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Sample records for hematologic malignancies experience

  1. Hematologic malignancies

    SciTech Connect

    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.

  2. Extracorporeal Life Support in Patients with Hematologic Malignancies: A Single Center Experience

    PubMed Central

    Choi, Kuk Bin; Kim, Hwan Wook; Jo, Keon Hyon; Kim, Do Yeon; Choi, Hang Jun; Hong, Seok Beom

    2016-01-01

    Background Extracorporeal life support (ECLS) in patients with hematologic malignancies is considered to have a poor prognosis. However, to date, there is only one case series reported in the literature. In this study, we compared the in-hospital survival of ECLS in patients with and without hematologic malignancies. Methods We reviewed a total of 66 patients who underwent ECLS for treatment of acute respiratory failure from January 2012 to December 2014. Of these patients, 22 (32%) were diagnosed with hematologic malignancies, and 13 (59%) underwent stem cell transplantation before ECLS. Results The in-hospital survival rate of patients with hematologic malignancies was 5% (1/22), while that of patients without malignancies was 26% (12/46). The number of platelet transfusions was significantly higher in patients with hematologic malignancies (9.69±7.55 vs. 3.12±3.42 units/day). Multivariate analysis showed that the presence of hematologic malignancies was a significant negative predictor of survival to discharge (odds ratio, 0.07; 95% confidence interval, 0.01–0.79); p=0.031). Conclusion ECLS in patients with hematologic malignancies had a lower in-hospital survival rate, compared to patients without hematologic malignancies. PMID:27525237

  3. Telomerase Activation in Hematological Malignancies

    PubMed Central

    Ropio, Joana; Merlio, Jean-Philippe; Soares, Paula; Chevret, Edith

    2016-01-01

    Telomerase expression and telomere maintenance are critical for cell proliferation and survival, and they play important roles in development and cancer, including hematological malignancies. Transcriptional regulation of the rate-limiting subunit of human telomerase reverse transcriptase gen (hTERT) is a complex process, and unveiling the mechanisms behind its reactivation is an important step for the development of diagnostic and therapeutic applications. Here, we review the main mechanisms of telomerase activation and the associated hematologic malignancies. PMID:27618103

  4. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

    The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation. The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer. PMID:26320065

  5. Epigenetics in the hematologic malignancies

    PubMed Central

    Fong, Chun Yew; Morison, Jessica; Dawson, Mark A.

    2014-01-01

    A wealth of genomic and epigenomic data has identified abnormal regulation of epigenetic processes as a prominent theme in hematologic malignancies. Recurrent somatic alterations in myeloid malignancies of key proteins involved in DNA methylation, post-translational histone modification and chromatin remodeling have highlighted the importance of epigenetic regulation of gene expression in the initiation and maintenance of various malignancies. The rational use of targeted epigenetic therapies requires a thorough understanding of the underlying mechanisms of malignant transformation driven by aberrant epigenetic regulators. In this review we provide an overview of the major protagonists in epigenetic regulation, their aberrant role in myeloid malignancies, prognostic significance and potential for therapeutic targeting. PMID:25472952

  6. Eosinophilic Dermatosis of Hematologic Malignancy.

    PubMed

    Lucas-Truyols, S; Rodrigo-Nicolás, B; Lloret-Ruiz, C; Quecedo-Estébanez, E

    2017-03-22

    Dermatosis characterized by tissue eosinophilia arising in the context of hematologic disease is known as eosinophilic dermatosis of hematologic malignancy. The most commonly associated malignancy is chronic lymphocytic leukemia. Eosinophilic dermatosis of hematologic malignancy is a rare condition with a wide variety of clinical presentations, ranging from papules, erythematous nodules, or blisters that simulate arthropod bites, to the formation of true plaques of differing sizes. Histology reveals the presence of abundant eosinophils. We present 4 new cases seen in Hospital Arnau de Vilanova, Valencia, during the past 7 years. Three of these cases were associated with chronic lymphocytic leukemia and 1 with mycosis fungoides. It is important to recognize this dermatosis as it can indicate progression of the underlying disease, as was the case in 3 of our patients.

  7. XYY male and hematologic malignancy.

    PubMed

    Oguma, N; Shigeta, C; Kamada, N

    1996-09-01

    Two cases of XYY male with refractory anemia with excess of blasts are reported, and previous reported XYY males with hematologic malignancy are reviewed. Altogether 26 cases were collected for analysis: acute myeloid leukemia (10), acute lymphocytic leukemia (seven), acute leukemia (two), chronic myelocytic leukemia (three), myelodysplastic syndrome (three), and essential thrombocythemia (one). The age at the time of diagnosis ranged in age from 7.5 to 81 years. In three of six XYY/XY mosaicism cases, XYY clone was associated with malignancy. However, in two cases XYY clone was not involved. The evidence presented here suggests that the event of an XYY male with hematologic malignancy is incidental rather than a genetic etiology.

  8. [Kinase inhibitors against hematological malignancies].

    PubMed

    Tojo, Arinobu

    2014-06-01

    Dysregulation of protein phosphorylation, especially on tyrosine residues, plays a crucial role in development and progression of hematological malignancies. Since remarkable success in imatinib therapy of CML and Ph+ALL, extensive efforts have made to explore candidate molecular targets and next breakthrough drugs. Now that next generation ABL kinase inhibitors are available for CML, the therapeutic algorithm has been revolutionized. As for AML and lymphoid malignancies, many kinase inhibitors targeting FLT3, BTK and aurora-A are on early and late clinical trials, and a number of promising drugs including ibrutinib are picked up for further evaluation.

  9. B-Cell Hematologic Malignancy Vaccination Registry

    ClinicalTrials.gov

    2016-12-28

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

  10. Targeting hedgehog in hematologic malignancy.

    PubMed

    Irvine, David A; Copland, Mhairi

    2012-03-08

    The Hedgehog pathway is a critical mediator of embryonic patterning and organ development, including hematopoiesis. It influences stem cell fate, differentiation, proliferation, and apoptosis in responsive tissues. In adult organisms, hedgehog pathway activity is required for aspects of tissue maintenance and regeneration; however, there is increasing awareness that abnormal hedgehog signaling is associated with malignancy. Hedgehog signaling is critical for early hematopoietic development, but there is controversy over its role in normal hematopoiesis in adult organisms where it may be dispensable. Conversely, hedgehog signaling appears to be an important survival and proliferation signal for a spectrum of hematologic malignancies. Furthermore, hedgehog signaling may be critical for the maintenance and expansion of leukemic stem cells and therefore provides a possible mechanism to selectively target these primitive cell subpopulations, which are resistant to conventional chemotherapy. Indeed, phase 1 clinical trials of hedgehog pathway inhibitors are currently underway to test this hypothesis in myeloid leukemias. This review covers: (1) the hedgehog pathway and its role in normal and malignant hematopoiesis, (2) the recent development of clinical grade small molecule inhibitors of the pathway, and (3) the potential utility of hedgehog pathway inhibition as a therapeutic strategy in hemato-oncology.

  11. Oncolytic Virotherapy for Hematological Malignancies

    PubMed Central

    Bais, Swarna; Bartee, Eric; Rahman, Masmudur M.; McFadden, Grant; Cogle, Christopher R.

    2012-01-01

    Hematological malignancies such as leukemias, lymphomas, multiple myeloma (MM), and the myelodysplastic syndromes (MDSs) primarily affect adults and are difficult to treat. For high-risk disease, hematopoietic stem cell transplant (HCT) can be used. However, in the setting of autologous HCT, relapse due to contamination of the autograft with cancer cells remains a major challenge. Ex vivo manipulations of the autograft to purge cancer cells using chemotherapies and toxins have been attempted. Because these past strategies lack specificity for malignant cells and often impair the normal hematopoietic stem and progenitor cells, prior efforts to ex vivo purge autografts have resulted in prolonged cytopenias and graft failure. The ideal ex vivo purging agent would selectively target the contaminating cancer cells while spare normal stem and progenitor cells and would be applied quickly without toxicities to the recipient. One agent which meets these criteria is oncolytic viruses. This paper details experimental progress with reovirus, myxoma virus, measles virus, vesicular stomatitis virus, coxsackievirus, and vaccinia virus as well as requirements for translation of these results to the clinic. PMID:22312362

  12. 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

  13. Pattern of trisomy 1q in hematological malignancies: a single institution experience.

    PubMed

    Djordjević, Vesna; Dencić-Fekete, Marija; Jovanović, Jelica; Drakulić, Danijela; Stevanović, Milena; Janković, Gradimir; Gotić, Mirjana

    2008-10-01

    An extra copy of 1q usually originates from the translocated unbalanced derivative chromosome, isochromosome, or "jumping translocation." We report a pattern of partial trisomies and unbalanced whole-arm translocations of 1q in 10 patients: 5 with myelodysplastic syndrome, 3 with acute myeloid leukemia, and a single patient with acute lymphoblastic leukemia and myeloproliferative syndrome. The trisomy of 1q was registered as the sole karyotype aberration in one patient, while it was accompanied by a limited number of additional chromosomal changes in nine patients. These patients are a subset of a larger group of 92 adults carrying a wide variety of chromosome 1 anomalies within a complex cytogenetic context observed over a period between 1994 and 2006 in a panel of 3,786 hematologic patients at the Institute of Hematology in Belgrade. Conventional cytogenetics was supplemented by fluorescence in situ hybridization with a probe specific for the paracentric region of 1q. Whole-arm 1q translocations involved chromosomes Y, 7, 14, 15, 16, and 19. This study suggests that gain of 1q as the sole cytogenetic abnormality may be sufficiently mutagenic to favor leukemogenesis and hematopoietic tissue degeneration (trilineage myelodysplasia).

  14. Targeting cell cycle regulators in hematologic malignancies

    PubMed Central

    Aleem, Eiman; Arceci, Robert J.

    2015-01-01

    Hematologic malignancies represent the fourth most frequently diagnosed cancer in economically developed countries. In hematologic malignancies normal hematopoiesis is interrupted by uncontrolled growth of a genetically altered stem or progenitor cell (HSPC) that maintains its ability of self-renewal. Cyclin-dependent kinases (CDKs) not only regulate the mammalian cell cycle, but also influence other vital cellular processes, such as stem cell renewal, differentiation, transcription, epigenetic regulation, apoptosis, and DNA repair. Chromosomal translocations, amplification, overexpression and altered CDK activities have been described in different types of human cancer, which have made them attractive targets for pharmacological inhibition. Mouse models deficient for one or more CDKs have significantly contributed to our current understanding of the physiological functions of CDKs, as well as their roles in human cancer. The present review focuses on selected cell cycle kinases with recent emerging key functions in hematopoiesis and in hematopoietic malignancies, such as CDK6 and its role in MLL-rearranged leukemia and acute lymphocytic leukemia, CDK1 and its regulator WEE-1 in acute myeloid leukemia (AML), and cyclin C/CDK8/CDK19 complexes in T-cell acute lymphocytic leukemia. The knowledge gained from gene knockout experiments in mice of these kinases is also summarized. An overview of compounds targeting these kinases, which are currently in clinical development in various solid tumors and hematopoietic malignances, is presented. These include the CDK4/CDK6 inhibitors (palbociclib, LEE011, LY2835219), pan-CDK inhibitors that target CDK1 (dinaciclib, flavopiridol, AT7519, TG02, P276-00, terampeprocol and RGB 286638) as well as the WEE-1 kinase inhibitor, MK-1775. The advantage of combination therapy of cell cycle inhibitors with conventional chemotherapeutic agents used in the treatment of AML, such as cytarabine, is discussed. PMID:25914884

  15. Epigenetics of hematopoiesis and hematological malignancies

    PubMed Central

    Hu, Deqing; Shilatifard, Ali

    2016-01-01

    Hematological malignancies comprise a diverse set of lymphoid and myeloid neoplasms in which normal hematopoiesis has gone awry and together account for ∼10% of all new cancer cases diagnosed in the United States in 2016. Recent intensive genomic sequencing of hematopoietic malignancies has identified recurrent mutations in genes that encode regulators of chromatin structure and function, highlighting the central role that aberrant epigenetic regulation plays in the pathogenesis of these neoplasms. Deciphering the molecular mechanisms for how alterations in epigenetic modifiers, specifically histone and DNA methylases and demethylases, drive hematopoietic cancer could provide new avenues for developing novel targeted epigenetic therapies for treating hematological malignancies. Just as past studies of blood cancers led to pioneering discoveries relevant to other cancers, determining the contribution of epigenetic modifiers in hematologic cancers could also have a broader impact on our understanding of the pathogenesis of solid tumors in which these factors are mutated. PMID:27798847

