissen, J-W; Balibalos, J; Liao-Chan, S; Babcock, M C; Wong, T; Cairns, B; Gonzalez, D; van der Horst, E H; Perez, M; Levashova, Z; Chinn, L; D‘Alessio, J A; Flory, M; Bermudez, A; Jackson, D Y; Ha, E; Monteon, J; Bruhns, M F; Chen, G; Migone, T-S

2015-01-01

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody–drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs. PMID:26024286

The PIM kinases in hematological cancers.

PubMed

Alvarado, Yesid; Giles, Francis J; Swords, Ronan T

2012-02-01

The PIM genes represent a family of proto-oncogenes that encode three different serine/threonine protein kinases (PIM1, PIM2 and PIM3) with essential roles in the regulation of signal transduction cascades, which promote cell survival, proliferation and drug resistance. PIM kinases are overexpressed in several hematopoietic tumors and support in vitro and in vivo malignant cell growth and survival, through cell cycle regulation and inhibition of apoptosis. PIM kinases do not have an identified regulatory domain, which means that these proteins are constitutively active once transcribed. They appear to be critical downstream effectors of important oncoproteins and, when overexpressed, can mediate drug resistance to available agents, such as rapamycin. Recent crystallography studies reveal that, unlike other kinases, they possess a hinge region, which creates a unique binding pocket for ATP, offering a target for an increasing number of potent small-molecule PIM kinase inhibitors. Preclinical studies in models of various hematologic cancers indicate that these novel agents show promising activity and some of them are currently being evaluated in a clinical setting. In this review, we profile the PIM kinases as targets for therapeutics in hematologic malignancies.

Emerging antibody-drug conjugates for treating lymphoid malignancies.

PubMed

Wolska-Washer, Anna; Robak, Pawel; Smolewski, Piotr; Robak, Tadeusz

2017-09-01

Antibody-drug conjugates (ADC) are monoclonal antibodies (Mabs) attached to biologically active drugs through specialized chemical linkers. They deliver and release cytotoxic agents at the tumor site, reducing the likelihood of systemic exposure and therefore toxicity. These agents should improve the potency of chemotherapy by increasing the accumulation of cytotoxic the drug within or near the neoplastic cells with reduced systemic effects. Areas covered: A literature review was conducted of the MEDLINE database PubMed for articles in English examining Mabs, B-cell receptor pathway inhibitors and immunomodulating drugs. Publications from 2000 through April 2017 were scrutinized. Conference proceedings from the previous five years of the American Society of Hematology, European Hematology Association, American Society of Clinical Oncology, and ACR/ARHP Annual Scientific Meetings were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. Expert opinion: Newer ADCs show promise as treatment for several hematologic malignancies, especially lymphoma, multiple myeloma, and leukemia. However, definitive data from ongoing and future clinical trials will aid in better defining the status of these agents in the treatment of these diseases.

Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies

ClinicalTrials.gov

2009-01-28

Leukemia, Acute Lymphocytic (ALL); Leukemia, Myeloid, Acute(AML); Leukemia, Myeloid, Chronic(CML); Juvenile Myelomonocytic Leukemia(JMML); Hemoglobinuria, Paroxysmal Nocturnal (PNH); Lymphoma, Non-Hodgkin (NHL); Myelodysplastic Syndrome (MDS)

Incorporation of Immune Checkpoint Blockade into Chimeric Antigen Receptor T Cells (CAR-Ts): Combination or Built-In CAR-T

PubMed Central

Yoon, Dok Hyun; Osborn, Mark J.; Tolar, Jakub; Kim, Chong Jai

2018-01-01

Chimeric antigen receptor (CAR) T cell therapy represents the first U.S. Food and Drug Administration approved gene therapy and these engineered cells function with unprecedented efficacy in the treatment of refractory CD19 positive hematologic malignancies. CAR translation to solid tumors is also being actively investigated; however, efficacy to date has been variable due to tumor-evolved mechanisms that inhibit local immune cell activity. To bolster the potency of CAR-T cells, modulation of the immunosuppressive tumor microenvironment with immune-checkpoint blockade is a promising strategy. The impact of this approach on hematological malignancies is in its infancy, and in this review we discuss CAR-T cells and their synergy with immune-checkpoint blockade. PMID:29364163

A Review of Molecular Mechanisms of the Anti-Leukemic Effects of Phenolic Compounds in Honey

PubMed Central

Abubakar, Murtala B.; Abdullah, Wan Zaidah; Sulaiman, Siti Amrah; Suen, Ang Boon

2012-01-01

Hematologic malignancies constitute about 9% of all new cases of cancers as reported via the GLOBOCAN series by International Agency for Research on Cancer (IARC) in 2008. So far, the conventional therapeutic and surgical approaches to cancer therapy have not been able to curtail the rising incidence of cancers, including hematological malignancies, worldwide. The last decade has witnessed great research interest in biological activities of phenolic compounds that include anticancer, anti-oxidation and anti-inflammation, among other things. A large number of anticancer agents combat cancer through cell cycle arrest, induction of apoptosis and differentiation, as well as through inhibition of cell growth and proliferation, or a combination of two or more of these mechanisms. Various phenolic compounds from different sources have been reported to be promising anticancer agents by acting through one of these mechanisms. Honey, which has a long history of human consumption both for medicinal and nutritional uses, contains a variety of phenolic compounds such as flavonoids, phenolic acids, coumarins and tannins. This paper presents a review on the molecular mechanisms of the anti-leukemic activity of various phenolic compounds on cell cycle, cell growth and proliferation and apoptosis, and it advocates that more studies should be conducted to determine the potential role of honey in both chemoprevention and chemotherapy in leukemia. PMID:23203111

Screening for specific chromosome involvement in hematological malignancies using a set of seven chromosome painting probes. An alternative approach for chromosome analysis using standard FISH instrumentation.

PubMed

Nacheva, E P; Gribble, S; Andrews, K; Wienberg, J; Grace, C D

2000-10-15

We report the application of multi-color fluorescence in situ hydribidization (FISH) for bone marrow metaphase cell analysis of hematological malignancies using a sub-set of the human karyotype for chromosome painting. A combination of chromosome probes labeled with three haptens enabled the construction of a "painting probe" which detects seven different chromosomes. The probe was used to screen three chronic myeloid leukemia (CML) derived cell lines and ten CML patient bone marrow samples for aberrations, additional to the Ph rearrangement, that are associated with the onset of blast crisis of CML. This approach was shown to identify karyotype changes commonly seen by conventional karyotyping, and in addition revealed chromosome changes unresolved or undetected by conventional cytogenetic analysis. The seven-color painting probe provides a useful, fast, and reliable complementary tool for chromosome analysis, especially in cases with poor chromosome morphology. This is a simple approach, since the probes can be displayed in a standard red/green/blue format accessible to standard fluorescence microscopes and image-processing software. The proposed approach using panels of locus-specific probes as well as chromosome paints will be useful in all diagnostic routine environments where analysis is directed towards screening for genetic rearrangements and/or specific patterns of chromosome involvement with diagnostic/prognostic value.

Systematic review of infectious events with the Bruton tyrosine kinase inhibitor ibrutinib in the treatment of hematologic malignancies.

PubMed

Tillman, Benjamin F; Pauff, James M; Satyanarayana, Gowri; Talbott, Mahsa; Warner, Jeremy L

2018-04-01

Ibrutinib is an irreversible inhibitor of Bruton tyrosine kinase (BTK) in B lymphocytes as well as other kinases including interleukin-2-inducible T-cell kinase (ITK) in CD4+ Th2 regulatory T cells. Increased infections have been observed in patients taking ibrutinib. The overall incidence has not been systematically evaluated. The published literature and conference abstracts of prospective clinical trials using ibrutinib in hematologic malignancies were identified and reviewed using PubMed, Google Scholar, and HemOnc.org per PRISMA guidelines. Infectious events with a focus on pneumonia were collated per the Common Terminology Criteria for Adverse Events Version 4.03 grading. Infectious complications are common, occurring in 56% of patients taking single-agent ibrutinib and 52% of those on combination therapy. Approximately one in 5 patients developed pneumonia, which was the major contributor to a 2% rate of death from infections. Many of the cases of pneumonia were due to opportunistic pathogens. Ibrutinib use requires prudent consideration of the impacts on host immunity. We identified a high rate of serious adverse infectious events within prospective clinical trials. Data suggest a role of both BTK and ITK inhibition for the increased events. There was considerable variability in the reporting of adverse events between trials, journals, and conference reports. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blood Basics

MedlinePlus

... CME) and recertification Educational Programs Programs to enhance knowledge, research, and expertise Advocacy In This Section Action ... Pacific Latin America Meeting on Hematologic Malignancies Gain knowledge, through “How I Treat” presentations, that can help ...

Study Evaluating AMD3100 for Transplantation of Sibling Donor Stem Cells in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-06-05

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic; Leukemia, Lymphoblastic, Acute; Lymphocytic Leukemia, Chronic; Myelodysplastic Syndromes; Multiple Myeloma; Lymphoma, Non-Hodgkin; Hodgkin Disease

Comparison of Diagnostic Yield of a FISH Panel Against Conventional Cytogenetic Studies for Hematological Malignancies: A South Indian Referral Laboratory Analysis Of 201 Cases

PubMed Central

Ashok, Vishal; Ranganathan, Ramya; Chander, Smitha; Damodar, Sharat; Bhat, Sunil; KS, Nataraj; A, Satish Kumar; Jadav, Sachin Suresh; Rajashekaraiah, Mahesh; TS, Sundareshan

2017-01-01

Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS. Results: Exhibited a greater diagnostic yield with a positive result in 39.8% of the cases, as compared to 17.9% of cases detected by CCS. Cases of chronic lymphocytic leukaemia (CLL) benefited the most by FISH testing, which identified chromosomal aberrations beyond the capacity of CCS. FISH was least beneficial in myelodysplastic syndrome (MDS) where the highest concordance with CCS was exhibited. Acute lymphocytic leukaemia (ALL) demonstrated greater benefit with CCS. In addition, we found the following abnormalities to be most prevalent in HMs by FISH panel testing: RUNX1 (21q22) amplification in ALL, deletion of D13S319/LAMP1 (13q14) in CLL, CKS1B (1q21) amplification in multiple myeloma and deletion of EGR1/RPS14 (5q31/5q32) in MDS, consistent with the literature. Conclusions: In conclusion, FISH was found to be advantageous in only a subset of HMs and cannot completely replace CCS. Utilization of the two modalities in conjunction or independently should depend on the indicated HM for an optimal approach to detecting chromosomal aberrations. PMID:29286619

A Study of Use of “PORT” Catheter in Patients with Cancer: A Single-Center Experience

PubMed Central

Madabhavi, Irappa; Patel, Apurva; Sarkar, Malay; Anand, Asha; Panchal, Harsha; Parikh, Sonia

2017-01-01

Background: Effective and reliable venous access is one of the cornerstones of modern medical therapy in oncology. Materials and methods: This is a prospective observational study, which collected data of patients who require “PORT” catheter insertion for any cancer, at a tertiary care oncology hospital in Ahmadabad, Gujarat, India, during a 2-year period. Aims and objectives: The main objective of this study was to study the various complications and outcomes related to “PORT” catheters. Results: “PORT” catheter was inserted in 100 patients and was most commonly used in solid malignancies (n = 86, 86%), followed by hematologic malignancies (n = 14, 14%). Among the solid malignancies, breast cancer (38, 38%) was the most common underlying disease, whereas among the hematologic malignancies, acute lymphoblastic leukemia (6, 6%) was the most common underlying disease for “PORT” catheter insertion. Chemotherapy was started on the first day of “PORT” catheter in 74% of patients in the “PORT” study group. The various complications developed in the “PORT” study group in the descending order are as follows: 4 patients (4%) developed early infection (⩽30 days after “PORT” placement), 4 (4%) late infection (⩾30 days after “PORT” placement), 4 (4%) bloodstream infection, 2 (2%) local skin infection at the “PORT” insertion site, 2 (2%) dislodgment of the “PORT” catheter, 2 (2%) fracture of the “PORT” catheter, and 1 recurrent pleural effusion. One patient (1%) developed thrombosis as the complication of “PORT” catheter insertion. Conclusions: The most disturbing aspect of treatment for a patient with cancer is multiple painful venipunctures made for administration of cytotoxic agents, antibiotics, blood products, and nutritional supplements. The focus of this prospective observational research is to study the various underlying diseases for which “PORT” catheter is needed in different solid and hematologic malignancies and the various complications and outcomes in pediatric and adult patients with cancer. PMID:28469510

Determinants of hematology-oncology trainees' postfellowship career pathways with a focus on nonmalignant hematology

PubMed Central

Jenkins, Sarah; Mikhael, Joseph; Gitlin, Scott D.

2018-01-01

Nonmalignant hematologic conditions are extremely prevalent and contribute significantly to the global burden of disease. The US health care system may soon face a shortage of specialists in nonmalignant hematology. We sought to identify factors that lead hematology-oncology fellows to pursue (or not to pursue) careers in nonmalignant hematology. Cross-sectional, web-based survey distributed to 149 graduates of a hematology-oncology fellowship program at a large academic medical center between 1998 and 2016. Eighty-six out of 149 graduates responded (57.7%); most (59 [68.6%]) practice at an academic medical center. Respondents spend a mean of 61% of their time in clinical practice, 23.7% conducting research, 5.2% in education, and 5.2% in administration. Those in clinical practice spend a mean of 52.1% of their time in solid tumor oncology, 37.5% in hematologic malignancies, and 10% in nonmalignant hematology; only 1 spent >50% of time practicing nonmalignant hematology. Factors most significantly affecting choice of patient population included clinical experience during fellowship and intellectual stimulation of the patient population/disease type. Factors that could have most significantly influenced a decision to spend more time in nonmalignant hematology included increased exposure/access to role models and mentors and opportunities for better career growth/advancement. Fellowship graduates spend >50% of their time in clinical practice, but almost none spend a significant amount of time practicing nonmalignant hematology. Given the growing number of patients with nonmalignant hematologic conditions and a possible future provider shortage, medical trainees should be encouraged to pursue careers in nonmalignant hematology. PMID:29463548

Polymorphism of alpha-1-antitrypsin in hematological malignancies

PubMed Central

2009-01-01

Alpha-1-antitrypsin (AAT) or serine protease inhibitor A1 (SERPINA1) is an important serine protease inhibitor in humans. The main physiological role of AAT is to inhibit neutrophil elastase (NE) released from triggered neutrophils, with an additional lesser role in the defense against damage inflicted by other serine proteases, such as cathepsin G and proteinase 3. Although there is a reported association between AAT polymorphism and different types of cancer, this association with hematological malignancies (HM) is, as yet, unknown. We identified AAT phenotypes by isoelectric focusing (in the pH 4.2-4.9 range) in 151 serum samples from patients with HM (Hodgkins lymphomas, non-Hodgkins lymphomas and malignant monoclonal gammopathies). Healthy blood-donors constituted the control group (n = 272). The evaluated population of patients as well as the control group, were at Hardy-Weinberg equilibrium for the AAT gene (χ2 = 4.42, d.f.11, p = 0.96 and χ2 = 4.71, d.f.11, p = 0.97, respectively). There was no difference in the frequency of deficient AAT alleles (Pi Z and Pi S) between patients and control. However, we found a significantly higher frequency of PiM1M1 homozygote and PiM1 allele in HM patients than in control (for phenotype: f = 0.5166 and 0.4118 respectively, p = 0.037; for allele: f = 0.7020 and 0.6360 respectively, p = 0.05). In addition, PiM homozygotes in HM-patients were more numerous than in controls (59% and 48%, respectively, p = 0.044). PiM1 alleles and PiM1 homozygotes are both associated with hematological malignancies, although this is considered a functionally normal AAT variant. PMID:21637443

Cognitive dysfunction among newly diagnosed older patients with hematological malignancy: frequency, clinical indicators and predictors.

PubMed

Aiki, Sayo; Okuyama, Toru; Sugano, Koji; Kubota, Yosuke; Imai, Fuminobu; Nishioka, Masahiro; Ito, Yoshinori; Iida, Shinsuke; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Akechi, Tatsuo

2018-01-01

Medical staff often overlook or underestimate the presence or severity of cognitive dysfunction. The purpose of this study was to clarify the frequency, clinical indicators and predictors of cognitive dysfunction among newly diagnosed older patients with hematologic malignancy receiving first-line chemotherapy. Patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were consecutively recruited. Cognitive dysfunction was evaluated using the Mini-Mental State Examination (MMSE) twice: before starting chemotherapy (T1) and 1 month later (T2). Participants also underwent a comprehensive geriatric assessment at T1. Potential clinical indicators that were associated with cognitive dysfunction were explored via cross-sectional analysis at T1. Predictors of cognitive dysfunction at T2 were also investigated among patients without cognitive dysfunction at T1. A total of 145 participants participated in the study; cognitive dysfunction at T1 was present in 20%. Multivariate analysis demonstrated that lower educational attainment and poorer instrumental activities of daily living were significant clinical indicators of cognitive dysfunction. Among 99 patients who did not have cognitive dysfunction at T1 and underwent cognitive assessment at T2, 7% developed dysfunction. Subjective perception of difficulty remembering at T1 was the only factor which significantly predicted new-onset cognitive dysfunction at T2. The prevalence rate of cognitive dysfunction was non-negligible among older patients with hematologic malignancy before and immediately after initial chemotherapy. Attention to the clinical indicators and predictors found in this study may provide facilitate the identification of cognitive dysfunction in patients with cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Iron in spleen and liver: Some cases of normal tissues and tissues from patients with hematological malignancies

NASA Astrophysics Data System (ADS)

Alenkina, Irina V.; Oshtrakh, Michael I.; Felner, Israel; Vinogradov, Alexander V.; Konstantinova, Tatiana S.; Semionkin, Vladimir A.

2016-10-01

Iron deposits in spleen and liver tissues obtained from several healthy people and patients with mantle cell lymphoma, acute myeloid leukemia and primary myelofibrosis were studied using Mössbauer spectroscopy and magnetization measurements. The results obtained demonstrated differences in the iron content in tissues as well as some variations in the ferrihydrite-like iron core structure in the iron storage proteins in these tissues. The presence of tiny amount of magnetite and paramagnetic component in spleen and liver tissue was also detected in different quantities in the studied tissues.

Infective endocarditis and meningitis due to Scedosporium prolificans in a renal transplant recipient.

PubMed

Uno, Kenji; Kasahara, Kei; Kutsuna, Satoshi; Katanami, Yuichi; Yamamoto, Yoshifumi; Maeda, Koichi; Konishi, Mitsuru; Ogawa, Taku; Yoneda, Tatsuo; Yoshida, Katsunori; Kimura, Hiroshi; Mikasa, Keiichi

2014-02-01

Scedosporium prolificans is a ubiquitous filamentous fungi that may cause disseminated diseases in neutropenic patients with hematological malignancies. We report a fatal case of renal transplant recipient who developed both infective endocarditis and meningitis due to S. prolificans during treatment with micafungin and itraconazole for chronic necrotizing aspergillosis. Breakthrough Scedosporium infection should be considered among differential diagnosis of invasive fungal diseases in patients with renal transplant recipients receiving antifungal agents. Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Candidiasis in pediatric patients with cancer interned in a university hospital

PubMed Central

De Carvalho Parahym, Ana Maria Rabelo; De Melo, Luciana Resende Bandeira; De Morais, Vera Lúcia Lins; Neves, Rejane Pereira

2009-01-01

Fungi are common causes of infection in immunocompromised patients. Candida species are frequently involved in these cases. In order to investigate candidiasis in pediatric patients with cancer, clinical samples were collected from one hundred and twenty two patients interned in the Oswaldo Cruz University Hospital in Recife, Brazil. Yeasts were isolated from thirty-four clinical samples. The species isolated were: Candida albicans (fourteen isolates), C. parapsilosis (nine isolates), C. guilliermondii (two isolates) and C. tropicalis (two isolates). We found that candidemia was most frequent in patients with malignant hematology and that C. parapsilosis infections caused the highest mortality. PMID:24031365

[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].

PubMed

Levy, A; Guitera, P; Kerob, D; Ollivaud, L; Archimbaud, A; Dubertret, L; Basset-Seguin, N

2006-02-01

Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis. Its clinical and hematological safety is usually good. Hypersensitivity in hepatic failure patients is the most serious side effect described. This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003. Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values). Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded. Twenty patients were included, 11 women and 9 men of median age 58.6 years (22-82 years) with multiple metastases in all cases. DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status. Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group. In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment. In 2 patients, treatment was stopped after the second course because of disease progression. In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment. Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively. In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology. Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment. Hypersensitivity with DTIC seems to be frequent, being observed in 20% of our patients, with early onset (after the first or second course) and absence of dose-dependence. We describe for the first time two cases of medullar aplasia occurring in association with DTIC hypersensitivity. During phase I studies, the hematologic toxicity of DTIC was moderate, rarely affecting red cells, and was observed with higher doses than those used in metastatic malignant melanoma. We suggest that this aplasia forms part of the signs of hypersensitivity because of the bone marrow morphology, the existence of anemia and concomitant resolution with all the others signs of hypersensitivity. Laboratory monitoring (NFS, liver enzymes) is thus justified, particularly after the first and second courses of DTIC. In case of fever and hypereosinophilia without liver dysfunction, DTIC may be continued together with symptomatic treatment. In the event of hepatic dysfunction, and of course severe hematological disorders, potentially fatal complications can occur and treatment must be stopped.

Williams syndrome and mature B-Leukemia: A random association?

PubMed

Decimi, Valentina; Fazio, Grazia; Dell'Acqua, Fabiola; Maitz, Silvia; Galbiati, Marta; Rizzari, Carmelo; Biondi, Andrea; Cazzaniga, Giovanni; Selicorni, Angelo

2016-12-01

Williams syndrome (WBS) is a rare neurodevelopmental disorder with specific phenotypic characteristics and cardiac abnormalities, but is not considered as a cancer predisposing condition. However, in rare cases, malignancies have been described in patients with WBS, with hematologic cancer (mainly Burkitt Lymphoma and Acute Lymphoblastic Leukemia) as the most represented. We report here the case of a boy with WS and B-NHL. This is the unique case within the large cohort of patients (n = 117) followed in our institution for long time (mean clinical follow-up, 13 years). We herewith propose that the BCL7B gene, located in the chromosomal region commonly deleted in Williams syndrome, could potentially have a role in this particular association. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Safety and Tolerability of HSC835 in Patients With Hematological Malignancies Undergoing Single Umbilical Cord Blood Transplant

ClinicalTrials.gov

2017-08-31

Single Umbilical Cord Blood Transplantation; Non-myeloablative Conditioning; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; Non-Hodgkin's Lymphoma; Multiple Myeloma; Chronic Lymphocytic Leukemia

Red blood cell transfusion in the resuscitation of septic patients with hematological malignancies.

PubMed

Mirouse, Adrien; Resche-Rigon, Matthieu; Lemiale, Virginie; Mokart, Djamel; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Darmon, Michaël; Azoulay, Elie; Pène, Frédéric

2017-12-01

Indications for red blood cell (RBC) transfusion in septic acute circulatory failure remain unclear. We addressed the practices and the prognostic impact of RBC transfusion in the early resuscitation of severe sepsis and septic shock in patients with hematological malignancies. We performed a retrospective analysis of a prospectively collected database of patients with hematological malignancies who required intensive care unit (ICU) admission in 2010-2011. Patients with a main admission diagnosis of severe sepsis or septic shock were included in the present study. We assessed RBC transfusion during the first two days as part of initial resuscitation. Among the 1011 patients of the primary cohort, 631 (62.4%) were admitted to the ICU for severe sepsis (55%) or septic shock (45%). Among them, 210 (33.3%) patients received a median of 2 [interquartile 1-3] packed red cells during the first 48 h. Hemoglobin levels were lower in transfused patients at days 1 and 2 and became similar to those of non-transfused patients at day 3. Early RBC transfusion was more likely in patients with myeloid neoplasms and neutropenia. Transfused patients displayed more severe presentations as assessed by higher admission SOFA scores and blood lactate levels and the further requirements for organ failure supports. RBC transfusion within the first two days was associated with higher day 7 (20.5 vs. 13.3%, p = 0.02), in-ICU (39 vs. 25.2%, p < 0.001) and in-hospital (51 vs. 36.6%, p < 0.001) mortality rates. RBC transfusion remained independently associated with increased in-hospital mortality in multivariate logistic regression (OR 1.52 [1.03-2.26], p = 0.03) and propensity score-adjusted (OR 1.64 [1.05-2.57], p = 0.03) analysis. RBC transfusion is commonly used in the early resuscitation of septic patients with hematological malignancies. Although it was preferentially provided to the most severe patients, we found it possibly associated with an increased risk of death.

Quality of life in survivors of hematological malignancies stratified by cancer type, time since diagnosis and stem cell transplantation.

PubMed

Esser, Peter; Kuba, Katharina; Mehnert, Anja; Johansen, Christoffer; Hinz, Andreas; Lordick, Florian; Götze, Heide

2018-06-01

Quality of life (QoL) has become an important tool to guide decision making in oncology. Given the heterogeneity among hematological cancer survivors, however, clinicians need comparative data across different subsets. This study recruited survivors of hematological malignancies (≥ 2.5 years after diagnosis) from two German cancer registries. QoL was assessed with the EORTC QLQ-C30. The sample was stratified by cancer type, time since diagnosis, treatment with stem cell transplantation (SCT) and type of SCT. First, levels of QoL were compared across subsamples when controlling for several covariates. Second, we contrasted subsamples with gender- and age-matched population controls obtained from the general population. Of 2001 survivors contacted by mail, 922 (46%) participated in the study. QoL did not significantly differ between the subsamples. All subsamples scored significantly lower in functioning and significantly higher in symptom burden compared to population controls (all p < .001). Almost all of these group effects reached clinically meaningful sizes (Cohen's d ≥ .5). Group differences in global health/QoL were mostly non-significant. Hematological cancer survivors are associated with practically relevant impairments irrespective of differences in central medical characteristics. Nevertheless, survivors seem to evaluate their overall situation as relatively well. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Risk for Health Care-Associated Bloodstream Infections in Pediatric Oncology Patients With Various Malignancies.

PubMed

Thurman, Cara B; Abbott, Maura; Liu, Jinfang; Larson, Elaine

This was a retrospective cohort study to identify the rates, predictors, and outcomes of health care-associated bloodstream infections (HA-BSI) among children with solid tumors, lymphoma, lymphoid leukemia, and myeloid leukemia. The study population included 4500 children ≤18 years old at a pediatric hospital in New York City from 2006 to 2014. A total of 147 HA-BSI cases were identified; using multivariable logistic regression modeling, children with a hematologic diagnosis (lymphoma, lymphoid leukemia, myeloid leukemia) were at greater risk for HA-BSI than those with a solid tumor diagnosis (all P values <.0001). The odds of mortality for patients with HA-BSI were 6.98 (95% confidence interval 3.02-16.10) times that of those without HA-BSI. Although malignancy type was identified as risk factor for HA-BSI, there was no significant difference in overall mortality from HA-BSI by tumor type ( P = .51).

Impact of case volume on survival of septic shock in patients with malignancies.

PubMed

Zuber, Benjamin; Tran, Thi-Chien; Aegerter, Philippe; Grimaldi, David; Charpentier, Julien; Guidet, Bertrand; Mira, Jean-Paul; Pène, Frédéric

2012-01-01

Septic shock is a frequent and severe complication in the course of malignancies. In a large multicenter cohort of septic shock patients with hematologic malignancies and solid tumors, we assessed the temporal trend in survival and the prognostic factors, with particular emphasis on case volume. A 12-yr multicenter retrospective cohort study of prospectively collected data. Cancer patients with septic shock were selected over a 12-yr period (1997-2008) from a French regional database (CUB-Réa). The following variables were extracted: demographic characteristics, type of malignancy, characteristics of infection, severity-of-illness score (Simplified Acute Physiology Score II), organ failure supports, and vital status. For each unit, a running mean annual volume of admissions was calculated for the purpose of categorization into volume tertiles. Prognostic factors were analyzed by a conditional multivariate logistic model after matching on a propensity score of being admitted to a high-volume unit and on the year of admission. None. A total of 3,437 patients were included in the study. The intensive care unit mortality rate dramatically dropped over time (from 70.4% in 1997 to 52.5% in 2008, relative decrease 25.4%, p < .001). Participating units were distributed into low-volume (< five patients per year), medium-volume (five to 12 patients per year), and high-volume (≥ 13 patients per year) tertiles. A medical cause for intensive care unit admission, Simplified Acute Physiology Score II, invasive mechanical ventilation, renal replacement therapy, fungal infections, and unknown microorganism were identified as poor prognostic factors. Case volume demonstrated a strong influence on survival, admission in a high-volume unit being associated with a marked decrease in mortality as compared to low-volume units (adjusted odds ratio 0.63; 95% confidence interval [0.46-0.87], p = .002). Survival of septic shock patients with malignancies markedly increased over the recent years. Furthermore, we identified case volume as a major prognostic factor in this setting.

[A wrong move in an amateur football player reveals a light chain myeloma].

PubMed

Peyneau, Marine; Nassiri, Shiva; Myara, Anne; Ohana, Salomon; Laplanche, Sophie

2016-01-01

Light chain multiple myeloma is a hematologic malignancy characterized by an excess of tumor plasma cells in the bone marrow and a monoclonal light chain in blood. It is generally diagnosed in patients aged 60-75 years old. Hypercalcemia, anemia, kidney failure, and bone pains are the main clinical and biological signs. Here is an atypical case report about a 30 year-old man who was diagnosed a light chain multiple myeloma. This patient had been suffering from back pain for 5 months. Osteolytic lesions were discovered on X-rays prescribed by the family practitioner. Admitted to the Emergency department, all blood tests showed results within the normal range. The serum protein electrophoresis was also normal. Only the urine analysis showed proteinuria. The urine immunofixation electrophoresis showed a massive κ light chain. The bone marrow aspiration cell count confirmed the myeloma diagnosis with an infiltration of dystrophic plasma cells. The patient was transferred to the hematology ward of Necker Hospital for treatment of light chain myeloma.

An Unusual Case of Constitutional Mismatch Repair Deficiency Syndrome With Anaplastic Ganglioglioma, Colonic Adenocarcinoma, Osteosarcoma, Acute Myeloid Leukemia, and Signs of Neurofibromatosis Type 1: Case Report.

PubMed

Daou, Badih; Zanello, Marc; Varlet, Pascale; Brugieres, Laurence; Jabbour, Pascal; Caron, Olivier; Lavoine, Noémie; Dhermain, Frederic; Willekens, Christophe; Beuvon, Frederic; Malka, David; Lechapt-Zalcmann, Emmanuèle; Abi Lahoud, Georges

2015-07-01

Constitutional mismatch repair deficiency (CMMRD) syndrome is a disorder with recessive inheritance caused by biallelic mismatch repair gene mutations, in which mismatch repair defects are inherited from both parents. This syndrome is associated with multiple cancers occurring in childhood. The most common tumors observed with CMMRD include brain tumors, digestive tract tumors, and hematological malignancies. The aim of this study was to report new phenotypic expressions of CMMRD syndrome and add new insight to the existing knowledge about this disease. A review of the literature was conducted and recommendation for surveillance and follow-up in patients with CMMRD are proposed. We report for the first time in the literature, the case of a 22-year-old female patient who was diagnosed with CMMRD syndrome, with the development of 2 unusual tumors: an anaplastic ganglioglioma and an osteosarcoma. She presented initially with an anaplastic ganglioglioma and later developed several malignancies including colonic adenocarcinoma, osteosarcoma, and acute myeloid leukemia. The patient had an atypical course of her disease with development of the initial malignancy at an older age and a remarkably long survival period despite developing aggressive tumors. Many aspects of this disease are still unknown. We identified a case of CMMRD in a patient presenting with an anaplastic ganglioglioma, who underwent successful surgical resection, chemotherapy, and radiotherapy and has had one of the longest survival periods known with this disease. This case broadens the tumor spectrum observed with CMMRD syndrome with anaplastic ganglioglioma and osteosarcoma as new phenotypic expressions of this genetic defect.

Molecular Methods To Improve Diagnosis and Identification of Mucormycosis▿

PubMed Central

Hammond, Sarah P.; Bialek, Ralf; Milner, Danny A.; Petschnigg, Eva M.; Baden, Lindsey R.; Marty, Francisco M.

2011-01-01

Mucormycosis is difficult to diagnose. Samples from suspected cases often fail to grow Mucorales in microbiologic cultures. We identified all hematologic malignancy and stem cell transplant patients diagnosed with proven mucormycosis between 2001 and 2009 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Seminested PCR targeting Mucorales 18S ribosomal DNA and sequencing were performed on formalin-fixed paraffin-embedded tissue samples. Of 29 cases of mucormycosis, 27 had tissue samples available for PCR and sequencing. Mucorales PCR was positive in 22. Among 12 culture-positive cases, 10 were PCR positive and sequencing was concordant with culture results to the genus level in 9. Among 15 culture-negative cases, PCR was positive and sequencing allowed genus identification in 12. Mucorales PCR is useful for confirmation of the diagnosis of mucormycosis and for further characterization of the infection in cases where cultures are negative. PMID:21508149

Molecular methods to improve diagnosis and identification of mucormycosis.