  16. Improved radioimmunotherapy of hematologic malignancies

    SciTech Connect

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  17. Mobilization of hematopoietic progenitor cells with granulocyte colony stimulating factors for autologous transplant in hematologic malignancies: a single center experience

    PubMed Central

    Gabús, Raul; Borelli, Gabriel; Ferrando, Martín; Bódega, Enrique; Citrín, Estela; Jiménez, Constanza Olivera; Álvarez, Ramón

    2011-01-01

    Background In 2006 the Hematology Service of Hospital Maciel published its experience with peripheral blood progenitor cell harvesting for autologous stem cell transplantation using Filgen JP (Clausen Filgrastim). After mobilization with a mean filgrastim dose of 78 mcg/Kg, 4.7 x 106 CD34+ cells/Kg were obtained by apheresis. Age above 50, multiple myeloma as underlying disease and a malignancy that was not in remission were identified as frequent characteristics among patients showing complex mobilization. Objective The aim of this study was to compare stem cell mobilization using different brands of filgrastim. Methods One hundred and fifty-seven mobilizations performed between 1997 and 2006 were analyzed. This retrospective analysis comparative two groups of patients: those mobilized with different brands of filgrastim (Group A) and those who received Filgen JP (Clausen Filgrastim) as mobilizing agent (Group B). A cluster analysis technique was used to identify four clusters of individuals with different behaviors differentiated by age, total dose of filgrastim required, number of apheresis and harvested CD34+ cells. Results The mean total dose of filgrastim administered was 105 mcg/Kg, the median number of apheresis was 2 procedures and the mean number of harvested stem cells was 4.98 x 106 CD34+ cells/Kg. No significant differences were observed between Groups A and B regarding the number of apheresis, harvested CD34+ cells and number of mobilization failures, however the total dose of filgrastim was significantly lower in Group B. Conclusions Among other factors, the origin of the cytokine used as mobilizing agent is an element to be considered when evaluating CD34+ cell mobilization results. PMID:23049356

  18. Vaccinations in patients with hematological malignancies.

    PubMed

    Tsigrelis, C; Ljungman, P

    2016-03-01

    Patients with hematological malignancies are at risk for a number of infections that are potentially preventable by vaccinations such as pneumococcal infections and influenza. Treatment, especially with anti-B-cell antibodies and hematopoietic stem cell transplantation (HSCT), negatively impacts the response to vaccination for several months. It is therefore recommended that patients be vaccinated before initiating immunosuppressive therapy if possible. The risk of side-effects with inactivated vaccines is low, but care has to be taken with live vaccines, such as varicella-zoster virus vaccine, since severe and fatal complications have been reported. HSCT patients require repeated doses of most vaccines to achieve long-lasting immune responses. New therapeutic options for patients with hematological malignancies that are rapidly being introduced into clinical practice will require additional research regarding the efficacy of vaccinations. New vaccines are also in development that will require well-designed studies to ascertain efficacy and safety.

  19. Fertility issues in patients with hematologic malignancies.

    PubMed

    Loren, Alison W

    2015-01-01

    An essential component of a cancer patient's comprehensive care is addressing potential threats to his or her reproductive health. Providers should discuss the risk of infertility with newly diagnosed patients and offer the chance to consult with a reproductive specialist as early as possible. Standard fertility preservation options include embryo or oocyte cryopreservation for women and sperm banking for men; all options for pre-pubertal children are experimental. Patients with hematologic malignancies are a distinct population in whom standard options may present special challenges, and alternative management strategies are being explored. Unique approaches in hematologic malignancy patients include experimental techniques, such as hormonal therapy, referrals to reproductive specialists after cancer treatment, or discontinuation of tyrosine kinase inhibitor therapy in appropriate chronic myelogenous leukemia patients. Importantly, expedited communication between hematologists and reproductive specialists may greatly enhance the quality of care for these patients. Facilitation of referrals will both improve the quality-of-life and expand the prospect of parenthood in survivors. There are ample opportunities to advance the field of oncofertility through additional research, especially in hematologic malignancy patients.

  20. Breast feeding and childhood hematological malignancy.

    PubMed

    Tripathy, A K; Mishra, L; Bakhshi, Sameer; Arya, L S

    2004-05-01

    Breast milk is known to have anti-infective and immunomodulating effects on infants, but its association with childhood cancer has not been well studied. Artificial feeding may affect the immune response in carcinogenesis. In this communication the authors have reviewed different articles describing the association between breast feeding (BF) and subsequent development of childhood hematological malignancy. It appears that BF may have a protective effect on childhood cancer, both the duration of BF as well as the quantity of milk ingested is probably critical to the beneficial immunological effects of BF against childhood cancer if any.

  1. BMI1: A Biomarker of Hematologic Malignancies

    PubMed Central

    Sahasrabuddhe, Anagh A.

    2016-01-01

    BMI1 oncogene is a catalytic member of epigenetic repressor polycomb group proteins. It plays a critical role in the regulation of gene expression pattern and consequently several cellular processes during development, including cell cycle progression, senescence, aging, apoptosis, angiogenesis, and importantly self-renewal of adult stem cells of several lineages. Preponderance of evidences indicates that deregulated expression of PcG protein BMI1 is associated with several human malignancies, cancer stem cell maintenance, and propagation. Importantly, overexpression of BMI1 correlates with therapy failure in cancer patients and tumor relapse. This review discusses the diverse mode of BMI1 regulation at transcriptional, posttranscriptional, and posttranslational levels as well as at various critical signaling pathways regulated by BMI1 activity. Furthermore, this review highlights the role of BMI1 as a biomarker and therapeutic target for several subtypes of hematologic malignancies and the importance to target this biomarker for therapeutic applications. PMID:27168727

  2. 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

  3. Impact of interleukin-6 in hematological malignancies.

    PubMed

    Burger, Renate

    2013-10-01

    Almost 3 decades have passed since the discovery and cloning of IL-6, and a tremendous amount of work has contributed to the current knowledge of the biological functions of this cytokine, its receptor, and the signaling pathways that are activated. The understanding of the role of IL-6 in human disease has led to the development of novel therapeutic strategies that block the biological functions of IL-6. In clinical studies, IL-6 and IL-6 receptor antibodies have proven efficacy in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease, conditions that are known to be driven by IL-6. The focus of this overview is the role of IL-6 in the pathophysiology of hematological malignancies.

  4. Asparaginase in the treatment of non-ALL hematologic malignancies.

    PubMed

    Emadi, Ashkan; Zokaee, Hania; Sausville, Edward A

    2014-05-01

    Asparaginases are among the most effective agents against acute lymphoblastic leukemia (ALL) and are Food and Drug Administration-approved for the treatment of pediatric and adult ALL. However, the efficacy of these drugs for the treatment of other hematologic malignancies particularly acute myeloid leukemia is not well established. The mechanism of action of asparaginases has thought to be related to a swift and sustained reduction in serum L-asparagine, which is required for rapid proliferation of metabolically demanding leukemic cells. However, asparagine depletion alone appears not to be sufficient for effective cytotoxic activity of asparaginase against leukemia cells, because glutamine can rescue asparagine-deprived cells by regeneration of asparagine via a transamidation chemical reaction. For this reason, glutamine reduction is also necessary for full anti-leukemic activity of asparaginase. Indeed, both Escherichia coli and Erwinia chrysanthemi asparaginases possess glutaminase enzymatic activity, and their administrations have shown to reduce serum glutamine level by deamidating glutamine to glutamate and ammonia. Emerging data have provided evidence that several types of neoplastic cells require glutamine for the synthesis of proteins, nucleic acids, and lipids. This fundamental role of glutamine and its metabolic pathways for growth and proliferation of individual malignant cells may identify a special group of patients whose solid or hematologic neoplasms may benefit significantly from interruption of glutamine metabolism. To this end, asparaginase products deserve a second look particularly in non-ALL malignant blood disorders. Here, we review mechanisms of anti-tumor activity of asparaginase focusing on importance of glutamine reduction, pharmacology of asparaginase products, in vitro activities as well as clinical experience of incorporating asparaginase in therapeutic regimens for non-ALL hematologic malignancies.

  5. 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

  6. Evaluation of Bloodstream Infections During Chemotherapy-Induced Febrile Neutropenia in Patients with Malignant Hematological Diseases: Single Center Experience

    PubMed Central

    Piukovics, Klára; Terhes, Gabriella; Lázár, Andrea; Tímár, Flóra; Borbényi, Zita; Urbán, Edit

    2015-01-01

    From year to year, it is important to get an overview of the occurrence of causative agents in febrile neutropenic patients to determine the empiric treatment. Thus our aims were to evaluate a four-year period regarding the prevalence of bloodstream infections and the most important causative agents. During this period, 1,361 patients were treated in our hematology ward because of various hematological disorders. 812 febrile episodes were recorded in 469 patients. At that time, 3,714 blood culture (BC) bottles were sent for microbiological investigations, 759 of them gave positive signal. From the majority of positive blood culture bottles (67.1%), Gram-positive bacteria, mainly coagulase-negative staphylococci (CNS), were grown. Gram-negative bacteria were isolated from 32.9% of the positive blood culture bottles, in these cases the leading pathogen was Escherichia coli. The high prevalence of CNS was attributed to mainly contamination, while lower positivity rate for Gram-negative bacteria was associated with the use of broad-spectrum empiric antibiotic treatment. PMID:26495130

  7. Role of leptin and leptin receptors in hematological malignancies.

    PubMed

    Uddin, Shahab; Mohammad, Ramzi M

    2016-01-01

    Leptin is an adipose-derived cytokine that has an important role in bodyweight homeostasis and energy balance. There are a number of studies which have suggested that leptin and its receptors dysregulation play a critical role in the development of malignancies including hematological malignancies, mainly via activation of the JAK/STAT pathway which regulates downstream signaling pathways such as PI3K/AKT signaling and ERK1/2. In this review, current understandings of leptin/leptin receptors mediated pathogenesis in various lymphoid malignancies are described. Blocking of the leptin receptor might be a unique therapeutic approach for many hematological malignancies.

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

    PubMed Central

    CHEN, NA; WANG, XIN

    2014-01-01

    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. PMID:24520283

  9. Improved radioimmunotherapy of hematologic malignancies. [Final report

    SciTech Connect

    Press, O.W.

    1992-03-24

    This research project proposes to develop novel new approaches of improving the radioimmunodetection and radioimmunotherapy of malignancies by augmenting retention of radioimmunoconjugates by tumor cells. The approaches shown to be effective in these laboratory experiments will subsequently be incorporated into out ongoing clinical trials in patients. Specific project objectives include: to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells; To examine the effects of lysosomotropic amines (e.g. chloroquine, amantadine), carboxylic ionophores (monensin, nigericin), and thioamides (propylthiouracil), on the retention of radiolabeled MoAbs by tumor cells; to examine the impact of newer radioiodination techniques (tyramine cellobiose, paraiodobenzoyl) on the metabolic degradation of radioiodinated antibodies; to compare the endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with different radionuclides ({sup 131}Iodine, {sup 111}Indium, {sup 90}Yttrium, {sup 99m}Technetium, {sup 186}Rhenium); and to examine the utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer.

  10. Hematologic malignancies: at the forefront of immunotherapeutic innovation

    PubMed Central

    Bachireddy, Pavan; Burkhardt, Ute E.; Rajasagi, Mohini; Wu, Catherine J.

    2015-01-01

    The recent successes of cancer immunotherapy have stimulated interest for the potential widespread application of these approaches; hematologic malignancies have provided both initial proofs-of-concept and an informative testing ground for a variety of immune-based therapeutics. The immune-cell origin of many of the blood malignancies provides a unique opportunity to both understand the mechanisms of human immune-responsiveness and immune-evasion as well as to exploit the unique therapeutic opportunities they provide. PMID:25786696

  11. Epidemiology of Monoclonal Gammopathy of Undetermined Significance (MGUS): The experience from the specialized registry of hematologic malignancies of Basse-Normandie (France).

    PubMed

    Cabrera, Quentin; Macro, Margaret; Hebert, Benedikte; Cornet, Edouard; Collignon, Albert; Troussard, Xavier

    2014-08-01

    Multiple myeloma (MM) is the third most common haematologic malignancy in European countries, and is usually preceded by Monoclonal Gammopathy of Undetermined Significance (MGUS). Therefore epidemiologic studies of MGUS are very limited in a population-based status. Here we report all new cases of MGUS exhaustively recorded by the Basse-Normandie Regional Registry for Hematologic Malignancies (a French region registry) between January 1997 and December 2005, and analyze outcome of patients until 2009 in term of evolution in MM or death. All cases were analyzed by an expert file review, and MGUS diagnosis was retained for: evidence of a monoclonal component <30 g/l and no CRAB criteria (hyperCalcemia, renal insufficiency, anemia, bone lesions). We showed that the world standardized incidence rate (WSR) for MGUS was 3.76 ± 0.26 per 100,000 inhabitants, increasing regularly with age, and that the median overall survival (OS) was 115.9 months (CI 95%: 10.5-130.2 months) with 78.3% patients alive at 5 years (CI 95%: 74.1-81.9%). We also observed a rate of progression to multiple myeloma of 1.41% per year, concordant with previous reports in a reallife exhaustive registry.

  12. Bacterial Infections Following Splenectomy for Malignant and Nonmalignant Hematologic Diseases

    PubMed Central

    Leone, Giuseppe; Pizzigallo, Eligio

    2015-01-01

    Splenectomy, while often necessary in otherwise healthy patients after major trauma, finds its primary indication for patients with underlying malignant or nonmalignant hematologic diseases. Indications of splenectomy for hematologic diseases have been reducing in the last few years, due to improved diagnostic and therapeutic tools. In high-income countries, there is a clear decrease over calendar time in the incidence of all indication splenectomy except nonmalignant hematologic diseases. However, splenectomy, even if with different modalities including laparoscopic splenectomy and partial splenectomy, continue to be a current surgical practice both in nonmalignant hematologic diseases, such as Immune Thrombocytopenic Purpura (ITP), Autoimmune Hemolytic Anemia (AIHA), Congenital Hemolytic Anemia such as Spherocytosis, Sickle Cell Anemia and Thalassemia and Malignant Hematological Disease, such as lymphoma. Today millions of people in the world are splenectomized. Splenectomy, independently of its cause, induces an early and late increase in the incidence of venous thromboembolism and infections. Infections remain the most dangerous complication of splenectomy. After splenectomy, the levels of antibody are preserved but there is a loss of memory B cells against pneumococcus and tetanus, and the loss of marginal zone monocytes deputed to immunological defense from capsulated bacteria. Commonly, the infections strictly correlated to the absence of the spleen or a decreased or absent splenic function are due to encapsulated bacteria that are the most virulent pathogens in this set of patients. Vaccination with polysaccharide and conjugate vaccines again Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis should be performed before the splenectomy. This practice reduces but does not eliminate the occurrence of overwhelming infections due to capsulated bacteria. At present, most of infections found in splenectomized patients are due to Gram

  13. Polo-like kinase inhibitors in hematologic malignancies.

    PubMed

    Talati, Chetasi; Griffiths, Elizabeth A; Wetzler, Meir; Wang, Eunice S

    2016-02-01

    Polo-like kinases (Plk) are key regulators of the cell cycle and multiple aspects of mitosis. Two agents that inhibit the Plk signaling pathway have shown promising activity in patients with hematologic malignancies and are currently in phase III trials. Volasertib is a Plk inhibitor under evaluation combined with low-dose cytarabine in older patients with acute myeloid leukemia (AML) ineligible for intensive induction therapy. Rigosertib, a dual inhibitor of the Plk and phosphatidylinositol 3-kinase pathways, is under investigation in patients with myelodysplastic syndrome (MDS) who have failed azacitidine or decitabine treatment. The prognosis for patients with AML, who are ineligible for intensive induction therapy, and for those with MDS refractory/relapsed after a hypomethylating agent, remains poor. Novel approaches, such as Plk inhibitors, are urgently needed for these patients. Here, we provide a comprehensive overview of the current state of development of Plk inhibitors for the treatment of hematologic malignancies.

  14. Target Therapy in Hematological Malignances: New Monoclonal Antibodies

    PubMed Central

    Szymczyk, Agnieszka; Pawlowski, Johannes

    2014-01-01

    Apart from radio- and chemotherapy, monoclonal antibodies (MoAbs) represent a new, more selective tool in the treatment of hematological malignancies. MoAbs bind with the specific antigens of the tumors. This interaction is a basis for targeted therapies which exhibit few side effects and significant antitumor activity. This review provides an overview of the functional characteristics of MoAbs, with some examples of their clinical application. The promising results in the treatment of hematological malignancies have led to the more frequent usage of MoAbs in the therapy. Development of MoAbs is a subject of extensive research. They are a promising method of cancer treatment in the future. PMID:27433507

  15. Monoclonal antibodies targeting CD38 in hematological malignancies and beyond.

    PubMed

    van de Donk, Niels W C J; Janmaat, Maarten L; Mutis, Tuna; Lammerts van Bueren, Jeroen J; Ahmadi, Tahamtan; Sasser, A Kate; Lokhorst, Henk M; Parren, Paul W H I

    2016-03-01

    CD38 is a multifunctional cell surface protein that has receptor as well as enzyme functions. The protein is generally expressed at low levels on various hematological and solid tissues, while plasma cells express particularly high levels of CD38. The protein is also expressed in a subset of hematological tumors, and shows especially broad and high expression levels in plasma cell tumors such as multiple myeloma (MM). Together, this triggered the development of various therapeutic CD38 antibodies, including daratumumab, isatuximab, and MOR202. Daratumumab binds a unique CD38 epitope and showed strong anti-tumor activity in preclinical models. The antibody engages diverse mechanisms of action, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, programmed cell death, modulation of enzymatic activity, and immunomodulatory activity. CD38-targeting antibodies have a favorable toxicity profile in patients, and early clinical data show a marked activity in MM, while studies in other hematological malignancies are ongoing. Daratumumab has single agent activity and a limited toxicity profile, allowing favorable combination therapies with existing as well as emerging therapies, which are currently evaluated in the clinic. Finally, CD38 antibodies may have a role in the treatment of diseases beyond hematological malignancies, including solid tumors and antibody-mediated autoimmune diseases.

  16. Advances in the treatment of hematologic malignancies using immunoconjugates

    PubMed Central

    Palanca-Wessels, Maria Corinna

    2014-01-01

    Monoclonal antibody therapy has revolutionized cancer treatment by significantly improving patient survival both in solid tumors and hematologic malignancies. Recent technological advances have increased the effectiveness of immunotherapy leading to its broader application in diverse treatment settings. Immunoconjugates (ICs) consist of a cytotoxic effector covalently linked to a monoclonal antibody that enables the targeted delivery of its therapeutic payload to tumors based on cell-surface receptor recognition. ICs are classified into 3 groups based on their effector type: immunotoxins (protein toxin), radioimmunoconjugates (radionuclide), and antibody drug conjugates (small-molecule drug). Optimization of each individual component of an IC (antibody, linker, and effector) is essential for therapeutic efficacy. Clinical trials have been conducted to investigate the effectiveness of ICs in hematologic malignancies both as monotherapy and in multiagent regimens in relapsed/refractory disease as well as frontline settings. These studies have yielded encouraging results particularly in lymphoma. ICs comprise an exciting group of therapeutics that promise to play an increasingly important role in the management of hematologic malignancies. PMID:24578502

  17. Human herpesvirus 6 in hematological malignancies.

    PubMed

    Ogata, Masao

    2009-11-01

    Pathogenetic roles of human herpesvirus (HHV)-6 in lymphoproliferative diseases have been of continued interest. Many molecular studies have tried to establish a pathogenic role for HHV-6 in lymphoid malignancies. However, whether HHV-6 plays a role in these pathologies remains unclear, as positive polymerase chain reaction results for HHV-6 in those studies may reflect latent infection or reactivation rather than presence of HHV-6 in neoplastic cells. A small number of studies have investigated HHV-6 antigen expression in pathologic specimens. As a result, the lack of HHV-6 antigen expression on neoplastic cells argues against any major pathogenic role of HHV-6. The role of HHV-6 in childhood acute lymphoblastic leukemia (ALL) has also been of interest but remains controversial, with 2 studies documenting higher levels of HHV-6 antibody in ALL patients, and another 2 large-scale studies finding no significant differences in HHV-6 seroprevalences between ALL patients and controls. Alternatively, HHV-6 is increasingly recognized as an important opportunistic pathogen. HHV-6 reactivation is common among recipients of allogeneic stem cell transplantation (SCT), and is linked to various clinical manifestations. In particular, HHV-6 encephalitis appears to be significant, life-threatening complication. Most HHV-6 encephalitis develops in patients receiving transplant from an unrelated donor, particularly cord blood, typically around the time of engraftment. Symptoms are characterized by short-term memory loss and seizures. Magnetic resonance imaging typically shows limbic encephalitis. Prognosis for HHV-6 encephalitis is poor, but appropriate prophylactic measures have not been established. Establishment of preventive strategies against HHV-6 encephalitis represents an important challenge for physicians involved with SCT.

  18. Cytogenetic effect of 5-azacytidine in patients with hematological malignancies

    PubMed Central

    Tsuda, Jessica Romy; Segato, Rosimeire; Barbosa, Waldênia; Smith, Marília de Arruda Cardoso; Payão, Spencer Luiz Marques

    2011-01-01

    Background Recently, the importance of cytogenetics has grown in the diagnosis, prognosis and treatment of leukemias and myelodysplastic syndromes. 5-azacytidine is a drug that has well-known cytogenetical effects and is approved in the treatment of myelodysplastic syndromes. To date, no studies have been performed to evaluate the impact of 5-azacytidine on the chromosomes of patients with hematological neoplasias. This study aimed to investigate the effects of 5-azacytidine on chromosomes of patients with different hematological malignancies using G-band analyses to identify possible cytogenetical alterations. Methods The peripheral blood of 18 patients with hematological malignancies and 18 controls was collected in heparinized tubes. 5-azacytidine was added, at a final concentration of 10-5M, to cultures 7 hours prior to harvest. Results Uncoiled centromeric/pericentromeric heterochromatin of chromosomes-1, 9 and 16 occurred more frequently in the patients than in controls. This higher frequency of uncoiled heterochromatin was statistically significant (p-value = 0.004) for chromosome-9. Conversely, we observed that the fragile site at 19q13 was more frequent in controls (p-value = 0.0468). Conclusions The results of this study suggest that satellite sequences, located in the heterochromatin of chromosome-9, are hypomethylated in hematological malignancies. This hypomethylation may contribute to the disease, activating transposable elements and/or promoting genomic instability, enabling the loss of heterozygosity of important tumor suppressor genes. An investigation of the 19q13 region may help to understand whether or not the predominant occurrence of the fragile site at 19q13 in controls is due to hypermethylation of this region. PMID:23049342

  19. Miniaturized FISH for screening of onco-hematological malignancies.

    PubMed

    Zanardi, Andrea; Bandiera, Dario; Bertolini, Francesco; Corsini, Chiara Antonia; Gregato, Giuliana; Milani, Paolo; Barborini, Emanuele; Carbone, Roberta

    2010-07-01

    Fluorescence in situ hybridization (FISH) represents a major step in the analysis of chromosomal aberrations in cancer. It allows the precise detection of specific rearrangements, both for diagnostic and prognostic purposes. Here we present a miniaturized FISH method performed on fresh and fixed hematological samples. This procedure has been developed together with a microfluidic device that integrates cluster-assembled nanostructured TiO2 (ns-TiO2) as a nanomaterial promoting hematopoietic cell immobilization in conditions of shear stress. As a result of miniaturization, FISH can be performed with at least a 10-fold reduction in probe usage and minimal cell requirements, creating the possibility of using FISH in genetic screening applications. We developed the protocol on tumor cells and bone marrow (BM) from a normal donor using commercially sex-specific and onco-hematology probes. The procedure was then validated using either BM or peripheral blood (PB) from six patients with hematological diseases, each associated with different genetic lesions. Miniaturized FISH demonstrated comparable performance to standard FISH, indicating that it is suitable for genetic screenings, in research, and in clinical settings for the diagnosis of samples from onco-hematological malignancies.