PubMed

Hammond, Sarah P; Bialek, Ralf; Milner, Danny A; Petschnigg, Eva M; Baden, Lindsey R; Marty, Francisco M

2011-06-01

Mucormycosis is difficult to diagnose. Samples from suspected cases often fail to grow Mucorales in microbiologic cultures. We identified all hematologic malignancy and stem cell transplant patients diagnosed with proven mucormycosis between 2001 and 2009 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Seminested PCR targeting Mucorales 18S ribosomal DNA and sequencing were performed on formalin-fixed paraffin-embedded tissue samples. Of 29 cases of mucormycosis, 27 had tissue samples available for PCR and sequencing. Mucorales PCR was positive in 22. Among 12 culture-positive cases, 10 were PCR positive and sequencing was concordant with culture results to the genus level in 9. Among 15 culture-negative cases, PCR was positive and sequencing allowed genus identification in 12. Mucorales PCR is useful for confirmation of the diagnosis of mucormycosis and for further characterization of the infection in cases where cultures are negative.

PDR001 Plus LAG525 for Patients With Advanced Solid and Hematologic Malignancies

ClinicalTrials.gov

2018-06-24

Small Cell Lung Cancer; Gastric Adenocarcinoma; Esophageal Adenocarcinoma; Castration Resistant Prostate Adenocarcinoma; Soft Tissue Sarcoma; Ovarian Adenocarcinoma; Advanced Well-differentiated Neuroendocrine Tumors; Diffuse Large B Cell Lymphoma

Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies

ClinicalTrials.gov

2009-02-12

Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Secondary AML; Myelodysplastic Syndrome (MDS); Secondary MDS; Chronic Myeloid Leukemia; Juvenile Myelomonocytic Leukemia (JMML); Paroxysmal Nocturnal Hemoglobinuria (PNH); Lymphoma, Non-Hodgkin; Hodgkin Disease

NF-κB in Hematological Malignancies

PubMed Central

Imbert, Véronique; Peyron, Jean-François

2017-01-01

NF-κB (Nuclear Factor Κ-light-chain-enhancer of activated B cells) transcription factors are critical regulators of immunity, stress response, apoptosis, and differentiation. Molecular defects promoting the constitutive activation of canonical and non-canonical NF-κB signaling pathways contribute to many diseases, including cancer, diabetes, chronic inflammation, and autoimmunity. In the present review, we focus our attention on the mechanisms of NF-κB deregulation in hematological malignancies. Key positive regulators of NF-κB signaling can act as oncogenes that are often prone to chromosomal translocation, amplifications, or activating mutations. Negative regulators of NF-κB have tumor suppressor functions, and are frequently inactivated either by genomic deletions or point mutations. NF-κB activation in tumoral cells is also driven by the microenvironment or chronic signaling that does not rely on genetic alterations. PMID:28561798

Antifungal susceptibility and pathogenic potential of environmental isolated filamentous fungi compared with colonizing agents in immunocompromised patients.

PubMed

Teixeira, A B A; Silva, M; Lyra, L; Luz, E A; Uno, J; Takada, H; Miyaji, M; Nishimura, K; Schreiber, A Z

2005-09-01

Infection is a major cause of morbidity and mortality in bone marrow transplant recipients and in patients with hematological malignancies. The source of infection is almost always endogenous flora or the hospital environment. The present study evaluated bone marrow transplant recipients and patients with hematological malignancies colonized and/or infected with filamentous fungi. During 1 year, environmental air samples were also taken from the bone marrow transplant unit by a modification of gravity air-setting plate (GASP) methodology. Fusarium spp. were the most prevalent genus in the fall and Cladosporium spp. in the winter. Clinically isolated strains grew better at 37 degrees C than environmental strains. According to NCCLS M-38P methods, environmental Aspergillus strains showed higher MICs to miconazol and itraconazol, and clinical Fusarium strains were less susceptible to fluconazole.

Methotrexate vs Cyclosporin A as a single agent for graft-versus-host disease prophylaxis in pediatric patients with hematological malignancies undergoing allogeneic bone marrow transplantation from HLA-identical siblings: a single-center analysis in Japan.

PubMed

Koga, Y; Nagatoshi, Y; Kawano, Y; Okamura, J

2003-07-01

The efficacy of methotrexate (MTX) as a single graft-versus-host disease (GVHD) prophylaxis agent was compared to that of cyclosporin A (CSA) in 62 pediatric patients (median age: 8 years) with hematological malignancies who had undergone bone marrow transplantation (BMT) from HLA-identical sibling donors at National Kyushu Cancer Center since 1977. In all, 30 patients received MTX by intravenous bolus injection, with a dose of 15 mg/m(2) on day +1, followed by 10 mg/m(2) on days +3, +6, and +11, and then once a week until day +100. A total of 32 patients were treated with CSA, which was given intravenously in the early stages and orally thereafter until day +100, and then gradually tapered and stopped 6 months after BMT. There were no differences between the groups in terms of rates of hematopoietic recovery after BMT. The probabilities of acute GVHD (grades II-IV) and chronic GVHD were 29.6 vs 40.6% (P=0.294) and 19 vs 20% (MTX vs CSA), respectively. Relapse rates and event-free survival were identical. These results suggest that MTX and CSA were equally effective when given after BMT in Japanese pediatric patients with hematological malignancies. Since MTX was given over a shorter time than CSA, it might be more practical in the management of such patients.

KB004, a first in class monoclonal antibody targeting the receptor tyrosine kinase EphA3, in patients with advanced hematologic malignancies: Results from a phase 1 study.

PubMed

Swords, Ronan T; Greenberg, Peter L; Wei, Andrew H; Durrant, Simon; Advani, Anjali S; Hertzberg, Mark S; Jonas, Brian A; Lewis, Ian D; Rivera, Gabriel; Gratzinger, Dita; Fan, Alice C; Felsher, Dean W; Cortes, Jorge E; Watts, Justin M; Yarranton, Geoff T; Walling, Jackie M; Lancet, Jeffrey E

2016-11-01

EphA3 is an Ephrin receptor tyrosine kinase that is overexpressed in most hematologic malignancies. We performed a first-in-human multicenter phase I study of the anti-EphA3 monoclonal antibody KB004 in refractory hematologic malignancies in order to determine safety and tolerability, along with the secondary objectives of pharmacokinetics (PK) and pharmacodynamics (PD) assessments, as well as preliminary assessment of efficacy. Patients were enrolled on a dose escalation phase (DEP) initially, followed by a cohort expansion phase (CEP). KB004 was administered by intravenous infusion on days 1, 8, and 15 of each 21-day cycle in escalating doses. A total of 50 patients (AML 39, MDS/MPN 3, MDS 4, DLBCL 1, MF 3) received KB004 in the DEP; an additional 14 patients were treated on the CEP (AML 8, MDS 6). The most common toxicities were transient grade 1 and grade 2 infusion reactions (IRs) in 79% of patients. IRs were dose limiting above 250mg. Sustained exposure exceeding the predicted effective concentration (1ug/mL) and covering the 7-day interval between doses was achieved above 190mg. Responses were observed in patients with AML, MF, MDS/MPN and MDS. In this study, KB004 was well tolerated and clinically active when given as a weekly infusion. Copyright © 2016 Elsevier Ltd. All rights reserved.

Escherichia coli Pyomyositis in an Immunocompromised Host

PubMed Central

Sharma, Umesh; Schwan, William R.; Agger, William A.

2015-01-01

Background Pyomyositis due to Escherichia coli (E. coli) is rarely reported in immunocompromised patients with hematological malignancy. Case Report We present a case report of a 34-year-old man who developed E. coli pyomyositis as a complication of acute myelogenous leukemia (AML). Magnetic resonance imaging (MRI) of the right hip suggested myofascial infection of the gluteal muscles, and a needle muscle aspiration grew E. coli phylogenetic group B2. The patient responded to intravenous piperacillin/tazobactam followed by prolonged oral levofloxacin. Conclusion Pyomyositis should be suspected in all immunocompromised patients complaining of muscle pain and may exhibit signs of localized muscle infection. Appropriate antibiotic therapy targeting fluoroquinolone-resistant E. coli should be considered for initial empiric therapy of pyomyositis in immunocompromised patients. PMID:22413629

Sepsis associated with hematological malignancies: prophylaxis of Pseudomonas aeruginosa sepsis.

PubMed

Sakamoto, M; Saruta, K; Nakazawa, Y; Shindo, N; Maezawa, H; Yoshikawa, K; Yoshida, M; Shiba, K; Sakai, O; Saito, A

1996-02-01

Underlying diseases, pathogenic bacteria, clinical background and outcome were studied during 91 febrile episodes complicated by sepsis in 55 patients with hematological malignancies, who had been admitted to our hospital (Jikei University Kashiwa Hospital) between January 1990 and December 1994. Particularly in patients with P. aeruginosa sepsis, we compared the prophylactic effect of ciprofloxacin (CPFX) alone with that of the combination of polymyxin B (PL-B) plus kanamycin (KM). The major underlying diseases were acute myelocytic leukemia and malignant lymphoma, followed by myelodysplastic syndrome, acute lymphocytic leukemia and chronic myelocytic leukemia. Nearly two-thirds of the pathogenic microorganisms isolated were gram-positive bacteria (including coagulase-negative staphylococci and Staphylococcus aureus); approximately one-quarter were gram-negative bacteria (such as Pseudomonas aeruginosa), and the remainder were fungi. These microorganisms usually induced sepsis when granulocyte counts were decreased. Sepsis was a direct cause of death in about 60% of the patients and P. aeruginosa sepsis had the worst outcome. Oral administration of CPFX was more effective than PL-B plus KM in preventing P. aeruginosa sepsis. The difference in effectiveness might depend on the absorption profile of the drugs.

Functional and genetic screening of acute myeloid leukemia associated with mediastinal germ cell tumor identifies MEK inhibitor as an active clinical agent.

PubMed

Leonard, Jessica T; Raess, Philipp W; Dunlap, Jennifer; Hayes-Lattin, Brandon; Tyner, Jeffrey W; Traer, Elie

2016-03-31

Hematologic malignancies arising in the setting of established germ cell tumors have been previously described and have a dismal prognosis. Identification of targetable mutations and pathway dysregulation through massively parallel sequencing and functional assays provides new approaches to disease management. Herein, we report the case of a 23-year-old male who was diagnosed with a mediastinal germ cell tumor and subsequent acute myeloid leukemia. A shared clonal origin was demonstrated through identification of identical NRAS and TP53 somatic mutations in both malignancies. The patient's leukemia was refractory to standard therapies with short interval relapse. Functional assays demonstrated the patient's blasts to be sensitive to the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, correlating with the activating NRAS mutation. The patient experienced a sustained partial remission while on trametinib therapy but ultimately suffered relapse of the germ cell tumor. The leukemic clone remained stable and sensitive to trametinib at that time. This case highlights the potential power of combining genetic sequencing and in vitro functional assays with targeted therapies in the treatment of rare diseases.

Infections with the tick-borne bacterium "Candidatus Neoehrlichia mikurensis" mimic noninfectious conditions in patients with B cell malignancies or autoimmune diseases.

PubMed

Grankvist, Anna; Andersson, Per-Ola; Mattsson, Mattias; Sender, Monica; Vaht, Krista; Höper, Linnea; Sakiniene, Egidija; Trysberg, Estelle; Stenson, Martin; Fehr, Jan; Pekova, Sona; Bogdan, Christian; Bloemberg, Guido; Wennerås, Christine

2014-06-01

Candidatus Neoehrlichia mikurensis is a newly discovered noncultivatable bacterium spread among ticks and rodents in Europe and Asia that can infect humans, particularly immunocompromised patients. We compiled clinical and laboratory data from 11 patients with hematological malignances or autoimmune diseases who were diagnosed with Candidatus N. mikurensis infection in Europe 2010-2013. Both published (6) and unpublished cases (5) were included. The patients had a median age of 67, were mostly male (8/11), and resided in Sweden, Switzerland, Germany, and the Czech Republic. All but one had ongoing or recent immune suppressive treatment and a majority were splenectomized (8/11). Less than half of them recalled tick exposure. The most frequent symptoms were fever (11/11), localized pain afflicting muscles and/or joints (8/11), vascular and thromboembolic events (6/11), that is, deep vein thrombosis (4), transitory ischemic attacks (2), pulmonary embolism (1), and arterial aneurysm (1). Typical laboratory findings were elevated C-reactive protein, leukocytosis with neutrophilia, and anemia. Median time from onset of symptoms to correct diagnosis was 2 months. In at least 4 cases, the condition was interpreted to be due to the underlying disease, and immunosuppressive therapy was scheduled. All patients recovered completely when doxycycline was administered. Candidatus N. mikurensis is an emerging tick-borne pathogen that may give rise to a systemic inflammatory syndrome in persons with hematologic or autoimmune diseases that could be mistaken for recurrence of the underlying disease and/or unrelated arteriosclerotic vascular events. Awareness of this new pathogen is warranted among rheumatologists, hematologists, oncologists, and infectious disease specialists. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Bone Marrow Transplant Using a Reduced Intensity Regimen That is Given in Two Steps

ClinicalTrials.gov

2016-11-28

Hematologic Malignancies; Acute Leukemia; Myelodysplastic Syndromes (MDS) Other Than RA or RARS Subtypes; Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma; Myeloma; Chronic Myelogenous (or Myeloid) Leukemia (CML) Resistant to STI Therapy

Oceans of Opportunity: Exploring Vertebrate Hematopoiesis in Zebrafish

PubMed Central

Carroll, Kelli J.; North, Trista E.

2015-01-01

Exploitation of the zebrafish model in hematology research has surged in recent years, becoming one of the most useful and tractable systems for understanding regulation of hematopoietic development, homeostasis, and malignancy. Despite the evolutionary distance between zebrafish and humans, remarkable genetic and phenotypic conservation in the hematopoietic system has enabled significant advancements in our understanding of blood stem and progenitor cell (HSPC) biology. The strengths of zebrafish in hematology research lie in the ability to perform real-time in vivo observations of hematopoietic stem, progenitor and effector cell emergence, expansion and function, as well as the ease with which novel genetic and chemical modifiers of specific hematopoietic processes or cell-types can be identified and characterized. Further, a myriad of transgenic lines have been developed including fluorescent reporter systems to aid in the visualization and quantification of specified cell types of interest and cell-lineage relationships, as well as effector lines that can be used to implement a wide range of experimental manipulations. As our understanding of the complex nature of HSPC biology during development, in response to infection or injury, or in the setting of hematological malignancy, continues to deepen, zebrafish will remain essential for exploring the spatio-temporal organization and integration of these fundamental processes, as well as the identification of efficacious small molecule modifiers of hematopoietic activity. In this review, we discuss the biology of the zebrafish hematopoietic system, including similarities and differences from mammals, and highlight important tools currently utilized in zebrafish embryos and adults to enhance our understanding of vertebrate hematology, with emphasis on findings that have impacted our understanding of the onset or treatment of human hematologic disorders and disease. PMID:24816275

The risk of cancer in patients with congenital heart disease: a nationwide population-based cohort study in Taiwan.

PubMed

Lee, Yu-Sheng; Chen, Yung-Tai; Jeng, Mei-Jy; Tsao, Pei-Chen; Yen, Hsiu-Ju; Lee, Pi-Chang; Li, Szu-Yuan; Liu, Chia-Jen; Chen, Tzeng-Ji; Chou, Pesus; Soong, Wen-Jue

2015-01-01

The relationship between congenital heart disease (CHD) and malignancies has not been determined. This study aimed to explore the association of CHD with malignancies and examine the risk factors for the development of cancer after a diagnosis of CHD. This nationwide, population-based cohort study on cancer risk evaluated 31,961 patients with newly diagnosed CHD using the Taiwan National Health Insurance Research Database (NHIRD) between 1998 and 2006. The standardized incidence ratios (SIRs) for all and specific cancer types were analyzed, while the Cox proportional hazard model was used to evaluate risk factors of cancer occurrence. Among patients with newly diagnosed CHD regardless of ages, 187 (0.6%) subsequently developed cancers after a diagnosis of CHD. Patients with CHD had increased risk of cancer (SIR, 1.45; 95% CI, 1.25-1.67), as well as significantly elevated risks of hematologic (SIR, 4.04; 95% CI, 2.76-5.70), central nervous system (CNS) (SIR, 3.51; 95% CI, 1.92-5.89), and head and neck (SIR, 1.81; 95% CI, 1.03-2.94) malignancies. Age (HR, 1.06; 95% CI, 1.05-1.06) and co-morbid chronic liver disease (HR, 1.91; 95% CI, 1.27-2.87) were independent risk factors for cancer occurrence among CHD patients. Patients with CHD have significantly increased cancer risk, particularly hematologic, CNS, and head and neck malignancies. Physicians who care for patients with CHD should be aware of their predisposition to malignancy after the diagnosis of CHD. Further studies are warranted to clarify the association between CHD and malignancies.

Simultaneous occurrence of a CD30 positive/ALK-negative high grade T-cell lymphoma and plasma cell myeloma: Report of a case.

PubMed

Nassif, Samer; El-Majzoub, Nadim; Abbas, Ossama; Temraz, Sally; Chakhachiro, Zaher

2015-03-01

Simultaneous occurrences of T-cell and B-cell neoplasms are rare, and etiological relationships between these two malignancies are poorly understood. We report the case of a 76-year-old man who presented with hypercalcemia, multiple skin nodular lesions, fatigue, episodic fever, and night sweats. PET/CT scan showed diffuse skin and subcutaneous fat plane active lesions, supra- and infra- diaphragmatic active lymph nodes, liver and spleen involvement, bone marrow infiltration, and nonspecific bilateral lung nodules. A skin biopsy showed a high grade CD30-positive/ALK-negative T-cell lymphoma. A bone marrow biopsy showed involvement by the same neoplastic cells. Additionally, a monoclonal lambda restricted plasma cell population (15% of marrow elements) was identified, which, in view of an IgA lambda spike in the serum, was consistent with plasma cell myeloma. To the best of our knowledge, this case is the first reported case of a plasma cell neoplasm associated with an aggressive CD30-positive ALK-negative systemic T-cell lymphoma with skin involvement. Reporting such cases is important as it adds to the pool of rare cases of concomitant T-cell neoplasms and plasma cell myelomas, and might help in determining an etiological relationship, if any, between these two hematological malignancies. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

PubMed

Fu, Jack B; Tennison, Jegy M; Rutzen-Lopez, Isabel M; Silver, Julie K; Morishita, Shinichiro; Dibaj, Seyedeh S; Bruera, Eduardo

2018-03-28

To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. Retrospective descriptive analysis. Comprehensive cancer center acute inpatient rehabilitation unit. Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. Bleeding events noted in the medical record. Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/μL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Plasma Cell Gingivitis: An Occasional Case Report.

PubMed

Mishra, M B; Sharma, Swati; Sharma, Alok

2015-01-01

Plasma cell gingivitis, an infrequently observed oral condition, has been clinically characterized by diffuse gingival enlargement, erythema and sometimes desquamation. These lesions are usually asymptomatic, but invariably the patient will complain of a burning sensation in the gingiva and bleeding from the mouth. The diagnosis requires hematological screening in addition to clinical and histopathological examinations. This case report outlines one such case of plasma cell gingivitis in a 15-year-old female caused by use of an herbal, homemade toothpowder. The case presented here highlights the adverse effects and irrational use of herbal agents in dentifrices. At the same time, it emphasizes the need for comprehensive history taking, careful clinical examination and appropriate diagnostic tests in order to arrive at a definitive diagnosis and treatment plan for gingival conditions that are refractory to conventional therapy and to exclude certain malignancies and oral manifestations of systemic diseases.

Concentration Study of High Sensitive C - reactive Protein and some Serum Trace Elements in Patients with Benign and Malignant Breast Tumor.

PubMed

Abdollahi, Alireza; Ali-Bakhshi, Abbas; Farahani, Zahra

2015-10-01

Background : Breast cancer is the most common invasive cancer in females worldwide. It accounts for 16% of all female cancers and 22.9% of invasive cancers in women. 18.2% of all cancer deaths worldwide including both males and females are from breast cancer. In this study we compared few serum elements in patients with benign and malignant breast tumor to find any related prognostic and predictive value. A case-control study was carried out in a hospital (Tehran - Iran) in 2012. Target population was divided in 2 groups; subjects with benign and malignant breast tumors. We did preoperative hematological test. Five milliliter fasting blood vein was collected, centrifuged in 3000 g for 15 minutes to obtain serum. We measured serum Calcium (Ca), Phosphorus (P), Magnesium (Mg), Zinc (Zn), and high sensitive-CRP, analyzed statistically and compared recorded elements in 2 groups by software package SPSS version 16. The level of significant was considered P < 0.05. Of 87 women, 49 cases with benign breast disease (group A) and 38 cases with breast cancer (group B) entered our study. Serum concentration of Ca, mg, and P in group A were higher than group B, however these differences were not significant. We found no significant correlation between serum Zn and type of tumor in our patients. On the other hand, a significant elevation in hs-CRP in patient with breast cancer was seen (P Value=.000). Conclusion : Our results have shown similar concentration of Ca, Mg, Zn, P and completely different hs-CRP concentration in patients with benign and malignant breast disease.

A Study of Withdrawal of Immunosuppression and Donor Lymphocyte Infusions Following Allogeneic Transplant for Pediatric Hematologic Malignancies

ClinicalTrials.gov

2016-05-18

Acute Leukemia; Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Biphenotypic Leukemia; Pre-leukemic Syndromes; Monosomy 7; Bone Marrow Clonal Malformations; Juvenile Myelomonocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia

Safety and Tolerability of HSC835 in Patients With Hematological Malignancies

ClinicalTrials.gov

2017-04-03

Acute Myelocytic Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Marginal Zone Lymphoma; Follicular Lymphomas; Large-cell Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Lymphomas; Mantle-cell Lymphoma; Lymphoplasmacytic Lymphoma

77 FR 41792 - Prospective Grant of Co-Exclusive License: The Development of Human Anti-CD22 Monoclonal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-16

... hematological malignancies such as hairy cell leukemia, chronic lymphocytic leukemia and pediatric acute lymphoblastic leukemia, and autoimmune disease such as lupus and Sjogren's syndrome. The specific antibodies...

77 FR 9678 - Prospective Grant of Exclusive License: The Development of Human Anti-CD22 Monoclonal Antibodies...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... hematological malignancies such as hairy cell leukemia, chronic lymphocytic leukemia and pediatric acute lymphoblastic leukemia, and autoimmune disease such as lupus and Sjogren's syndrome. The specific antibodies...

Mismatched Family Member Donor Transplantation for Children and Young Adults With High Risk Hematological Malignancies

ClinicalTrials.gov

2018-05-09

Leukemia, Acute Lymphocytic (ALL); Leukemia, Myeloid, Acute(AML); Leukemia, Myeloid, Chronic(CML); Juvenile Myelomonocytic Leukemia (JMML); Hemoglobinuria, Paroxysmal Nocturnal (PNH); Hodgkin Lymphoma; Lymphoma, Non-Hodgkin (NHL); Myelodysplastic Syndrome (MDS)

Alterations of cyclin-dependent kinase 4 inhibitor (p16INK4A/MTS1) gene structure and expression in acute lymphoblastic leukemias.

PubMed

Delmer, A; Tang, R; Senamaud-Beaufort, C; Paterlini, P; Brechot, C; Zittoun, R

1995-07-01

The cyclin-dependent kinase 4 (cdk4) inhibitor (p16INK4/MTS1/CDKN2) gene has been recently identified as a putative tumor suppressor gene because of the high frequency of homozygous deletion observed in numerous human tumor cell lines, including leukemias. However, results obtained from uncultured tumor samples have led to discussion of the relevance of these findings. Using reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis, we have investigated p16INK4A gene at both RNA and genomic levels in various types of leukemias: acute myeloid leukemia (AML) (n = 23); acute lymphocytic leukemia (ALL) (n = 22) and B cell chronic lymphoproliferative disorders (CLPD) (n = 33). p16INK4A mRNA expression was not found in only 1/20 AML and 2/23 CLPD samples. Conversely, p16INK4A mRNA was not detected in 5/17 ALL cases, and intensity of PCR products were barely detectable in seven additional cases, possibly related to the contamination by normal cells in some cases. By Southern blotting, a homozygous deletion of p16INK4A gene was found in 6/17 ALL cases (35%) among which 4/6 were negative or weakly positive by RT-PCR assay. None of the five AML and 20 CLL samples studied had p16INK4A deletion. Sequence analysis of p16INK4A exon 2 did not show point mutation in two of these cases lacking mRNA expression. Our data provide further evidence that among hematological malignancies, ALL are the most likely to be associated with p16INK4A inactivation, mainly by homozygous gene deletion. Since most hematological malignancies-except ALL-are infrequently associated with p16INK4A and retinoblastoma (Rb) gene alteration it seems worthwhile to explore cdk4 and cdk6 expression to determine whether or not the disruption of the p16INK4A/Rb/cdk4/cdk6 regulatory loop might play a role in their pathogenesis.

FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

PubMed Central

Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

2015-01-01

Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative regimens of a variety of other hematological and non-hematological malignancies. The addition of newer agents to conditioning like bortezomib or lenalidomide for myeloma, or clofarabine for myeloid malignancies, may improve antitumor effects for transplantation, while in combination with alemtuzumab may represent a backbone for future cellular therapy due to reliable engraftment and low toxicity profile. This review summarizes the development and the current use of this remarkable drug in hematopoietic stem-cell transplantation. PMID:22922522

Clonal evolution in hematologic malignancies and therapeutic implications

PubMed Central

Landau, Dan A.; Carter, Scott L.; Getz, Gad; Wu, Catherine J.

2014-01-01

The ability of cancer to evolve and adapt is a principal challenge to therapy in general, and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution, and inspire the development of novel prognostic and therapeutic strategies. PMID:23979521

Intravenous apoptotic cell infusion as a cell-based therapy toward improving hematopoietic cell transplantation outcome.

PubMed

Saas, Philippe; Gaugler, Béatrice; Perruche, Sylvain

2010-10-01

Allogeneic hematopoietic cell transplantation (AHCT) is an efficient therapy for different malignant and nonmalignant hematological diseases. However, the use of this therapeutic approach is still limited by some severe toxic side effects, mainly graft-versus-host disease (GvHD). Today, the risk of fatal GvHD restrains the wider application of AHCT to many patients in need of an effective therapy for their high-risk hematologic malignancies. Thus, new strategies, including cell-based therapy approaches, are required. We propose to use intravenous donor apoptotic leukocyte infusion to improve AHCT outcome. In experimental AHCT models, we demonstrated that intravenous apoptotic leukocyte infusion, simultaneously with allogeneic bone marrow grafts, favors hematopoietic engraftment, prevents allo-immunization, and delays acute GvHD onset. Here, we review the different mechanisms and the potential beneficial effects associated with the immunomodulatory properties of apoptotic cells in the AHCT setting. © 2010 New York Academy of Sciences.

Streptococcus pneumoniae: distribution of serotypes and antimicrobial susceptibility in patients with cancer.

PubMed

Soto-Noguerón, Araceli; Carnalla-Barajas, María Noemí; Cornejo-Juárez, Patricia; Volkow-Fernández, Patricia; Velázquez-Meza, María Elena; Echániz-Aviles, Gabriela

2018-01-01

To describe the distribution of pneumococcal serotypes causing infectious diseases in patients with hematological malignancies and solid tumors and their antimicrobial susceptibility before and after introduction of pneumococcal conjugate vaccine (PCV7) in Mexico. Consecutive pneumococcal isolates from hospitalized patients from the SIREVA-network were serotyped using the Quellung reaction and antimicrobial susceptibility was performed using the broth microdilution method. A total of 175 pneumococcal isolates were recovered, 105 from patients with hematological malignancies and 70 with solid tumors. Serotypes 19A (22.7%), 19F (20.4%), and 35B (17.7%) were the most frequent isolates in the first group and serotypes 3 (27.2%) and 19A (28.6%) in the second group. No decreased susceptibility to beta-lactams or TMP/SMX was observed after introduction of PCV7. An increase in non-vaccine types is observed without significate changes in antimicrobial susceptibility after introduction of PCV7.

T-cell and natural killer cell therapies for hematologic malignancies after hematopoietic stem cell transplantation: enhancing the graft-versus-leukemia effect

PubMed Central

Cruz, C. Russell; Bollard, Catherine M.

2015-01-01

Hematopoietic stem cell transplantation has revolutionized the treatment of hematologic malignancies, but infection, graft-versus-host disease and relapse are still important problems. Calcineurin inhibitors, T-cell depletion strategies, and immunomodulators have helped to prevent graft-versus-host disease, but have a negative impact on the graft-versus-leukemia effect. T cells and natural killer cells are both thought to be important in the graft-versus-leukemia effect, and both cell types are amenable to ex vivo manipulation and clinical manufacture, making them versatile immunotherapeutics. We provide an overview of these immunotherapeutic strategies following hematopoietic stem cell transplantation, with discussions centered on natural killer and T-cell biology. We discuss the contributions of each cell type to graft-versus-leukemia effects, as well as the current research directions in the field as related to adoptive cell therapy after hematopoietic stem cell transplantation. PMID:26034113

Rare incidence of tumor lysis syndrome in metastatic prostate cancer following treatment with docetaxel.

PubMed

Bhardwaj, Sharonlin; Varma, Seema

2018-03-01

Tumor lysis syndrome is a serious and sometimes lethal complication of cancer treatment that is comprised of a set of metabolic disturbances along with clinical manifestations. Initiating chemotherapy in bulky, rapidly proliferating tumors causes rapid cell turnover that in turn releases metabolites into circulation that give rise to metabolic derangements that can be dangerous. This syndrome is usually seen in high-grade hematological malignancies. Less commonly, tumor lysis syndrome can present in solid tumors and even rarely in genitourinary tumors. In this report, the authors describe a specific case of tumor lysis syndrome in a patient with metastatic prostate cancer following treatment with docetaxel.

Room contamination, patient colonization pressure, and the risk of vancomycin-resistant Enterococcus colonization on a unit dedicated to the treatment of hematologic malignancies and hematopoietic stem cell transplantation.

PubMed

Ford, Clyde D; Lopansri, Bert K; Gazdik, Michaela A; Webb, Brandon; Snow, Gregory L; Hoda, Daanish; Adams, Barbara; Petersen, Finn Bo

2016-10-01

Contaminated surfaces and colonization pressure are risk factors for vancomycin-resistant Enterococcus (VRE) colonization in intensive care units (ICUs). Whether these apply to modern units dedicated to the care of hematologic malignancies and hematopoietic stem cell transplant (HSCT) procedures is unknown. We reviewed the records of 780 consecutive admissions for acute leukemia, autologous HSCT, or allogeneic HSCT in which the patient was at risk for hospital-acquired VRE and underwent weekly surveillance. We also obtained staff and room cultures, observed staff behavior, and performed VRE molecular strain typing on selected isolates. The overall rate of VRE colonization was 11.4 cases/1,000 patient days. Cultures of room surfaces revealed VRE isolates in 10% of terminally cleaned rooms. A prior VRE-colonized room occupant did not increase risk, and paired isolates from 20 patients and prior occupants were indistinguishable on molecular typing in only 1 pair. VRE colonization pressure was significantly associated with acquisition. Cultures of unit personnel and shared equipment were negative except for weighing scales. Observation of unit clinical personnel showed high compliance for hand sanitation and but less so for gowns. Conversely, ancillary staff showed poor compliance. Transmission of VRE from room surfaces seems to be an infrequent event. Encouraging adherence to surveillance, disinfection, and contact isolation protocols may decrease VRE colonization rates. Copyright © 2016. Published by Elsevier Inc.

Post-marketing surveillance of thrombomodulin alfa, a novel treatment of disseminated intravascular coagulation - safety and efficacy in 1,032 patients with hematologic malignancy.

PubMed

Asakura, Hidesaku; Takahashi, Hoyu; Tsuji, Hajime; Matsushita, Tadashi; Ninomiya, Hideyuki; Honda, Goichi; Mimuro, Jun; Eguchi, Yutaka; Kitajima, Isao; Sakata, Yoichi

2014-03-01

Post-marketing surveillance of thrombomodulin alfa (TM-α) was performed to evaluate safety and efficacy in patients with disseminated intravascular coagulation (DIC) with hematologic malignancy. All patients treated with TM-α from May 2008 to April 2010 in Japan were included. Information about baseline characteristics, safety, and efficacy were collected. The DIC resolution rate, survival rate on Day 28 after the last TM-α administration, and changes in DIC score and coagulation tests were evaluated. The underlying diseases associated with DIC were acute myeloid leukemia (except for acute promyelocytic leukemia, n=350), lymphoma (n=199), acute promyelocytic leukemia (n=172), acute lymphoblastic leukemia (n=156), myelodysplastic syndromes (n=61), and other (n=94). The incidence rates of bleeding-related adverse events and adverse drug reactions were 17.8% and 4.6%, respectively. In subjects with bleeding symptoms at baseline, 55.0% were assessed as disappeared or improved based on symptoms after TM-α treatment. The DIC resolution and survival rates were 55.9% and 70.7%, respectively. The DIC score and coagulation tests including thrombin-antithrombin complex (TAT) were significantly improved. Coagulation tests were significantly improved after TM-α treatment even in subjects whose clinical course of underlying disease was assessed as unchanged or exacerbated. This surveillance confirmed the safety and efficacy of TM-α in clinical practice, thus TM-α may be an ideal treatment for patients with DIC based upon hematologic malignancy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study.