  20. Development of a Workshop for Malignant Hematology Nursing Education.

    PubMed

    Martina, Karelin; Ghadimi, Lucia; Incekol, Diana

    2016-02-01

    As part of a comprehensive orientation for nurses caring for patients with hematologic malignancies, nurses are expected to attend general corporate orientation immediately followed by hospital site-specific nursing orientation. The orientation is comprised of lectures, e-learning, and clinical observership, as well as clinical practice under supervision of a preceptor. Nurses also are expected to attend foundational courses. The goal of these courses is to consolidate practical and theoretical knowledge in a specific oncology nursing specialty. A workshop was developed that offers a unique vision by interweaving theory, practice, and patient voice.
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  1. 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

  2. Information transfer by exosomes: A new frontier in hematologic malignancies.

    PubMed

    Boyiadzis, Michael; Whiteside, Theresa L

    2015-09-01

    Exosomes are small (30-150 mm) vesicles secreted by all cell types and present in all body fluids. They are emerging as vehicles for delivery of membrane-tethered signaling molecules and membrane enclosed genes to target cells. Exosome-mediated information transfer allows for crosstalk of cells within the hematopoietic system and for interactions between hematopoietic cells and local or distant tissue cells. Exosomes carry physiological signals essential for health and participate in pathological processes, including malignant transformation. In hematologic malignancies, exosomes reprogram the bone marrow microenvironment, creating a niche for abnormal cells and favoring their expansion. The molecular and genetic mechanisms exosomes utilize to shuttle information between cells are currently being examined as are the potential roles exosomes play as biomarkers of disease or future therapeutic targets.

  3. Reduced-intensity conditioning regimen using low-dose total body irradiation before allogeneic transplant for hematologic malignancies: Experience from the European Group for Blood and Marrow Transplantation

    SciTech Connect

    Belkacemi, Yazid . E-mail: y-belkacemi@o-lambret.fr; Labopin, Myriam; Hennequin, Christophe; Hoffstetter, Sylvette; Mungai, Raffaello; Wygoda, Marc; Lundell, Marie; Finke, Jurgen; Aktinson, Chris; Lorchel, Frederic; Durdux, Catherine; Basara, Nadezda

    2007-02-01

    Purpose: The high rate of toxicity is the limitation of myelobalative regimens before allogeneic transplantation. A reduced intensity regimen can allow engraftment of stem cells and subsequent transfer of immune cells for the induction of a graft-vs.-tumor reaction. Methods and Materials: The data from 130 patients (80 males and 50 females) treated between 1998 and 2003 for various hematologic malignancies were analyzed. The median patient age was 50 years (range, 3-72 years). Allogeneic transplantation using peripheral blood or bone marrow, or both, was performed in 104 (82%), 22 (17%), and 4 (3%) patients, respectively, from HLA identical sibling donors (n = 93, 72%), matched unrelated donors (n = 23, 18%), mismatched related donors (4%), or mismatched unrelated donors (6%). Total body irradiation (TBI) at a dose of 2 Gy delivered in one fraction was given to 101 patients (78%), and a total dose of 4-6 Gy was given in 29 (22%) patients. The median dose rate was 14.3 cGy/min (range, 6-16.4). Results: After a median follow-up period of 20 months (range, 1-62 months), engraftment was obtained in 122 patients (94%). Acute graft-vs.-host disease of Grade 2 or worse was observed in 37% of patients. Multivariate analysis showed three favorable independent factors for event-free survival: HLA identical sibling donor (p < 0.0001; relative risk [RR], 0.15), complete remission (p < 0.0001; RR, 3.08), and female donor to male patient (p = 0.006; RR 2.43). For relapse, the two favorable prognostic factors were complete remission (p < 0.0001, RR 0.11) and HLA identical sibling donor (p = 0.0007; RR 3.59). Conclusions: In this multicenter study, we confirmed high rates of engraftment and chimerism after the reduced intensity regimen. Our results are comparable to those previously reported. Radiation parameters seem to have no impact on outcome. However, the lack of a statistically significant difference in terms of dose rate may have been due, in part, to the small population

  4. Notch signaling: its roles and therapeutic potential in hematological malignancies.

    PubMed

    Gu, Yisu; Masiero, Massimo; Banham, Alison H

    2016-05-17

    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.

  5. 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.

  6. 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

  7. 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

  8. Donor Derived Second Hematologic Malignancies after Cord Blood Transplantation

    PubMed Central

    Ballen, Karen K; Cutler, Corey; Yeap, Beow Y; McAfee, Steven L; Dey, Bimalangshu R; Attar, Eyal C; Chen, Yi-Bin; Haspel, Richard L; Liney, Deborah; Koreth, John; Ho, Vincent; Alyea, Edwin P; Soiffer, Robert J; Spitzer, Thomas R; Antin, Joseph H

    2010-01-01

    Double umbilical cord blood transplantation with a reduced intensity regimen is an effective strategy for adult patients without matched donors. However, the risk of second cancers is not yet established. Ninety-eight adults with hematologic malignancies received a double umbilical cord blood transplant. Seventy patients received the reduced intensity regimen of fludarabine 30 mg/m2/day × 6 days, melphalan 100 mg/m2/day × 1 day, and rabbit antithymocyte globulin 1.5 mg/kg/day × 4 days, and 28 patients received an ablative total body radiation containing conditioning regimen. Sixty-three patients received sirolimus-based graft versus host disease prophylaxis and 35 patients received non-sirolimus based graft versus host disease prophylaxis. Median age was 48 (range 19-67) years. Eighteen patients developed a second malignancy at a median of 134 days after transplant. Sixteen patients had lymphoma and two patients had myelodysplasia/myeloproliferative disorder. Sixteen of these second cancers (both MDS/MPD and fourteen of the lymphomas) were donor derived; the origin of the others was not determined. GVHD prophylaxis, HLA matching, primary disease, age, total nucleated cell dose, and CD34+ cell dose were not associated with a higher rate of second malignancy. Second myeloid malignancies of donor origin occur after double umbilical cord blood transplantation, suggesting that a search for donor origin should be performed in all patients with suspected relapse. PMID:20178854

  9. Tetraspanins as therapeutic targets in hematological malignancy: a concise review

    PubMed Central

    Beckwith, Kyle A.; Byrd, John C.; Muthusamy, Natarajan

    2015-01-01

    Tetraspanins belong to a family of transmembrane proteins which play a major role in the organization of the plasma membrane. While all immune cells express tetraspanins, most of these are present in a variety of other cell types. There are a select few, such as CD37 and CD53, which are restricted to hematopoietic lineages. Tetraspanins associate with numerous partners involved in a diverse set of biological processes, including cell activation, survival, proliferation, adhesion, and migration. The historical view has assigned them a scaffolding role, but recent discoveries suggest some tetraspanins can directly participate in signaling through interactions with cytoplasmic proteins. Given their potential roles in supporting tumor survival and immune evasion, an improved understanding of tetraspanin activity could prove clinically valuable. This review will focus on emerging data in the study of tetraspanins, advances in the clinical development of anti-CD37 therapeutics, and the future prospects of targeting tetraspanins in hematological malignancy. PMID:25852576

  10. CircRNAs in hematopoiesis and hematological malignancies

    PubMed Central

    Bonizzato, A; Gaffo, E; te Kronnie, G; Bortoluzzi, S

    2016-01-01

    Cell states in hematopoiesis are controlled by master regulators and by complex circuits of a growing family of RNA species impacting cell phenotype maintenance and plasticity. Circular RNAs (circRNAs) are rapidly gaining the status of particularly stable transcriptome members with distinctive qualities. RNA-seq identified thousands of circRNAs with developmental stage- and tissue-specific expression corroborating earlier suggestions that circular isoforms are a natural feature of the cell expression program. CircRNAs are abundantly expressed also in the hematopoietic compartment. There are a number of studies on circRNAs in blood cells, a specific overview is however lacking. In this review we first present current insight in circRNA biogenesis discussing the relevance for hematopoiesis of the highly interleaved processes of splicing and circRNA biogenesis. Regarding molecular functions circRNAs modulate host gene expression, but also compete for binding of microRNAs, RNA-binding proteins or translation initiation and participate in regulatory circuits. We examine circRNA expression in the hematopoietic compartment and in hematologic malignancies and review the recent breakthrough study that identified pathogenic circRNAs derived from leukemia fusion genes. CircRNA high and regulated expression in blood cell types indicate that further studies are warranted to inform the position of these regulators in normal and malignant hematopoiesis. PMID:27740630

  11. Palliative care in pediatric patients with hematologic malignancies.

    PubMed

    Humphrey, Lisa; Kang, Tammy I

    2015-01-01

    Children with advanced cancer, including those with hematologic malignancies, can benefit from interdisciplinary palliative care services. Palliative care includes management of distressing symptoms, attention to psychosocial and spiritual needs, and assistance with navigating complex medical decisions with the ultimate goal of maximizing the quality-of-life of the child and family. Palliative care is distinct from hospice care and can assist with the care of patients throughout the cancer continuum, irrespective of prognosis. While key healthcare organizations, including the Institute of Medicine, the American Academy of Pediatrics and the American Society of Clinical Oncology among many others endorse palliative care for children with advanced illness, barriers to integration of palliative care into cancer care still exist. Providing assistance with advance care planning, guiding patients and families through prognostic uncertainty, and managing transitions of care are also included in goals of palliative care involvement. For patients with advanced malignancy, legislation, included in the Patient Protection and Affordable Health Care Act allows patients and families more options as they make the difficult transition from disease directed therapy to care focused on comfort and quality-of-life.

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

    PubMed Central

    Grotzer, Michael A.; Niggli, Felix; Zimmermann, Dieter; Rushing, Elisabeth

    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. PMID:27524931

  13. Skylab experiment results: Hematology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Ritzmann, S. E.; Mengel, C. E.; Fischer, C. L.

    1975-01-01

    Studies were conducted to evaluate specific aspects of man's immunologic and hematologic systems that might be altered by or respond to the space flight environment. Biochemical functions investigated included cytogenetic damage to blood cells, immune resistance to disease, regulation of plasma and red cell volumes, metabolic processes of the red blood cell, and physicochemical aspects of red blood cell function. Measurements of hematocrit value showed significant fluctuations postflight, reflecting observed changes in red cell mass and plasma volume. The capacity of lymphocytes to respond to an in vitro mitogenic challenge was repressed postflight, and appeared to be related to mission duration. Most other deviations from earth function in these systems were minor or transient.

  14. Acquired uniparental disomy of chromosome 9p in hematologic malignancies.

    PubMed

    Wang, Linghua; Wheeler, David A; Prchal, Josef T

    2016-08-01

    Acquired uniparental disomy (aUPD) is a common and recurrent molecular event in human cancers that leads to homozygosity for tumor suppressor genes as well as oncogenes, while retaining the diploid chromosomal complement. Because of the lack of copy number change, aUPD is undetectable by comparative genome hybridization, so the magnitude of this genetic change was underappreciated in the past. 9p aUPD was first described in 2002 in patients with polycythemia vera (PV). Since then, systematic application of genomewide single-nucleotide polymorphism arrays has indicated that 9p aUPD is the most common chromosomal aberration in myeloproliferative neoplasms (MPNs), contributing to discovery of the PV-defining mutation JAK2V617F21. It was also found in other myeloid and lymphoid malignancies, though at a relatively lower frequency. By leading to JAK2V617F 23 homozygosity, 9p aUPD plays a causal role in the development of PV and is also associated with less favorable clinical outcomes. It is also possible that new targets other than JAK2V617F 25 are present within 9p aUPD that may contribute to diversity of PV outcome and phenotype. This review summarizes recent discoveries on 9p aUPD in hematologic malignancies and discusses possible underlying mechanisms and potential roles of 9p aUPD in the pathogenesis of PV, the relationship between 9p aUPD and JAK2V617F29, and possible new cancer-related targets within the 9p aUPD region.

  15. Epigenetics, autoimmunity and hematologic malignancies: a comprehensive review.

    PubMed

    Ngalamika, Owen; Zhang, Yiqun; Yin, Heng; Zhao, Ming; Gershwin, M Eric; Lu, Qianjin

    2012-12-01

    The relationships between immunological dysfunction, loss of tolerance and hematologic malignancies have been a focus of attention in attempts to understand the appearance of a higher degree of autoimmune disease and lymphoma in children with congenital immunodeficiency. Although multiple hypotheses have been offered, it is clear that stochastic processes play an important role in the immunopathology of these issues. In particular, accumulating evidence is defining a role of epigenetic mechanisms as being critical in this continuous spectrum between autoimmunity and lymphoma. In this review, we focus attention predominantly on the relationships between T helper 17 (Th17) and T regulatory populations that alter local microenvironments and ultimately the expression or transcription factors involved in cell activation and differentiation. Abnormal expression in any of the molecules involved in Th17 and/or Treg development alter immune homeostasis and in genetically susceptible hosts may lead to the appearance of autoimmunity and/or lymphoma. These observations have clinical significance in explaining the discordance of autoimmunity in identical twins. They are also particularly important in the relationships between primary immune deficiency syndromes, immune dysregulation and an increased risk of lymphoma. Indeed, defining the factors that determine epigenetic alterations and their relationships to immune homeostasis will be a challenge greater or even equal to the human genome project.

  16. Chimeric Antigen Receptor T Cells in Hematologic Malignancies.

    PubMed

    Shank, Brandon R; Do, Bryan; Sevin, Adrienne; Chen, Sheree E; Neelapu, Sattva S; Horowitz, Sandra B

    2017-03-01

    Patients with B-cell hematologic malignancies who progress through first- or second-line chemotherapy have a poor prognosis. Early clinical trials with autologous anti-CD19 chimeric antigen receptor (CAR) T cells have demonstrated promising results for patients who have relapsed or refractory disease. Lymphodepleting conditioning regimens, including cyclophosphamide, fludarabine, pentostatin, bendamustine, interleukin-2, and total body irradiation, are often administered before the infusion of CAR T cells, allowing for greater T-cell expansion. The major toxicity associated with CAR T-cell infusions is cytokine release syndrome (CRS), a potentially life-threatening systemic inflammatory disorder. The quick onset and progression of CRS require rapid detection and intervention to reduce treatment-related mortality. Management with tocilizumab can help ameliorate the symptoms of severe CRS, allowing steroids, which diminish the expansion and persistence of CAR T cells, to be reserved for tocilizumab-refractory patients. Other toxicities of CAR T-cell therapy include neutropenia and/or febrile neutropenia, infection, tumor lysis syndrome, neurotoxicity and nausea/vomiting. A review of patients' medications is imperative to eliminate medications that may contribute to treatment-related toxicities. Studies are ongoing to help optimize patient selection, preparation, safety, and management of individuals receiving CAR T cells. Long-term follow-up will help establish the place of CAR T cells in therapy.

  17. Epidemiology of Candida kefyr in Patients with Hematologic Malignancies

    PubMed Central

    Dufresne, Simon F.; Sydnor, Emily; Staab, Janet F.; Karp, Judith E.; Lu, Kit; Zhang, Sean X.; Lavallée, Christian; Perl, Trish M.; Neofytos, Dionysios

    2014-01-01

    Candida kefyr is an emerging pathogen among patients with hematologic malignancies (HM). We performed a retrospective study at Johns Hopkins Hospital to evaluate the epidemiology of C. kefyr colonization and infection in HM patients between 2004 and 2010. Eighty-three patients were colonized and/or infected with C. kefyr, with 8 (9.6%) having invasive candidiasis (IC). The yearly incidence of C. kefyr colonization and candidemia increased over the study period (P < 0.01), particularly after 2009. In 2010, C. kefyr caused 16.7% of candidemia episodes. The monthly incidence of C. kefyr was higher during the summer throughout the study. In a cohort of patients with acute myelogenic leukemia receiving induction chemotherapy, risks for C. kefyr colonization included the summer season (odds ratio [OR], 3.1; P = 0.03); administration of an azole (OR, 0.06; P < 0.001) or amphotericin B (OR, 0.35; P = 0.05) was protective. Fingerprinting of 16 isolates by repetitive sequence-based PCR showed that all were different genotypes. The epidemiology of C. kefyr candidemia was evaluated in another hospital in Montreal, Canada; data confirmed higher rates of C. kefyr infection in the summer. C. kefyr appears to be increasing in HM patients, with prominent summer seasonality. These findings raise questions about the effect of antifungal agents and health care exposures (e.g., yogurt) on the epidemiology of this yeast. PMID:24622105

  18. Statistics of hematologic malignancies in Korea: incidence, prevalence and survival rates from 1999 to 2008

    PubMed Central

    Park, Hyeon Jin; Park, Eun-Hye; Jung, Kyu-Won; Kong, Hyun-Joo; Won, Young-Joo; Lee, Joo Young; Yoon, Jong Hyung; Park, Byung-Kiu; Lee, Hyewon; Eom, Hyeon-Seok

    2012-01-01

    Background The nationwide statistical analysis of hematologic malignancies in Korea has not been reported yet. Methods The Korea Central Cancer Registry and the Korean Society of Hematology jointly investigated domestic incidence rates and prevalence of hematologic malignancies occurred between 1999 and 2008, and analyzed survival rates of patients who were diagnosed between 1993 and 2008. Data of hematologic malignancies from 1993 to 2008 were obtained from the Korean National Cancer Incidence Data base. The crude incidence rates, age-specific incidence rates, age-standardized incidence rates, annual percentage change of incidence, and prevalence from 1999-2008 were calculated. Survival rates for patients diagnosed in 1993-2008 were estimated. Results In 2008, a total of 8,006 cases of hematologic malignancies were occurred, which comprised 4.5% of all malignancies. In all genders, non-Hodgkin lymphoma, myeloid leukemia, and multiple myeloma were most frequent diseases. In terms of age, ages between 60 and 69 were most prevalent. From 1999 to 2008, the age-standardized incidence rates increased from 10.2 to 13.7, and the annual percentage change was 3.9%. The 5-year survival rate increased from 38.2% during 1993-1995 to 55.2% during 2004-2008. As of January 2009, number of patients with 10-year prevalence was 33,130, and with 5- to 10-year prevalence was 10,515. Conclusion This is the first nationwide statistical report of hematologic malignancies in Korea. It could be used as the basic information to help investigate epidemiologic characteristics, evaluate progress during the past years, and establish future strategies for hematologic malignancies. Periodic statistical analysis of hematologic malignancies in Korea should be continued. PMID:22479275

  19. Targeting hedgehog signaling in myelofibrosis and other hematologic malignancies

    PubMed Central

    2014-01-01

    Treatment of myelofibrosis (MF), a BCR-ABL–negative myeloproliferative neoplasm, is challenging. The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. The remaining patients are treated with palliative therapies to manage MF-related anemia and splenomegaly. Identification of a mutation in the Janus kinase 2 (JAK2) gene (JAK2 V617F) in more than half of all patients with MF has prompted the discovery and clinical development of inhibitors that target JAK2. Although treatment with JAK2 inhibitors has been shown to improve symptom response and quality of life in patients with MF, these drugs do not alter the underlying disease; therefore, novel therapies are needed. The hedgehog (Hh) signaling pathway has been shown to play a role in normal hematopoiesis and in the tumorigenesis of hematologic malignancies. Moreover, inhibitors of the Hh pathway have been shown to inhibit growth and self-renewal capacity in preclinical models of MF. In a mouse model of MF, combined inhibition of the Hh and JAK pathways reduced JAK2 mutant allele burden, reduced bone marrow fibrosis, and reduced white blood cell and platelet counts. Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification. PMID:24598114

  20. Treatment of febrile neutropenia and prophylaxis in hematologic malignancies: a critical review and update.

    PubMed

    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.

  1. 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

  2. Chimeric antigen receptors for the adoptive T cell therapy of hematologic malignancies.

    PubMed

    Davila, Marco L; Bouhassira, Diana C G; Park, Jae H; Curran, Kevin J; Smith, Eric L; Pegram, Hollie J; Brentjens, Renier

    2014-04-01

    The genetic modification of autologous T cells with chimeric antigen receptors (CARs) represents a breakthrough for gene engineering as a cancer therapy for hematologic malignancies. By targeting the CD19 antigen, we have demonstrated robust and rapid anti-leukemia activity in patients with heavily pre-treated and chemotherapy-refractory B cell acute lymphoblastic leukemia (B-ALL). We demonstrated rapid induction of deep molecular remissions in adults, which has been recently confirmed in a case report involving a child with B-ALL. In contrast to the results when treating B-ALL, outcomes have been more modest in patients with chronic lymphocytic leukemia (CLL) or other non-hodgkin's lymphoma (NHL). We review the clinical trial experience targeting B-ALL and CLL and speculate on the possible reasons for the different outcomes and propose potential optimization to CAR T cell therapy when targeting CLL or other indolent NHL. Lastly, we discuss the pre-clinical development and potential for clinical translation for using CAR T cells against multiple myeloma and acute myeloid leukemia. We highlight the potential risks and benefits by targeting these poor outcome hematologic malignancies.

  3. Epidemiology and clinical manifestation of fungal infection related to Mucormycosis in hematologic malignancies

    PubMed Central

    Noorifard, M; Sekhavati, E; Jalaei Khoo, H; Hazraty, I; Tabrizi, R

    2015-01-01

    Introduction: Mucormycosis is an opportunist fungus infection with acute and rapidly progressive nature in the hematologic malignancy patients. This study was done to investigate the prevalence and clinical manifestations of this infection among hematologic malignancies. Methodology:This cross-sectional study (descriptive-analytical) was performed while investigating medical records of 30 patients with hematologic malignancy affected by Mucormycosis in Imam Reza Hospital between 2001 and 2013. After collecting the data, it was entered in SPSS 19 Software with a provided checklist that included demographic characteristics, clinical manifestations, and it was analyzed by using descriptive (mean, frequency) and inferential (chi- square and independent -t-test) statistical methods (p-value < 0.05 was considered as statistically significant). Findings:Overall, the prevalence of Mucormycosis was 4.29 per 100 patient hematologic malignancies. The infection proportion among men and women was 72. 2, 27.6%, respectively. The maximum cases of Mucormycosis were observed among AML patients (62.1%). The most common place of involvement was lung (89.4%) and fever was the most popular sign of the infection (100%). The most considerable and effective factor in the prognosis of infection was using combined therapy of Amphotericin Band surgery (debridement) that has statistically significant correlation (p<0.05). Conclusion:Considerable prevalence and death related to Mucormycosis infection among patients of hematologic malignancy showed the importance of having strategies for its prevention and early diagnosis especially among acute leukemia patients.

  4. Targeted Marrow Irradiation, Fludarabine Phosphate, and Busulfan Before Donor Progenitor Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2017-01-04

    Acute Myeloid Leukemia; Hematologic Malignancies; Acute Lymphocytic Leukemia; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Myelodysplastic Syndrome; Chronic Lymphocytic Leukemia; Chronic Myeloid Leukemia; Myelofibrosis; Myeloproliferative Syndrome

  5. Antibody-modified T cells: CARs take the front seat for hematologic malignancies

    PubMed Central

    Maus, Marcela V.; Grupp, Stephan A.; Porter, David L.

    2014-01-01

    T cells redirected to specific antigen targets with engineered chimeric antigen receptors (CARs) are emerging as powerful therapies in hematologic malignancies. Various CAR designs, manufacturing processes, and study populations, among other variables, have been tested and reported in over 10 clinical trials. Here, we review and compare the results of the reported clinical trials and discuss the progress and key emerging factors that may play a role in effecting tumor responses. We also discuss the outlook for CAR T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies. Many questions remain in the field of CAR T cells directed to hematologic malignancies, but the encouraging response rates pave a wide road for future investigation. PMID:24578504

  6. Antibody-modified T cells: CARs take the front seat for hematologic malignancies.

    PubMed

    Maus, Marcela V; Grupp, Stephan A; Porter, David L; June, Carl H

    2014-04-24

    T cells redirected to specific antigen targets with engineered chimeric antigen receptors (CARs) are emerging as powerful therapies in hematologic malignancies. Various CAR designs, manufacturing processes, and study populations, among other variables, have been tested and reported in over 10 clinical trials. Here, we review and compare the results of the reported clinical trials and discuss the progress and key emerging factors that may play a role in effecting tumor responses. We also discuss the outlook for CAR T-cell therapies, including managing toxicities and expanding the availability of personalized cell therapy as a promising approach to all hematologic malignancies. Many questions remain in the field of CAR T cells directed to hematologic malignancies, but the encouraging response rates pave a wide road for future investigation.