PubMed

Libert, Yves; Borghgraef, Cindy; Beguin, Yves; Delvaux, Nicole; Devos, Martine; Doyen, Chantal; Dubruille, Stéphanie; Etienne, Anne-Marie; Liénard, Aurore; Merckaert, Isabelle; Reynaert, Christine; Slachmuylder, Jean-Louis; Straetmans, Nicole; Van Den Neste, Eric; Bron, Dominique; Razavi, Darius

2017-12-01

Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy. We assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non-novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail-Making, Digit Span and FCSR-IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT-Cog questionnaire. In novel and non-novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non-novel context. Older, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non-novel contexts. Copyright © 2017 John Wiley & Sons, Ltd.

Chemotherapy and Cardiotoxicity in Hematologic Malignancies.

PubMed

Stellitano, Antonio; Fedele, Roberta; Barilla, Santina; Iaria, Antonino; Rao, Carmelo Massimiliano; Martino, Massimo

2017-01-01

Antineoplastic agents affect the cardiovascular system, and the incidence of cardiotoxicity is continuously growing in patients with hematologic malignancies and treated with antineoplastic therapy. In this mini-review, we analyzed existing literature which evaluates the likelihood of cardiotoxicity related to the main agents employed in the treatment of hematologic malignancies. There is a significant need to optimize the early identification of patients who are at risk of cardiotoxicity. The conventional echocardiographic measurements used to detect cardiac alterations, such as LVEF, fractional shortening, diameters and volumes, allow only a late diagnosis of cardiac dysfunction, which might be already irreversible. The early identification of patients at risk for rapid progression towards irreversible cardiac failure has a primary purpose, the opportunity for them to benefit from early preventive and therapeutic measures. A useful imaging technique that points in this direction detecting subclinical LVD may be the speckle tracking echocardiography, that has demonstrated a previous detection of myocardial contractile dysfunction compared to the traditional left ventricular ejection fraction. In this view, the discovery of new biomarkers to identify patients at a high risk for the development of these complications is another priority. Cardiotoxicity induced by anticancer drugs is always the outcome of several concurrent factors. It is plausible that an asymptomatic dysfunction precedes clinical events. During this asymptomatic phase, an early treatment prepares the patient for cardiovascular "safety" conditions; on the other hand, a late or missing treatment paves the ground for the development of future cardiac events. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Efficacy of Oral Cryotherapy on Oral Mucositis Prevention in Patients with Hematological Malignancies Undergoing Hematopoietic Stem Cell Transplantation: A Meta-Analysis of Randomized Controlled Trials

PubMed Central

Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

2015-01-01

Objectives Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. Methods PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Results Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Conclusions Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT. PMID:26024220

Potent Activity of Ponatinib (AP24534) in Models of FLT3-Driven Acute Myeloid Leukemia and Other Hematologic Malignancies

PubMed Central

Gozgit, Joseph M.; Wong, Matthew J.; Wardwell, Scott; Tyner, Jeffrey W.; Loriaux, Marc M.; Mohemmad, Qurish K.; Narasimhan, Narayana I.; Shakespeare, William C.; Wang, Frank; Druker, Brian J.; Clackson, Tim; Rivera, Victor M.

2011-01-01

Ponatinib (AP24534) is a novel multitargeted kinase inhibitor that potently inhibits native and mutant BCR-ABL at clinically achievable drug levels. Ponatinib also has in vitro inhibitory activity against a discrete set of kinases implicated in the pathogenesis of other hematologic malignancies, including FLT3, KIT, fibroblast growth factor receptor 1 (FGFR1), and platelet derived growth factor receptor α (PDGFRα). Here, using leukemic cell lines containing activated forms of each of these receptors, we show that ponatinib potently inhibits receptor phosphorylation and cellular proliferation with IC50 values comparable to those required for inhibition of BCR-ABL (0.3 to 20 nmol/L). The activity of ponatinib against the FLT3-ITD mutant, found in up to 30% of acute myeloid leukemia (AML) patients, was particularly notable. In MV4-11 (FLT3-ITD+/+) but not RS4;11 (FLT3-ITD−/−) AML cells, ponatinib inhibited FLT3 signaling and induced apoptosis at concentrations of less than 10 nmol/L. In an MV4-11 mouse xenograft model, once daily oral dosing of ponatinib led to a dose-dependent inhibition of signaling and tumor regression. Ponatinib inhibited viability of primary leukemic blasts from a FLT3-ITD positive AML patient (IC50 4 nmol/L) but not those isolated from 3 patients with AML expressing native FLT3. Overall, these results support the investigation of ponatinib in patients with FLT3-ITD–driven AML and other hematologic malignancies driven by KIT, FGFR1, or PDGFRα. PMID:21482694

Efficacy of oral cryotherapy on oral mucositis prevention in patients with hematological malignancies undergoing hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials.

PubMed

Wang, Li; Gu, Zhenyang; Zhai, Ruiren; Zhao, Shasha; Luo, Lan; Li, Dandan; Zhao, Xiaoli; Wei, Huaping; Pang, Zhaoxia; Wang, Lili; Liu, Daihong; Wang, Quanshun; Gao, Chunji

2015-01-01

Controversy exists regarding whether oral cryotherapy can prevent oral mucositis (OM) in patients with hematological malignancies undergoing hematopoietic stem cell transplantation (HSCT). The aim of the present meta-analysis was to evaluate the efficacy of oral cryotherapy for OM prevention in patients with hematological malignancies undergoing HSCT. PubMed and the Cochrane Library were searched through October 2014. Randomized controlled trials (RCTs) comparing the effect of oral cryotherapy with no treatment or with other interventions for OM in patients undergoing HSCT were included. The primary outcomes were the incidence, severity, and duration of OM. The secondary outcomes included length of analgesic use, total parenteral nutrition (TPN) use, and length of hospital stay. Seven RCTs involving eight articles analyzing 458 patients were included. Oral cryotherapy significantly decreased the incidence of severe OM (RR = 0.52, 95% CI = 0.27 to 0.99) and OM severity (SMD = -2.07, 95% CI = -3.90 to -0.25). In addition, the duration of TPN use and the length of hospitalization were markedly reduced (SMD = -0.56, 95% CI = -0.92 to -0.19; SMD = -0.44, 95% CI = -0.76 to -0.13; respectively). However, the pooled results were uncertain for the duration of OM and analgesic use (SMD = -0.13, 95% CI = -0.41 to 0.15; SMD = -1.15, 95% CI = -2.57 to 0.27; respectively). Oral cryotherapy is a readily applicable and cost-effective prophylaxis for OM in patients undergoing HSCT.

[Constitutional mismatch repair-deficiency syndrome (CMMR-D) - a case report of a family with biallelic MSH6 mutation].

PubMed

Ilenčíková, D

2012-01-01

This work gives comprehensive information about new recessively inherited syndrome characterized by development of childhood malignancies. Behind this new described syndrome, called Constitutional mismatch repair-deficiency syndrome (CMMR-D), there are biallelic mutations in genes, which cause adult cancer syndrom termed Lynch syndrom (Hereditary non-polyposis cancer syndrom-HNPCC) if they are heterozygous mutations. Biallelic germline mutations of genes MLH1, MSH2, MSH6 and PMS2 in CMMR-D are characterized by increased risk of hematological malignancies, atypical brain tumors and early onset of colorectal cancers. An accompanying manifestation of the disease are skin spots with diffuse margins and irregular pigmentation reminiscent of Café au lait spots of NF1. This paper reports a case of a family with CMMR-D caused by novel homozygous MSH6 mutations leading to gliomatosis cerebri, T-ALL in an 11-year-old female and glioblastoma multiforme in her 10-year-old brother, both with rapid progression of the diseases. A literature review of brain tumors in CMMR-D families shows that they are treatment-resistant and lead to early death. Therefore, this work highlights the importance of early identification of patients with CMMR-D syndrome - in terms of initiation of a screening program for early detection of malignancies as well as early surgical intervention.

Case Report of Myeloid Sarcoma Masquerading as In-Transit Metastasis at a Previous Melanoma Site: Avoiding a Diagnostic Pitfall.

PubMed

Curry, Jonathan L; Tetzlaff, Michael T; Wang, Sa A; Landon, Gene; Alouch, Nail; Patel, Sapna P; Nagarajan, Priyadharsini; Gupta, Shiva; Aung, Phyu P; Devine, Catherine E; Khoury, Joseph D; Loghavi, Sanam; Prieto, Victor G; DiNardo, Courtney D; Gershenwald, Jeffrey E

2018-06-01

Myeloid sarcoma is a rare extramedullary hematologic malignancy. Accurate and timely diagnosis may be challenging because myeloid sarcoma is known to mimic solid tumors, including hepatobiliary, nasopharyngeal, and breast carcinomas. We report a case of myeloid sarcoma that developed in the primary tumor lymphatic drainage field of a previously treated intermediate-thickness cutaneous melanoma, clinically and radiographically mimicking an in-transit metastasis, in a patient with myelodysplastic syndrome. The diagnosis of myeloid sarcoma was achieved after surgical excision of the mass and pathological examination that included extensive immunohistochemical studies. Awareness of such an unusual clinical presentation can help reduce diagnostic delay and ensure that adequate tissue is obtained for pathological examination and ancillary studies that are critical for accurate diagnosis and appropriate patient management.

Inflammatory fibrous histiocytoma presenting leukemoid reaction.

PubMed

Takahashi, K; Kimura, Y; Naito, M; Yoshimura, T; Uchida, H; Araki, S

1989-05-01

A case of inflammatory fibrous histiocytoma presenting leukemoid reaction is reported. A tumor had developed at the right scapular region 10 years ago and recurred twice with fever and leukocytosis, and finally with leukemoid reaction. Besides the histopathological features typical of malignant fibrous histiocytoma, this tumor showed prominent and diffuse infiltration of neutrophilic leukocytes. Hematologic examination of the bone marrow aspirates disclosed myeloid hyperplasia. Bacteriological examination revealed no pathogenic microorganisms in the tumor tissue. Chemotactic activity of the neutrophilic leukocytes was demonstrated in the extract obtained from the tumor, and subcutaneous injection of the extract into rats induced myeloid hyperplasia in the bone marrow and neutrophil infiltration in the liver and spleen of the animals. These results suggest the possibility of the case as a colony-stimulating factor-producing tumor.

Listeria monocytogenes meningitis in an immunocompromised patient.

PubMed

Barocci, Simone; Mancini, Alessio; Canovari, Benedetta; Petrelli, Enzo; Sbriscia-Fioretti, Emanuela; Licci, Alberto; D'Addesa, Simona; Petrini, Giancarlo; Giacomini, Marinella; Renzi, Antonella; Migali, Antonio; Briscolini, Sara

2015-01-01

This report describes a case of meningitis caused by Listeria monocytogenes in a stem cell transplant recipient on immunosuppressive therapy for cutaneous chronic graft-versus host disease. A 59-year-old woman had undergone allogeneic stem cell transplantation (from a matched unrelated donor) 13 months previously for chronic lymphocytic leukemia. She was on regular hematologic follow-up. Though her previous malignancy has been in remission, she was immunosuppressed due to the pharmacological treatment. We describe a meningitis caused by a typical food-borne pathogen, dangerous in patients with impaired cell-mediated immunity. Moreover the bacterium had a multidrug resistance, a rare characteristic in clinical listeriosis. Rapid diagnosis and treatment are key factors in these cases. We chose ampicillin and rifampicin that allowed a complete resolution of the clinical manifestations.

Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia

ClinicalTrials.gov

2012-11-07

Acute Myeloid Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Follicular Lymphoma; Multiple Myeloma; NHL; Myeloproliferative Diseases; Chronic Myeloid Leukemia; Renal Cell Carcinoma; Aplastic Anemia

A Pilot Study Treatment of Malignant Tumors Using [18F] Fluorodeoxyglucose (FDG)

ClinicalTrials.gov

2018-05-08

Radiosensitive Stage IV Solid and Hematological Tumors With High FDG Uptake Not Responding to Standard of Care; Lung Cancer, Head and Neck Cancer, Breast Cancer, Gastric Cancer, Pancreatic Cancer, Colon Cancer, Lymphomas, Sarcomas, Etc

The incidence of hematological neoplasms morbidity on radiation-contaminated territories in Cherkasy region.

PubMed

Paramonov, V V

2017-12-01

The main goal was to analyze the incidence of the morbidity in 1980, 1989, 2001, 2014 years and the structures of the absolute number of hematopoietic and lymphoid neoplasms cases during the period 1980-2014 on radiation contaminated and not contaminated territories in Cherkasy region. The epidemiological indecies of hematological neoplasms were analyzed on radiation con taminated and not contaminated territories in Cherkasy region during the period from 1980 to 2014. Referring the territory in Cherkasy region to radiation contaminated is based on settlements dosimetry certification of Ukraine after the Chornobyl accident. 63 settlements were enrolled to radiation contaminated areas in Cherkasy region and 11 settlements assigned as not contaminated areas. The first positions in the list of the hematological neoplasms structure and frequency among new cases during 1980-2014 on not contaminated territories in Cherkasy region occupied by lymphoid leukemia, Hodgkin's lymphoma and myeloid leukemia and on the radiation contaminated territories - chronic, acute lymphoid and myeloid leukemia and lymphoma, diffuse large cell lymphoma. In the structure of hematological neoplasms record ed on the contaminated territories in Cherkasy region, there is a smaller proportion of Hodgkin's lymphoma cases (C81) than 0.84 fold (RR = 0.84; 95 % CI = 0.75-0.93) and more than 1.15 times (RR = 1.15; 95 % CI = 1.02-1.30) other unspecified malignant lymphoid and hematopoietic neoplasms. In 2001 on the radiation contaminated terri tories in Cherkasy region increase the incidence of acute and chronic myeloid leukemia in 2.46 times (p = 0.024) observed compared to non contaminated areas there (5.30 per 100 000, 95% CI = 3.03-8.33 versus 2.15 per 100,000, 95 % CI = 0.66-3.64). It was calculated that RR of acute and chronic myeloid leukemia (C92) in 2001 on radiation contaminated areas in Cherkasy region is 1.40 (95 % CI = 1.12-1.17) and Hodgkin's lymphoma (C81) on condition ally clean areas Cherkasy region - 1.70 (95 % CI = 1.36-2.12). V. V. Paramonov.

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

PubMed

Kindwall-Keller, Tamila L; Ballen, Karen K

2017-09-01

Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic stem cell transplant will have a donor. © AlphaMed Press 2017.

Risk of Hematologic Malignancies After Radioiodine Treatment of Well-Differentiated Thyroid Cancer.

PubMed

Molenaar, Remco J; Sidana, Surbhi; Radivoyevitch, Tomas; Advani, Anjali S; Gerds, Aaron T; Carraway, Hetty E; Angelini, Dana; Kalaycio, Matt; Nazha, Aziz; Adelstein, David J; Nasr, Christian; Maciejewski, Jaroslaw P; Majhail, Navneet S; Sekeres, Mikkael A; Mukherjee, Sudipto

2017-12-18

Purpose To investigate the risk and outcomes of second hematologic malignancies (SHMs) in a population-based cohort of patients with well-differentiated thyroid cancer (WDTC) treated or not with radioactive iodine (RAI). Methods Patients with WDTC were identified from SEER registries. Competing risk regression analysis was performed to calculate the risks of SHMs that occurred after WDTC treatment and outcomes after SHM development were assessed. Results Of 148,215 patients with WDTC, 53% received surgery alone and 47% received RAI. In total, 783 patients developed an SHM after a median interval of 6.5 years (interquartile range, 3.3 to 11.2 years) from WDTC diagnosis. In multivariable analysis, compared with those undergoing thyroidectomy alone, RAI treatment was associated with an increased early risk of developing acute myeloid leukemia (AML; hazard ratio, 1.79; 95% CI, 1.13 to 2.82; P = .01) and chronic myeloid leukemia (CML; hazard ratio, 3.44; 95% CI, 1.87 to 6.36; P < .001). This increased risk of AML and CML after RAI treatment was seen even in low-risk and intermediate-risk WDTC tumors. Occurrence of AML but not CML in patients with WDTC was associated with shorter median overall survival compared with matched controls (8.0 years v 31.0 years; P = .001). In addition, AML developing after RAI trended toward inferior survival compared with matched controls with de novo AML (median overall survival, 1.2 years v 2.9 years; P = .06). Conclusion Patients with WDTC treated with RAI had an increased early risk of developing AML and CML but no other hematologic malignancies. AML that arises after RAI treatment has a poor prognosis. RAI use in patients with WDTC should be limited to patients with high-risk disease features, and patients with WDTC treated with adjuvant RAI should be monitored for myeloid malignancies as part of cancer surveillance.

Microenvironmental oxygen partial pressure in acute myeloid leukemia: Is there really a role for hypoxia?

PubMed

Rieger, Christina T; Fiegl, Michael

2016-07-01

Reduced oxygen partial pressure (pO2) has been recognized as being relevant in hematopoiesis and the pathophysiology of malignant diseases. Although hypoxic (meaning insufficient supply of oxygen) and anoxic areas are present and of pathophysiologic importance (by hypoxia-induced pathways such as HiF1α) in solid tumors, this may not be true for (malignant) hematologic cells. Hematopoiesis occurs in the stem cell niche, which is characterized, among other things, by extremely low pO2. However, in contrast to solid tumors, in this context, the low pO2 is physiological and this feature, among others, is shared by the malignant stem cell niche harboring leukemia-initiating cells. Upon differentiation, hematopoietic cells are constantly exposed to changes in pO2 as they travel throughout the human body and encounter arterial and venous blood and migrate into oxygen-carrier-free tissue with low pO2. Hematologic malignancies such as acute myeloid leukemia (AML) make little difference in this respect and, whereas low oxygen is the usual environment of AML cells, recent evidence suggests no role for real hypoxia. Although there is no evidence that AML pathophysiology is related to hypoxia, leukemic blasts still show several distinct biological features when exposed to reduced pO2: they down- or upregulate membrane receptors such as CXCR4 or FLT3, activate or inhibit intracellular signaling pathways such as PI3K, and specifically secrete cytokines (IL-8). In summary, reduced pO2 should not be mistaken for hypoxia (nor should it be so called), and it does not automatically induce hypoxia-response mechanisms; therefore, a strict distinction should be made between physiologically low pO2 (physoxia) and hypoxia. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

Compatibility of Biosimilar Filgrastim with Cytotoxic Chemotherapy during the Treatment of Malignant Diseases (VENICE): A Prospective, Multicenter, Non-Interventional, Longitudinal Study.

PubMed

Fruehauf, Stefan; Otremba, Burkhard; Stötzer, Oliver; Rudolph, Christine

2016-11-01

Febrile neutropenia (FN) is a serious and frequent complication of cytotoxic chemotherapy. Biosimilar filgrastim (Nivestim™, Hospira Inc, A Pfizer Company, Lake Forest, IL, USA) is a granulocyte-colony stimulating factor licensed for the treatment of neutropenia and FN induced by myelosuppressive chemotherapy. The primary goal of this VENICE study (ClinicalTrials.gov identifier, NCT01627990) was to observe the tolerability, safety and efficacy of biosimilar filgrastim in patients receiving cancer chemotherapy. This was a prospective, multicenter, non-interventional, longitudinal study. Consenting adult patients with solid tumors or hematologic malignancies for whom cytotoxic chemotherapy and treatment with biosimilar filgrastim was planned were enrolled. Among the enrolled patients (N = 386), 81% were female, with a median age (range) of 61 (22-92) years, with 39% >65 years old. Most patients (n = 338; 88%) had solid tumors and the remainder (n = 49; 13%) had hematological malignancies. The majority of the patients (64%) received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis. At the follow-up visits, for the majority of patients (95.6%) there had been no change in chemotherapy dose due to FN. For two patients (0.5%) the chemotherapy was discontinued due to FN and for four patients (1.0%) the chemotherapy dose was reduced due to FN. For the majority of patients (96.9%) the chemotherapy cycle following the first biosimilar filgrastim treatment was not delayed due to FN. For 3 patients (0.8%), the chemotherapy was delayed following the first biosimilar filgrastim treatment. Less than one-third (29.8%) of the patients experienced ≥1 adverse event that was at least potentially related to biosimilar filgrastim treatment. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic setting in patients undergoing chemotherapy for solid tumors and hematological malignancies. ClinicalTrials.gov identifier, NCT01627990. Hospira Inc, A Pfizer Company, Lake Forest, IL, USA.

Ex vivo T-cell-depleted allogeneic stem cell transplantation for hematologic malignancies: The search for an optimum transplant T-cell dose and T-cell add-back strategy.

PubMed

Anandi, Prathima; Tian, Xin; Ito, Sawa; Muranski, Pawel; Chokshi, Puja D; Watters, Noelle; Chawla, Upneet; Hensel, Nancy; Stroncek, David F; Battiwalla, Minoo; Barrett, A John

2017-06-01

T-cell depletion (TCD) of allogeneic stem cell transplants (SCT) can reduce graft-versus-host disease but may negatively affect transplant outcome by delaying immune recovery. To optimize TCD in HLA-matched siblings with hematologic malignancies, we explored varying the transplant CD3+ T-cell dose between 2 and 50 × 10 4 /kg (corresponding to 3-4 log depletion) and studied the impact of 0-6 × 10 7 /kg CD3+ donor lymphocyte infusion (DLI) "add-back" on immune recovery post-SCT. Two hundred seventeen consecutive patients (age range, 10-75 years) with hematologic malignancy (excluding chronic leukemias) underwent ex vivo TCD SCT from HLA-identical sibling donors from 1994-2015. Ninety-four patients had standard-risk disease (first remission acute leukemia [AL] and early stage myelodysplastic syndromes [MDS]) and 123 had high-risk disease (AL beyond first complete remission, advanced MDS or refractory B-cell malignancy). Median follow-up was 8.5 years. At 20 years post-SCT, overall survival (OS) was 40%, nonrelapse mortality (NRM) was 27% and relapse incidence was 39%. Factors affecting outcome in multivariate analysis were transplantation era, with OS increasing from 38% in the period 1994-2000 to 58% in 2011-2015, disease risk (hazard ratio [HR], 1.68 for high risk) and increasing age (HR, 1.19 per decade). Neither the T-cell dose or the add back of T cells in the first 100 days had any effect on OS, NRM and relapse. Outcomes for TCD SCT have greatly improved. However, our data do not support the need to precisely manipulate transplant CD3+ T-cell dose provided at least 3-log depletion is achieved or the use of T-cell add-back. Future improvements for TCD SCT await better strategies to prevent relapse, especially in high-risk recipients. Published by Elsevier Inc.

[Results of a post-marketing surveillance of meropenem for febrile neutropenia].

PubMed

Wakisaka, Koji; Tani, Shunsuke; Ishibashi, Kazuo; Nukui, Kazuhiko; Nagao, Munehiko

2015-08-01

The post-marketing surveillance of meropenem (Meropen) for febrile neutropenia (FN) was conducted between July 2010 and June 2012 to evaluate safety and efficacy under actual clinical use. There were 1191 and 1124 evaluable cases for safety and efficacy respectively, of 1207 case cards collected from 180 institutions. In safety analysis, the incidence of adverse drug reactions (ADRs) associated with use of meropenem (including abnormal laboratory findings) was 15.7% (187/1191 cases), and the main ADRs were alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hepatic function abnormal, and liver disorder, which were similar to these observed in the clinical study for FN or post marketing surveillances of meropenem conducted before. In efficacy analysis, the overall efficacy was 81.8% (919/1124 cases). Also, it was 79.2% (708/894 cases) for hematological malignancy and 91.8% (213/232 cases) for solid cancer. These results confirmed meropenem (Meropen) is one of the well-tolerated and potent antimicrobial agents for febrile neutropenia.

Age-related mutations associated with clonal hematopoietic expansion and malignancies.

PubMed

Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D; Johnson, Kimberly J; Wendl, Michael C; McMichael, Joshua F; Schmidt, Heather K; Yellapantula, Venkata; Miller, Christopher A; Ozenberger, Bradley A; Welch, John S; Link, Daniel C; Walter, Matthew J; Mardis, Elaine R; Dipersio, John F; Chen, Feng; Wilson, Richard K; Ley, Timothy J; Ding, Li

2014-12-01

Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. The Cancer Genome Atlas (TCGA) provides a unique resource for comprehensive discovery of mutations and genes in blood that may contribute to the clonal expansion of hematopoietic stem/progenitor cells. Here, we analyzed blood-derived sequence data from 2,728 individuals from TCGA and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia and/or lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5-6% of people older than 70 years) contain mutations that may represent premalignant events that cause clonal hematopoietic expansion.

Reference method for detection of Pgp mediated multidrug resistance in human hematological malignancies: a method validated by the laboratories of the French Drug Resistance Network.

PubMed

Huet, S; Marie, J P; Gualde, N; Robert, J

1998-12-15

Multidrug resistance (MDR) associated with overexpression of the MDR1 gene and of its product, P-glycoprotein (Pgp), plays an important role in limiting cancer treatment efficacy. Many studies have investigated Pgp expression in clinical samples of hematological malignancies but failed to give definitive conclusion on its usefulness. One convenient method for fluorescent detection of Pgp in malignant cells is flow cytometry which however gives variable results from a laboratory to another one, partly due to the lack of a reference method rigorously tested. The purpose of this technical note is to describe each step of a reference flow cytometric method. The guidelines for sample handling, staining and analysis have been established both for Pgp detection with monoclonal antibodies directed against extracellular epitopes (MRK16, UIC2 and 4E3), and for Pgp functional activity measurement with Rhodamine 123 as a fluorescent probe. Both methods have been validated on cultured cell lines and clinical samples by 12 laboratories of the French Drug Resistance Network. This cross-validated multicentric study points out crucial steps for the accuracy and reproducibility of the results, like cell viability, data analysis and expression.

EuroFlow antibody panels for standardized n-dimensional flow cytometric immunophenotyping of normal, reactive and malignant leukocytes

PubMed Central

van Dongen, J J M; Lhermitte, L; Böttcher, S; Almeida, J; van der Velden, V H J; Flores-Montero, J; Rawstron, A; Asnafi, V; Lécrevisse, Q; Lucio, P; Mejstrikova, E; Szczepański, T; Kalina, T; de Tute, R; Brüggemann, M; Sedek, L; Cullen, M; Langerak, A W; Mendonça, A; Macintyre, E; Martin-Ayuso, M; Hrusak, O; Vidriales, M B; Orfao, A

2012-01-01

Most consensus leukemia & lymphoma antibody panels consist of lists of markers based on expert opinions, but they have not been validated. Here we present the validated EuroFlow 8-color antibody panels for immunophenotyping of hematological malignancies. The single-tube screening panels and multi-tube classification panels fit into the EuroFlow diagnostic algorithm with entries defined by clinical and laboratory parameters. The panels were constructed in 2–7 sequential design–evaluation–redesign rounds, using novel Infinicyt software tools for multivariate data analysis. Two groups of markers are combined in each 8-color tube: (i) backbone markers to identify distinct cell populations in a sample, and (ii) markers for characterization of specific cell populations. In multi-tube panels, the backbone markers were optimally placed at the same fluorochrome position in every tube, to provide identical multidimensional localization of the target cell population(s). The characterization markers were positioned according to the diagnostic utility of the combined markers. Each proposed antibody combination was tested against reference databases of normal and malignant cells from healthy subjects and WHO-based disease entities, respectively. The EuroFlow studies resulted in validated and flexible 8-color antibody panels for multidimensional identification and characterization of normal and aberrant cells, optimally suited for immunophenotypic screening and classification of hematological malignancies. PMID:22552007

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

PubMed

Maserati, Emanuela; Aprili, Fiorenza; Vinante, Fabrizio; Locatelli, Franco; Amendola, Giovanni; Zatterale, Adriana; Milone, Giuseppe; Minelli, Antonella; Bernardi, Franca; Lo Curto, Francesco; Pasquali, Francesco

2002-01-01

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.

Results of Four-Year Rectal Vancomycin-Resistant Enterococci Surveillance in a Pediatric Hematology-Oncology Ward: From Colonization to Infection.

PubMed

Aktürk, Hacer; Sütçü, Murat; Somer, Ayper; Karaman, Serap; Acar, Manolya; Ünüvar, Ayşegül; Anak, Sema; Karakaş, Zeynep; Özdemir, Aslı; Sarsar, Kutay; Aydın, Derya; Salman, Nuran

2016-09-05

To investigate the clinical impact of vancomycin-resistant enterococci (VRE) colonization in patients with hematologic malignancies and associated risk factors. Patients colonized and infected with VRE were identified from an institutional surveillance database between January 2010 and December 2013. A retrospective case-control study was performed to identify the risk factors associated with development of VRE infection in VRE-colonized patients. Fecal VRE colonization was documented in 72 of 229 children (31.4%). Seven VRE-colonized patients developed subsequent systemic VRE infection (9.7%). Types of VRE infections included bacteremia (n=5), urinary tract infection (n=1), and meningitis (n=1). Enterococcus faecium was isolated in all VRE infections. Multivariate analysis revealed severe neutropenia and previous bacteremia with another pathogen as independent risk factors for VRE infection development in colonized patients [odds ratio (OR): 35.4, confidence interval (CI): 1.7-72.3, p=0.02 and OR: 20.6, CI: 1.3-48.6, p=0.03, respectively]. No deaths attributable to VRE occurred. VRE colonization has important consequences in pediatric cancer patients.

Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments.

PubMed

Horne, Gillian A; Copland, Mhairi

2017-05-01

Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia.

PubMed

Barwe, Sonali P; Quagliano, Anthony; Gopalakrishnapillai, Anilkumar

2017-04-01

Acute lymphoblastic leukemia (ALL) is a malignant hematological disease afflicting hematopoiesis in the bone marrow. While 80%-90% of patients diagnosed with ALL will achieve complete remission at some point during treatment, ALL is associated with high relapse rate, with a 5-year overall survival rate of 68%. The initial remission failure and the high rate of relapse can be attributed to intrinsic chemoprotective mechanisms that allow persistence of ALL cells despite therapy. These mechanisms are mediated, at least in part, through the engagement of cell adhesion molecules (CAMs) within the bone marrow microenvironment. This review assembles CAMs implicated in protection of leukemic cells from chemotherapy. Such studies are limited in ALL. Therefore, CAMs that are associated with poor outcomes or are overexpressed in ALL and have been shown to be involved in chemoprotection in other hematological cancers are also included. It is likely that these molecules play parallel roles in ALL because the CAMs identified to be a factor in ALL chemoresistance also work similarly in other hematological malignancies. We review the signaling mechanisms activated by the engagement of CAMs that provide protection from chemotherapy. Development of targeted therapies against CAMs could improve outcome and raise the overall cure rate in ALL. Copyright © 2017 Elsevier Inc. All rights reserved.

PET/CT in paediatric malignancies - An update

PubMed Central

Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga; Tewari, Anshu

2016-01-01

18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established imaging modality in adult oncological practice. Its role in childhood malignancies needs to be discussed as paediatric malignancies differ from adults in tumor subtypes and they have different tumor biology and FDG uptake patterns. This is also compounded by smaller body mass, dosimetric restrictions, and physiological factors that can affect the FDG uptake. It calls for careful planning of the PET study, preparing the child, the parents, and expertise of nuclear physicians in reporting pediatric positron emission tomography/computed tomography (PET/CT) studies. In a broad perspective, FDG-PET/CT has been used in staging, assessment of therapy response, identifying metastases and as a follow-up tool in a wide variety of pediatric malignancies. This review outlines the role of PET/CT in childhood malignancies other than hematological malignancies such as lymphoma and leukemia. PMID:27688605

Experimental Theileria lestoquardi infection in sheep: Biochemical and hematological changes.