  7. Epimutational profile of hematologic malignancies as attractive target for new epigenetic therapies

    PubMed Central

    Fratta, Elisabetta; Montico, Barbara; Rizzo, Aurora; Colizzi, Francesca; Sigalotti, Luca; Dolcetti, Riccardo

    2016-01-01

    In recent years, recurrent somatic mutations in epigenetic regulators have been identified in patients with hematological malignancies. Furthermore, chromosomal translocations in which the fusion protein partners are themselves epigenetic regulators or where epigenetic regulators are recruited/targeted by oncogenic fusion proteins have also been described. Evidence has accumulated showing that “epigenetic drugs” are likely to provide clinical benefits in several hematological malignancies, granting their approval for the treatment of myelodysplastic syndromes and cutaneous T-cell lymphomas. A large number of pre-clinical and clinical trials evaluating epigenetic drugs alone or in combination therapies are ongoing. The aim of this review is to provide a comprehensive summary of known epigenetic alterations and of the current use of epigenetic drugs for the treatment of hematological malignancies. PMID:27329599

  8. 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

  9. Serious outbreak of human metapneumovirus in patients with hematologic malignancies.

    PubMed

    Hoellein, Alexander; Hecker, Judith; Hoffmann, Dieter; Göttle, Franziska; Protzer, Ulrike; Peschel, Christian; Götze, Katharina

    2016-01-01

    Human metapneumovirus (hMPV) is an important cause of lower respiratory tract infection. In healthy subjects infections are usually mild and rarely necessitate hospitalization. However, more serious outcomes have been described for allogeneic stem cell transplant recipients. This study reports an outbreak of hMPV A2 infection in severely immunocompromised adult hematologic cancer patients in a tertiary care unit. HMPV RNA was detected in bronchoalveolar lavage or produced sputum from patients presenting with typical clinical features. A total of 15 patients were diagnosed in a period of 7 weeks. Molecular subtyping revealed infection with genotype A2a virus, implicating nosocomial transmission. Eleven patients (73%) were treated with intravenous immunoglobulins and ribavirin. Ten patients (65%) presented with severe dyspnea, five (33%) required mechanical ventilation. Four patients (26.6%) died from hMPV-associated pneumonia and consequent multi-organ failure. Thus, hMPV is a critical pathogen for patients with hematologic cancers warranting early detection.

  10. 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.

  11. Nutritional status of children and adolescents at diagnosis of hematological and solid malignancies

    PubMed Central

    Lemos, Priscila dos Santos Maia; de Oliveira, Fernanda Luisa Ceragioli; Caran, Eliana Maria Monteiro

    2014-01-01

    Objective To assess the nutritional status of child and adolescent patients with cancer at diagnosis. Methods A total of 1154 patients were included and divided into two groups: solid and hematological malignancies. The parameters used for nutritional assessment were weight, height, triceps skinfold thickness, mid-upper arm circumference, arm muscle circumference, body mass index and percentage weight loss. Results At diagnosis, below adequate body mass index was observed by anthropometric analysis in 10.85% of the patients – 12.2% in the solid tumor group and 9.52% in the hematologic group. The average weight loss adjusted for a period of 7 days was −2.82% in the hematologic group and −2.9% in the solid tumor group. Conclusions The prevalence of malnutrition is higher among patients with malignancies than in the general population, even though no difference was observed between the two groups. PMID:25453652

  12. T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

    ClinicalTrials.gov

    2014-03-04

    Hematologic Malignancy; Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia in Blast Crisis; Anemia, Refractory, With Excess of Blasts; Chronic Myeloproliferative Disease; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Marginal Zone B-cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Lymphoma; Large Cell Non-Hodgkin's Lymphoma; Lymphoblastic Lymphoma; Burkitt's Lymphoma; High Grade Non-Hodgkin's Lymphoma

  13. Invasive infection due to Saprochaete capitata in a young patient with hematological malignancies

    PubMed Central

    Parahym, Ana Maria Rabelo de Carvalho; Rolim, Pedro José; da Silva, Carolina Maria; Domingos, Igor de Farias; Gonçalves, Sarah Santos; Leite, Edinalva Pereira; de Morais, Vera Lúcia Lins; Macêdo, Danielle Patrícia Cerqueira; de Lima, Reginaldo Gonçalves; Neves, Rejane Pereira

    2015-01-01

    We report a case of invasive infection due to Saprochaete capitata in a patient with hematological malignancies after chemotherapy treatment and empiric antifungal therapy with caspofungin. Although severely immunocompromised the patient survived been treated with amphotericin B lipid complex associated with voriconazole. PMID:26273269

  14. Parental Age at Birth and Risk of Hematological Malignancies in Older Adults.

    PubMed

    Teras, Lauren R; Gaudet, Mia M; Blase, Jennifer L; Gapstur, Susan M

    2015-07-01

    The proportion of parents aged ≥35 years at the birth of their child continues to increase, but long-term health consequences for these children are not fully understood. A recent prospective study of 110,999 adult women showed an association between paternal-but not maternal-age at birth and sporadic hematological cancer risk. To further investigate this topic, we examined these associations in women and men in the American Cancer Society Cancer Prevention Study-II Nutrition Cohort. Among 138,003 Cancer Prevention Study-II participants, 2,532 incident hematological cancers were identified between 1992 and 2009. Multivariable-adjusted hazard ratios and 95% confidence intervals were computed by using Cox proportional hazards regression. There was no clear linear trend in the risk of hematological malignancies by either paternal or maternal age. However, there was a strong, positive association with paternal age among participants without siblings. In that group, the hazard ratio for fathers aged ≥35 years compared with <25 years at birth was 1.63 (95% confidence interval: 1.19, 2.23), and a linear dose-response association was suggested (Pspline = 0.002).There were no differences by subtype of hematological cancer. Results of this study support the need for further research to better understand the association between paternal age at birth and hematological malignancies.

  15. Parental Age at Birth and Risk of Hematological Malignancies in Older Adults

    PubMed Central

    Teras, Lauren R.; Gaudet, Mia M.; Blase, Jennifer L.; Gapstur, Susan M.

    2015-01-01

    The proportion of parents aged ≥35 years at the birth of their child continues to increase, but long-term health consequences for these children are not fully understood. A recent prospective study of 110,999 adult women showed an association between paternal—but not maternal—age at birth and sporadic hematological cancer risk. To further investigate this topic, we examined these associations in women and men in the American Cancer Society Cancer Prevention Study-II Nutrition Cohort. Among 138,003 Cancer Prevention Study-II participants, 2,532 incident hematological cancers were identified between 1992 and 2009. Multivariable-adjusted hazard ratios and 95% confidence intervals were computed by using Cox proportional hazards regression. There was no clear linear trend in the risk of hematological malignancies by either paternal or maternal age. However, there was a strong, positive association with paternal age among participants without siblings. In that group, the hazard ratio for fathers aged ≥35 years compared with <25 years at birth was 1.63 (95% confidence interval: 1.19, 2.23), and a linear dose-response association was suggested (Pspline = 0.002).There were no differences by subtype of hematological cancer. Results of this study support the need for further research to better understand the association between paternal age at birth and hematological malignancies. PMID:25964260

  16. Programmed death-1 immune checkpoint blockade in the treatment of hematological malignancies.

    PubMed

    Tsirigotis, Panagiotis; Savani, Bipin N; Nagler, Arnon

    2016-09-01

    The use of tumor-specific monoclonal antibodies (MAbs) has revolutionize the field of cancer immunotherapy. Although treatment of malignant diseases with MAbs is promising, many patients fail to respond or relapse after an initial response. Both solid tumors and hematological malignancies develop mechanisms that enable them to evade the host immune system by usurping immune checkpoint pathways such as PD-1, PD-2, PDL-1, or PDL-2 (programmed cell death protein-1 or 2 and PD-Ligand 1 or 2), which are expressed on activated T cells and on T-regulatory, B cells, natural killers, monocytes, and dendritic cells. One of the most exciting anticancer development in recent years has been the immune checkpoint blockade therapy by using MAbs against immune checkpoint receptor and/or ligands. Anti-PD1 antibodies have been tested in clinical studies that included patients with hematological malignancies and showed remarkable efficacy in Hodgkin lymphoma (HL). In our review, we will focus on the effect of PD-1 activation on hematological malignancies and its role as a therapeutic target. Key messages The programmed death 1 (PD1) immune checkpoint is an important homeostatic mechanism of the immune system that helps in preventing autoimmunity and uncontrolled inflammation in cases of chronic infections. However, PD1 pathway is also operated by a wide variety of malignancies and represents one of the most important mechanisms by which tumor cells escape from the surveillance of the immune system. Blocking of immune checkpoints by the use of monoclonal antibodies opened a new era in the field of cancer immunotherapy. Results from clinical trials are promising, and currently, this approach has been proven effective and safe in patients with solid tumors and hematological malignancies.

  17. The Therapeutic Outcomes of Mechanical Ventilation in Hematological Malignancy Patients with Respiratory Failure.

    PubMed

    Fujiwara, Yusuke; Yamaguchi, Hiroki; Kobayashi, Katsuya; Marumo, Atsushi; Omori, Ikuko; Yamanaka, Satoshi; Yui, Shunsuke; Fukunaga, Keiko; Ryotokuji, Takeshi; Hirakawa, Tsuneaki; Okabe, Masahiro; Wakita, Satoshi; Tamai, Hayato; Okamoto, Muneo; Nakayama, Kazutaka; Takeda, Shinhiro; Inokuchi, Koiti

    2016-01-01

    Objective In hematological malignancy patients, the complication of acute respiratory failure often reaches a degree of severity that necessitates mechanical ventilation. The objective of the present study was to investigate the therapeutic outcomes of mechanical ventilation in hematological malignancy patients with respiratory failure and to analyze the factors that are associated with successful treatment in order to identify the issues that should be addressed in the future. Methods The present study was a retrospective analysis of 71 hematological malignancy patients with non-cardiogenic acute respiratory failure who were treated with mechanical ventilation at Nippon Medical School Hospital between 2003 and 2014. Results Twenty-six patients (36.6%) were treated with mechanical ventilation in an intensive care unit (ICU). Non-invasive positive pressure ventilation (NPPV) was applied in 29 cases (40.8%). The rate of successful mechanical ventilation treatment with NPPV alone was 13.8%. The rate of endotracheal extubation was 17.7%. A univariate analysis revealed that the following factors were associated with the successful extubation of patients who received invasive mechanical ventilation: respiratory management in an ICU (p=0.012); remission of the hematological disease (p=0.011); female gender (p=0.048); low levels of accompanying non-respiratory organ failure (p=0.041); and the non-use of extracorporeal circulation (p=0.005). A subsequent multivariate analysis revealed that respiratory management in an ICU was the only variable associated with successful extubation (p=0.030). Conclusion The outcomes of hematological malignancy patients who receive mechanical ventilation treatment for respiratory failure are very poor. Respiratory management in an ICU environment may be useful in improving the therapeutic outcomes of such patients.

  18. Mothering and self-othering: the impact of uncertain reproductive capability in young women after hematological malignancy.

    PubMed

    Halliday, Lesley E; Boughton, Maureen A; Kerridge, Ian

    2014-01-01

    We explored the experiences of uncertain fertility, pregnancy, and motherhood in 12 young women treated for hematological malignancy during their reproductive years. It is demonstrated how, through interpretations of the women's own words, these women lived and coped with a sense of "otherness" in relation to their peers. The concept of otherness is described and discussed in relation to relevant existing literature and it is concluded that, regardless of their cancer history, young women's uncertainty in this context has a broad impact on their psychosocial health and requires sensitive and empathic information, discussion, and support.

  19. Emerging concepts of epigenetic dysregulation in hematological malignancies

    PubMed Central

    Ntziachristos, Panagiotis; Abdel-Wahab, Omar; Aifantis, Iannis

    2016-01-01

    The past decade brought a revolution in understanding of the structure, topology and disease-inducing lesions of RNA and DNA, fueled by unprecedented progress in next-generation sequencing. This technological revolution has also affected understanding of the epigenome and has provided unique opportunities for the analysis of DNA and histone modifications, as well as the first map of the non–protein-coding genome and three-dimensional (3D) chromosomal interactions. Overall, these advances have facilitated studies that combine genetic, transcriptomics and epigenomics data to address a wide range of issues ranging from understanding the role of the epigenome in development to targeting the transcription of noncoding genes in human cancer. Here we describe recent insights into epigenetic dysregulation characteristic of the malignant differentiation of blood stem cells based on studies of alterations that affect epigenetic complexes, enhancers, chromatin, long noncoding RNAs (lncRNAs), RNA splicing, nuclear topology and the 3D conformation of chromatin. PMID:27478938

  20. Clinical trials of dendritic cell-based cancer vaccines in hematologic malignancies

    PubMed Central

    Pyzer, Athalia R; Avigan, David E; Rosenblatt, Jacalyn

    2015-01-01

    The potential for the immune system to target hematological malignancies is demonstrated in the allogeneic transplant setting, where durable responses can be achieved. However, allogeneic transplantation is associated with significant morbidity and mortality related to graft versus host disease. Cancer immunotherapy has the capacity to direct a specific cytotoxic immune response against cancer cells, particularly residual cancer cells, in order to reduce the likelihood of disease relapse in a more targeted and tolerated manner. Ex vivo dendritic cells can be primed in various ways to present tumor associated antigen to the immune system, in the context of co-stimulatory molecules, eliciting a tumor specific cytotoxic response in patients. Several approaches to prime dendritic cells and overcome the immunosuppressive microenvironment have been evaluated in pre-clinical and early clinical trials with promising results. In this review, we summarize the clinical data evaluating dendritic cell based vaccines for the treatment of hematological malignancies. PMID:25625926

  1. 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.