PubMed

Yaghfoori, Saeed; Mohri, Mehrdad; Razmi, Gholamreza

2017-09-01

Malignant theileriosis (Theileria lestoquardi infection) is a hemoparasitic tick-borne disease that affects both wild and domestic small ruminants. The aim of this study was to evaluate biochemical and hematological characteristics of sheep after being experimentally infected by T. lestoquardi. T. lestoquardi infection was induced in seven Baluchi sheep of six-to-eight months old via experimentally-infected Hyalomma anatolicum adult ticks. Biochemical and hematological parameters were measured twice a week during the three weeks' post infection. Twenty-three biochemical analytes and seven hematological ones were measured. After three to four days infection, body temperature rose above 40 ° C. Maximum and minimum parasitaemia were 3.3% and 0.28%, respectively. Piroplasms and schizont were seen on average from days 7.2 and 4 post infection, respectively. The concentrations and activities of Alb, HDL, ALT, T3, T4, Ca, Fe, Mg, iP, WBC, RBC, PCV, Hb, Plt, neutrophil and lymphocytes significantly decreased (P≤0.05) during experimental infection. However, concentrations and activities of BT, GGT, Glu, BUN, Crea, FIB and Cu significantly increased (P≤0.05). There was no significant change in the serum amounts of Chol, LDL, TG, VLDL and Zn. The observed hypoalbuminemia and increase of FIB concentrations referred to pro-inflammatory cytokines production. Moreover, the raising of GGT activity indicates liver damage, cholestatic disorders or schizont infiltration. The disease stress and corticosteroids are suspected to cause the Glu concentration increase. The present study is aimed at improving the knowledge of malignant theileriosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of leukemias with ETV6-ABL1 fusion

PubMed Central

Zaliova, Marketa; Moorman, Anthony V.; Cazzaniga, Giovanni; Stanulla, Martin; Harvey, Richard C.; Roberts, Kathryn G.; Heatley, Sue L.; Loh, Mignon L.; Konopleva, Marina; Chen, I-Ming; Zimmermannova, Olga; Schwab, Claire; Smith, Owen; Mozziconacci, Marie-Joelle; Chabannon, Christian; Kim, Myungshin; Frederik Falkenburg, J. H.; Norton, Alice; Marshall, Karen; Haas, Oskar A.; Starkova, Julia; Stuchly, Jan; Hunger, Stephen P.; White, Deborah; Mullighan, Charles G.; Willman, Cheryl L.; Stary, Jan; Trka, Jan; Zuna, Jan

2016-01-01

To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with tyrosine kinase inhibitors should be considered for patients with this fusion. PMID:27229714

Factors Associated to Prevalence and Incidence of Carbapenem-Resistant Enterobacteriaceae Fecal Carriage: A Cohort Study in a Mexican Tertiary Care Hospital

PubMed Central

Torres-Gonzalez, Pedro; Cervera-Hernandez, Miguel Enrique; Niembro-Ortega, María Dolores; Leal-Vega, Francisco; Cruz-Hervert, Luis Pablo; García-García, Lourdes; Galindo-Fraga, Arturo; Martinez-Gamboa, Areli; Bobadilla-del Valle, Miriam; Sifuentes-Osornio, Jose; Ponce-de-Leon, Alfredo

2015-01-01

Background Carbapenem-resistant Enterobacteriaceae (CRE) infections have emerged as a serious threat to health worldwide. They are associated with increased morbidity and mortality and are capable of silently colonizing the gastrointestinal tract. Because of this, there is great interest to characterize the epidemiology of CRE carriage and acquisition in healthcare facilities. The aim of this study was to determine the prevalence and factors associated with CRE fecal carriage (CRE-fc), and risk factors for incident cases. Methods/Results A cohort study was conducted at a tertiary care hospital from January 1st to April 30th, 2014 during a CRE outbreak. Weekly rectal swabs were performed in patients considered at risk until discharge. CRE-fc prevalence was 10.9% (CI 95% 7.7–14.7) among 330 patients. Treatment with carbapenems (OR 2.54, CI 95% 1.15–5.62); transfer from an institution (OR 2.16, CI 95% 1.02–4.59); multi-drug resistant infection within the previous six months (OR 2.81, CI 95% 1.47–5.36); intensive care unit admission (OR 0.42, CI 95% 0.20–0.88); hematologic malignancy (OR 4.02, CI 95% 1.88–8.06); invasive procedures (OR 2.18, CI 95% 1.10–4.32); and sharing a room with a known CRE carrier (OR 3.0, CI 95% 1.43–6.31) were independently associated factors for CRE-fc. Risk factors associated with CRE-fc incidence were determined for 87 patients initially negative and with subsequent screening; the incidence rate was 2.5 cases, per 1000 person-years (CI 95% 1.5–3.9). Independently associated risk factors were carbapenem treatment (HR 2.68, CI 95% 1.03–6.98), hematologic malignancy (HR 5.74, 95% CI 2.46–13.4) and a mean daily colonization pressure ≥10% (HR 5.03, IC 95% 1.77–14.28). OXA-48-like (OXA-232) and CTX-M-15 were the predominantly identified mechanisms of resistance. Conclusions We found an elevated incidence and prevalence of CRE-fc in our hospital. Hematologic patients need to be considered a population at risk, and antibiotic stewardship along with infection control programs need to be improved to avoid nosocomial spread. PMID:26431402

Safety and Efficacy of BL-8040 for the Mobilization of Donor Hematopoietic Stem Cells and Allogeneic Transplantation in Patients With Advanced Hematological Malignancies

ClinicalTrials.gov

2018-05-09

Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelogenous Leukemia; Non-Hodgkin's Lymphoma; Non-Hodgkin Lymphoma; Hodgkin Disease; Hodgkins Disease; Hodgkin's Disease; Multiple Myeloma; Myelodysplastic Syndrome; Myeloproliferative Neoplasm

Management and cost analysis of cancer patients treated with G-CSF: a cohort study based on the French national healthcare insurance database.

PubMed

Tilleul, Patrick; Jacot, William; Emery, Corinne; Lafuma, Antoine; Gourmelen, Julie

2017-12-01

To describe the management and costs associated with G-CSF therapy in cancer patients in France. This study analyzed a representative random population sample from the French national healthcare insurance database, focusing on 1,612 patients with hematological or solid malignancies who were reimbursed in 2013 or 2014 for at least one G-CSF treatment dispensed in a retail pharmacy. Patient characteristics and treatment costs were analyzed according to the type of cancer. Then the costs and characteristics of patients associated with the use of different G-CSF products were analyzed in the sub-set of breast cancer patients. The most frequent malignancies in the database population were breast cancer (23.3%), hematological malignancies (22.2%), and lung cancer (12.4%). The reimbursed G-CSF was pegfilgrastim in 34.1% of cases, lenograstim in 26.7%, and filgrastim in 17.9%. More than one G-CSF product was reimbursed to 21.3% of patients. The total annual reimbursed health expenses per patient, according to the type of G-CSF, were €27,001, €24,511, and €20,802 for patients treated with filgrastim, lenograstim, and pegfilgrastim, respectively. Ambulatory care accounted for, respectively, 35%, 38%, and 41% of those costs. In patients with breast cancer, ambulatory care cost was €7,915 with filgrastim, €7,750 with lenograstim, and €6,989 with pegfilgrastim, and the respective cost of G-CSF was €1,733, €1,559, and €3,668. All available G-CSF products have been shown to be effective in cancer patients, and both daily G-CSFs and pegylated G-CSF are recommended in international guidelines. Nevertheless, this analysis of G-CSF reimbursement indicates that the choice of product can markedly affect the total cost of ambulatory care.

Ageing, exposure to pollution, and interactions between climate change and local seasons as oxidant conditions predicting incident hematologic malignancy at KINSHASA University clinics, Democratic Republic of CONGO (DRC).

PubMed

Nkanga, Mireille Solange Nganga; Longo-Mbenza, Benjamin; Adeniyi, Oladele Vincent; Ngwidiwo, Jacques Bikaula; Katawandja, Antoine Lufimbo; Kazadi, Paul Roger Beia; Nzonzila, Alain Nganga

2017-08-23

The global burden of hematologic malignancy (HM) is rapidly rising with aging, exposure to polluted environments, and global and local climate variability all being well-established conditions of oxidative stress. However, there is currently no information on the extent and predictors of HM at Kinshasa University Clinics (KUC), DR Congo (DRC). This study evaluated the impact of bio-clinical factors, exposure to polluted environments, and interactions between global climate changes (EL Nino and La Nina) and local climate (dry and rainy seasons) on the incidence of HM. This hospital-based prospective cohort study was conducted at Kinshasa University Clinics in DR Congo. A total of 105 black African adult patients with anaemia between 2009 and 2016 were included. HM was confirmed by morphological typing according to the French-American-British (FAB) Classification System. Gender, age, exposure to traffic pollution and garages/stations, global climate variability (El Nino and La Nina), and local climate (dry and rainy seasons) were potential independent variables to predict incident HM using Cox regression analysis and Kaplan Meier curves. Out of the total 105 patients, 63 experienced incident HM, with an incidence rate of 60%. After adjusting for gender, HIV/AIDS, and other bio-clinical factors, the most significant independent predictors of HM were age ≥ 55 years (HR = 2.4; 95% CI 1.4-4.3; P = 0.003), exposure to pollution and garages or stations (HR = 4.9; 95% CI 2-12.1; P < 0.001), combined local dry season + La Nina (HR = 4.6; 95%CI 1.8-11.8; P < 0.001), and combined local dry season + El Nino (HR = 4; 95% CI 1.6-9.7; P = 0.004). HM types included acute myeloid leukaemia (28.6% n = 18), multiple myeloma (22.2% n = 14), myelodysplastic syndromes (15.9% n = 10), chronic myeloid leukaemia (15.9% n = 10), chronic lymphoid leukaemia (9.5% n = 6), and acute lymphoid leukaemia (7.9% n = 5). After adjusting for confounders using Cox regression analysis, age ≥ 55 years, exposure to pollution, combined local dry season + La Nina and combined local dry season + El Nino were the most significant predictors of incident hematologic malignancy. These findings highlight the importance of aging, pollution, the dry season, El Nino and La Nina as related to global warming as determinants of hematologic malignancies among African patients from Kinshasa, DR Congo. Cancer registries in DRC and other African countries will provide more robust database for future researches on haematological malignancies in the region.

Escherichia coli pyomyositis in an immunocompromised host.

PubMed

Sharma, Umesh; Schwan, William R; Agger, William A

2011-08-01

Pyomyositis due to Escherichia coli (E. coil) is rarely reported in immunocompromised patients with hematological malignancy. We present a case report of a 34-year-old man who developed E. coli pyomyositis as a complication of acute myelogenous leukemia (AML). Magnetic resonance imaging (MRI) of the right hip suggested myofascial infection of the gluteal muscles, and a needle muscle aspiration grew E. coli phylogenetic group B2. The patient responded to intravenous piperacillin/tazobactam followed by prolonged oral levofloxacin. Pyomyositis should be suspected in all immunocompromised patients complaining of muscle pain and may exhibit signs of localized muscle infection. Appropriate antibiotic therapy targeting fluoroquinolone-resistant E. coli should be considered for initial empiric therapy of pyomyositis in immunocompromised patients.

ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies

PubMed Central

Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O.; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E.; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C.; Orlowski, Robert; Sarbassov, Dos D.; Lorenzi, Philip L.; Huang, Xuelin; Neelapu, Sattva S.; McDonnell, Timothy; Miranda, Roberto N.; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R. Eric.; Andreeff, Michael

2016-01-01

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. PMID:26884599

Low usage rate of banked sibling cord blood units in hematopoietic stem cell transplantation for children with hematological malignancies: implications for directed cord blood banking policies.

PubMed

Goussetis, Evgenios; Peristeri, Ioulia; Kitra, Vasiliki; Papassavas, Andreas C; Theodosaki, Maria; Petrakou, Eftichia; Spiropoulos, Antonia; Paisiou, Anna; Soldatou, Alexandra; Stavropoulos-Giokas, Catherine; Graphakos, Stelios

2011-02-15

Directed sibling cord blood banking is indicated in women delivering healthy babies who already have a sibling with a disease that is potentially treatable with an allogeneic cord blood transplant. We evaluated the effectiveness of a national directed cord blood banking program in sibling HLA-identical stem cell transplantation for hematological malignancies and the factors influencing the usage rate of the stored cord blood units. Fifty families were enrolled from which, 48 cord blood units were successfully collected and 2 collections failed due to damaged cord/placenta at delivery. Among enrolled families 4 children needed transplantation; however, only one was successfully transplanted using the collected cord blood unit containing 2×10(7) nucleated cells/kg in conjunction with a small volume of bone marrow from the same HLA-identical donor. Two children received grafts from matched unrelated donors because their sibling cord blood was HLA-haploidentical, while the fourth one received bone marrow from his HLA-identical brother, since cord blood could not be collected due to damaged cord/placenta at delivery. With a median follow-up of 6 years (range, 2-12) for the 9 remaining HLA-matched cord blood units, none from the prospective recipients needed transplantation. The low utilization rate of sibling cord blood in the setting of hematopoietic stem cell transplantation for pediatric hematological malignant diseases necessitates the development of directed cord blood banking programs that limit long-term storage for banked cord blood units with low probability of usage such as non-HLA-identical or identical to patients who are in long-term complete remission. Copyright © 2010 Elsevier Inc. All rights reserved.

Investigational Aurora A kinase inhibitor alisertib (MLN8237) as an enteric-coated tablet formulation in non-hematologic malignancies: Phase 1 dose-escalation study

PubMed Central

Falchook, Gerald; Kurzrock, Razelle; Gouw, Launce; Hong, David; McGregor, Kimberly A.; Zhou, Xiaofei; Shi, Hongliang; Fingert, Howard; Sharma, Sunil

2014-01-01

Background This phase 1b study evaluated an enteric-coated tablet (ECT) formulation of the investigational Aurora A kinase inhibitor, alisertib (MLN8237). Methods Patients with advanced, non-hematologic malignancies received oral alisertib ECT for 7 days BID followed by 14 days treatment-free (21-day cycles; 3+3 dose escalation schema). Objectives were to assess safety, pharmacokinetics, and antitumor activity, and to define a recommended phase 2 dose (RP2D) of alisertib. Results 24 patients were treated. Median age was 57 years. Patients received a median of 2 cycles (range 1–12). The RP2D was determined as 50 mg BID for 7 days (21-day cycles). A cycle 1 dose-limiting toxicity of grade 4 febrile neutropenia was observed in 1 of 13 patients at RP2D. The most common drug-related adverse event (AE) was neutropenia (50%). At doses ≥40 mg BID, 7 patients had drug-related AEs that were serious but largely reversible/manageable by dose reduction and supportive care, including 3 with febrile neutropenia. Pharmacokinetic data were available in 24 patients. Following administration of alisertib ECT, the plasma peak concentration of alisertib was achieved at ~3 h; systemic exposure increased with increasing dose over 10–60 mg BID. Mean t½ was ~21 h following multiple dosing. Renal clearance was negligible. Nine patients achieved stable disease (3.98*, 5.59, 1.28*, 2.56, 5.45*, 3.48, 3.15, 8.31, and 6.93* months; *censored). Conclusions Alisertib ECT was generally well tolerated in adults with advanced, non-hematologic malignancies. The RP2D is 50 mg BID for 7 days and is being evaluated in ongoing phase 2 studies. PMID:24879333

Anti-CD22 immunotoxin RFB4(dsFv)-PE38 (BL22) for CD22-positive hematologic malignancies of childhood: preclinical studies and phase I clinical trial.

PubMed

Wayne, Alan S; Kreitman, Robert J; Findley, Harry W; Lew, Glen; Delbrook, Cynthia; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Fitzgerald, David J; Pastan, Ira

2010-03-15

Although most children with B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma are cured, new agents are needed to overcome drug resistance and reduce toxicities of chemotherapy. We hypothesized that the novel anti-CD22 immunotoxin, RFB4(dsFv)-PE38 (BL22, CAT-3888), would be active and have limited nonspecific side effects in children with CD22-expressing hematologic malignancies. We conducted the first preclinical and phase I clinical studies of BL22 in that setting. Lymphoblasts from children with B-lineage ALL were assessed for CD22 expression by flow cytometry and for BL22 sensitivity by in vitro cytotoxicity assay. BL22 was evaluated in a human ALL murine xenograft model. A phase I clinical trial was conducted for pediatric subjects with CD22+ ALL and non-Hodgkin lymphoma. All samples screened were CD22+. BL22 was cytotoxic to blasts in vitro (median IC(50), 9.8 ng/mL) and prolonged the leukemia-free survival of murine xenografts. Phase I trial cohorts were treated at escalating doses and schedules ranging from 10 to 40 microg/kg every other day for three or six doses repeated every 21 or 28 days. Treatment was associated with an acceptable safety profile, adverse events were rapidly reversible, and no maximum tolerated dose was defined. Pharmacokinetics were influenced by disease burden consistent with rapid drug binding by CD22+ blasts. Although no responses were observed, transient clinical activity was seen in most subjects. CD22 represents an excellent target and anti-CD22 immunotoxins offer therapeutic promise in B-lineage hematologic malignancies of childhood.

Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy.

PubMed

Baldini, L; Guffanti, A; Cesana, B M; Colombi, M; Chiorboli, O; Damilano, I; Maiolo, A T

1996-02-01

The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenström macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow-up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low-risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.

Erythrocyte Osmotic Fragility Testing and the Prediction of Canine Malignant Hyperthermia Susceptibility

PubMed Central

Cribb, Peter H.; Olfert, Ernest A.; Reynolds, F. Barry

1986-01-01

A Doberman-German Shepherd cross-bred male dog, previously diagnosed as malignant hyperthermia susceptible, was mated to an unrelated nonsusceptible German Shepherd cross-bred female. The resultant litter was subjected to hematological, biochemical and erythrocyte osmotic fragility testing in an endeavor to predict the susceptibility of individuals to malignant hyperthermia. Laboratory evaluations were repeated at one year of age and the litter subjected to the halothane challenge test. No significant difference in erythrocyte osmotic fragility was found between malignant hyperthermia susceptible and nonsusceptible siblings at six weeks or at one year of age. Erythrocyte osmotic fragility, in both malignant hyperthermia susceptible and nonsusceptible animals, increased between six weeks and one year of age. Dantrolene sodium was an effective treatment for malignant hyperthermia in the dog when administered early in an episode and in adequate dosage. The initial sign of a malignant hyperthermia episode was a very rapid increase in end tidal partial pressure of carbon dioxide. This finding reinforces the value of capnographic monitoring in anesthesia. PMID:17422730

Characteristics Associated with In-Hospital Death among Commercially Insured Decedents with Cancer.

PubMed

Brooks, Gabriel A; Stuver, Sherri O; Zhang, Yichen; Gottsch, Stephanie; Fraile, Belen; McNiff, Kristen; Dodek, Anton; Jacobson, Joseph O

2017-01-01

A majority of patients with poor-prognosis cancer express a preference for in-home death; however, in-hospital deaths are common. We sought to identify characteristics associated with in-hospital death. Case series. Commercially insured patients with cancer who died between July 2010 and December 2013 and who had at least two outpatient visits at a tertiary cancer center during the last six months of life. Patient characteristics, healthcare utilization, and in-hospital death (primary outcome) were ascertained from institutional records and healthcare claims. Bivariate and multivariable analyses were used to evaluate the association of in-hospital death with patient characteristics and end-of-life outcome measures. We identified 904 decedents, with a median age of 59 years at death. In-hospital death was observed in 254 patients (28%), including 110 (12%) who died in an intensive care unit. Hematologic malignancy was associated with a 2.57 times increased risk of in-hospital death (95% confidence interval [CI] 1.91-3.45, p < 0.001), and nonenrollment in hospice was associated with a 14.5 times increased risk of in-hospital death (95% CI 9.81-21.4, p < 0.001). Time from cancer diagnosis to death was also associated with in-hospital death (p = 0.003), with the greatest risk among patients dying within six months of cancer diagnosis. All significant associations persisted in multivariable analyses that were adjusted for baseline characteristics. In-hospital deaths are common among commercially insured cancer patients. Patients with hematologic malignancy and patients who die without receiving hospice services have a substantially higher incidence of in-hospital death.

A French observational study describing the use of human polyvalent immunoglobulins in hematological malignancy-associated secondary immunodeficiency.

PubMed

Benbrahim, Omar; Viallard, Jean-François; Choquet, Sylvain; Royer, Bruno; Bauduer, Frédéric; Decaux, Olivier; Crave, Jean-Charles; Fardini, Yann; Clerson, Pierre; Levy, Vincent

2018-04-12

To describe the characteristics of patients suffering from secondary immunodeficiencies (SID) associated with hematological malignancies (HM), who started immunoglobulins replacement therapy (IgRT), physicians' expectations regarding IgRT and IgRT modalities. Non-interventional, prospective French cross-sectional study. The analysis included 231 patients (66±12 years old) suffering from multiple myeloma (MM) (N=64), chronic lymphoid leukemia (CLL) (N=84), aggressive non-Hodgkin B-cell lymphoma (aNHL) (N=32), indolent NHL (N=39), acute leukemia (N=6), Hodgkin disease (N=6). Of the HM, 47% were currently treated, 42% were relapsing or refractory, 23% of patients had received an autologous hematopoietic stem-cell transplant and 5% an allograft. Serum immunoglobulins trough levels in 195 individuals were less than 5g/L in 68.7% of cases. Most patients had a history of recurrent infections. Immunoglobulin dose was about 400 mg/kg/month. Half of patients started with subcutaneous infusion. When starting IgRT, physicians mainly expected to prevent severe and moderate infections. They also anticipated improvement in quality of life and survival which is beyond evidence-based medicine. NHL is a frequent condition motivating IgRT besides well recognized indications. Physicians mainly based the decision of starting IgRT on hypogammaglobulinemia and recurrence of infections but, irrespective of current recommendations, were also prepared to start IgRT prophylactically even in the absence of a history of infections. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction

PubMed Central

Özen, Mehmet; Yılmaz, Gülden; Coşkun, Belgin; Topçuoğlu, Pervin; Öztürk, Bengi; Gündüz, Mehmet; Atilla, Erden; Arslan, Önder; Özcan, Muhit; Demirer, Taner; İlhan, Osman; Konuk, Nahide; Balık, İsmail; Gürman, Günhan; Akan, Hamdi

2016-01-01

Objective: The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. Materials and Methods: Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. Results: There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. Conclusion: Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia. PMID:26376622

A Quasi-Experimental Study Analyzing the Effectiveness of Portable High-Efficiency Particulate Absorption Filters in Preventing Infections in Hematology Patients during Construction.

PubMed

Özen, Mehmet; Yılmaz, Gülden; Coşkun, Belgin; Topçuoğlu, Pervin; Öztürk, Bengi; Gündüz, Mehmet; Atilla, Erden; Arslan, Önder; Özcan, Muhit; Demirer, Taner; İlhan, Osman; Konuk, Nahide; Balık, İsmail; Gürman, Günhan; Akan, Hamdi

2016-03-05

The increased risk of infection for patients caused by construction and renovation near hematology inpatient clinics is a major concern. The use of high-efficiency particulate absorption (HEPA) filters can reduce the risk of infection. However, there is no standard protocol indicating the use of HEPA filters for patients with hematological malignancies, except for those who have undergone allogeneic hematopoietic stem cell transplantation. This quasi-experimental study was designed to measure the efficacy of HEPA filters in preventing infections during construction. Portable HEPA filters were placed in the rooms of patients undergoing treatment for hematological malignancies because of large-scale construction taking place near the hematology clinic. The rates of infection during the 6 months before and after the installation of the portable HEPA filters were compared. A total of 413 patients were treated during this 1-year period. There were no significant differences in the antifungal prophylaxis and treatment regimens between the groups. The rates of infections, clinically documented infections, and invasive fungal infections decreased in all of the patients following the installation of the HEPA filters. When analyzed separately, the rates of invasive fungal infections were similar before and after the installation of HEPA filters in patients who had no neutropenia or long neutropenia duration. HEPA filters were significantly protective against infection when installed in the rooms of patients with acute lymphocytic leukemia, patients who were undergoing consolidation treatment, and patients who were neutropenic for 1-14 days. Despite the advent of construction and the summer season, during which environmental Aspergillus contamination is more prevalent, no patient or patient subgroup experienced an increase in fungal infections following the installation of HEPA filters. The protective effect of HEPA filters against infection was more pronounced in patients with acute lymphocytic leukemia, patients undergoing consolidation therapy, and patients with moderate neutropenia.

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review

PubMed Central

Moloudizargari, Milad; Mortaz, Esmaeil; Asghari, Mohammad Hossein; Adcock, Ian M.; Redegeld, Frank A.; Garssen, Johan

2018-01-01

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo, following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens. PMID:29545942

Effects of the polyunsaturated fatty acids, EPA and DHA, on hematological malignancies: a systematic review.

PubMed

Moloudizargari, Milad; Mortaz, Esmaeil; Asghari, Mohammad Hossein; Adcock, Ian M; Redegeld, Frank A; Garssen, Johan

2018-02-20

Omega-3 polyunsaturated fatty acids (PUFAs) have well established anti-cancer properties. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are among this biologically active family of macromolecules for which various anti-cancer effects have been explained. These PUFAs have a high safety profile and can induce apoptosis and inhibit growth of cancer cells both in vitro and in vivo , following a partially selective manner. They also increase the efficacy of chemotherapeutic agents by increasing the sensitivity of different cell lines to specific anti-neoplastic drugs. Various mechanisms have been proposed for the anti-cancer effects of these omega-3 PUFAs; however, the exact mechanisms still remain unknown. While numerous studies have investigated the effects of DHA and EPA on solid tumors and the responsible mechanisms, there is no consensus regarding the effects and mechanisms of action of these two FAs in hematological malignancies. Here, we performed a systematic review of the beneficial effects of EPA and DHA on hematological cell lines as well as the findings of related in vivo studies and clinical trials. We summarize the key underlying mechanisms and the therapeutic potential of these PUFAs in the treatment of hematological cancers. Differential expression of apoptosis-regulating genes and Glutathione peroxidase 4 (Gp-x4), varying abilities of different cancerous and healthy cells to metabolize EPA into its more active metabolites and to uptake PUFAS are among the major factors that determine the sensitivity of cells to DHA and EPA. Considering the abundance of data on the safety of these FAs and their proven anti-cancer effects in hematological cell lines and the lack of related human studies, further research is warranted to find ways of exploiting the anticancer effects of DHA and EPA in clinical settings both in isolation and in combination with other therapeutic regimens.

Hematological aftermath of the radiation accident in Istanbul.

PubMed

Engin, Velittin Selcuk; Tufan, Fatih; Kalayoglu Besisik, Sevgi; Engin, Gulgun; Ozturk, Mustafa; Ersoy, Suleyman

2015-01-01

The effects of radiation exposure are long-lasting. Long-term monitoring is imperative to diagnose late effects and improve our far-sightedness about possible events in the future. A radiation accident occurred in Istanbul in 1998 that resulted in mild to moderate acute radiation syndrome (ARS). In this study we aimed to investigate the changes in hematological parameters at the long-term follow-up of ARS patients. Ten adults were hospitalized after exposure to a 60Co source. Seven were diagnosed as having ARS and had severe and symptomatic pancytopenia. All of the exposed people recovered following intensive treatment. Treatment was supportive with transfusion, granulocyte-colony stimulating factor, and anti- infective management covering antifungal agents. Patients were closely monitored. Nine years after the accident, the initial and follow-up complete blood count examinations and peripheral blood smears (PBS) were comparatively evaluated by an experienced hematologist. The hematological laboratory values of the patients on admission, after treatment, and nine years after the accident were documented and compared. Biodosimetric analysis revealed that whole-body doses ranged from 1-1.9 Gy. All subjects have shown complete recovery of the hematological laboratory values after treatment. All but one of the subjects showed complete blood cell recovery. The improvement of the blood cell count of the excepted patient stalled at a mildly reduced level and his bone marrow was still hypocellular nine years after the accident; however, no malignant changes were detected. Values at admission were significantly different compared with post treatment and present values of all patients. Post treatment and follow-up values were similar. One of the patients died of lung cancer. None of the patients developed hematological malignancy. In this study, the recovery from ARS was complete after treatment. The small population, short follow-up period, and the relatively small doses resulted in no long-term adverse effects, as would be predicted.

Age-related cancer mutations associated with clonal hematopoietic expansion

PubMed Central

Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li

2015-01-01

Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion. PMID:25326804

Toxicity of iron overload and iron overload reduction in the setting of hematopoietic stem cell transplantation for hematologic malignancies.

PubMed

Leitch, Heather A; Fibach, Eitan; Rachmilewitz, Eliezer

2017-05-01

Iron is an essential element for key cellular metabolic processes. However, transfusional iron overload (IOL) may result in significant cellular toxicity. IOL occurs in transfusion dependent hematologic malignancies (HM), may lead to pathological clinical outcomes, and IOL reduction may improve outcomes. In hematopoietic stem cell transplantation (SCT) for HM, IOL may have clinical importance; endpoints examined regarding an impact of IOL and IOL reduction include transplant-related mortality, organ function, infection, relapse risk, and survival. Here we review the clinical consequences of IOL and effects of IOL reduction before, during and following SCT for HM. IOL pathophysiology is discussed as well as available tests for IOL quantification including transfusion history, serum ferritin level, transferrin saturation, hepcidin, labile plasma iron and other parameters of iron-catalyzed oxygen free radicals, and organ IOL by imaging. Data-based recommendations for IOL measurement, monitoring and reduction before, during and following SCT for HM are made. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of PIXE to measure serum copper, zinc, selenium, and bromine in patients with hematologic malignancies

NASA Astrophysics Data System (ADS)

Beguin, Y.; Bours, V.; Delbrouck, J.-M.; Robaye, G.; Roelandts, I.; Fillet, G.; Weber, G.

1990-04-01

The use of PIXE allowed for a simultaneous determination of serum copper (Cu), zinc (Zn), selenium (Se) and bromine (Br), in various groups of patients with hematologic malignancies. In 78 patients with acute nonlymphocytic leukemia, it was observed that (1) serum Se was significantly lower than in healthy controls and correlated inversely with the tumor burden; (2) serum bromine was normal at diagnosis but dropped dramatically after intensive chemotherapy, before recovering progressively over a period of months; and (3) pretreatment serum copper and zinc were significant prognostic factors of the chance to achieve a complete remission. In 50 patients with chronic lymphocytic leukemia, it was observed that (1) serum Cu and Cu/Zn ratio were useful indices of the disease activity, which were independent of a nonspecific acute phase reaction; and (2) Zn deficiency could contribute to immune dysfunction. In 119 patients with myeloproliferative disorders or myelodysplasic syndromes, serum Cu and Zn levels were mostly dependent on nonspecific factors, such as age and inflammation.

Overview on association of different types of leukemias with radiation exposure.

PubMed

Gluzman, D F; Sklyarenko, L M; Zavelevich, M P; Koval, S V; Ivanivska, T S; Rodionova, N K

2015-06-01

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10-25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

CD 123 is a membrane biomarker and a therapeutic target in hematologic malignancies

PubMed Central

2014-01-01

Recent studies indicate that abnormalities of the alpha-chain of the interleukin-3 receptor (IL-3RA or CD123) are frequently observed in some leukemic disorders and may contribute to the proliferative advantage of leukemic cells. This review analyzes the studies indicating that CD123 is overexpressed in various hematologic malignancies, including a part of acute myeloid and B-lymphoid leukemias, blastic plasmocytoid dendritic neoplasms (BPDCN) and hairy cell leukemia. Given the low/absent CD123 expression on normal hematopoietic stem cells, attempts have been made at preclinical first, and then at clinical level to target this receptor. Since the IL-3R is a membrane receptor there are two relatively simple means to target this molecule, either using its natural ligand or neutralizing monoclonal antibodies. Recent reports using a fusion molecule composed by human IL-3 coupled to a truncated diphteria toxin have shown promising antitumor activity in BPDCN and AML patients. PMID:24513123

Concise reviews: cancer stem cells: from concept to cure.

PubMed

Matchett, K B; Lappin, T R

2014-10-01

In 1953, noting a remarkable consistency between the agents causing mutations and those associated with cancer, Carl Nordling, a Finnish-born architect, proposed that cancer results from an accumulation of genetic mutations. It is now generally accepted that inherited mutations and environmental carcinogens can lead to the development of premalignant clones. After further mutations, one cell reaches a critical state which confers a survival or growth advantage over normal cells. Such cells have the ability to initiate a malignant tumour. They share many of the features of normal stem cells, including the capacity for self-renewal and differentiation, and are widely termed cancer stem cells (CSCs). Although CSCs have been well characterized in hematological malignancies, their existence in some other tissues has been questioned. Here, we review recent work in which stem cells and stem cell-like cells have been used to investigate the pathogenesis of cancer and potential anticancer treatment strategies, in the context of both hematological and somatic tissue disease. © 2014 AlphaMed Press.

The development of gastric cancer in a patient with polycythemia Vera, 3P deletion, and JAK2 V617F mutation.

PubMed

Ayvaz, Ozlem; Yavasoglu, Irfan; Kadikoylu, Gurhan; Meydan, Nezih; Barutca, Sabri; Bolaman, Zahit

2010-12-01

3p deletion which is frequently associated with solitary tumors and hematological malignancies is a chromosomal abnormality. Recently, Janus kinase-2 (JAK2) V617F mutation has an important role in the diagnosis of myeloproliferative disorders, especially in polycythemia vera (PV). We reported the development of gastric cancer in a 75-year-old patient with PV, 3p 12-14 deletion and JAK2 V617F mutation. PV was diagnosed according to the classification of World Health Organization. JAK2 V617F mutation with polymerase chain reaction and 3p12-14 deletion with cytogenetic examination of the bone marrow were detected. We investigated solitary tumors in the patient using computed tomographies of thorax, neck, ear, nose, and throat. However, they were normal. After 2 years, gastric cancer appeared in the patient. In conclusion, cytogenetic examination may be important in both the development and the diagnosis of hematological malignancies and solitary tumors. So the patients should be followed closely.

Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase

PubMed Central

Davids, Matthew S; Brown, Jennifer R

2015-01-01

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton’s tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin’s lymphoma, such as diffuse large B-cell lymphoma and Waldenström’s macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies. PMID:24941982

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.

PubMed

Davids, Matthew S; Brown, Jennifer R

2014-05-01

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.

DNMT3A and TET2 in the Pre-Leukemic Phase of Hematopoietic Disorders

PubMed Central

Sato, Hanae; Wheat, Justin C.; Steidl, Ulrich; Ito, Keisuke

2016-01-01

In recent years, advances in next-generation sequencing (NGS) technology have provided the opportunity to detect putative genetic drivers of disease, particularly cancers, with very high sensitivity. This knowledge has substantially improved our understanding of tumor pathogenesis. In hematological malignancies such as acute myeloid leukemia and myelodysplastic syndromes, pioneering work combining multi-parameter flow cytometry and targeted resequencing in leukemia have clearly shown that different classes of mutations appear to be acquired in particular sequences along the hematopoietic differentiation hierarchy. Moreover, as these mutations can be found in “normal” cells recovered during remission and can be detected at relapse, there is strong evidence for the existence of “pre-leukemic” stem cells (pre-LSC). These cells, while phenotypically normal by flow cytometry, morphology, and functional studies, are speculated to be molecularly poised to transform owing to a limited number of predisposing mutations. Identifying these “pre-leukemic” mutations and how they propagate a pre-malignant state has important implications for understanding the etiology of these disorders and for the development of novel therapeutics. NGS studies have found a substantial enrichment for mutations in epigenetic/chromatin remodeling regulators in pre-LSC, and elegant genetic models have confirmed that these mutations can predispose to a variety of hematological malignancies. In this review, we will discuss the current understanding of pre-leukemic biology in myeloid malignancies, and how mutations in two key epigenetic regulators, DNMT3A and TET2, may contribute to disease pathogenesis. PMID:27597933

Nursing diagnoses (NANDA-I) in hematology-oncology: a Delphi-study.

PubMed

Speksnijder, Herma T; Mank, Arno P; van Achterberg, Theo

2011-01-01

To identify NANDA-I diagnoses that are most relevant to hematology-oncology nursing in Europe. In a two-round, electronic, quantitative Delphi study, 28 experts from nine European countries assessed the relevance of NANDA-I diagnoses and health problems. This study identified 64 relevant diagnoses and three health problems. All experts listed 11 diagnoses: "imbalanced nutrition: less than body requirements,"diarrhea,"fatigue,"risk for bleeding,"risk for infection,"impaired oral mucous membrane,"risk for impaired skin integrity,"impaired skin integrity,"hyperthermia,"nausea,"acute pain," and the health problem "pruritis." The "NANDA-I classification 2009-2011" describes, in almost all disease- and treatment-related problems, nursing diagnoses as relevant to the adult patient with hematological malignancy. These diagnoses are therefore recommended. © 2011, The Authors. International Journal of Nursing Terminologies and Classifications © 2011, NANDA International.

Bacterial bloodstream infections and antimicrobial susceptibility pattern in pediatric hematology/oncology patients after anticancer chemotherapy.

PubMed

Al-Mulla, Naima A; Taj-Aldeen, Saad J; El Shafie, Sittana; Janahi, Mohammed; Al-Nasser, Abdullah A; Chandra, Prem

2014-01-01

Bloodstream infections in pediatric hematology and oncology represent a major problem worldwide, but this has not been studied in Qatar. In this study, we investigated the burden of infection and the resistance pattern in the bacterial etiology, in the only tertiary pediatric hematology and oncology center in Qatar. All pediatric cancer patients (n=185) were evaluated retrospectively during the period 2004-2011; a total of 70 (38%) patients were diagnosed with bloodstream infections. Bacterial etiology was determined, along with their susceptibility patterns. Neutropenia, duration of neutropenia, fever, duration of fever, and C-reactive protein (CRP) were evaluated throughout the study. A total of 70 patients (38%) were diagnosed with acute leukemias, lymphomas, solid tumors, or brain tumors; those patients experienced 111 episodes of bacteremia. The most common Gram-positive (n=64 [55%]) isolates were Staphylococcus epidermidis (n=26), Staphylococcus hominis (n=9), and Staphylococcus haemolyticus (n=7), and the common Gram-negative (n=52 [45%]) isolates were Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=10), and Escherichia coli (n=7). There was a significant association observed between fever with positive blood culture and different types of cancer (P=0.035). The majority of bacteremia (n=68 [61.3%]) occurred in nonneutropenic episodes. Elevated values of CRP (≥5 mg/L) were detected in 82 (95.3%) episodes and were negatively correlated with absolute neutrophil count (ANC) (r=-0.18; P=0.248) among all cases. However, the infection-related fatality rate was 2.2% (n=4), with three caused by Gram-negative pathogens. Multidrug resistant organisms were implicated in 33 (28.4%) cases and caused three of the mortality cases. Multidrug resistant organisms cause mortality in pediatric cancer patients. Investigation of antimicrobial susceptibility of these organisms may guide successful antimicrobial therapy and improve the surveillance and quality of pediatric malignancy care.

Anti-cancer vaccine therapy for hematologic malignancies: An evolving era.

PubMed

Nahas, Myrna R; Rosenblatt, Jacalyn; Lazarus, Hillard M; Avigan, David

2018-02-15

The potential promise of therapeutic vaccination as effective therapy for hematologic malignancies is supported by the observation that allogeneic hematopoietic cell transplantation is curative for a subset of patients due to the graft-versus-tumor effect mediated by alloreactive lymphocytes. Tumor vaccines are being explored as a therapeutic strategy to re-educate host immunity to recognize and target malignant cells through the activation and expansion of effector cell populations. Via several mechanisms, tumor cells induce T cell dysfunction and senescence, amplifying and maintaining tumor cell immunosuppressive effects, resulting in failure of clinical trials of tumor vaccines and adoptive T cell therapies. The fundamental premise of successful vaccine design involves the introduction of tumor-associated antigens in the context of effective antigen presentation so that tolerance can be reversed and a productive response can be generated. With the increasing understanding of the role of both the tumor and tumor microenvironment in fostering immune tolerance, vaccine therapy is being explored in the context of immunomodulatory therapies. The most effective strategy may be to use combination therapies such as anti-cancer vaccines with checkpoint blockade to target critical aspects of this environment in an effort to prevent the re-establishment of tumor tolerance while limiting toxicity associated with autoimmunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Adoptive immunotherapy for hematological malignancies using T cells gene-modified to express tumor antigen-specific receptors.

PubMed

Fujiwara, Hiroshi

2014-12-15

Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as "cellular drugs". As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.

Treatment of febrile neutropenia with cefepime monotherapy.

PubMed

Jándula, B M; Martino, R; Gurgi, M; Manteiga, R; Sierra, J

2001-01-01

The empirical administration of a broad-spectrum beta-lactam antibiotic, either as monotherapy or in combination with an aminoglycoside, is an essential component of the initial management of patients with fever and severe neutropenia. Multiple antibiotics have been tested for this indication. Cefepime is a fourth-generation cephalosporin with in vitro activity against most gram-negative and many gram-positive bacteria. We have studied the use of this agent as monotherapy in this indication. One hundred and twenty-six episodes of febrile neutropenia in 98 adults with hematological malignancies were treated with cefepime monotherapy. Cefepime was given at a dose of 2 g every 8 h i.v. Most episodes (49%) were fever of unexplained origin, while a microbiologically documented and clinically documented infection occurred in 25% episodes each. Seventy-six (61%) episodes occurred after conventional chemotherapy, while 51 (41%) after a hematopoietic stem cell transplantation. Twelve episodes (10%) were not evaluable for response. Among the 114 evaluable episodes, 69 (55% of the initial sample and 61% of those evaluable) responded to cefepime monotherapy, while therapy failed in 45 cases (36% of the initial sample and 39% of those evaluable), including 14 cases who developed breakthrough bacteremia during therapy. There were no deaths due to bacterial infection. At the end of all antibiotic therapy (final outcome) 69 episodes were cured only with monotherapy, 47 were cured with modification of therapy and 10 patients died from an unrelated cause. The only variable that appeared to correlate with response to therapy was the duration of neutropenia, which was longer among patients who failed or developed breakthrough bacteremia than among those who responded to monotherapy. Initial empirical antibiotic therapy with cefepime as a single agent in patients with febrile neutropenia and a hematological malignancy is effective, but patients with prolonged neutropenia appear to be at higher risk for failure. However, with appropriate therapeutic changes the risk of dying from a bacterial infection is very low. Copyright 2001 S. Karger AG, Basel

Major Histocompatibility Mismatch and Donor Choice for Second Allogeneic Bone Marrow Transplantation.

PubMed

Imus, Philip H; Blackford, Amanda L; Bettinotti, Maria; Iglehart, Brian; Dietrich, August; Tucker, Noah; Symons, Heather; Cooke, Kenneth R; Luznik, Leo; Fuchs, Ephraim J; Brodsky, Robert A; Matsui, William H; Huff, Carol Ann; Gladstone, Douglas; Ambinder, Richard F; Borrello, Ivan M; Swinnen, Lode J; Jones, Richard J; Bolaños-Meade, Javier

2017-11-01

Large alternative donor pools provide the potential for selecting a different donor for a second allogeneic (allo) bone or marrow transplant (BMT). As HLA disparity may contribute to the graft-versus-tumor effect, utilizing new mismatched haplotype donors may potentially improve the antitumor activity for relapsed hematologic malignancies despite a previous alloBMT. Data from patients who received a second alloBMT for relapsed hematologic malignancies at Johns Hopkins were analyzed. Outcomes were compared between patients who received a second allograft with the same MHC composition and those who received an allograft with a new mismatched haplotype. Loss of heterozygosity analysis was performed for patients with acute myeloid leukemia (AML) whose first allograft was haploidentical. Between 2005 and 2015, 40 patients received a second BMT for a relapsed hematologic malignancy. The median follow-up is 750 (range, 26 to 2950) days. The median overall survival (OS) in the cohort is 928 days (95% confidence interval [CI], 602 to not reached [NR]); median event-free survival (EFS) for the cohort is 500 days (95% CI, 355 to NR). The 4-year OS is 40% (95% CI, 25% to 64%), and the 4-year EFS is 36% (95% CI, 24% to 55%). The cumulative incidence of nonrelapsed mortality by 2 years was 27% (95% CI, 13% to 42%). The cumulative incidence of grade 3 to 4 acute graft-versus-host disease (GVHD) at 100 days was 15% (95% CI, 4% to 26%); the cumulative incidence of extensive chronic GVHD at 2 years was 22% (95% CI, 9% to 36%). The median survival was 552 days (95% CI, 376 to 2950+) in the group who underwent transplantation with a second allograft that did not harbor a new mismatched haplotype, while it was not reached in the group whose allograft contained a new mismatched haplotype (hazard ratio [HR], .36; 95% CI, .14 to .9; P = .02). EFS was also longer in the group who received an allograft containing a new mismatched haplotype, (NR versus 401 days; HR, .50; 95% CI, .22 to 1.14; P = .09). Although the allograft for this patient's second BMT contained a new mismatched haplotype, AML nevertheless relapsed a second time. Second BMTs are feasible and provide a reasonable chance of long-term survival. An allograft with a new mismatched haplotype may improve outcomes after second BMTs for relapsed hematologic malignancies. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Palonosetron versus other 5-HT₃ receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States.

PubMed

Craver, Chris; Gayle, Julie; Balu, Sanjeev; Buchner, Deborah

2011-01-01

This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting. Patients aged ≥ 18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed. Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p = 0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p = 0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p = 0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p = 0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship. In this retrospective hospital study, patients with hematologic malignancies treated with HEC or MEC and initiated on antiemetic prophylaxis with palonosetron in the hospital outpatient setting were more likely to experience significantly lower CINV event rates (in the hospital outpatient, inpatient, and emergency room settings) versus patients initiated on other 5-HT₃ RAs.

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience.

PubMed

Salles, Gilles; Barrett, Martin; Foà, Robin; Maurer, Joerg; O'Brien, Susan; Valente, Nancy; Wenger, Michael; Maloney, David G

2017-10-01

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue. F. Hoffmann-La Roche Ltd., Basel, Switzerland.

All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies.

PubMed

Karmali, Reem; Dalovisio, Andrew; Borgia, Jeffrey A; Venugopal, Parameswaran; Kim, Brian W; Grant-Szymanski, Kelly; Hari, Parameswaran; Lazarus, Hillard

2015-03-01

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of intensified conditioning on Epstein-Barr virus and cytomegalovirus infections in allogeneic hematopoietic stem cell transplantation for hematological malignancies

PubMed Central

2012-01-01

Background Intensified conditioning regimens (increasing the intensity of standard myeloablative conditioning) for hematological malignancies in allogeneic hematopoietic stem cell transplantation (allo-HSCT) could reduce the relapse rate of the underlying disease, but it might simultaneously increase the transplant-related mortality including the mortality of infections. To explore whether intensified conditioning affected Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections, 185 patients undergoing allo-HSCT were enrolled. Methods A total of 104 cases received standard and 81 intensified conditioning. Cyclosporine A (CsA) withdrawal and/or donor lymphocyte infusion (DLI) were conducted in high-risk patients. The EBV-DNA and CMV-DNA levels of blood were monitored regularly by quantitative real-time polymerase chain reaction (RQ-PCR) and immune reconstitution of recipients were analyzed by flow cytometry. Results The 3-year cumulative incidence of EBV viremia, EBV-associated diseases and mortality of EBV-associated diseases were 25.3% ± 4.6%, 10.5% ± 3.4% and 0.0% ± 0.0% in the standard group, compared with 45.6% ± 6.5%, 26.0% ±5.3% and 7.3% ± 3.1% in the intensified group (P = 0.002, P = 0.002, P = 0.008). The 3-year cumulative incidence of CMV viremia and CMV-associated diseases, mortality of CMV-associated diseases and incidence of bacterial and fungal infections were similar between the two groups (P = 0.855, P = 0.581, P = 0.933, P = 0.142, P = 0.182, respectively). Multivariate analysis showed that intensified conditioning was one of the risk factors for EBV viremia and EBV-associated diseases (P = 0.037, P = 0.037), but it had no effects on CMV infections. The percentage of CD4+ T cells and CD4+/CD8+ ratio at 3 months post-transplantation were lower in the intensified group (P = 0.032, P = 0.022). The 3-year OS and DFS in the standard group were 62.2% ± 5.8% and 60.6% ± 5.6%, compared with 51.6% ± 6.2% and 51.1% ± 5.9% in the intensified group (P = 0.029, P = 0.063). Conclusions Intensified conditioning represents a promising approach for high-risk hematological malignancies, although it affects early immune reconstitution of recipients and increases the incidence and mortality of EBV infections. PMID:22856463

Systemic Sclerosis and Malignancy: A Review of Current Data

PubMed Central

Zeineddine, Nabil; Khoury, Lara El; Mosak, Joseph

2016-01-01

Systemic sclerosis (SSc) is associated with increased risk of malignancy. The organ systems most commonly affected are the lungs, the breasts and the hematological system. Risk factors predisposing a SSc patient for development of malignancy are not well defined, and the pathogenic basis of the association is yet to be explained. The incidence of malignancies in SSc patients is variable from one report to another, but most importantly, questions regarding the role of immunosuppressive therapies and the effect of autoantibodies have weak or sometimes contradictory answers in most of the currently available literature and physicians have no available guidelines to screen their SSc patients for malignancies. The lack of a concretely defined high-risk profile and the absence of malignancy screening guidelines tailored for SSc patients raise the importance of the need for more studies on the association of SSc and cancer and should incite rheumatology colleges to develop specific recommendations for the clinician to follow while approaching patients with SSc. PMID:27540435

The skin as a window to the blood: Cutaneous manifestations of myeloid malignancies.

PubMed

Li, Alvin W; Yin, Emily S; Stahl, Maximilian; Kim, Tae Kon; Panse, Gauri; Zeidan, Amer M; Leventhal, Jonathan S

2017-11-01

Cutaneous manifestations of myeloid malignancies are common and have a broad range of presentations. These skin findings are classified as specific, due to direct infiltration by malignant hematopoietic cells, or non-specific. Early recognition and diagnosis can have significant clinical implications, as skin manifestations may be the first indication of underlying hematologic malignancy, can reflect the immune status and stage of disease, and cutaneous reactions may occur from conventional and targeted agents used to treat myeloid disease. In addition, infections with cutaneous involvement are common in immunocompromised patients with myeloid disease. Given the varying presentations, dermatologic findings associated with myeloid malignancies can pose diagnostic challenges for hematologists and dermatologists. In this clinical review intended for the practicing hematologist/oncologist, we discuss the presentation, diagnosis, treatment, and prognostic value of the most common cutaneous manifestations associated with myeloid malignancies using illustrative macro- and microscopic figures and with a special emphasis on practical considerations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Pattern of Duplicate Presentations at National Hematology-Oncology Meetings: Influence of the Pharmaceutical Industry.

PubMed

Ramchandren, Radhakrishnan; Schiffer, Charles A

2016-03-01

The major large US hematology-oncology meetings sponsored by the American Society of Hematology (ASH) and American Society of Clinical Oncology (ASCO) have specific guidelines in place discouraging submission of scientific information presented previously at other meetings. Nonetheless, duplicate submissions are frequent. The incidence and motivations for duplicate hematologic presentations and the influence of the pharmaceutical industry on this process have not been thoroughly analyzed. Therefore, were viewed four consecutive ASH and ASCO meetings to assess the frequency of duplicate abstract presentations. All abstracts presented at ASCO2010 in the area of malignant hematology were compared with abstracts from ASCO and ASH 2009 and ASH 2010, and funding sources were reviewed. More than half (54%) of all abstracts submitted to ASCO 2010 acknowledged pharmaceutical company support. Almost one third (31%) of ASCO 2010 abstracts were resubmitted in the 2-year time period, and it was notable that a high fraction (75%) of these duplicate abstracts had pharmaceutical industry sponsorship, compared with 42% of the abstracts that were submitted only once. Despite current guidelines prohibiting duplicate abstract presentation, a substantial proportion (31%) of abstracts at large international hematology-oncology meetings are duplicative, with potential negative consequences. In addition, a disproportionate percentage of the duplicate abstracts rely on pharmaceutical industry support (75%), suggesting that marketing strategies may be a motivation for some of these repetitive submissions.

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease

PubMed Central

Paulsson, Kajsa; Cazier, Jean-Baptiste; MacDougall, Finlay; Stevens, Jane; Stasevich, Irina; Vrcelj, Nikoletta; Chaplin, Tracy; Lillington, Debra M.; Lister, T. Andrew; Young, Bryan D.

2008-01-01

We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). A 500K SNP array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. The resolution level of this SNP array study is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared among different clinical, morphological, and cytogenetic subgroups. PMID:18458336

Broad-Range PCR Coupled with Electrospray Ionization Time of Flight Mass Spectrometry for Detection of Bacteremia and Fungemia in Patients with Neutropenic Fever

PubMed Central

Maertens, J.; Bueselinck, K.; Lagrou, K.

2016-01-01

Infection is an important complication in patients with hematologic malignancies or solid tumors undergoing intensive cytotoxic chemotherapy. In only 20 to 30% of the febrile neutropenic episodes, an infectious agent is detected by conventional cultures. In this prospective study, the performance of broad-range PCR coupled with electrospray ionization time of flight mass spectrometry (PCR/ESI-MS) technology was compared to conventional blood cultures (BC) in a consecutive series of samples from high-risk hematology patients. In 74 patients, BC and a whole-blood sample for PCR/ESI-MS (Iridica BAC BSI; Abbott, Carlsbad, CA, USA) were collected at the start of each febrile neutropenic episode and, in case of persistent fever, also at day 5. During 100 different febrile episodes, 105 blood samples were collected and analyzed by PCR/ESI-MS. There was evidence of a bloodstream infection (BSI) in 36/105 cases (34%), based on 14 cases with both PCR/ESI-MS and BC positivity, 17 cases with BC positivity only, and 5 cases with PCR/ESI-MS positivity only. The sensitivity of PCR/ESI-MS was 45%, specificity was 93%, and the negative predictive value was 80% compared to blood culture. PCR/ESI-MS detected definite pathogens (Fusobacterium nucleatum and Streptococcus pneumoniae) missed by BC, whereas it missed both Gram-negative and Gram-positive organisms detected by BC. PCR/ESI-MS testing detected additional microorganisms but showed a low sensitivity (45%) compared to BC in neutropenic patients. Our results indicate a lower concordance between BC and PCR/ESI-MS in the neutropenic population than what has been previously reported in other patient groups with normal white blood cell distribution, and a lower sensitivity than other PCR-based methods. PMID:27440820

Bloodstream infections in pediatric oncology outpatients: a new healthcare systems challenge.

PubMed

Smith, Theresa L; Pullen, Gregg T; Crouse, Vonda; Rosenberg, Jon; Jarvis, William R

2002-05-01

To investigate a perceived increase in central venous catheter (CVC)-associated bloodstream infections (BSIs) among pediatric hematology-oncology outpatients. A case-control study. A pediatric hematology-oncology outpatient clinic at Fresno Children's Hospital. Pediatric hematology-oncology clinic outpatients with CVCs at Fresno Children's Hospital between November 1994 and October 1997. A case-patient was defined as any hematology-oncology outpatient with a CVC-associated BSI at Fresno Children's Hospital from November 1996 to October 1997 (study period) without a localizable infection. To identify case-patients, we reviewed Fresno Children's Hospital records for all hematology-oncology clinic patients, those with CVCs and those with CVCs and BSIs. Control-patients were randomly selected hematology-oncology outpatients with a CVC but no BSI during the study period. Case-patient and control-patient demographics, diagnoses, caretakers, catheter types, catheter care, and water exposure were compared. Twenty-five case-patients had 42 CVC-associated BSIs during the study period. No significant increase in CVC-associated BSI rates occurred among pediatric hematology-oncology patients. However, there was a statistically significant increase in nonendogenous, gram-negative (eg, Pseudomonas species) BSIs during summer months (May-October) compared with the rest of the year. Case-patients and control-patients differed only in catheter type; case-patients were more likely than control-patients to have a transcutaneous CVC. Summertime recreational water exposures were similar and high in the two groups. Hematology-oncology clinic patients with transcutaneous CVCs are at greater risk for CVC-associated BSI, particularly during the summer. Caretakers should be instructed on proper care of CVCs, particularly protection of CVCs during bathing and recreational summer water activities, to reduce the risk of nonendogenous, gram-negative BSIs.

Rituximab desensitization in three patients with severe rituximab allergy.

PubMed

Öztürk, Erman; Özyiğit, Leyla Pur; Öztürk, Ayşe Bilge; Akay, Meltem Olga; Çetiner, Mustafa; Ferhanoğlu, Burhan

Rituximab is a chimeric monoclonal antibody that targets CD20 positive B cells and has a positive effect on both overall and progression-free survival in B-cell lymphoid malignancies. Combination rituximab with chemotherapy treatment provide survival improvement. Although rituximab is an important treatment option in hematological malignancies, the risk of allergic reactions is high. These reactions are usually IgE-mediated and can be varied in regard of severity from urticaria to anaphylaxis. It is an option to interrupt the treatment and ommit rituximab therapy who had allergic reactions. Drug desensitization is another option and successful results have been reported by applying desensitization to such reactions. Drug desensitization alters the immune response to induce a state of temporary clinical tolerance to the allergic drug by giving gradual increasing of doses of drug at fixed time intervals. Herein, we present 3 cases successfully treated with rituximab desensitization. The cases were using rituximab with the diagnosis of Burkitt lymphoma, follicular lymphoma, and marginal zone lymphoma, respectively. Two cases had grade 2 and 1 case had grade 3 systemic allergic reaction with rituximab. There was no known allergy history in all 3 cases. All patients tolerated the desensitization protocol. The subsequent treatments of the patients were also given by desensitization protocol. A total of 12 desensitizations were administered to 3 cases. No severe or life-threating reactions were observed in subsequent applications. To date applying desensitization protocols ensure rituximab treatment safely. Rituximab desensitization can be performed at trained allergy centers, and it may be an appropriate option for rituximab allergic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Successful Treatment of BK Virus Hemorrhagic Cystitis (HC) Post Allogenic Hematopoietic Stem Cell Transplantation with Low Dose Cidofovir.

PubMed

Arora, R; Jasmita; Singh, M; Garg, A; Gupta, M; Gupta, N

2017-05-01

BK virus (BKV) hemorrhagic cystitis (HC) is a serious cause of morbidity and mortality after allogeneic hematopoietic SCT (allo-HSCT) in patients with hematological malignancies. Around half of allogenic HSCT patients present with BKV viruria at some point after HSCT; about 5-40% of these patients subsequently develop active HC. Supportive care including bladder irrigation, blood transfusions and symptomatic pain management remains the mainstay of therapy; the acyclic nucleoside analogue cidofovir is currently the front-line drug for BKV-HC treatment. Here we report the first case of severe hemorrhagic cystitis from India who was successfully treated with low dose cidofovir therapy. © Journal of the Association of Physicians of India 2011.

A young man with polyuria and lethargy.

PubMed

Imtiaz, Salman; Qayyum, Shahid; Kafouri, Hala; Al Khoiter, Mohammad; Askar, Akram

2011-07-01

We report a 20-year-old man who presented to our emergency room with a history of polyuria, weakness, constipation, nausea, and vomiting of two months duration. History and clinical examination revealed a significant weight loss and mild hepatomegaly. Laboratory investigations revealed hypokalemia, hypernatremia, and severe metabolic acidosis and anemia. Ultra-sound of the abdomen revealed enlarged kidneys without hydronerphrosis. The patient developed paralysis due to further decline in serum potassium level, which improved after an aggressive fluid and electrolyte management. He was investigated extensively for polyuria and type of acidosis. The kidney biopsy showed interstitial leukemic infiltration. He was managed accordingly and recovered from the condition. This case demonstrates an unusual presentation of a hematological malignancy, which was a diagnostic as well as a management challenge.

Prolonged viremia in dengue virus infection in hematopoietic stem cell transplant recipients and patients with hematological malignancies.

PubMed

de Souza Pereira, Bárbara Brito; Darrigo Junior, Luiz Guilherme; de Mello Costa, Thalita Cristina; Felix, Alvina Clara; Simoes, Belinda P; Stracieri, Ana Beatriz; da Silva, Paula Moreira; Mauad, Marcos; Machado, Clarisse M

2017-08-01

Fever, skin rash, headache, and thrombocytopenia are considered hallmarks of dengue infection. However, these symptoms are frequently observed in infectious and non-infectious complications of hematopoietic stem cell transplant recipients and oncohematological patients. Thus, laboratory confirmation of dengue is relevant for prompt intervention and proper management of dengue in endemic and non-endemic regions. Because no prospective study of dengue has been conducted in these populations, the actual morbidity and mortality of dengue is unknown. In the present series, we describe five cases of dengue in patients living in endemic areas, emphasizing the prolonged course of the disease and the occurrence of prolonged viremia. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Slime production by clinical isolates of Blastoschizomyces capitatus from patients with hematological malignancies and catheter-related fungemia.

PubMed

D'Antonio, D; Parruti, G; Pontieri, E; Di Bonaventura, G; Manzoli, L; Sferra, R; Vetuschi, A; Piccolomini, R; Romano, F; Staniscia, T

2004-10-01

In order to expand the present knowledge of the pathogenic potential of Blastoschizomyces capitatus in central venous catheter (CVC)-related bloodstream infections, six strains of the organism recovered from three leukemic patients with CVC-related fungemia in different years were investigated. Isolates and control strains were tested for their genetic relatedness and for their ability to produce slime in glucose-containing solutions. DNA restriction enzyme analysis revealed that all strains of B. capitatus were identical, whereas slime production assays and examination of ex vivo material showed that they were able to produce large amounts of slime. Slime production may therefore play a relevant pathogenic role in cases of CVC-related fungemia caused by B. capitatus.

Development of CAR T cells designed to improve antitumor efficacy and safety

PubMed Central

Jaspers, Janneke E.; Brentjens, Renier J.

2017-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are ‘on-target, off-tumor’ toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models. PMID:28342824

Development of CAR T cells designed to improve antitumor efficacy and safety.

PubMed

Jaspers, Janneke E; Brentjens, Renier J

2017-10-01

Chimeric antigen receptor (CAR) T cell therapy has shown promising efficacy against hematologic malignancies. Antitumor activity of CAR T cells, however, needs to be improved to increase therapeutic efficacy in both hematologic and solid cancers. Limitations to overcome are 'on-target, off-tumor' toxicity, antigen escape, short CAR T cell persistence, little expansion, trafficking to the tumor and inhibition of T cell activity by an inhibitory tumor microenvironment. Here we will discuss how optimizing the design of CAR T cells through genetic engineering addresses these limitations and improves the antitumor efficacy of CAR T cell therapy in pre-clinical models. Published by Elsevier Inc.

Accelerating drug development in pediatric cancer: a novel Phase I study design of venetoclax in relapsed/refractory malignancies.

PubMed

Place, Andrew E; Goldsmith, Kelly; Bourquin, Jean-Pierre; Loh, Mignon L; Gore, Lia; Morgenstern, Daniel A; Sanzgiri, Yeshwant; Hoffman, David; Zhou, Ying; Ross, Jeremy A; Prine, Betty; Shebley, Mohamad; McNamee, Megan; Farazi, Thalia; Kim, Su Young; Verdugo, Maria; Lash-Fleming, Leanne; Zwaan, C Michel; Vormoor, Josef

2018-03-29

Venetoclax is a highly selective, potent BCL-2 inhibitor that is approved for some patients previously treated for chronic lymphocytic leukemia, and has shown promising activity in adult studies across several hematologic malignancies. Preclinical studies have demonstrated venetoclax activity in pediatric patient-derived xenograft models and cell lines; however, clinical studies in pediatric patients have yet to be conducted. The prognosis is poor for children with most relapsed/refractory malignancies, and limited treatment options result in unmet clinical need. Herein, we describe the rationale and design of the first study of venetoclax in pediatric patients with relapsed/refractory malignancies: a Phase I trial investigating the safety and pharmacokinetics of venetoclax monotherapy followed by the addition of chemotherapy (Trial registration: EudraCT 2017-000439-14; NCT03236857).

Complementary and Alternative Medicine: A Clinical Study in 1,016 Hematology/Oncology Patients.

PubMed

Hierl, Marina; Pfirstinger, Jochen; Andreesen, Reinhard; Holler, Ernst; Mayer, Stephanie; Wolff, Daniel; Vogelhuber, Martin

2017-01-01

Surveys state a widespread use of complementary and alternative medicine (CAM) in patients with malignant diseases. CAM methods might potentially interfere with the metabolization of tumor-specific therapy. However, there is little communication about CAM use in hematology/oncology patients between patients, CAM providers, and oncologists. A self-administered questionnaire was handed out to all patients attending to the hematology/oncology outpatient clinic of Regensburg University Hospital. Subsequently, a chart review of all CAM users was performed. Questionnaires of 1,016 patients were analyzed. Of these patients, 30% used CAM, preferably vitamins and micronutrients. Main information sources for CAM methods were physicians/nonmedical practitioners and friends/relatives. CAM therapies were provided mainly by licensed physicians (29%), followed by nonmedical practitioners (14%) and the patients themselves (13%). Although 62% of the CAM users agreed that the oncologist may know about their CAM therapy, a chart entry about CAM use was found only in 41%. CAM is frequently used by hematology/oncology patients. Systematic communication about CAM is essential to avoid possible drug interactions. © 2017 S. Karger AG, Basel.

Netting Novel Regulators of Hematopoiesis and Hematologic Malignancies in Zebrafish.

PubMed

Kwan, Wanda; North, Trista E

2017-01-01

Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis. Significantly, perturbations in many of the key developmental signals controlling hematopoiesis are associated with hematological disorders and disease, including anemia, bone marrow failure syndromes, and leukemia. Thus, understanding the regulatory pathways controlling HSPC production and function has important clinical implications. In this review, we describe how the blood system forms and is maintained in zebrafish, with particular focus on new insights into vertebrate hematological regulation gained using this model. The interplay of factors controlling development and disease in the hematopoietic system combined with the unique attributes of the zebrafish make this a powerful platform to discover novel targets for the treatment of hematological disease. © 2017 Elsevier Inc. All rights reserved.

Chimeric Antigen Receptors T Cell Therapy in Solid Tumor: Challenges and Clinical Applications.

PubMed

Mirzaei, Hamid R; Rodriguez, Analiz; Shepphird, Jennifer; Brown, Christine E; Badie, Behnam

2017-01-01

Adoptive cellular immunotherapy (ACT) employing engineered T lymphocytes expressing chimeric antigen receptors (CARs) has demonstrated promising antitumor effects in advanced hematologic cancers, such as relapsed or refractory acute lymphoblastic leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma, supporting the translation of ACT to non-hematological malignancies. Although CAR T cell therapy has made remarkable strides in the treatment of patients with certain hematological cancers, in solid tumors success has been limited likely due to heterogeneous antigen expression, immunosuppressive networks in the tumor microenvironment limiting CAR T cell function and persistence, and suboptimal trafficking to solid tumors. Here, we outline specific approaches to overcome barriers to CAR T cell effectiveness in the context of the tumor microenvironment and offer our perspective on how expanding the use of CAR T cells in solid tumors may require modifications in CAR T cell design. We anticipate these modifications will further expand CAR T cell therapy in clinical practice.