  2. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies.

    PubMed

    Choudary, Iqra; Barr, Paul M; Friedberg, Jonathan

    2015-12-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential.

  3. Recent advances in the development of Aurora kinases inhibitors in hematological malignancies

    PubMed Central

    Choudary, Iqra; Barr, Paul M.; Friedberg, Jonathan

    2015-01-01

    Over the last two decades, since the discovery of Drosophila mutants in 1995, much effort has been made to understand Aurora kinase biology. Three mammalian subtypes have been identified thus far which include the Aurora A, B and C kinases. These regulatory proteins specifically work at the cytoskeleton and chromosomal structures between the kinetochores and have vital functions in the early phases of the mitotic cell cycle. Today, there are multiple phase I and phase II clinical trials as well as numerous preclinical studies taking place looking at Aurora kinase inhibitors in both hematologic and solid malignancies. This review focuses on the preclinical and clinical development of Aurora kinase inhibitors in hematological malignancy and discusses their therapeutic potential. PMID:26622997

  4. The emerging role of Twist proteins in hematopoietic cells and hematological malignancies

    PubMed Central

    Merindol, N; Riquet, A; Szablewski, V; Eliaou, J-F; Puisieux, A; Bonnefoy, N

    2014-01-01

    Twist1 and Twist2 (Twist1–2) are two transcription factors, members of the basic helix-loop-helix family, that have been well established as master transcriptional regulators of embryogenesis and developmental programs of mesenchymal cell lineages. Their role in oncogenesis in epithelium-derived cancer and in epithelial-to-mesenchymal transition has also been thoroughly characterized. Recently, emerging evidence also suggests a key role for Twist1–2 in the function and development of hematopoietic cells, as well as in survival and development of numerous hematological malignancies. In this review, we summarize the latest data that depict the role of Twist1–2 in monocytes, T cells and B lymphocyte activation, and in associated hematological malignancies. PMID:24769647

  5. Optimizing T-cell receptor gene therapy for hematologic malignancies

    PubMed Central

    Morris, Emma C.

    2016-01-01

    Recent advances in genetic engineering have enabled the delivery of clinical trials using patient T cells redirected to recognize tumor-associated antigens. The most dramatic results have been seen with T cells engineered to express a chimeric antigen receptor (CAR) specific for CD19, a differentiation antigen expressed in B cells and B lineage malignancies. We propose that antigen expression in nonmalignant cells may contribute to the efficacy of T-cell therapy by maintaining effector function and promoting memory. Although CAR recognition is limited to cell surface structures, T-cell receptors (TCRs) can recognize intracellular proteins. This not only expands the range of tumor-associated self-antigens that are amenable for T-cell therapy, but also allows TCR targeting of the cancer mutagenome. We will highlight biological bottlenecks that potentially limit mutation-specific T-cell therapy and may require high-avidity TCRs that are capable of activating effector function when the concentrations of mutant peptides are low. Unexpectedly, modified TCRs with artificially high affinities function poorly in response to low concentration of cognate peptide but pose an increased safety risk as they may respond optimally to cross-reactive peptides. Recent gene-editing tools, such as transcription activator–like effector nucleases and clustered regularly interspaced short palindromic repeats, provide a platform to delete endogenous TCR and HLA genes, which removes alloreactivity and decreases immunogenicity of third-party T cells. This represents an important step toward generic off-the-shelf T-cell products that may be used in the future for the treatment of large numbers of patients. PMID:27207802

  6. Obinutuzumab in hematologic malignancies: lessons learned to date.

    PubMed

    Illidge, Tim; Klein, Christian; Sehn, Laurie H; Davies, Andrew; Salles, Gilles; Cartron, Guillaume

    2015-11-01

    The routine use of anti-CD20 monoclonal antibodies (mAbs) has improved patient outcomes in CD20-positive non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Despite the clinical success achieved with rituximab, relapses are still common with further improvements in anti-CD20 mAb efficacy required. Many novel anti-CD20 antibodies are in development, but obinutuzumab is currently the only type II glycoengineered anti-CD20 mAb in clinical testing. Obinutuzumab has increased antibody-dependent cell-mediated cytotoxicity, reduced complement-dependent cytotoxicity and enhanced direct non-apoptotic cell death. In preclinical models, obinutuzumab induced superior tumor remission compared with rituximab at the equivalent dose levels, and was active in rituximab-refractory tumors. Obinutuzumab exhibits encouraging efficacy as monotherapy in NHL, and combined with chemotherapy in relapsed/refractory NHL and treatment-naïve symptomatic CLL. In a recent randomized, phase III trial in patients with untreated comorbid CLL, overall response rate was significantly greater (78% vs. 65%, P<0.0001) and median progression-free survival was significantly prolonged (26.7 vs. 15.2months, P<0.0001) for obinutuzumab plus chlorambucil vs. rituximab plus chlorambucil. Obinutuzumab is a type II anti-CD20 antibody that utilizes distinct mechanisms of action relative to type I antibodies like rituximab and has led to significant clinical improvement over rituximab in a phase III trial in CLL. Further trials are ongoing to determine whether such improvements in outcome will be seen in CD20-positive B-cell malignancies.

  7. Improved radioimmunotherapy of hematologic malignancies. Final technical report

    SciTech Connect

    Press, O.W.

    1996-08-15

    Experiments were performed to study the rates of endocytosis, intracellular routing, and metabolic degradation of radiolabeled monoclonal antibodies targeting tumor-associated antigens on human leukemia and lymphoma cells. An attempt was made to examine in vivo the effects of lysosomotropic amines and thioamides on the retention of radiolabeled monoclonal antibodies by tumor cells. Experiments also examined the impact of newer radioiodination techniques on the metabolic degradation of radioiodinated antibodies, and on the radioimmunoscintigraphy and radioimmunotherapy of neoplasms. The endocytosis, intracellular routing, and degradation of radioimmunoconjugates prepared with I-131, In-111, and Y-90 were compared. The utility of radioimmunoconjugates targeting oncogene products for the radioimmunotherapy and radioimmunoscintigraphy of cancer was investigated.

  8. Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses hematological malignancy

    PubMed Central

    Wang, Ying-Hua; Kalaitzidis, Demetrios; Ramachandran, Janani; Sykes, David B.; Raje, Noopur; Scadden, David T.

    2016-01-01

    Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 (STAT3Y705). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and pSTAT3Y705 and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways. PMID:26927669

  9. A Risk Prediction Score for Invasive Mold Disease in Patients with Hematological Malignancies

    PubMed Central

    Stanzani, Marta; Lewis, Russell E.; Fiacchini, Mauro; Ricci, Paolo; Tumietto, Fabio; Viale, Pierluigi; Ambretti, Simone; Baccarani, Michele; Cavo, Michele; Vianelli, Nicola

    2013-01-01

    Background A risk score for invasive mold disease (IMD) in patients with hematological malignancies could facilitate patient screening and improve the targeted use of antifungal prophylaxis. Methods We retrospectively analyzed 1,709 hospital admissions of 840 patients with hematological malignancies (2005-2008) to collect data on 17 epidemiological and treatment-related risk factors for IMD. Multivariate regression was used to develop a weighted risk score based on independent risk factors associated with proven or probable IMD, which was prospectively validated during 1,746 hospital admissions of 855 patients from 2009-2012. Results Of the 17 candidate variables analyzed, 11 correlated with IMD by univariate analysis, but only 4 risk factors (neutropenia, lymphocytopenia or lymphocyte dysfunction in allogeneic hematopoietic stem cell transplant recipients, malignancy status, and prior IMD) were retained in the final multivariate model, resulting in a weighted risk score 0-13. A risk score of < 6 discriminated patients with low (< 1%) versus higher incidence rates (> 5%) of IMD, with a negative predictive value (NPV) of 0.99, (95% CI 0.98-0.99). During 2009-2012, patients with a calculated risk score at admission of < 6 had significantly lower 90-day incidence rates of IMD compared to patients with scores > 6 (0.9% vs. 10.6%, P <0.001). Conclusion An objective, weighted risk score for IMD can accurately discriminate patients with hematological malignancies at low risk for developing mold disease, and could possibly facilitate “screening-out” of low risk patients less likely to benefit from intensive diagnostic monitoring or mold-directed antifungal prophylaxis. PMID:24086555

  10. Detection and Identification of Hematologic Malignancies and Solid Tumors by an Electrochemical Technique

    PubMed Central

    Zhang, Bowen; Zhang, Xiaoping; Wang, Xuemei; Cheng, Jian; Chen, Baoan

    2016-01-01

    Purpose Develop and evaluate an electrochemical method to identify healthy individuals, malignant hematopathic patients and solid tumor patients by detecting the leukocytes in whole-blood. Methods A total of 114 individual blood samples obtained from our affiliated hospital in China (June 2015- August 2015) were divided into three groups: healthy individuals (n = 35), hematologic malignancies (n = 41) and solid tumors (n = 38). An electrochemical workstation system was used to measure differential pulse voltammetry due to the different electrochemical behaviors of leukocytes in blood samples. Then, one-way analysis of variance (ANOVA) was applied to analyze the scanning curves and to compare the peak potential and peak current. Results The scanning curve demonstrated the specific electrochemical behaviors of the blank potassium ferricyanide solution and that mixed with blood samples in different groups. Significant differences in mean peak potentials of mixture and shifts (ΔEp (mV)) were observed of the three groups (P< = 0.001). 106.00±9.00 and 3.14±7.48 for Group healthy individuals, 120.90±11.18 and 18.10±8.81 for Group hematologic malignancies, 136.84±11.53 and 32.89±10.50 for Group solid tumors, respectively. In contrast, there were no significant differences in the peak currents and shifts. Conclusions The newly developed method to apply the electrochemical workstation system to identify hematologic malignancies and solid tumors with good sensitivity and specificity might be effective, suggesting a potential utility in clinical application. PMID:27115355

  11. Genetic modification of human T lymphocytes for the treatment of hematologic malignancies

    PubMed Central

    Hoyos, Valentina; Savoldo, Barbara; Dotti, Gianpietro

    2012-01-01

    Modern chemotherapy regimens and supportive care have produced remarkable improvements in the overall survival of patients with hematologic malignancies. However, the development of targeted small molecules, monoclonal antibodies, and biological therapies that demonstrate greater efficacy and lower toxicity remains highly desirable in hematology, and oncology in general. In the context of biological therapies, T-lymphocyte based treatments have enormous potential. Donor lymphocyte infusion in patients relapsed after allogeneic hematopoietic stem cell transplant pioneered the concept that T lymphocytes can effectively control tumor growth, and this was then followed by the development of cell culture strategies to generate T lymphocytes with selective activity against tumor cells. Over the past decade, it has become clear that the adoptive transfer of ex vivo expanded antigen-specific cytotoxic T lymphocytes promotes sustained antitumor effects in patients with virus-associated lymphomas, such as Epstein-Barr virus related post-transplant lymphomas and Hodgkin's lymphomas. Because of this compelling clinical evidence and the concomitant development of methodologies for robust gene transfer to human T lymphocytes, the field has rapidly evolved, offering new opportunities to extend T-cell based therapies. This review summarizes the most recent biological and clinical developments using genetically manipulated T cells for the treatment of hematologic malignancies. PMID:22929977

  12. Risk stratification for invasive fungal infections in patients with hematological malignancies: SEIFEM recommendations.