Central venous catheter-related infections in hematology and oncology: 2012 updated guidelines on diagnosis, management and prevention by the Infectious Diseases Working Party of the German Society of Hematology and Medical Oncology.

PubMed

Hentrich, M; Schalk, E; Schmidt-Hieber, M; Chaberny, I; Mousset, S; Buchheidt, D; Ruhnke, M; Penack, O; Salwender, H; Wolf, H-H; Christopeit, M; Neumann, S; Maschmeyer, G; Karthaus, M

2014-05-01

Cancer patients are at increased risk for central venous catheter-related infections (CRIs). Thus, a comprehensive, practical and evidence-based guideline on CRI in patients with malignancies is warranted. A panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) has developed a guideline on CRI in cancer patients. Literature searches of the PubMed, Medline and Cochrane databases were carried out and consensus discussions were held. Recommendations on diagnosis, management and prevention of CRI in cancer patients are made, and the strength of the recommendation and the level of evidence are presented. This guideline is an evidence-based approach to the diagnosis, management and prevention of CRI in cancer patients.

High times, low sats: diffuse pulmonary infiltrates associated with chronic synthetic cannabinoid use.

PubMed

Alhadi, Sameir; Tiwari, Anupama; Vohra, Rais; Gerona, Roy; Acharya, Janak; Bilello, Kathryn

2013-06-01

In recent years, cases of severe adverse effects from recreational use of synthetic cannabinoids (SC) have established that these agents represent a novel toxicologic hazard. A 21-year-old male presenting as a vehicular trauma victim was noted with diffuse pulmonary infiltrates related to chronic inhalation of multiple synthetic cannabinoid-containing products. Chest imaging revealed bilateral, subacute lung infiltrates; histopathological analysis of bronchial and alveolar tissues revealed an inflammatory process. An extensive workup failed to identify infectious, malignant, autoimmune, or hematologic causes of the syndrome, and toxicological analysis of the blood and body fluids confirmed the presence of multiple synthetic cannabinoids and metabolites. The patient recovered after an 8-day ICU course, wherein he received antibiotics, steroids, and mechanical ventilation. This case contributes to the currently evolving knowledge about SC agents, adding a rarely described pulmonary complication to the growing list of adverse effects associated with these products.

Increasing Pneumocystis pneumonia, England, UK, 2000-2010.

PubMed

Maini, Rishma; Henderson, Katherine L; Sheridan, Elizabeth A; Lamagni, Theresa; Nichols, Gordon; Delpech, Valerie; Phin, Nick

2013-03-01

After an increase in the number of reported cases of Pneumocystis jirovecii pneumonia in England, we investigated data from 2000-2010 to verify the increase. We analyzed national databases for microbiological and clinical diagnoses of P. jirovecii pneumonia and associated deaths. We found that laboratory-confirmed cases in England had increased an average of 7% per year and that death certifications and hospital admissions also increased. Hospital admissions indicated increased P. jirovecii pneumonia diagnoses among patients not infected with HIV, particularly among those who had received a transplant or had a hematologic malignancy. A new risk was identified: preexisting lung disease. Infection rates among HIV-positive adults decreased. The results confirm that diagnoses of potentially preventable P. jirovecii pneumonia among persons outside the known risk group of persons with HIV infection have increased. This finding warrants further characterization of risk groups and a review of P. jirovecii pneumonia prevention strategies.

Eosinophilic myositis: an updated review.

PubMed

Selva-O'Callaghan, A; Trallero-Araguás, E; Grau, J M

2014-01-01

Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. Copyright © 2014 Elsevier B.V. All rights reserved.

The management of hodgkin lymphomas in pregnancies.

PubMed

Moshe, Yakir; Bentur, Ohad Shimshon; Lishner, Michael; Avivi, Irit

2017-11-01

Hodgkin lymphoma is the most common hematological malignancy in pregnancy. Its management presents several unique challenges, as decisions have to take both maternal and fetal risks into consideration. Using three hypothetical cases, we review current evidence and guidelines and suggest our recommendations for managing pregnant Hodgkin lymphoma patients. The opportunity for a prompt and accurate diagnosis should not be missed; this may be achieved by vigilance to suggestive symptoms, performance of biopsy which is not contraindicated during pregnancy and use of MRI for staging. Most patients should receive treatment with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) after completion of the first trimester. Bridging therapy with corticosteroids or vinblastine should be considered during the first trimester. In most cases of early disease, the addition of chemotherapy cycles to the treatment plan seems preferable to radiation therapy. Diagnosis at relapse raises unique dilemmas regarding second-line chemotherapeutic regimens and timing of consolidation with high-dose therapy and autologous stem cell transplantation, an approach which is contraindicated during pregnancy. Considering the excellent outcomes of Hodgkin lymphoma outside pregnancy, every effort should be made to strive toward a curative treatment plan while balancing the multiple issues and dilemmas which arise when treating this malignancy in a pregnant patient. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Medical history, lifestyle, family history, and occupational risk factors for adult acute lymphocytic leukemia: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

PubMed

Skibola, Christine F; Slager, Susan L; Berndt, Sonja I; Lightfoot, Tracy; Sampson, Joshua N; Morton, Lindsay M; Weisenburger, Dennis D

2014-08-01

Acute lymphoblastic leukemia/lymphoma (ALL) in adults is a rare malignancy with a poor clinical outcome, and few reported etiologic risk factors. We performed an exploratory pooled study of 152 ALL cases and 23096 controls from 16 case-control studies to investigate the role of medical history, lifestyle, family history, and occupational risk factors and risk of ALL. Age- race/ethnicity-, sex-, and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. An increased risk of ALL was found in those with a family history of a hematological malignancy (OR = 2.6, 95% CI = 1.22 to 5.54) and in leather (OR = 3.91, 95% CI = 1.35 to 11.35) and sewing/embroidery workers (OR = 2.92, 95% CI = 1.00 to 8.49). Consumers of alcohol had an increased risk of B-cell ALL (OR = 2.87, 95% CI = 1.18 to 6.95). The small number of statistically significant risk factors identified out of the 112 variables examined could be chance findings and will require further replication to assess their role in the etiology of adult ALL. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Cytophagic and S-100 protein immunoreactive myeloid leukemia cutis.

PubMed

Thomas, Crystal G; Patel, Rajiv M; Bergfeld, Wilma F

2010-03-01

Myeloid leukemia cutis (LC) is the cutaneous involvement by neoplastic leukocytes of the myeloid series. Myeloid LC may occur de novo or concurrently with acute myeloid leukemias, chronic myeloid leukemias, other myeloproliferative disorders or myelodysplastic syndromes. We describe an unusual case of cytophagic S-100 protein immunoreactive leukemia cutis presenting in an 87-year-old woman without prior history of myeloid leukemia or other hematologic disorders. We outline key histologic and immunohistochemical features that aide in the diagnosis of LC. The presence of cytophagocytosis on histologic examination, a phenomenon more commonly associated with lymphoid rather than myeloid malignancies, provided a clue to the possibility of a malignant process. The atypical myeloid infiltrate showed S-100 protein positivity, an unusual finding that may be seen in LC. Although not commonly reported in LC, the presence of S-100 protein positivity and cytophagocytosis should not lead to the premature exclusion of LC as a possible diagnosis until a thorough clinical, histologic and immunohistochemical evaluation is performed. In addition, the presence of cytophagocytosis has been shown to have prognostic significance for patients with myeloid leukemia.

Measles Outbreak in Pediatric Hematology and Oncology Patients in Shanghai, 2015

PubMed Central

Ge, Yan-Ling; Zhai, Xiao-Wen; Zhu, Yan-Feng; Wang, Xiang-Shi; Xia, Ai-Mei; Li, Yue-Fang; Zeng, Mei

2017-01-01

Background: Despite substantial progress toward measles control are making in China, measles outbreaks in immunocompromised population still pose a challenge to interrupt endemic transmission. This study aimed to investigate the features of measles in pediatric hematology and oncology patients and explore the reasons behind the outbreak. Methods: We collected demographic, epidemiological, and clinical data of immunocompromised measles children. All suspected measles cases were laboratory-confirmed based on the presence of measles IgM and/or identification of measles RNA. The clinical data were statistically analyzed by t-test for continuous variables and Fisher's exact test for categorical variables. Results: From March 9 to July 25 in 2015, a total of 23 children with malignancies and post hematopoietic stem cell transplantation (post-HSCT) were notified to develop measles in Shanghai. Of these 23 patients with the median age of 5.5 years (range: 11 months–14 years), 20 (87.0%) had received 1–3 doses of measles vaccine previously; all patients had fever with the median fever duration of 8 days; 21 (91.3%) had cough; 18 (78.3%) had rash; 13 (56.5%) had Koplik's spot; 13 (56.5%) had complications including pneumonia and acute liver failure; and five (21.7%) vaccinated patients died from severe pneumonia or acute liver failure. Except the first patient, all patients had hospital visits within 7–21 days before measles onset and 20 patients were likely to be exposed to each other. Conclusions: The outcome of measles outbreak in previously vaccinated oncology and post-HSCT pediatric patients during chemotherapy and immunosuppressant medication was severe. Complete loss of protective immunity induced by measles vaccine during chemotherapy was the potential reason. Improved infection control practice was critical for the prevention of measles in malignancy patients and transplant recipients. PMID:28524832

Bronchiectasis in a diverse US population: effects of ethnicity on etiology and sputum culture.

PubMed

McShane, Pamela J; Naureckas, Edward T; Strek, Mary E

2012-07-01

Previous studies of patients with bronchiectasis have found that the cause is idiopathic in the majority of cases, but these studies were done in homogeneous populations. We hypothesized that the etiology of bronchiectasis can be determined in a higher percentage of patients in a diverse US population and will differ significantly based on ethnicity. One hundred twelve patients with bronchiectasis confirmed by chest CT scan entered the study. Data from 106 patients were available for full evaluation. Clinical questionnaire, pulmonary function tests, sputum microbiology, laboratory data, and immune function testing were done. Results were analyzed by ethnicity and etiology. Patients were 61.6% European American (EA), 26.8% African American (AA), 8.9% Hispanic American (HA), and 2.7% Asian American. A cause of bronchiectasis was determined in 93.3% of patients. In 63.2% of patients, bronchiectasis was caused by immune dysregulation, including deficiency (n = 18 [17%]), autoimmune disease (n = 33 [31.1%]), hematologic malignancy (n = 15 [14.2%]), and allergic bronchopulmonary aspergillosis (n = 1 [0.9%]). Rheumatoid arthritis was the cause of bronchiectasis in 28.6% of AA patients vs 6.2% of EA patients (P < .05). Hematologic malignancy was the etiology in 20.0% of the EA patients vs none of the AA patients (P = .02). A significantly higher percentage of HA patients had Pseudomonas aeruginosa in their sputum compared with AA and EA patients (P = .01). The etiology of bronchiectasis can be determined in the majority of patients in a heterogeneous US population and is most often due to immune dysregulation. Rheumatoid arthritis is more likely in AA patients than EA patients. HA patients are more likely to have P aeruginosa in their sputum.

Clinical and pathogenic features of ETV6-related thrombocytopenia with predisposition to acute lymphoblastic leukemia

PubMed Central

Melazzini, Federica; Palombo, Flavia; Balduini, Alessandra; De Rocco, Daniela; Marconi, Caterina; Noris, Patrizia; Gnan, Chiara; Pippucci, Tommaso; Bozzi, Valeria; Faleschini, Michela; Barozzi, Serena; Doubek, Michael; Di Buduo, Christian A.; Kozubik, Katerina Stano; Radova, Lenka; Loffredo, Giuseppe; Pospisilova, Sarka; Alfano, Caterina; Seri, Marco; Balduini, Carlo L.; Pecci, Alessandro; Savoia, Anna

2016-01-01

ETV6-related thrombocytopenia is an autosomal dominant thrombocytopenia that has been recently identified in a few families and has been suspected to predispose to hematologic malignancies. To gain further information on this disorder, we searched for ETV6 mutations in the 130 families with inherited thrombocytopenia of unknown origin from our cohort of 274 consecutive pedigrees with familial thrombocytopenia. We identified 20 patients with ETV6-related thrombocytopenia from seven pedigrees. They have five different ETV6 variants, including three novel mutations affecting the highly conserved E26 transformation-specific domain. The relative frequency of ETV6-related thrombocytopenia was 2.6% in the whole case series and 4.6% among the families with known forms of inherited thrombocytopenia. The degree of thrombocytopenia and bleeding tendency of the patients with ETV6-related thrombocytopenia were mild, but four subjects developed B-cell acute lymphoblastic leukemia during childhood, resulting in a significantly higher incidence of this condition compared to that in the general population. Clinical and laboratory findings did not identify any particular defects that could lead to the suspicion of this disorder from the routine diagnostic workup. However, at variance with most inherited thrombocytopenias, platelets were not enlarged. In vitro studies revealed that the maturation of the patients’ megakaryocytes was defective and that the patients have impaired proplatelet formation. Moreover, platelets from patients with ETV6-related thrombocytopenia have reduced ability to spread on fibrinogen. Since the dominant thrombocytopenias due to mutations in RUNX1 and ANKRD26 are also characterized by normal platelet size and predispose to hematologic malignancies, we suggest that screening for ETV6, RUNX1 and ANKRD26 mutations should be performed in all subjects with autosomal dominant thrombocytopenia and normal platelet size. PMID:27365488

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

PubMed

Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E; Laskowski, Tamara; McNamara, George; Cooper, Laurence J N

2016-01-01

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

Chimeric antigen receptor-modified T cells for the treatment of solid tumors: Defining the challenges and next steps☆

PubMed Central

Beatty, Gregory L.; O’Hara, Mark

2016-01-01

Chimeric antigen receptor (CAR) T cell therapy has shown promise in CD19 expressing hematologic malignancies, but how to translate this success to solid malignancies remains elusive. Effective translation of CAR T cells to solid tumors will require an understanding of potential therapeutic barriers, including factors that regulate CAR T cells expansion, persistence, trafficking, and fate within tumors. Herein, we describe the current state of CAR T cells in solid tumors; define key barriers to CAR T cell efficacy and mechanisms underlying these barriers, outline potential avenues for overcoming these therapeutic obstacles, and discuss the future of translating CAR T cells for the treatment of patients with solid malignancies. PMID:27373504

Trichosporon asahii sepsis in a patient with pediatric malignancy.

PubMed

Ozkaya-Parlakay, Aslinur; Karadag-Oncel, Eda; Cengiz, Ali Bulent; Kara, Ates; Yigit, Atilla; Gucer, Safak; Gur, Deniz

2016-02-01

Trichosporon asahii is a rare opportunistic infection, especially in children, causing a life-threatening fungal infection underlying hematologic malignancies. Predisposing factors for infection with this pathogen are immunodeficiency including underlying malignancy, organ transplantation, extensive burns, human immunodeficiency virus infection, corticosteroid therapy, prosthetic valve surgery, and peritoneal dialysis. In the literature, a breakthrough under caspofungin, micafungin therapy is reported. In this article we report on a 16-year-old patient with Ewing sarcoma who had T. asahii sepsis. The patient died although he had been receiving caspofungin for less than 3 months and amphotericin B therapy for 3 days. A postmortem study of conchal tissues revealed T. asahii and mucormycosis histopathologically, and blood culture grew T. asahii. Copyright © 2013. Published by Elsevier B.V.

78 FR 5186 - Clinical Flow Cytometry in Hematologic Malignancies; Public Workshop; Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-24

... in the diagnosis of leukemia and lymphoma and more recently in the detection of minimal residual... chronic lymphocytic leukemia (CLL); (3) Third-party flow cytometry data analysis software; and (4... held February 27, 2013 (77 FR 76051, December 26, 2012). An FDA workshop for acute lymphocytic leukemia...

Allogeneic Stem Cell Transplantationin Relapsed Hematological Malignancy: Early GVHD Prophylaxis

ClinicalTrials.gov

2018-01-29

Hodgkin's Lymphoma; Lymphoid Leukemia; Lymphoma; Leukemia; Myeloma; Acute Lymphocytic Leukemia; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Multiple Myeloma; Chronic Myelogenous Leukemia; Myelodysplastic Syndromes; Recurrent Acute Myeloid Leukemia, Adult; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia

Hematopathology, 2nd Edition | Center for Cancer Research

Cancer.gov

The world's leading reference in hematopathology returns with this completely updated second edition. Authored by international experts in the field, it covers a broad range of hematologic disorders -- both benign and malignant -- with information on the pathogenesis, clinical and pathologic diagnosis, and treatment for each. Comprehensive in scope, it's a must-have resource

Provision of TCRγδ T Cells and Memory T Cells Plus Selected Use of Blinatumomab in Naïve T-cell Depleted Haploidentical Donor Hematopoietic Cell Transplantation for Hematologic Malignancies Relapsed or Refractory Despite Prior Transplantation

ClinicalTrials.gov

2018-01-03

Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

Diagnostic medical imaging radiation exposure and risk of development of solid and hematologic malignancy.

PubMed

Fabricant, Peter D; Berkes, Marschall B; Dy, Christopher J; Bogner, Eric A

2012-05-01

Limiting patients' exposure to ionizing radiation during diagnostic imaging is of concern to patients and clinicians. Large single-dose exposures and cumulative exposures to ionizing radiation have been associated with solid tumors and hematologic malignancy. Although these associations have been a driving force in minimizing patients' exposure, significant risks are found when diagnoses are missed and subsequent treatment is withheld. Therefore, based on epidemiologic data obtained after nuclear and occupational exposures, dose exposure limits have been estimated. A recent collaborative effort between the US Food and Drug Administration and the American College of Radiology has provided information and tools that patients and imaging professionals can use to avoid unnecessary ionizing radiation scans and ensure use of the lowest feasible radiation dose necessary for studies. Further collaboration, research, and development should focus on producing technological advances that minimize individual study exposures and duplicate studies. This article outlines the research used to govern safe radiation doses, defines recent initiatives in decreasing radiation exposure, and provides orthopedic surgeons with techniques that may help decrease radiation exposure in their daily practice. Copyright 2012, SLACK Incorporated.

Aberrant RNA splicing and mutations in spliceosome complex in acute myeloid leukemia.

PubMed

Zhou, Jianbiao; Chng, Wee-Joo

2017-01-01

The spliceosome, the cellular splicing machinery, regulates RNA splicing of messenger RNA precursors (pre-mRNAs) into maturation of protein coding RNAs. Recurrent mutations and copy number changes in genes encoding spliceosomal proteins and splicing regulatory factors have tumor promoting or suppressive functions in hematological malignancies, as well as some other cancers. Leukemia stem cell (LSC) populations, although rare, are essential contributors of treatment failure and relapse. Recent researches have provided the compelling evidence that link the erratic spicing activity to the LSC phenotype in acute myeloid leukemia (AML). In this article, we describe the diverse roles of aberrant splicing in hematological malignancies, particularly in AML and their contributions to the characteristics of LSC. We review these promising strategies to exploit the addiction of aberrant spliceosomal machinery for anti-leukemic therapy with aim to eradicate LSC. However, given the complexity and plasticity of spliceosome and not fully known functions of splicing in cancer, the challenges facing the development of the therapeutic strategies targeting RAN splicing are highlighted and future directions are discussed too.

Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives.

PubMed

Lo Presti, Vania; Nierkens, Stefan; Boelens, Jaap Jan; van Til, Niek P

2018-03-01

Hematopoietic cell transplantation is a potentially lifesaving procedure for patients with hematological malignancies who are refractory to conventional chemotherapy and/or irradiation treatment. Umbilical cord blood (CB) transplantation, as a hematopoietic stem and progenitor cell (HSPC) source, has several advantages over bone marrow transplantation with respect to matching and prompt availability for transplantation. Additionally, CB has some inherent features, such as rapid expansion of T cells, lower prevalence of graft-versus-host disease and higher graft versus tumor efficacy that make this HSPC cell source more favorable over other HSPC sources. Areas covered: This review summarizes the current CB and CB derived T cell applications aiming to better disease control for hematological malignancies and discusses future directions to more effective therapies. Expert commentary: CB transplantation could be used as a platform to extract cord blood derived T cells for ex vivo expansion and/or gene modification to improve cellular immunotherapies. In addition, combining cord blood gene-engineered T cell products with vaccination strategies, such as cord blood derived dendritic cell based vaccines, may provide synergistic immunotherapies with enhanced anti-tumor effects.

Design issues in a randomized controlled trial of a pre-emptive versus empiric antifungal strategy for invasive aspergillosis in patients with high-risk hematologic malignancies.

PubMed

Morrissey, C Orla; Chen, Sharon C-A; Sorrell, Tania C; Bradstock, Kenneth F; Szer, Jeffrey; Halliday, Catriona L; Gilroy, Nicole M; Schwarer, Anthony P; Slavin, Monica A

2011-02-01

Invasive aspergillosis (IA) is a major cause of mortality in patients with hematological malignancies, due largely to the inability of traditional culture and biopsy methods to make an early or accurate diagnosis. Diagnostic accuracy studies suggest that Aspergillus galactomannan (GM) enzyme immunoassay (ELISA) and Aspergillus PCR-based methods may overcome these limitations, but their impact on patient outcomes should be evaluated in a diagnostic randomized controlled trial (D-RCT). This article describes the methodology of a D-RCT which compares a new pre-emptive strategy (GM-ELISA- and Aspergillus PCR-driven antifungal therapy) with the standard fever-driven empiric antifungal treatment strategy. Issues including primary end-point and patient selection, duration of screening, choice of tests for the pre-emptive strategy, antifungal prophylaxis and bias control, which were considered in the design of the trial, are discussed. We suggest that the template presented herein is considered by researchers when evaluating the utility of new diagnostic tests (ClinicalTrials.gov number, NCT00163722).

4-1BB Costimulation Ameliorates T Cell Exhaustion Induced by Tonic Signaling of Chimeric Antigen Receptors

PubMed Central

Long, Adrienne H.; Haso, Waleed M.; Shern, Jack F.; Wanhainen, Kelsey M.; Murgai, Meera; Ingaramo, Maria; Smith, Jillian P.; Walker, Alec J.; Kohler, M. Eric; Venkateshwara, Vikas R.; Kaplan, Rosandra N.; Patterson, George H.; Fry, Terry J.; Orentas, Rimas J.; Mackall, Crystal L.

2015-01-01

Chimeric antigen receptors (CARs) targeting CD19 have mediated dramatic anti-tumor responses in hematologic malignancies, but tumor regression has rarely occurred using CARs targeting other antigens. It remains unknown whether the impressive effects of CD19 CARs relate to greater susceptibility of hematologic malignancies to CAR therapies, or superior functionality of the CD19 CAR itself. We discovered that tonic CAR CD3ζ phosphorylation, triggered by antigen-independent clustering of CAR scFvs, can induce early exhaustion of CAR T cells that limits anti-tumor efficacy. Such activation is present to varying degrees in all CARs studied, with the exception of the highly effective CD19 CAR. We further identify that CD28 costimulation augments, while 4-1BB costimulation ameliorates, exhaustion induced by persistent CAR signaling. Our results provide biological explanations for the dramatic anti-tumor effects of CD19 CARs and for the observations that CD19.BBz CAR T cells are more persistent than CD19.28z CAR T cells in clinical trials. PMID:25939063

Characterization of leukemias with ETV6-ABL1 fusion.

PubMed

Zaliova, Marketa; Moorman, Anthony V; Cazzaniga, Giovanni; Stanulla, Martin; Harvey, Richard C; Roberts, Kathryn G; Heatley, Sue L; Loh, Mignon L; Konopleva, Marina; Chen, I-Ming; Zimmermannova, Olga; Schwab, Claire; Smith, Owen; Mozziconacci, Marie-Joelle; Chabannon, Christian; Kim, Myungshin; Frederik Falkenburg, J H; Norton, Alice; Marshall, Karen; Haas, Oskar A; Starkova, Julia; Stuchly, Jan; Hunger, Stephen P; White, Deborah; Mullighan, Charles G; Willman, Cheryl L; Stary, Jan; Trka, Jan; Zuna, Jan

2016-09-01

To characterize the incidence, clinical features and genetics of ETV6-ABL1 leukemias, representing targetable kinase-activating lesions, we analyzed 44 new and published cases of ETV6-ABL1-positive hematologic malignancies [22 cases of acute lymphoblastic leukemia (13 children, 9 adults) and 22 myeloid malignancies (18 myeloproliferative neoplasms, 4 acute myeloid leukemias)]. The presence of the ETV6-ABL1 fusion was ascertained by cytogenetics, fluorescence in-situ hybridization, reverse transcriptase-polymerase chain reaction and RNA sequencing. Genomic and gene expression profiling was performed by single nucleotide polymorphism and expression arrays. Systematic screening of more than 4,500 cases revealed that in acute lymphoblastic leukemia ETV6-ABL1 is rare in childhood (0.17% cases) and slightly more common in adults (0.38%). There is no systematic screening of myeloproliferative neoplasms; however, the number of ETV6-ABL1-positive cases and the relative incidence of acute lymphoblastic leukemia and myeloproliferative neoplasms suggest that in adulthood ETV6-ABL1 is more common in BCR-ABL1-negative chronic myeloid leukemia-like myeloproliferations than in acute lymphoblastic leukemia. The genomic profile of ETV6-ABL1 acute lymphoblastic leukemia resembled that of BCR-ABL1 and BCR-ABL1-like cases with 80% of patients having concurrent CDKN2A/B and IKZF1 deletions. In the gene expression profiling all the ETV6-ABL1-positive samples clustered in close vicinity to BCR-ABL1 cases. All but one of the cases of ETV6-ABL1 acute lymphoblastic leukemia were classified as BCR-ABL1-like by a standardized assay. Over 60% of patients died, irrespectively of the disease or age subgroup examined. In conclusion, ETV6-ABL1 fusion occurs in both lymphoid and myeloid leukemias; the genomic profile and clinical behavior resemble BCR-ABL1-positive malignancies, including the unfavorable prognosis, particularly of acute leukemias. The poor outcome suggests that treatment with tyrosine kinase inhibitors should be considered for patients with this fusion. Copyright© Ferrata Storti Foundation.

Comparative pharmacokinetic study of high-dose etoposide and etoposide phosphate in patients with lymphoid malignancy receiving autologous stem cell transplantation.

PubMed

Dorr, R T; Briggs, A; Kintzel, P; Meyers, R; Chow, H-H S; List, A

2003-04-01

The pharmacokinetics of two etoposide (E) formulations were evaluated in patients with refractory hematologic malignancies receiving high-dose conditioning with autologous stem cell transplantation. Patients were randomized to either E at 800 mg/m(2) (containing polysorbate 80 and polyethylene glycol) or etoposide phosphate (EP) at 910 mg/m(2) on days -7 and -5, prior to melphalan, 80 mg/m(2) on day -5. On day -3, EP was repeated. Plasma E was analyzed after each formulation on days -7 and -5 to compare intrapatient pharmacokinetics. In total, 10 patients were treated: four each with multiple myeloma or Hodgkin's disease and two with non-Hodgkin's lymphoma. Mucositis was the major toxicity with seven patients. EP first produced grade 3 mucositis. There was no procedure-related mortality and eight patients remained alive 1 year post-transplant. Cumulative etoposide exposure (AUC) was slightly greater with EP (P=0.056). Conversely, the volume of distribution was slightly, 33%, larger (P=0.052) and clearance was increased with the E infusion (P=0.14). As none of the differences reached statistical significance, both E formulations appear to be pharmacokinetically equivalent in the high-dose transplant setting. The combination of high-dose EP with melphalan is an active preparative regimen prior to ABMT for hematologic malignancies.

Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

PubMed

Bhatt, Shruti; Sarosiek, Kristopher A; Lossos, Izidore S

2017-01-01

Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4 + /CD8 + T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

Timely disclosure of progress in long-term cancer survival: the boomerang method substantially improved estimates in a comparative study.

PubMed

Brenner, Hermann; Jansen, Lina

2016-02-01

Monitoring cancer survival is a key task of cancer registries, but timely disclosure of progress in long-term survival remains a challenge. We introduce and evaluate a novel method, denoted "boomerang method," for deriving more up-to-date estimates of long-term survival. We applied three established methods (cohort, complete, and period analysis) and the boomerang method to derive up-to-date 10-year relative survival of patients diagnosed with common solid cancers and hematological malignancies in the United States. Using the Surveillance, Epidemiology and End Results 9 database, we compared the most up-to-date age-specific estimates that might have been obtained with the database including patients diagnosed up to 2001 with 10-year survival later observed for patients diagnosed in 1997-2001. For cancers with little or no increase in survival over time, the various estimates of 10-year relative survival potentially available by the end of 2001 were generally rather similar. For malignancies with strongly increasing survival over time, including breast and prostate cancer and all hematological malignancies, the boomerang method provided estimates that were closest to later observed 10-year relative survival in 23 of the 34 groups assessed. The boomerang method can substantially improve up-to-dateness of long-term cancer survival estimates in times of ongoing improvement in prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Medical Decision-Making Incapacity among Newly Diagnosed Older Patients with Hematological Malignancy Receiving First Line Chemotherapy: A Cross-Sectional Study of Patients and Physicians

PubMed Central

Sugano, Koji; Okuyama, Toru; Iida, Shinsuke; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Uchida, Megumi; Nakaguchi, Tomohiro; Kubota, Yosuke; Ito, Yoshinori; Takahashi, Kazuhisa; Akechi, Tatsuo

2015-01-01

Background Decision-making capacity to provide informed consent regarding treatment is essential among cancer patients. The purpose of this study was to identify the frequency of decision-making incapacity among newly diagnosed older patients with hematological malignancy receiving first-line chemotherapy, to examine factors associated with incapacity and assess physicians’ perceptions of patients’ decision-making incapacity. Methods Consecutive patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were recruited. Decision-making capacity was assessed using the Structured Interview for Competency and Incompetency Assessment Testing and Ranking Inventory-Revised (SICIATRI-R). Cognitive impairment, depressive condition and other possible associated factors were also evaluated. Results Among 139 eligible patients registered for this study, 114 completed the survey. Of these, 28 (25%, 95% confidence interval [CI]: 17%-32%) were judged as having some extent of decision-making incompetency according to SICIATRI-R. Higher levels of cognitive impairment and increasing age were significantly associated with decision-making incapacity. Physicians experienced difficulty performing competency assessment (Cohen’s kappa -0.54). Conclusions Decision-making incapacity was found to be a common and under-recognized problem in older patients with cancer. Age and assessment of cognitive impairment may provide the opportunity to find patients that are at a high risk of showing decision-making incapacity. PMID:26296202

ATF4 induction through an atypical integrated stress response to ONC201 triggers p53-independent apoptosis in hematological malignancies.

PubMed

Ishizawa, Jo; Kojima, Kensuke; Chachad, Dhruv; Ruvolo, Peter; Ruvolo, Vivian; Jacamo, Rodrigo O; Borthakur, Gautam; Mu, Hong; Zeng, Zhihong; Tabe, Yoko; Allen, Joshua E; Wang, Zhiqiang; Ma, Wencai; Lee, Hans C; Orlowski, Robert; Sarbassov, Dos D; Lorenzi, Philip L; Huang, Xuelin; Neelapu, Sattva S; McDonnell, Timothy; Miranda, Roberto N; Wang, Michael; Kantarjian, Hagop; Konopleva, Marina; Davis, R Eric; Andreeff, Michael

2016-02-16

The clinical challenge posed by p53 abnormalities in hematological malignancies requires therapeutic strategies other than standard genotoxic chemotherapies. ONC201 is a first-in-class small molecule that activates p53-independent apoptosis, has a benign safety profile, and is in early clinical trials. We found that ONC201 caused p53-independent apoptosis and cell cycle arrest in cell lines and in mantle cell lymphoma (MCL) and acute myeloid leukemia (AML) samples from patients; these included samples from patients with genetic abnormalities associated with poor prognosis or cells that had developed resistance to the nongenotoxic agents ibrutinib and bortezomib. Moreover, ONC201 caused apoptosis in stem and progenitor AML cells and abrogated the engraftment of leukemic stem cells in mice while sparing normal bone marrow cells. ONC201 caused changes in gene expression similar to those caused by the unfolded protein response (UPR) and integrated stress responses (ISRs), which increase the translation of the transcription factor ATF4 through an increase in the phosphorylation of the translation initiation factor eIF2α. However, unlike the UPR and ISR, the increase in ATF4 abundance in ONC201-treated hematopoietic cells promoted apoptosis and did not depend on increased phosphorylation of eIF2α. ONC201 also inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling, likely through ATF4-mediated induction of the mTORC1 inhibitor DDIT4. Overexpression of BCL-2 protected against ONC201-induced apoptosis, and the combination of ONC201 and the BCL-2 antagonist ABT-199 synergistically increased apoptosis. Thus, our results suggest that by inducing an atypical ISR and p53-independent apoptosis, ONC201 has clinical potential in hematological malignancies. Copyright © 2016, American Association for the Advancement of Science.

Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies

PubMed Central

Choi, Joon Young; Lee, Hea Yon; Lee, Jong Wook; Lee, Dong Gun

2017-01-01

Background The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. Methods We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. Results A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. Conclusions The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status. PMID:28061469

Diagnosis of cytomegalovirus pneumonia by quantitative polymerase chain reaction using bronchial washing fluid from patients with hematologic malignancies.

PubMed

Lee, Hwa Young; Rhee, Chin Kook; Choi, Joon Young; Lee, Hea Yon; Lee, Jong Wook; Lee, Dong Gun

2017-06-13

The incidence of cytomegalovirus (CMV) pneumonia is increasing in patients diagnosed with hematologic malignancies. The utility of CMV-DNA viral load measurement has not been standardized, and viral cut-off values have not been established. This study was designed to investigate the utility of CMV quantitative real-time PCR (qRT-PCR) using bronchial washing fluid. We retrospectively reviewed the microbiologic and pathologic results of bronchial washing fluid and biopsy specimens in addition to the patients' clinical characteristics. A total of 565 CMV qRT-PCR assays were performed using bronchial washing fluid from patients with hematologic malignancies. Among them, 101 were positive for CMV by qRT-PCR; of these, 24 were diagnosed with CMV pneumonia and 70 with CMV infection, and 7 were excluded due to a diagnosis of invasive pulmonary aspergillosis rather than viral pneumonia. The median CMV load determined by qPCR was 1.8 × 105 copies/mL (3.6 103-1.5 × 108) in CMV pneumonia patients and 3.0 × 103 copies/mL (5.0 × 102-1.1 × 105) in those diagnosed with CMV infection (P < 0.01). Using the ROC curve, the optimal inflection points were 18,900 copies/mL (137,970 IU/mL) in post-bone marrow transplantation (BMT) patients, 316,415 copies/mL (2,309,825 IU/mL) in no-BMT patients and 28,774 copies/mL (210,054 IU/mL) in all patients. The CMV titers in bronchial washing fluid determined by qRT-PCR differed significantly between patients diagnosed with CMV pneumonia and those with CMV infection. The viral cut-off values in bronchial washing fluid were suggested for the diagnosis of CMV pneumonia, which were different depending on the BMT status.

Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.

PubMed

Jamme, Matthieu; Daviaud, Fabrice; Charpentier, Julien; Marin, Nathalie; Thy, Michaël; Hourmant, Yannick; Mira, Jean-Paul; Pène, Frédéric

2017-12-01

To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications. An 8-year (2008-2015) monocenter retrospective study. A medical ICU in a tertiary care center. Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis. None. Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively. The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.

A T-cell-directed chimeric antigen receptor for the selective treatment of T-cell malignancies.

PubMed

Mamonkin, Maksim; Rouce, Rayne H; Tashiro, Haruko; Brenner, Malcolm K

2015-08-20

Options for targeted therapy of T-cell malignancies remain scarce. Recent clinical trials demonstrated that chimeric antigen receptors (CARs) can effectively redirect T lymphocytes to eradicate lymphoid malignancies of B-cell origin. However, T-lineage neoplasms remain a more challenging task for CAR T cells due to shared expression of most targetable surface antigens between normal and malignant T cells, potentially leading to fratricide of CAR T cells or profound immunodeficiency. Here, we report that T cells transduced with a CAR targeting CD5, a common surface marker of normal and neoplastic T cells, undergo only limited fratricide and can be expanded long-term ex vivo. These CD5 CAR T cells effectively eliminate malignant T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoma lines in vitro and significantly inhibit disease progression in xenograft mouse models of T-ALL. These data support the therapeutic potential of CD5 CAR in patients with T-cell neoplasms. © 2015 by The American Society of Hematology.

Coexistence of pyoderma gangrenosum and sweet's syndrome in a patient with ulcerative colitis.

PubMed

Ajili, Faida; Souissi, Asmahan; Bougrine, Fathi; Boussetta, Najah; Abdelhafidh, Nadia Ben; Sayhi, Sameh; Louzir, Bassem; Doss, Nejib; Laabidi, Janet; Othmani, Salah

2015-01-01

Pyoderma gangrenosum (PG) and Sweet's Syndrome (SS) are inflammatory skin diseases caused by the accumulation of neutrophils in the skin and, rarely, in internal organs. These neutrophilic dermatosis (NDs) are distinguished by the existence of forms of transition or overlap. They are frequently associated to systemic diseases especially hematologic and gastrointestinal ones. We report a case of a patient with ulcerative colitis (UC) who successively developed two types of NDs: PG then SS. A 66 years old patient with a history of UC consulted in July 2012 for an erythematous swelling of the back of the right hand treated with antibiotics without improvement. At that time, bacteriological samples were negative. In October 2012, he was hospitalized for polyarthralgia and impaired general condition. In physical examination, he had vesiculobullous plaque of 10 cm long of the right hand and wrist, infiltrated erythematous plaque on the right leg and another topped with a large pustule at the left ankle. Skin biopsy showed at the back of the right hand an aspect of PG and at the infiltrated plaques of the ankle an aspect of SS. Prednisone was started with improvement of the skin lesions and a recovery condition. The combination of PG and SS has already been described in cases of hematologic malignancy and rarely in UC. There is also the notion of passage from a neutrophilic dermatosis to another. Indeed, a typical lesion initially of SS can evolve to a future PG. This case demonstrates that neutrophilic dermatoses form a continous spectrum of entities that may occur in UC.

Recommendations for accreditation of laboratories in molecular biology of hematologic malignancies.

PubMed

Flandrin-Gresta, Pascale; Cornillet, Pascale; Hayette, Sandrine; Gachard, Nathalie; Tondeur, Sylvie; Mauté, Carole; Cayuela, Jean-Michel

2015-01-01

Over recent years, the development of molecular biology techniques has improved the hematological diseases diagnostic and follow-up. Consequently, these techniques are largely used in the biological screening of these diseases; therefore the Hemato-oncology molecular diagnostics laboratories must be actively involved in the accreditation process according the ISO 15189 standard. The French group of molecular biologists (GBMHM) provides requirements for the implementation of quality assurance for the medical molecular laboratories. This guideline states the recommendations for the pre-analytical, analytical (methods validation procedures, quality controls, reagents), and post-analytical conditions. In addition, herein we state a strategy for the internal quality control management. These recommendations will be regularly updated.

[Clinical and etiologic study of 90 cases of chronic diarrhea].

PubMed

Farfán Flores, G; Sánchez, G; Tello, R; Villanueva, G

1993-01-01

90 patients with chronic diarrhoea underwent this prospective study. They were seen in a private hospital of Lima during 1990 and 1991. According to a methodologic plan for determining sources and the diseases that originate chronic diarrhoea. In all patients hematologic, bioquimic, coprocultures, coproparasitologic exams were done, chest and intestinal transit X-rays. All underwent duodenal content culture. Colon X-ray in 25 cases; proctosigmoidoscopy in 14 and upper digestive endoscopy in 19 patients. Abdominal echography in 12 and TAC in 2 cases. The final results showed as determinant diseases for chronic diarrhoea, according to their frequency: enteroparasitosis (23.3%), functional digestive disorders (20.0%), intestinal bacterial overpopulation (15.5%) of unknown origin (8.8%), colon diverticulus (7.7%) proven and probably (5.5%), lactose intolerance (3.3%), diabetes mellitus (2.2%), and in one case (1.1%) the following: intestinal linfoma, pancreas malignancy, AIDS, colonic and deformation and megaloblastic anemia. The causes of chronic diarrhoea are several and multifactorals and in this study we prove the preeminence of the intestinal parasitosis, functional disorders and intestinal bacterial overpopulation and with less frequency other pathologies.

[Infection due to Rothia mucilaginosa. A respiratory pathogen?].

PubMed

Ramos, José M; Mateo, Ignacio; Vidal, Inmaculada; Rosillo, Eva M; Merino, Esperanza; Portilla, Joaquín

2014-05-01

To describe the spectrum of infections caused by Rothia mucilaginosa. Retrospective study of 20 cases diagnosed with R. mucilaginosa from 2009 to 2012. Pulmonary infection was the most frequent clinical presentation (n=14, 70%): bronchiectasis infected (10), followed by pleural empyema (2), pneumonia (1) and acute bronchitis (1). Two episodes were of gastrointestinal origin: cholangitis secondary to biliary drainage and secondary peritonitis. Two episodes included bacteremia in patients with hematological malignancy. One patient had a surgical wound infection with bacteremia, and another had a bacteremic urinary tract infection in a patient with nephrostomy. R. mucilaginosa may be responsible for infections of the lower respiratory tract in predisposed patients. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Resolution of hematocolpos in adolescents affected with Graft Versus Host Disease.

PubMed

Michala, Lina; Vlachopapadopoulou, Elpis; Tsimaris, Pandelis; Papaioannou, Georgia; Paisiou, Anna; Peristeri, Ioulia; Michalacos, Stephanos; Kitra, Vassiliki

2018-05-29

Bone Marrow Transplant (BMT) is a lifesaving procedure for a range of serious benign or malignant hematological conditions. A proportion of patients however will develop Graft Versus Host Disease (GVHD), acute or chronic, with serious long term sequalae. We present two cases of hematocolpos that developed in adolescence because of vaginal synechiae due to GVHD. The condition was initially asymptomatic, resolved spontaneously at first and recurred. In one girl blunt lysis of the adhesions was performed under general anesthetic, followed thereafter by local hydrocortisone and estriol treatment. Genital symptoms may not be readily reported by adolescents post BMT. Physicians should be aware of possible late effects of GVHD on genitalia, inquire about symptoms and be acquainted with addressing complications, such as vaginal obstruction. Copyright © 2018. Published by Elsevier Inc.

Selective Immunophenotyping for Diagnosis of B-cell Neoplasms: Immunohistochemistry and Flow Cytometry Strategies and Results

PubMed Central

Boyd, Scott D.; Natkunam, Yasodha; Allen, John R.; Warnke, Roger A.

2012-01-01

Determining the immunophenotype of hematologic malignancies is now an indispensible part of diagnostic classification, and can help to guide therapy, or to predict clinical outcome. Diagnostic workup should be guided by morphologic findings and evaluate clinically important markers, but ideally should avoid the use of overly-broad panels of immunostains that can reveal incidental findings of uncertain significance and give rise to increased costs. Here, we outline our approach to diagnosis of B cell neoplasms, combining histologic and clinical data with tailored panels of immunophenotyping reagents, in the context of the 2008 World Health Organization classification. We present data from cases seen at our institution from 2004-8 using this approach, to provide a practical reference for findings seen in daily diagnostic practice. PMID:22820658

CureOne Registry: Advanced Malignancy or Myelodysplasia, Tested by Standard Sequencing and Treated by Physician Choice

ClinicalTrials.gov

2017-10-02

Neoplasms; Lung Neoplasms; Colon Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Prostate Neoplasms; Kidney Neoplasms; Liver Neoplasms; Rectal Neoplasms; Hematologic Neoplasms; Multiple Myeloma; Myelodysplastic Syndromes; Ovarian Neoplasms; Bladder Neoplasms; Testicular Neoplasms; Endometrial Neoplasms; Brain Neoplasms; Biliary Tract Neoplasms; Head and Neck Neoplasms; Uterine Cervical Neoplasms; Skin Neoplasms; Melanoma; Gastric Neoplasms; Anal Neoplasms; Sarcoma

Spatial variation in mortality risk for haematological malignancies near a petrochemical refinery: a population-based case-control study

PubMed Central

Di Salvo, Francesca; Meneghini, Elisabetta; Vieira, Veronica; Baili, Paolo; Mariottini, Mauro; Baldini, Marco; Micheli, Andrea; Sant, Milena

2015-01-01

Introduction The study investigated the geographic variation of mortality risk for hematological malignancies (HMs) in order to identify potential high-risk areas near an Italian petrochemical refinery. Material and methods A population-based case-control study was conducted and residential histories for 171 cases and 338 sex- and age-matched controls were collected. Confounding factors were obtained from interviews with consenting relatives for 109 HM deaths and 267 controls. To produce risk mortality maps, two different approaches were applied. We mapped (1) adptive kernel density relative risk estimation (KDE) for case-control studies which estimates a spatial relative risk function using the ratio between cases and controls’ densities, and (2) estimated odds ratios for case-control study data using generalized additive models (GAMs) to smooth the effect of location, a proxy for exposure, while adjusting for confounding variables. Results No high-risk areas for HM mortality were identified among all subjects (men and women combined), by applying both approaches. Using the adaptive KDE approach, we found a significant increase in death risk only among women in a large area 2–6 km southeast of the refinery and the application of GAMs also identified a similarly-located significant high-risk area among women only (global p-value<0.025). Potential confounding risk factors we considered in the GAM did not alter the results. Conclusion Both approaches identified a high-risk area close to the refinery among women only. Those spatial methods are useful tools for public policy management to determine priority areas for intervention. Our findings suggest several directions for further research in order to identify other potential environmental exposures that may be assessed in forthcoming studies based on detailed exposure modeling. PMID:26073202

A Druggable TCF4 and BRD4 dependent Transcriptional Network Sustains Malignancy in Blastic Plasmacytoid Dendritic Cell Neoplasm

PubMed Central

Ceribelli, Michele; Hou, Zhiying Esther; Kelly, Priscilla N.; Huang, Da Wei; Wright, George; Ganapathi, Karthik; Evbuomwan, Moses O.; Pittaluga, Stefania; Shaffer, Arthur L.; Marcucci, Guido; Forman, Stephen J.; Xiao, Wenming; Guha, Rajarshi; Zhang, Xiaohu; Ferrer, Marc; Chaperot, Laurence; Plumas, Joel; Jaffe, Elaine S.; Thomas, Craig J.; Reizis, Boris; Staudt, Louis M.

2016-01-01

SUMMARY Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive and largely incurable hematologic malignancy originating from plasmacytoid dendritic cells (pDCs). Using RNA interference screening, we identified the E-box transcription factor TCF4 as a master regulator of the BPDCN oncogenic program. TCF4 served as a faithful diagnostic marker of BPDCN, and its downregulation caused the loss of the BPDCN-specific gene expression program and apoptosis. High-throughput drug screening revealed that bromodomain and extra-terminal domain inhibitors (BETi’s) induced BPDCN apoptosis, which was attributable to disruption of a BPDCN-specific transcriptional network controlled by TCF4-dependent super-enhancers. BETi’s retarded the growth of BPDCN xenografts, supporting their clinical evaluation in this recalcitrant malignancy. PMID:27846392

Therapeutic radiation and the potential risk of second malignancies.

PubMed

Kamran, Sophia C; Berrington de Gonzalez, Amy; Ng, Andrea; Haas-Kogan, Daphne; Viswanathan, Akila N

2016-06-15

Radiation has long been associated with carcinogenesis. Nevertheless, it is an important part of multimodality therapy for many malignancies. It is critical to assess the risk of secondary malignant neoplasms (SMNs) after radiation treatment. The authors reviewed the literature with a focus on radiation and associated SMNs for primary hematologic, breast, gynecologic, and pediatric tumors. Radiation appeared to increase the risk of SMN in all of these; however, this risk was found to be associated with age, hormonal influences, chemotherapy use, environmental influences, genetic predisposition, infection, and immunosuppression. The risk also appears to be altered with modern radiotherapy techniques. Practitioners of all specialties who treat cancer survivors in follow-up should be aware of this potential risk. Cancer 2016;122:1809-21. © 2016 American Cancer Society. © 2016 American Cancer Society.

The prevention of oral mucositis in patients with blood cancers: current concepts and emerging landscapes.

PubMed

Niscola, Pasquale; Tendas, Andrea; Cupelli, Luca; Catalano, Gianfranco; Scaramucci, Laura; Giovannini, Marco; Trinchieri, Vito; Sharma, Atul; Efficace, Fabio; Cartoni, Claudio; Piccioni, Daniela; Perrotti, Alessio; Dentamaro, Teresa; de Fabritiis, Paolo; Keefe, Dorothy M K

2012-12-01

The prevention of oral mucositis (OM) in the management of hematological malignancies continues to represent an unmet clinical need. Addressing this issue has major clinical implications as OM can also greatly impair patient's quality of life. To review currently available measures and investigational agents to prevent OM in hematological patients. we searched for OM and related issues using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. Many agents targeting different mechanisms of mucosal damage have been applied in order to prevent OM; most of them have failed or its efficacy has not been fully demonstrated. Palifermin is the first pharmaceutical/biological agent approved for the prevention of OM; its use is currently restricted to patients who have received radiotherapy-containing conditioning regimens prior to autologous hematopoietic stem cell transplantation. No clear benefit by this agent has been demonstrated outside of this specific setting and its application should be limited to clinical trials. Other interventions, such as other growth factors and non mitogenic measures are under investigation or in development and their application in the hematological setting is expected in the short term.

Clinical outcome and prognostic markers for patients with gynecologic malignancies in phase 1 clinical trials: a single institution experience from 1999 to 2010.

PubMed

Hou, June Y; Aparo, Santiago; Ghalib, Mohammad; Chaudhary, Imran; Shah, Umang; Swami, Umang; Einstein, Mark; Goldberg, Gary L; Mani, Sridhar; Goel, Sanjay

2013-10-01

There is a scarcity of outcome data regarding phase 1 trials for patients with gynecologic malignancy. The objective of this study was to assess toxicity, clinical benefit and prognosticators in gynecologic oncology patients participating in phase 1 trials. All phase 1 oncology trials conducted at Albert Einstein Cancer Center from 1999 to 2010 were reviewed and extracted for relevant demographic and clinical data concerning patients with gynecologic malignancy. Cox-proportional and logistic regression modeling were used for multivariate analysis. 120 distinct patients with gynecologic malignancy participated in 41 trials, constituting 30.6% of all phase 1 patients enrolled in the same time period. The median age is 59 years. Out of the 184 patients enrolled, 160 individual responses were evaluable. Seventeen DLT events (9.2%) occurred, including 1 (0.5%) treatment-related mortality. There were 27.2%≥ grade 3 hematologic and 24.4% non-hematologic toxicity. Eighty patients had stable disease (SD, 50%), including 21.9% with SD ≥ 4 months, 11 (6.3%) with partial response (PR), and 3 (1.9%) achieving complete response (CR). The clinical benefit rate (CBR=SD+CR+PR) was 58.1%. Albumin (Alb)≤ 3.5 g/dL and abnormal ANC were independent negative prognosticators of survival. We also found a continuous correlation between changes in Albumin (p=0.02) and LDH (p=0.02) and odds of achieving CBR≥4month. Our clinical outcome and safety data suggested that phase 1 trials may be a reasonable option for patients with advanced and recurrent gynecologic cancer. The potential prognosticators identified should be further validated in larger trials. © 2013.

[From JSLH (The Japanese Society for Laboratory Hematology): An Active Team Approach to Medicine as Laboratory Technologists, through Showing Bone Marrow and Peripheral Blood Samples Directly to Patients with Hematological Malignancy].

PubMed

Shimizu, Sanae; Kojima, Yukari; Saito, Kyoko; Wada, Hisako; Yamamoto, Masahiro; Morinaga, Koji; Kawai, Yasukazu; Haba, Toshihiro

2014-11-01

The clinical path for the treatment of acute myeloid leukemia (AML) patients has been in practice in our hospital since 2003. In the clinical path, laboratory technologists take on the role of explaining the microscopic findings in bone marrow and peripheral blood samples to patients (with or without their families) using the view-sharing microscope in our laboratory. From July 2003 to October 2014, 56 patients were enrolled in the AML clinical path and given an explanation of their bone marrow and peripheral blood samples. The patients' median age was 62, and the median time spent for explanation was 40 minutes. We conducted a questionnaire feedback survey involving those who enrolled, and the results showed significant improvement in the recognition of the disease pathophysiology, treatment efficacy, and the importance of precautions against infectious diseases. Based on the feedback, we have made marked efforts to provide patients with an improved environment during the explanatory session. This includes installing a special display for the patients, drawing a schematic illustration that shows how the blood cells differentiate, and putting them into operation in a hematology ward to promote patient privacy and precautions against infectious diseases. Hematological laboratory technologists have played an important role in patient care in our hospital. To perform their role as effectively as possible, hematological laboratory technologists participate in the conferences of the Department of Hematology and Oncology regularly, in which medical staff members can discuss the conditions and clinical courses of patients. We aim to contribute to patient satisfaction by sophisticating specialized knowledge as hematological laboratory technologists and cooperate with other medical staff members.

CD30 expression utilization for the accuracy of classical Hodgkin's lymphoma staging.

PubMed

Flangea, Corina; Potencz, Elena; Mihăescu, Rodica; Anghel, A; Gîju, S; Motoc, Marilena; Dogaru, C

2006-01-01

The presence of Reed-Sternberg malignant cells is absolutely necessary for Hodgkin's lymphoma diagnostic, but it is not always sufficient because can be observed Reed-Sternberg-like cells in other malignant and benign diseases, too. The CD30 expression at Hodgkin and Reed-Sternberg level can give us supplementary information in differential diagnostic and can be used as progressive disease factor. Our study was composed from 63 cases histopathological diagnosed with Hodgkin's lymphoma and hospitalized in Hematology Department of County Hospital Timişoara. CD30 expression was immunohistochemical semi-quantitative evaluated using clone BerH2 as primary antibody and APAAP-New Fuchsin as visualization system. The increasing of CD30 expression occurs in the same time with advanced stages and the disease progression (p =0.001). For I and II stages CD30 expression does not overcome (-/+) category while the III and IV stages, all the cases are situated in (+/-) and (+) categories. No connection can be noticed between histological type and CD30 expression (p < or = 1). We consider that using this staining, although less used in Romania, must be done in all Hodgkin's lymphoma and Hodgkin's lymphoma-like cases. We say that because the main cause of relapses is represented by inadequate clinical staging and diagnostic. In our study, the increasing of CD30 expression is associated with advanced disease stage. We recommend reinvestigating and restaging all cases that was included into an incipient stages and they have a CD30 expression situated in (+/-) and (+) intervals because some lymph nodes could be overlooked.

Biological therapy of hematologic malignancies: toward a chemotherapy-free era.

PubMed

Klener, Pavel; Etrych, Tomas; Klener, Pavel

2017-10-06

Less than 70 years ago, the vast majority of hematologic malignancies were untreatable diseases with fatal prognoses. The development of modern chemotherapy agents, which had begun after the Second World War, was markedly accelerated by the discovery of the structure of DNA and its role in cancer biology and tumor cell division. The path travelled from the first temporary remissions observed in children with acute lymphoblastic leukemia treated with single-agent antimetabolites until the first cures achieved by multi-agent chemotherapy regimens was incredibly short. Despite great successes, however, conventional genotoxic cytostatics suffered from an inherently narrow therapeutic index and extensive toxicity, which in many instances limited their clinical utilization. In the last decade of the 20th century, increasing knowledge on the biology of certain malignancies resulted in the conception and development of first molecularly targeted agents designed to inhibit specific druggable molecules involved in the survival of cancer cells. Advances in technology and genetic engineering enabled the production of structurally complex anticancer macromolecules called biologicals, including therapeutic monoclonal antibodies, antibody-drug conjugates and antibody fragments. The development of drug delivery systems (DDSs), in which conventional drugs were attached to various types of carriers including nanoparticles, liposomes or biodegradable polymers, represented an alternative approach to the development of new anticancer agents. Despite the fact that the antitumor activity of drugs attached to DDSs was not fundamentally different, the improved pharmacokinetic profiles, decreased toxic side effects and significantly increased therapeutic indexes resulted in their enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of the first immune checkpoint inhibitor for the treatment of cancer in 2011 initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific T-cell engagers, adoptive T-cell approaches and cancer vaccines have joined the platform so far, represented mainly by recombinant cytokines, therapeutic monoclonal antibodies and immunomodulatory agents. In specific clinical indications, conventional drugs have already been supplanted by multi-agent, chemotherapy-free regimens comprising diverse immunotherapy and/or targeted agents. The very distinct mechanisms of the anticancer activity of new immunotherapy approaches not only call for novel response criteria, but also might fundamental change treatment paradigms of certain types of hematologic malignancies in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Strategies for the Identification of T Cell–Recognized Tumor Antigens in Hematological Malignancies for Improved Graft-versus-Tumor Responses after Allogeneic Blood and Marrow Transplantation

PubMed Central

Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

2015-01-01

Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient’s cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient’s existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies. PMID:25459643

Strategies for the identification of T cell-recognized tumor antigens in hematological malignancies for improved graft-versus-tumor responses after allogeneic blood and marrow transplantation.

PubMed

Zilberberg, Jenny; Feinman, Rena; Korngold, Robert

2015-06-01

Allogeneic blood and marrow transplantation (allo-BMT) is an effective immunotherapeutic treatment that can provide partial or complete remission for patients with hematological malignancies. Mature donor T cells in the donor inoculum play a central role in mediating graft-versus-tumor (GVT) responses by destroying residual tumor cells that persist after conditioning regimens. Alloreactivity towards minor histocompatibility antigens (miHA), which are varied tissue-related self-peptides presented in the context of major histocompatibility complex (MHC) molecules on recipient cells, some of which may be shared on tumor cells, is a dominant factor for the development of GVT. Potentially, GVT can also be directed to tumor-associated antigens or tumor-specific antigens that are more specific to the tumor cells themselves. The full exploitation of allo-BMT, however, is greatly limited by the development of graft-versus-host disease (GVHD), which is mediated by the donor T cell response against the miHA expressed in the recipient's cells of the intestine, skin, and liver. Because of the significance of GVT and GVHD responses in determining the clinical outcome of patients, miHA and tumor antigens have been intensively studied, and one active immunotherapeutic approach to separate these two responses has been cancer vaccination after allo-BMT. The combination of these two strategies has an advantage over vaccination of the patient without allo-BMT because his or her immune system has already been exposed and rendered unresponsive to the tumor antigens. The conditioning for allo-BMT eliminates the patient's existing immune system, including regulatory elements, and provides a more permissive environment for the newly developing donor immune compartment to selectively target the malignant cells. Utilizing recent technological advances, the identities of many human miHA and tumor antigenic peptides have been defined and are currently being evaluated in clinical and basic immunological studies for their ability to produce effective T cell responses. The first step towards this goal is the identification of targetable tumor antigens. In this review, we will highlight some of the technologies currently used to identify tumor antigens and anti-tumor T cell clones in hematological malignancies. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Survival and Late Effects after Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancy at Less than Three Years of Age.

PubMed

Vrooman, Lynda M; Millard, Heather R; Brazauskas, Ruta; Majhail, Navneet S; Battiwalla, Minoo; Flowers, Mary E; Savani, Bipin N; Akpek, Görgün; Aljurf, Mahmoud; Bajwa, Rajinder; Baker, K Scott; Beitinjaneh, Amer; Bitan, Menachem; Buchbinder, David; Chow, Eric; Dandoy, Christopher; Dietz, Andrew C; Diller, Lisa; Gale, Robert Peter; Hashmi, Shahrukh K; Hayashi, Robert J; Hematti, Peiman; Kamble, Rammurti T; Kasow, Kimberly A; Kletzel, Morris; Lazarus, Hillard M; Malone, Adriana K; Marks, David I; O'Brien, Tracey A; Olsson, Richard F; Ringden, Olle; Seo, Sachiko; Steinberg, Amir; Yu, Lolie C; Warwick, Anne; Shaw, Bronwen; Duncan, Christine

2017-08-01

Very young children undergoing hematopoietic cell transplantation (HCT) are a unique and vulnerable population. We analyzed outcomes of 717 patients from 117 centers who survived relapse free for ≥1 year after allogeneic myeloablative HCT for hematologic malignancy at <3 years of age, between 1987 and 2012. The median follow-up was 8.3 years (range, 1.0 to 26.4 years); median age at follow-up was 9 years (range, 2 to 29 years). Ten-year overall and relapse-free survival were 87% (95% confidence interval [CI], 85% to 90%) and 84% (95% CI, 81% to 87%). Ten-year cumulative incidence of relapse was 11% (95% CI, 9% to 13%). Of 84 deaths, relapse was the leading cause (43%). Chronic graft-versus-host-disease 1 year after HCT was associated with increased risk of mortality (hazard ratio [HR], 2.1; 95% CI, 1.3 to 3.3; P = .0018). Thirty percent of patients experienced ≥1 organ toxicity/late effect >1 year after HCT. The most frequent late effects included growth hormone deficiency/growth disturbance (10-year cumulative incidence, 23%; 95% CI, 19% to 28%), cataracts (18%; 95% CI, 15% to 22%), hypothyroidism (13%; 95% CI, 10% to 16%), gonadal dysfunction/infertility requiring hormone replacement (3%; 95% CI, 2% to 5%), and stroke/seizure (3%; 95% CI, 2% to 5%). Subsequent malignancy was reported in 3.6%. In multivariable analysis, total body irradiation (TBI) was predictive of increased risk of cataracts (HR, 17.2; 95% CI, 7.4 to 39.8; P < .001), growth deficiency (HR, 3.5; 95% CI, 2.2 to 5.5; P < .001), and hypothyroidism (HR, 5.3; 95% CI, 3.0 to 9.4; P < .001). In summary, those who survived relapse free ≥1 year after HCT for hematologic malignancy at <3 years of age had favorable overall survival. Chronic graft-versus-host-disease and TBI were associated with adverse outcomes. Future efforts should focus on reducing the risk of relapse and late effects after HCT at early age. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Adipocyte-derived players in hematologic tumors: useful novel targets?

PubMed

Jöhrer, Karin; Ploner, Christian; Thangavadivel, Shanmugapriya; Wuggenig, Philipp; Greil, Richard

2015-01-01

Adipocytes and their products play essential roles in tumor establishment and progression. As the main cellular component of the bone marrow, adipocytes may contribute to the development of hematologic tumors. This review summarizes experimental data on adipocytes and their interaction with various cancer cells. Special focus is set on the interactions of bone marrow adipocytes and normal and transformed cells of the hematopoietic system such as myeloma and leukemia cells. Current in vitro and in vivo data are summarized and the potential of novel therapeutic targets is critically discussed. Targeting lipid metabolism of cancer cells and adipocytes in combination with standard therapeutics might open novel therapeutic avenues in these cancer entities. Adipocyte-derived products such as free fatty acids and specific adipokines such as adiponectin may be vital anti-cancer targets in hematologic malignancies. However, available data on lipid metabolism is currently mostly referring to peripheral fat cell/cancer cell interactions and results need to be evaluated specifically for the bone marrow niche.

Peripherally Inserted Central Venous Catheters in Pediatric Hematology/Oncology Patients in Tertiary Care Setting: A Developing Country Experience.

PubMed

Fadoo, Zehra; Nisar, Muhammad I; Iftikhar, Raza; Ali, Sajida; Mushtaq, Naureen; Sayani, Raza

2015-10-01

Peripherally inserted central venous catheters (PICC) have been successfully used to provide central access for chemotherapy and frequent transfusions. The purpose of this study was to assess the feasibility of PICCs and determine PICC-related complications in pediatric hematology/oncology patients in a resource-poor setting. All pediatric patients (age below 16 y) with hematologic and malignant disorders who underwent PICC line insertion at Aga Khan University Hospital from January 2008 to June 2010 were enrolled in the study. Demographic features, primary diagnosis, catheter days, complications, and reasons for removal of device were recorded. Total of 36 PICC lines were inserted in 32 pediatric patients. Complication rate of 5.29/1000 catheter days was recorded. Our study showed comparable complication profile such as infection rate, occlusion, breakage, and dislodgement. The median catheter life was found to be 69 days. We conclude that PICC lines are feasible in a resource-poor setting and recommend its use for chemotherapy administration and prolonged venous access.

Breakthrough Invasive Mold Infections in the Hematology Patient: Current Concepts and Future Directions.

PubMed

Lionakis, Michail S; Lewis, Russell E; Kontoyiannis, Dimitrios P

2018-05-31

Although the widespread use of mold-active agents (especially the new-generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including co-morbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.

Donor Chimerism of B Cells and Nature Killer Cells Provides Useful Information to Predict Hematologic Relapse following Allogeneic Hematopoietic Stem Cell Transplantation.

PubMed

Jiang, Ying; Wan, Liping; Qin, Youwen; Wang, Xiaorui; Yan, Shike; Xie, Kuangcheng; Wang, Chun

2015-01-01

In this study we investigated the correlation between donor chimerism status and disease relapse following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The chimerism of Fluorescence-activated cell sorter (FACS) sorted CD3+T lymphocytes of 153 cases, CD56+CD16+NK lymphocytes of 153 cases and CD19+B lymphocytes of 31 cases with acute B lymphoblastic leukemia (B-ALL) was analyzed post-transplant utilizing polymerase chain reaction amplification of short tandem repeats (PCR-STR). A total of 33 patients (33/153, 21.6%) had recurrent disease. The positive predictive values of declining donor chimerism for hematologic and isolated extramedullary relapse were 58.8% and 10% (P=0.018, Chi-Square). The positive predictive values of declining donor chimerism in BMB, BMT, BMNK and PBB for hematologic relapse were 11.6%, 0%, 0% and 0% under close monitoring in patients with B-ALL. Only the donor chimerism in BMB significantly decreased in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.00, Independent-samples T test) in patients with B-ALL. The median drop of donor chimerism in PBT, BMT, PBNK and BMNK were 0%, 0%, 5.9% and 2.8% one or two weeks prior to hematologic relapse in patients with non-B-ALL. The donor chimerism in PBNK significantly decreased prior to hematologic relapse in the group with hematologic relapse as compared with the group without hematologic relapse (P=0.022, Independent-samples T test).These data suggest donor chimerism of BMB can be used to predict the occurrence of hematologic relapse in patients with B-ALL. Donor chimerism decrease in PBNK was associated with a somewhat increased risk of hematologic relapse in patients with non-B-ALL. Therefore, our results reveal a more effective path to individually predict for hematologic relapse by dynamic monitoring different cell lineages in different disease.

Invasive Haemophilus influenzae Infection in Patients With Cancer.

PubMed

Singh, Vivek; Nanjappa, Sowmya; Pabbathi, Smitha; Greene, John N

2017-01-01

A major cause of morbidity and mortality in patients with cancer is infection. Since the introduction of the Haemophilus influenzae type b (Hib) vaccine in the United States in the 1990s, invasive H influenzae infection has become less common. We report on 5 patients with cancer and invasive H influenzae infection. A literature review was also performed of the dominant Haemophilus subtype and the clinical features associated with the infection and concomitant cancer. Of the 17 cases found in the literature, had hematological malignancies and 1 case each had thymoma, schwannoma, teratoma, and pancreatic, Merkel cell, pharyngeal, laryngeal, and rectal carcinomas. Two cases occurred with AIDS and Kaposi sarcoma. Pneumonia with bacteremia was seen in 8 cases, whereas pleuritis, neck cellulitis, septic arthritis, meningitis, and mediastinitis were diagnosed in the others. No focus of infection was identified in 2 cases. Nontypable H influenzae (NTHi) occurred in 4 cases, and Hib was isolated in 2 cases; serotyping was not reported in the others. Leukocytosis occurred in 7 cases and lymphopenia in 3; no cases presented with neutropenia. Four isolates were positive for beta-lactamase. Susceptibility data were unavailable in 5 case patients. Among serotyped cases, 67% were of the NTHi strain - a finding consistent with the change in the epidemiology of H influenzae since the introduction of the Hib vaccine.

Biermer anemia: Hematologic characteristics of 66 patients in a Clinical Hematology Unit at Senegal.

PubMed

Seynabou, F; Fatou Samba Diago, N; Oulimata Diop, D; Abibatou Fall, S; Nafissatou, D

2016-11-01

Hematological manifestations can lead to diagnosis of pernicious anemia, also known as Biermer disease and Biermer anemia. This disease has been little studied among black Africans. Our aim is to describe its diagnostic and therapeutic aspects and outcome in our practice. This descriptive study retrospectively examined the records of 66 patients with pernicious anemia seen at the Clinical Hematology Unit of Le Dantec Hospital in Senegal from January 1, 2000, to June 30, 2014. Symptoms were anemic syndrome (40 cases), hemolytic anemia (13), anemic heart failure (7), isolated pallor of the mucous membranes (5), and venous thrombosis (2). Their mean hemoglobin on diagnosis was 6.52 g/dL [1.3-15.2 g/dL], macrocytosis (52), normocytosis (14), hypochromia (4), thrombocytopenia (39), and leukopenia (28 cases). Cytopenia was associated with pancytopenia (25) and bicytopenia (18). Cytologic abnormalities were documented in 42 cases: megaloblastic erythrosis (37 cases) and hypersegmented neutrophils (24 cases). After vitamin B12 therapy - intramuscular (52) or oral (14) -, a reticulocyte crisis was noted on the 8th day and followed by correction of the blood count. Macrocytic anemia, frequently associated with thrombocytopenia and/or leukopenia, is the main hematologic sign evoking pernicious anemia. Venous thrombosis is a rare circumstance of diagnosis that must not be ignored. Intramuscular or oral vitamin B12 is recognized to be effective in these cases and reverses hematological manifestations.

Efficacy and side effects of dacarbazine in comparison with temozolomide in the treatment of malignant melanoma: a meta-analysis consisting of 1314 patients.

PubMed

Teimouri, Fatemeh; Nikfar, Shekoufeh; Abdollahi, Mohammad

2013-10-01

The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the palliative treatment of malignant melanoma: intravenous administration of single-agent dacarbazine or oral administration of temozolomide. The aim of this study was to compare the effectiveness and side effects of dacarbazine with those of temozolomide through a meta-analysis. A thorough literature bibliography search was conducted up to 2012 to gather and review all randomized clinical trials comparing the use of dacarbazine with that of temozolomide in the treatment of malignant melanoma. Three head-to-head randomized clinical trials comprising 1314 patients met the criteria and were included. Comparison of temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83 [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control rate. The RR for nonhematologic side effects and hematologic side effects, such as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with dacarbazine in patients with malignant melanoma was nonsignificant in all cases, but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79 (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to administer oral medication, according to the results, there is no significant difference in the efficacy and side effects of these two drugs. Owing to the higher cost of treatment with temozolomide and the increased prevalence of lymphopenia on using temozolomide, use of dacarbazine as the first choice treatment for malignant melanoma is suggested.

The Rise, Fall and Subsequent Triumph of Thalidomide: Lessons Learned in Drug Development

PubMed Central

Rehman, Waqas; Arfons, Lisa M.; Lazarus, Hillard M.

2011-01-01

Perhaps no other drug in modern medicine rivals the dramatic revitalization of thalidomide. Originally marketed as a sedative, thalidomide gained immense popularity worldwide among pregnant women because of its effective anti-emetic properties in morning sickness. Mounting evidence of human teratogenicity marked a dramatic fall from grace and led to widespread social, legal and economic ramifications. Despite its tragic past thalidomide emerged several decades later as a novel and highly effective agent in the treatment of various inflammatory and malignant diseases. In 2006 thalidomide completed its remarkable renaissance becoming the first new agent in over a decade to gain approval for the treatment of plasma cell myeloma. The catastrophic collapse yet subsequent revival of thalidomide provides important lessons in drug development. Never entirely abandoned by the medical community, thalidomide resurfaced as an important drug once the mechanisms of action were further studied and better understood. Ongoing research and development of related drugs such as lenalidomide now represent a class of irreplaceable drugs in hematological malignancies. Further, the tragedies associated with this agent stimulated the legislation which revamped the FDA regulatory process, expanded patient informed consent procedures and mandated more transparency from drug manufacturers. Finally, we review recent clinical trials summarizing selected medical indications for thalidomide with an emphasis on hematologic malignancies. Herein, we provide a historic perspective regarding the up-and-down development of thalidomide. Using PubMed databases we conducted searches using thalidomide and associated keywords highlighting pharmacology, mechanisms of action, and clinical uses. PMID:23556097

Diagnosis and treatment of a dermal malignant melanoma in an African lion (Panthera leo).

PubMed

Steeil, James C; Schumacher, Juergen; Baine, Katherine; Ramsay, Edward C; Sura, Patricia; Hodshon, Rebecca; Donnell, Robert L; Lee, Nathan D

2013-09-01

A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.

Targeted nanoparticle delivery overcomes off-target immunostimulatory effects of oligonucleotides and improves therapeutic efficacy in chronic lymphocytic leukemia

PubMed Central

Yu, Bo; Mao, Yicheng; Bai, Li-Yuan; Herman, Sarah E. M.; Wang, Xinmei; Ramanunni, Asha; Jin, Yan; Mo, Xiaokui; Cheney, Carolyn; Chan, Kenneth K.; Jarjoura, David; Marcucci, Guido; Lee, Robert J.; Byrd, John C.

2013-01-01

Several RNA-targeted therapeutics, including antisense oligonucleotides (ONs), small interfering RNAs, and miRNAs, constitute immunostimulatory CpG motifs as an integral part of their design. The limited success with free antisense ONs in hematologic malignancies in recent clinical trials has been attributed to the CpG motif–mediated, TLR-induced prosurvival effects and inefficient target modulation in desired cells. In an attempt to diminish their off-target prosurvival and proinflammatory effects and specific delivery, as a proof of principle, in the present study, we developed an Ab-targeted liposomal delivery strategy using a clinically relevant CD20 Ab (rituximab)–conjugated lipopolyplex nanoparticle (RIT-INP)– and Bcl-2–targeted antisense G3139 as archetypical antisense therapeutics. The adverse immunostimulatory responses were abrogated by selective B cell–targeted delivery and early endosomal compartmentalization of G3139-encapsulated RIT-INPs, resulting in reduced NF-κB activation, robust Bcl-2 down-regulation, and enhanced sensitivity to fludarabine-induced cytotoxicity. Furthermore, significant in vivo therapeutic efficacy was noted after RIT-INP–G3139 administration in a disseminated xenograft leukemia model. The results of the present study demonstrate that CD20-targeted delivery overcomes the immunostimulatory properties of CpG-containing ON therapeutics and improves efficient gene silencing and in vivo therapeutic efficacy for B-cell malignancies. The broader implications of similar approaches in overcoming immunostimulatory properties of RNA-directed therapeutics in hematologic malignancies are also discussed. PMID:23165478

Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor.

PubMed

Monsalvo, Silvia; Serrano, Cristina; Prieto, Elena; Fernández-Sanz, Guillermo; Puente, Maria-Camino; Rodriguez-Pinilla, Maria; Garcia Raso, Aranzazu; Llamas, Pilar; Cordoba, Raul

2017-07-01

The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV-positive patient with masquerade syndrome presenting unilateral uveitis. 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. © 2016 International Clinical Cytometry Society. © 2016 International Clinical Cytometry Society.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Zahedi Niaki, Omid; Labrecque, Jeremy; Schanberg, Laura E; Silverman, Earl D; Hayward, Kristen; Imundo, Lisa; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; Oen, Kiem; Wagner-Weiner, Linda; Rosenberg, Alan M; O'Neil, Kathleen M; Duffy, Ciarán M; von Scheven, Emily; Joseph, Lawrence; Lee, Jennifer L; Ramsey-Goldman, Rosalind

2017-10-01

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Subchronic Toxicities of HZ1006, a Hydroxamate-Based Histone Deacetylase Inhibitor, in Beagle Dogs and Sprague-Dawley Rats.

PubMed

Zhang, Xiaofang; Zhang, Xiaodong; Yuan, Bojun; Ren, Lijun; Zhang, Tianbao; Lu, Guocai

2016-11-30

Histone deacetylase inhibitors (HDACIs), such as vorinostat and panobinostat, have been shown to have active effects on many hematologic malignancies, including multiple myeloma and cutaneous T-cell lymphoma. Hydroxamate-based (Hb) HDACIs have very good toxicity profiles and are currently being tested in phases I and II clinical trials with promising results in selected neoplasms, such as bladder carcinoma. One of the Hb-HDACIs, HZ1006, has been demonstrated to be a promising drug for clinical use. The aim of our study was to determine the possible target of toxicity and to identify a non-toxic dose of HZ1006 for clinical use. In our studies, the repeated dosage toxicity of HZ1006 in Beagle dogs and Sprague Dawley (SD) rats was identified. Dogs and rats received HZ1006 orally (0-80 and 0-120 mg/kg/day, respectively) on a continuous daily dosing agenda for 28 days following a 14-day dosage-free period. HZ1006's NOAEL (No Observed Adverse Effect Level) by daily oral administration for dogs and rats was 5 mg/kg and 60 mg/kg, respectively, and the minimum toxic dose was 20 and 120 mg/kg, respectively. All the side effects indicated that the digestive tract, the male reproductive tract, the respiratory tract and the hematological systems might be HZ1006 toxic targets in humans. HZ1006 could be a good candidate or a safe succedaneum to other existing HDACIs for the treatment of some solid tumor and hematologic malignancies.

Chimeric antigen receptor T cells: power tools to wipe out leukemia and lymphoma.

PubMed

Riet, Tobias; Abken, Hinrich

2015-08-01

Adoptive cell therapy for malignant diseases is showing promise in recent early-phase trials in the treatment of B cell leukemia/lymphoma. Genetically engineered with a tumor-specific chimeric antigen receptor, patient's T cells produce lasting and complete leukemia regression. However, treatment is associated with some toxicity which needs our attention and the field still faces some hurdles at the scientific, technologic and clinical levels. Surmounting these obstacles will establish chimeric antigen receptor T cell therapy as a powerful approach to cure hematologic malignancies, paving the way for the treatment of other common types of cancer in the future.

Improved radioimmunotherapy of hematologic malignancies. Progress report, November 1, 1993--October 31, 1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

Press, O.W.

1994-08-04

This report summaries progress made during the time interval between November 1, 1993 and October 31, 1994 and briefly describes studies on the metabolism of antibodies targeting B cell antigens, retention of labeled antibodies by human B cell lymphocytes, and tissue distribution of Chloramine T and tyramine cellobiose labeled antibodies in mice harboring a human erythroleukemia tumor transplant.

Targeting the Hedgehog pathway in cancer: can the spines be smoothened?

PubMed

Ailles, Laurie; Siu, Lillian L

2011-04-15

Aberrant Hedgehog (Hh) pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematologic malignancies. GDC-0449 is a novel first-in-human, first-in-class smoothened (SMO) inhibitor, which has completed its phase I evaluation and achieved proof of concept in tumors with Hh pathway mutations. ©2011 AACR.

Nods for Atezolizumab and Nivolumab from FDA.

PubMed

2016-08-01

The FDA has conditionally approved atezolizumab, the first PD-L1 inhibitor, for metastatic urothelial carcinoma, along with a companion diagnostic, the Ventana PD-L1 (SP142) assay. The agency has also expanded nivolumab's indications to include classical Hodgkin lymphoma, making this PD-1 inhibitor the first to be approved for a hematologic malignancy. ©2016 American Association for Cancer Research.

Fusion proteins in head and neck neoplasms: Clinical implications, genetics, and future directions for targeting

PubMed Central

Escalante, Derek A.; Wang, He; Fundakowski, Christopher E.

2016-01-01

ABSTRACT Fusion proteins resulting from chromosomal rearrangements are known to drive the pathogenesis of a variety of hematological and solid neoplasms such as chronic myeloid leukemia and non-small-cell lung cancer. Efforts to elucidate the role they play in these malignancies have led to important diagnostic and therapeutic triumphs, including the famous development of the tyrosine kinase inhibitor dasatinib targeting the BCR-ABL fusion. Until recently, there has been a paucity of research investigating fusion proteins harbored by head and neck neoplasms. The discovery and characterization of novel fusion proteins in neoplasms originating from the thyroid, nasopharynx, salivary glands, and midline head and neck structures offer substantial contributions to our understanding of the pathogenesis and biological behavior of these neoplasms, while raising new therapeutic and diagnostic opportunities. Further characterization of these fusion proteins promises to facilitate advances on par with those already achieved with regard to hematologic malignancies in the precise, molecularly guided diagnosis and treatment of head and neck neoplasms. The following is a subsite specific review of the clinical implications of fusion proteins in head and neck neoplasms and the future potential for diagnostic targeting. PMID:27636353

Targeting the TAM Receptors in Leukemia.

PubMed

Huey, Madeline G; Minson, Katherine A; Earp, H Shelton; DeRyckere, Deborah; Graham, Douglas K

2016-11-08

Targeted inhibition of members of the TAM (TYRO-3, AXL, MERTK) family of receptor tyrosine kinases has recently been investigated as a novel strategy for treatment of hematologic malignancies. The physiologic functions of the TAM receptors in innate immune control, natural killer (NK) cell differentiation, efferocytosis, clearance of apoptotic debris, and hemostasis have previously been described and more recent data implicate TAM kinases as important regulators of erythropoiesis and megakaryopoiesis. The TAM receptors are aberrantly or ectopically expressed in many hematologic malignancies including acute myeloid leukemia, B- and T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. TAM receptors contribute to leukemic phenotypes through activation of pro-survival signaling pathways and interplay with other oncogenic proteins such as FLT3, LYN, and FGFR3. The TAM receptors also contribute to resistance to both cytotoxic chemotherapeutics and targeted agents, making them attractive therapeutic targets. A number of translational strategies for TAM inhibition are in development, including small molecule inhibitors, ligand traps, and monoclonal antibodies. Emerging areas of research include modulation of TAM receptors to enhance anti-tumor immunity, potential roles for TYRO-3 in leukemogenesis, and the function of the bone marrow microenvironment in mediating resistance to TAM inhibition.

Adoptive T-cell therapy for hematological malignancies using T cells gene-modified to express tumor antigen-specific receptors.

PubMed

Fujiwara, Hiroshi

2014-02-01

The functional properties of the adoptive immune response mediated by effector T lymphocytes are decisively regulated by their T-cell receptors (TCRs). Transfer of genes encoding target antigen-specific receptors enables polyclonal T cells to redirect toward cancer cells and virally infected cells expressing those defined antigens. Using this technology, a large population of redirected T cells displaying uniform therapeutic properties has been produced, powerfully advancing their clinical application as "cellular drugs" for adoptive immunotherapy against cancer. Clinically, anticancer adoptive immunotherapy using these genetically engineered T cells has an impressive and proven track record. Notable examples include the dramatic benefit of chimeric antigen receptor gene-modified T cells redirected towards B-cell lineage antigen CD19 in patients with chronic lymphocytic leukemia, and the impressive outcomes in the use of TCR gene-modified T cells redirected towards NY-ESO-1, a representative cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. In this review, we briefly overview the current status of this treatment option in the context of hematological malignancy, and discuss a number of challenges that still pose an obstacle to the full effectiveness of this strategy.

Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.

PubMed

Galaup, Ariane; Paci, Angelo

2013-03-01

Among the dimethanesulfonates, busulfan, in combination with other alkylating agents or nucleoside analogues, is the cornerstone of high-dose chemotherapy. It is used, and followed hematopoietic stem cell transplantation, for the treatment of various hematologic malignancies and immunodeficiencies. Treosulfan, which is a hydrophilic analogue of busulfan, was the first dimethanesufonate registered for the treatment of ovarian cancer. Recently, treosulfan has been investigated for the treatment of hematologic malignancies in combination with the same second agents before hematopoietic stem cell transplantation. This work reviews the pharmacological data of these two dimethanesulfonates alkylating agents. Specifically, the article looks at their chemistry, metabolism, anticancer activity, and their pharmacokinetics and pharmacodynamics. Busulfan has been investigated widely for more than three decades leading to a large and precise handling of this agent with numerous studies on activity and pharmacokinetics and pharmacodynamics. In contrast, the behavior of treosulfan is still under investigation and not fully described. The complexity of treosulfan's metabolism and mechanism of action gives rise to the need of a deeper understanding of its pharmacological activity in a context of high-dose chemotherapy. Specifically, there is a great need to better understand its pharmacokinetics/pharmacodynamics relationship.

Alterations in bone marrow and blood mononuclear cell polyamine and methylglyoxal bis(guanylhydrazone) levels: phase I evaluation of alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone) treatment of human hematological malignancies.

PubMed

Maddox, A M; Freireich, E J; Keating, M J; Haddox, M K

1988-03-01

Nine patients with hematological malignancies were treated with difluoromethylornithine and methylglyoxal bis(guanylhydrazone). The number of circulating blast cells decreased in all of the patients treated with DFMO and MGBG for longer than 1 wk. Morphological evidence of myeloid maturation was evident in four patients with leukemia and the circulating M Protein decreased in one patient with multiple myeloma. The polyamine content of the mononuclear cells in both the peripheral blood and bone marrow was transiently increased after the initial MGBG dose. During administration of DFMO decreases were achieved in the peripheral blood mononuclear cell putrescine levels in 7 patients, spermidine levels in 5 patients, and spermine levels in 4 patients. Alterations in bone marrow mononuclear cell polyamine levels were similar to those which occurred in the peripheral cells. An average of 9 days of DFMO treatment was required to lower mononuclear cell polyamine levels. Three of the 4 evaluable patients receiving multiple MGBG doses had an increased mononuclear cell content of MGBG after DFMO pretreatment. Enhancement of cellular MGBG levels was not directly correlated to the degree of cellular polyamine depletion.

Clinical sequencing in leukemia with the assistance of artificial intelligence.

PubMed

Tojo, Arinobu

2017-01-01

Next generation sequencing (NGS) of cancer genomes is now becoming a prerequisite for accurate diagnosis and proper treatment in clinical oncology. Because the genomic regions for NGS expand from a certain set of genes to the whole exome or whole genome, the resulting sequence data becomes incredibly enormous and makes it quite laborious to translate the genomic data into medicine, so-called annotation and curation. We organized a clinical sequencing team and established a bidirectional (bed-to-bench and bench-to-bed) system to integrate clinical and genomic data for hematological malignancies. We also started a collaborative research project with IBM Japan to adopt the artificial intelligence Watson for Genomics (WfG) to the pipeline of medical informatics. Genomic DNA was prepared from malignant as well as normal tissues in each patient and subjected to NGS. Sequence data was analyzed using an in-house semi-automated pipeline in combination with WfG, which was used to identify candidate driver mutations and relevant pathways from which applicable drug information was deduced. Currently, we have analyzed more than 150 patients with hematological disorders, including AML and ALL, and obtained many informative findings. In this presentation, I will introduce some of the achievements we have made so far.

Novel immunotherapies for hematological malignancies

PubMed Central

Nelson, Michelle H.; Paulos, Chrystal M.

2014-01-01

Summary The immune system is designed to discriminate between self and tumor tissue. Through genetic recombination, there is fundamentally no limit to the number of tumor antigens that immune cells can recognize. Yet, tumors use a variety of immunosuppressive mechanisms to evade immunity. Insight into how the immune system interacts with tumors is expanding rapidly and has accelerated the translation of immunotherapies into medical breakthroughs. Herein, we appraise the state of the art in immunotherapy with a focus on strategies that exploit the patient’s immune system to kill cancer. We review various forms of immune-based therapies, which have shown significant promise in patients with hematological malignancies, including (i) conventional monoclonal therapies like rituximab, (ii) engineered monoclonal antibodies called bispecific T cell engagers (BiTEs), (iii) monoclonal antibodies and pharmaceutical drugs that block inhibitory T-cell pathways (i.e. PD-1, CTLA-4 and IDO), and (iv) adoptive cell transfer (ACT) therapy with T cells engineered to express chimeric antigen receptors (CARs) or T-cell receptors (TCRs). We also assess the idea of using these therapies in combination and conclude by suggesting multi-prong approaches to improve treatment outcomes and curative responses in patients. PMID:25510273

Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients.

PubMed

D'Arena, Giovanni; Simeon, Vittorio; Laurenti, Luca; Cimminiello, Michele; Innocenti, Idanna; Gilio, Michele; Padula, Angela; Vigliotti, Maria Luigia; De Lorenzo, Sonya; Loseto, Giacomo; Passarelli, Anna; Di Minno, Matteo Nicola Dario; Tucci, Marco; De Feo, Vincenzo; D'Auria, Fiorella; Silvestris, Francesco; Di Minno, Giovanni; Musto, Pellegrino

2017-11-01

Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies.

Medical History, Lifestyle, Family History, and Occupational Risk Factors for Adult Acute Lymphocytic Leukemia: The InterLymph Non-Hodgkin Lymphoma Subtypes Project

PubMed Central

Slager, Susan L.; Berndt, Sonja I.; Lightfoot, Tracy; Sampson, Joshua N.; Morton, Lindsay M.; Weisenburger, Dennis D.

2014-01-01

Background Acute lymphoblastic leukemia/lymphoma (ALL) in adults is a rare malignancy with a poor clinical outcome, and few reported etiologic risk factors. Methods We performed an exploratory pooled study of 152 ALL cases and 23096 controls from 16 case–control studies to investigate the role of medical history, lifestyle, family history, and occupational risk factors and risk of ALL. Age- race/ethnicity-, sex-, and study-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. Results An increased risk of ALL was found in those with a family history of a hematological malignancy (OR = 2.6, 95% CI = 1.22 to 5.54) and in leather (OR = 3.91, 95% CI = 1.35 to 11.35) and sewing/embroidery workers (OR = 2.92, 95% CI = 1.00 to 8.49). Consumers of alcohol had an increased risk of B-cell ALL (OR = 2.87, 95% CI = 1.18 to 6.95). Conclusions The small number of statistically significant risk factors identified out of the 112 variables examined could be chance findings and will require further replication to assess their role in the etiology of adult ALL. PMID:25174033

Pathogenesis diagnosis and management of paraneoplastic glomerulonephritis

PubMed Central

Lien, Yeong-Hau H.; Lai, Li-Wen

2011-01-01

Paraneoplastic glomerulonephritis is a rare complication of malignancy that is frequently mistaken for idiopathic glomerulonephritis. Failure to recognize paraneoplastic glomerulonephritis can subject patients to ineffective and potentially harmful therapy. Pathology of paraneoplastic glomerulonephritis varies between different types of malignancies. This Review describes the association of glomerulonephritis with both solid tumors and hematological malignancies The pathogenetic mechanisms of many glomerular lesions seem to relate to altered immune responses in the presence of a malignancy Studies in the Buffalo/Mna rat model of spontaneous thymoma and nephrotic syndrome indicate that polarization of the immune response toward a T-helper-2 (TH2) profile has an important role in the development of thymoma-associated glomerular lesions. Furthermore, overexpression of the TH2 cytokine interleukin 13 in transgenic rats induces minimal change disease. Such findings from experimental studies might facilitate the identification of biomarkers that can distinguish paraneoplastic glomerulonephritis from idiopathic and other secondary glomerulonephritides. This Review describes potential pathogenetic mechanisms for paraneoplastic glomerulonephritides associated with different malignancies and highlights the need for a multidisciplinary approach to the management of patients with paraneoplastic glomerulonephritis. PMID:21151207

Prevalence and spread of pseudomonas aeruginosa and Klebsiella pneumoniae strains in patients with hematological malignancies.

PubMed

Kolar, Milan; Sauer, Pavel; Faber, Edgar; Kohoutova, Jarmila; Stosová, Tatana; Sedlackova, Michaela; Chroma, Magdalena; Koukalova, Dagmar; Indrak, Karel

2009-01-01

The aim of the study was to determine the prevalence of Pseudomonas aeruginosa and Klebsiella pneumoniae strains in patients with acute leukemias, to assess their clinical significance, and to define the sources and ways of their spread using genetic analysis. Thirty-four patients were investigated during the observed period. Twenty-one strains of Pseudomonas aeruginosa and 35 strains of Klebsiella pneumoniae were isolated from patient samples. In the case of Pseudomonas aeruginosa, 47.6% of strains were identified as pathogens and caused infection. By contrast, only 4 isolates (11.4%) of Klebsiella pneumoniae could be regarded as etiological agents of bacterial infection. Based on the obtained results, Klebsiella pneumoniae strains are assumed to be of mostly endogenous origin. In the case of Pseudomonas aeruginosa strains, the proportion of identical strains detected in various patients was higher and exogenous sources were more significant. In addition, our results confirmed the ability of Pseudomonas aeruginosa strains to survive on a particular site in the hospital for a longer time.

Intrathoracic tumor of the chest wall: A case of Castleman's disease mimicking myositis of the lower extremities.

PubMed

Tampakis, Athanasios; Tampaki, Ekaterini Christina; Daikeler, Thomas; Lardinois, Didier

2017-11-01

Castleman's disease refers to a group of uncommon lymphoproliferative disorders which exhibit common lymph-node histological features. A 72-year-old male patient presented with signs of lower limb myositis. Detailed work-up focused initially on evaluating hematological malignancies, the presence of a solid tumor, autoimmune diseases and degenerative disorders of the peripheral nerves. Finally, a PET-CT scan was performed to exclude paraneoplastic manifestations of a primary tumor, revealing  however a tumor of the thoracic wall. The definite histological diagnosis confirmed the presence of unicentric Castleman's disease of the chest wall. The manifestations of the present case suggest that a systemic inflammation might occur in the unicentric form of the disease possibly due to cytokine hypersecretion. The unicentric manifestation of the disease should be well distinguished from the multicentric appearance. Unicentric disease is a surgical condition and warrants a follow-up based on the systemic inflammation that might occur.

Coccidioidomycosis, immunoglobulin deficiency: safety challenges with CAR T cells therapy for relapsed lymphoma.

PubMed

Zahid, Umar; Shaukat, Al-Aman; Hassan, Nida; Anwer, Faiz

2017-10-01

Treatment of patients with relapsed or refractory lymphoma may require allogenic hematopoietic stem cell transplant (HSCT), but treatment of post-transplant relapse disease remains very challenging. Donor lymphocyte infusion and blinatumomab have been used with limited success for the treatment of relapse. Initial data on donor-derived CAR T cells has shown this modality to be safe and highly effective in various hematological malignancies. We present a case of a patient with highly refractory, transformed follicular lymphoma who failed both autologous and allogenic HSCT. Patient achieved long-lasting complete remission with the use of donor origin CD19 CAR T-cell therapy, without any evidence of graft-versus-host disease flare. Our patient later developed disseminated coccidioidomycosis and persistent hypogammaglobulinemia. Immunotherapy using CD19 CAR T cells can be a highly effective salvage modality, especially in cases of focal lymphoma relapse. Long-term immunosuppression secondary to B cell lymphopenia, hypogammaglobulinemia, immunoglobulin subclass deficiency, fungal infections and other infectious complications need to be monitored and promptly treated as indicated.

Can we incorporate geriatric assessment in the management of acute lymphoblastic leukemia in older adults?

PubMed

Loh, Kah Poh; Liesveld, Jane L; O'Dwyer, Kristen M

2018-04-05

Acute lymphoblastic leukemia (ALL) is an uncommon disease. Approximately 14% of new ALL cases occur in adults aged 60 and over, and the three-year overall survival in this population is poor at 12.8%. Older adults with ALL are heterogeneous in terms of their underlying health status, which can make treatment selection challenging given the disease rarity and limited inclusion of older patients in clinical trials. A comprehensive geriatric assessment (CGA) is a compilation of tools to assess multiple domains such as physical function and cognition, and may assist in guiding treatment selection and supportive care interventions. However, studies on the use of CGA are limited in older adults with ALL. In this review, we discuss the utility of CGA in patients with various hematologic malignancies. Using two patient cases of ALL, we also describe how CGA may be use to guide treatment and supportive care interventions. Copyright © 2018 Elsevier Inc. All rights reserved.

Wnt Signaling in Normal and Malignant Hematopoiesis

PubMed Central

Lento, William; Congdon, Kendra; Voermans, Carlijn; Kritzik, Marcie; Reya, Tannishtha

2013-01-01

One of the most remarkable characteristics of stem cells is their ability to perpetuate themselves through self-renewal while concomitantly generating differentiated cells. In the hematopoietic system, stem cells balance these mechanisms to maintain steady-state hematopoiesis for the lifetime of the organism, and to effectively regenerate the system following injury. Defects in the proper control of self-renewal and differentiation can be potentially devastating and contribute to the development of malignancies. In this review, we trace the emerging role of Wnt signaling as a critical regulator of distinct aspects of self-renewal and differentiation, its contribution to the maintenance of homeostasis and regeneration, and how the pathway can be hijacked to promote leukemia development. A better understanding of these processes could pave the way to enhancing recovery after injury and to developing better therapeutic approaches for hematologic malignancies. PMID:23378582

Childhood colon cancer in a patient with ataxia telangiectasia

PubMed Central

Jo, Kyeong Min; Park, Jong Ha; Kim, Tae Oh; Jeong, Heui Jeong; Heo, Chang Min; Jang, Ji Hoon; Hur, So Chong; Jeong, Na Ri; Jeong, Su Jin; Seol, Sang Hoon; Nam, Kyung Han

2016-01-01

Background Ataxia-telangiectasia (AT) is a rare autosomal recessive disease characterized by progressive neurologic impairment and cerebellar ataxia. In addition, patients with this disease are known to have an inherent increased susceptibility to the development of cancer, predominantly hematologic malignancies. Methods We report the case of a young boy with AT from Russia, who had abdominal pain. Laboratory tests and radiologic examinations were performed to him. Results After abdominal computed tomography (CT), colonoscopy and surgical interventions, the young boy was diagnosed with colon cancer that had signet ring cell features. Conclusions It is known that the patient with AT appeared to be predisposed to various tumors, including leukemia or lymphoma, which are more common in childhood. Even if the patient with AT could have solid tumor such as stomach cancer or breast cancer, it is less likely to have colon cancer, especially signet ring cell type. Actually, no case of colon cancer has ever been reported, especially in young patient and hence, we have focused on this point and are hereby reporting this unique case. PMID:26855947

Chronic inflammatory demyelinating polyneuropathy and malignancy: A systematic review.

PubMed

Rajabally, Yusuf A; Attarian, Shahram

2018-06-01

A systematic review of the literature was performed on the association of chronic inflammatory demyelinating polyneuropathy (CIDP) with malignancy. Hematological disorders are the most common association, particulalry non-Hodgkin lymphoma. CIDP frequently precedes the malignancy diagnosis, and there is a favorable CIDP response to treatment more than 70% of the time. Melanoma is the second most common association and may be accompanied by antiganglioside antibodies; CIDP shows a good response to immunotherapy. Other cancers are rare, with variable timings and presentations but good responses to immunomodulation and/or cancer therapy. Unusual neurological features such as ataxia, distal/upper limb predominance, or cranial/respiratory/autonomic involvement may suggest associated malignancy as may abdominal pain, diarrhea/constipation, poor appetite/weight loss, dermatological lesions, and lymphadenopathy. In the appropriate clinical and electrophysiological setting, CIDP associated with cancer should be considered. Immunomodulatory therapy, cancer treatment alone, or a combination may be effective. Muscle Nerve 57: 875-883, 2018. © 2017 Wiley Periodicals, Inc.