    PubMed

    Pagano, Livio; Busca, Alessandro; Candoni, Anna; Cattaneo, Chiara; Cesaro, Simone; Fanci, Rosa; Nadali, Gianpaolo; Potenza, Leonardo; Russo, Domenico; Tumbarello, Mario; Nosari, Annamaria; Aversa, Franco

    2017-03-01

    Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in immunocompromised patients. Patients with hematological malignancies undergoing conventional chemotherapy, autologous or allogeneic hematopoietic stem cell transplantation are considered at high risk, and Aspergillus spp. represents the most frequently isolated micro-organisms. In the last years, attention has also been focused on other rare molds (e.g., Zygomycetes, Fusarium spp.) responsible for devastating clinical manifestations. The extensive use of antifungal prophylaxis has reduced the infections from yeasts (e.g., candidemia) even though they are still associated with high mortality rates. This paper analyzes concurrent multiple predisposing factors that could favor the onset of fungal infections. Although neutropenia is common to almost all hematologic patients, other factors play a key role in specific patients, in particular in patients with AML or allogeneic HSCT recipients. Defining those patients at higher risk of IFIs may help to design the most appropriate diagnostic work-up and antifungal strategy.

  13. How I manage pulmonary nodular lesions and nodular infiltrates in patients with hematologic malignancies or undergoing hematopoietic cell transplantation.

    PubMed

    Wingard, John R; Hiemenz, John W; Jantz, Michael A

    2012-08-30

    Pulmonary nodules and nodular infiltrates occur frequently during treatment of hematologic malignancies and after hematopoietic cell transplantation. In patients not receiving active immunosuppressive therapy, the most likely culprits are primary lung cancer, chronic infectious or inactive granulomata, or even the underlying hematologic disease itself (especially in patients with lymphoma). In patients receiving active therapy or who are otherwise highly immunosuppressed, there is a wider spectrum of etiologies with infection being most likely, especially by bacteria and fungi. Characterization of the pulmonary lesion by high-resolution CT imaging is a crucial first diagnostic step. Other noninvasive tests can often be useful, but invasive testing by bronchoscopic evaluation or acquisition of tissue by one of several biopsy techniques should be performed for those at risk for malignancy or invasive infection unless contraindicated. The choice of the optimal biopsy technique should be individualized, guided by location of the lesion, suspected etiology, skill and experience of the diagnostic team, procedural risk of complications, and patient status. Although presumptive therapy targeting the most likely etiology is justified in patients suspected of serious infection while evaluation proceeds, a structured evaluation to determine the specific etiology is recommended. Interdisciplinary teamwork is highly desirable to optimize diagnosis and therapy.

  14. Influenza and Pneumococcal Vaccination in Hematological Malignancies: a Systematic Review of Efficacy, Effectiveness, and Safety

    PubMed Central

    La Torre, Giuseppe; Mannocci, Alice; Colamesta, Vittoria; D’Egidio, Valeria; Sestili, Cristina; Spadea, Antonietta

    2016-01-01

    Background The risk of getting influenza and pneumococcal disease is higher in cancer patients, and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To assess flu and pneumococcal vaccinations efficacy, effectiveness, and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in the scientific literature about the flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 22 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI=6–62%) for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI=23.2 – 63.3 %) and 39.6 % (95% CI=26%–54.1%) for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI=19.7–51.2%) for H1N1, 23% (95% CI=16.6–31.5%) for H3N2, 29% (95% CI=21.3–37%) for B. Conclusion Despite the low rate of response, flu, and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines. PMID:27648207

  15. Genetically Modified T-Cell-Based Adoptive Immunotherapy in Hematological Malignancies

    PubMed Central

    Ye, Baixin; Gao, Qingping; Wang, Qiongyu; Zeng, Zhi

    2017-01-01

    A significant proportion of hematological malignancies remain limited in treatment options. Immune system modulation serves as a promising therapeutic approach to eliminate malignant cells. Cytotoxic T lymphocytes (CTLs) play a central role in antitumor immunity; unfortunately, nonspecific approaches for targeted recognition of tumor cells by CTLs to mediate tumor immune evasion in hematological malignancies imply multiple mechanisms, which may or may not be clinically relevant. Recently, genetically modified T-cell-based adoptive immunotherapy approaches, including chimeric antigen receptor (CAR) T-cell therapy and engineered T-cell receptor (TCR) T-cell therapy, promise to overcome immune evasion by redirecting the specificity of CTLs to tumor cells. In clinic trials, CAR-T-cell- and TCR-T-cell-based adoptive immunotherapy have produced encouraging clinical outcomes, thereby demonstrating their therapeutic potential in mitigating tumor development. The purpose of the present review is to (1) provide a detailed overview of the multiple mechanisms for immune evasion related with T-cell-based therapies; (2) provide a current summary of the applications of CAR-T-cell- as well as neoantigen-specific TCR-T-cell-based adoptive immunotherapy and routes taken to overcome immune evasion; and (3) evaluate alternative approaches targeting immune evasion via optimization of CAR-T and TCR-T-cell immunotherapies. PMID:28116322

  16. Targeting the PI3K/AKT/mTOR Signaling Axis in Children with Hematologic Malignancies

    PubMed Central

    Barrett, David; Brown, Valerie I.; Grupp, Stephan A.; Teachey, David T.

    2014-01-01

    The phosphatidylinositiol 3-kinase (PI3K), AKT, mammalian target of rapamycin (mTOR) signaling pathway (PI3K/AKT/mTOR) is frequently dysregulated in disorders of cell growth and survival, including a number of pediatric hematologic malignancies. The pathway can be abnormally activated in childhood acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML), as well as in some pediatric lymphomas and lymphoproliferative disorders. Most commonly, this abnormal activation occurs as a consequence of constitutive activation of AKT, providing a compelling rationale to target this pathway in many of these conditions. A variety of agents, beginning with the rapamycin analogue (rapalog) sirolimus, have been used successfully to target this pathway in a number of pediatric hematologic malignancies. Rapalogs demonstrate significant preclinical activity against ALL, which has led to a number of clinical trials. Moreover, rapalogs can synergize with a number of conventional cytotoxic agents and overcome pathways of chemotherapeutic resistance for drugs commonly used in ALL treatment, including methotrexate and corticosteroids. Based on preclinical data, rapalogs are also being studied in AML, CML, and non-Hodgkin’s lymphoma. Recently, significant progress has been made using rapalogs to treat pre-malignant lymphoproliferative disorders, including the autoimmune lymphoproliferative syndrome (ALPS); complete remissions in children with otherwise therapy-resistant disease have been seen. Rapalogs only block one component of the pathway (mTORC1), and newer agents are under preclinical and clinical development that can target different and often multiple protein kinases in the PI3K/AKT/mTOR pathway. Most of these agents have been tolerated in early-phase clinical trials. A number of PI3K inhibitors are under investigation. Of note, most of these also target other protein kinases. Newer agents are under development that target both m

  17. 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

  18. Preemptive Antifungal Therapy for Febrile Neutropenic Hematological Malignancy Patients in China

    PubMed Central

    Yuan, Wei; Ren, Jinhai; Guo, Xiaonan; Guo, Xiaoling; Cai, Shengxin

    2016-01-01

    Background The aim of this study was to evaluate the efficiency, adverse effects, and pharmacoeconomic impact of empirical and preemptive antifungal therapy for febrile neutropenic hematological malignancy patients in China. Material/Methods Patients with febrile neutropenia during hematological malignancy were randomly divided into an empirical group and a preemptive group. The preemptive antifungal treatment was initiated if patient status was confirmed by clinical manifestation, imaging diagnosis, 1-3-β-D glucan(G) testing, and galactomannan (GM) test. The treatment was ended 2 weeks later if the patient was recovered from neutropenia. Voriconazole was used as the first-line medicine. All patients received intravenous administration of voriconazole every 12 h, with an initiating dose of 400 mg, then the dose was reduced to 200 mg. Results The overall survival rate was 97.1% and 94.6% in the empirical group and preemptive group, respectively, with no significant difference observed (χ2=1.051, P=0.305). However, the occurrence rate of invasive fungal disease (IFD) in the preemptive group was 9.2% vs. 2.2% in the empirical group. Moreover, the mortality rate due to IFD was 0.7% and 2.3% for the empirical group and preemptive group, respectively. The average duration and cost of preemptive antifungal therapy were 13.8±4.7 days and 8379.00±2253.00 RMB, respectively, which were lower than for empirical therapy. However, no significant differences were observed for incidence of adverse effects and hospital stay between the 2 groups. Conclusions Preemptive antifungal therapy for patients with febrile neutropenic hematological malignancy demonstrated a similar survival rate as with empirical therapy but is economically favorable in a Chinese population. PMID:27819257

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

    SciTech Connect

    Kunos, Charles A.; Debernardo, Robert; Radivoyevitch, Tomas; Fabien, Jeffrey; Dobbins, Donald C.; Zhang Yuxia; Brindle, James

    2012-09-01

    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, 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.

  20. Fighting against hematological malignancy in China: from unique system to global impact.

    PubMed

    Lv, Meng; Huang, XiaoJun

    2015-12-01

    During recent decades, substantial progress has been made in clinical strategies for treating hematological malignancies. Not only did China benefit from the global progression in the management of acute promyelocytic leukemia, risk-stratification-directed strategies for acute or chronic leukemia and haploidentical hematopoietic stem cell transplantation, the unique system developed by Chinese doctors has also become inspiration for refining global clinical practice. The multicenter trials and collaborations adhering to international standards might further strengthen the global impact and lead the way in specific fields of research worldwide.

  1. Emerging therapeutic paradigms to target the dysregulated JAK/STAT pathways in hematological malignancies

    PubMed Central

    Mughal, Tariq I.; Girnius, Saulius; Rosen, Steven T.; Kumar, Shaji; Wiestner, Adrian; Abdel-Wahab, Omar; Kiladjian, Jean-Jacques; Wilson, Wyndham H.; Van Etten, Richard A.

    2014-01-01

    Over the past decade, there has been increasing biochemical evidence that the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is aberrantly activated in malignant cells from patients with a wide spectrum of cancers of the blood and immune systems. The emerging availability of small molecule inhibitors of JAK kinases and other signaling molecules in the JAK-STAT pathway has allowed preclinical studies validating an important role of this pathway in the pathogenesis of many hematologic malignancies, and provided motivation for new strategies for treatment of these diseases. Here, a roundtable panel of experts reviews the current preclinical and clinical landscape of the JAK-STAT pathway in acute lymphoid and myeloid leukemias, lymphomas and myeloma, and chronic myeloid neoplasms. PMID:24206094

  2. Virus infection facilitates the development of severe pneumonia in transplant patients with hematologic malignancies

    PubMed Central

    Xu, Duorong; Wu, Jim; Pan, Yujia; Yan, JinSong; Liu, Min; Liu, Quentin

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for patients with hematologic malignancies. Severe pneumonia is associated with high mortality rate in HSCT recipients. Viral co-infection indicates a poor prognosis of HSCT recipients. In this study, a total of 68 allogeneic HSCT recipients were included. Cytomegalovirus (CMV) and Respiratory syncytial virus (RSV) infection was assessed by testing peripheral blood and oropharynx swabs, respectively, collected in the first 180 days after transplantation. We analysed the correlation of CMV and RSV co-infection with severe pneumonia and mortality. The incidence of CMV and RSV co-infection was 26.5% (18/68). Severe pneumonia was diagnosed in 61% (11/18) cases with co-infection compared to only 10% (5/50) cases with mono-infection or no infection. The analysis of potential risk factors for severe pneumonia showed that CMV and RSV co-infection was significantly associated with severe pneumonia (p < 0.001). The 5 patients who died of severe pneumonia were all co-infected with CMV and RSV. In conclusion, CMV and RSV co-infection appears to be an important factor and facilitates the development of severe pneumonia in allogeneic HSCT patients with hematologic malignancies. PMID:27340772

  3. Copper Chelator ATN-224 Induces Peroxynitrite-Dependent Cell Death in Hematological Malignancies

    PubMed Central

    Lee, Kristy; Briehl, Margaret M.; Mazar, Andrew P.; Batinic-Haberle, Ines; Reboucas, Julio S.; Glinsmann-Gibson, Betty; Rimsza, Lisa M.; Tome, Margaret E.

    2013-01-01

    Chemoresistance, due to oxidative stress resistance or upregulation of Bcl-2, contributes to poor outcome in the treatment of hematological malignancies. In this study, we utilize the copper chelator drug, ATN-224 (choline tetrathiomolybdate), to induce cell death in oxidative stress resistant cells and cells overexpressing Bcl-2 by modulating the cellular redox environment and causing mitochondrial dysfunction. ATN-224 treatment decreases superoxide dismutase 1 (SOD1) activity, increases intracellular oxidants and induces peroxynitrite-dependent cell death. ATN-224 also targets the mitochondria, decreasing both cytochrome c oxidase (CcOX) activity and mitochondrial membrane potential (ΔΨm). The concentration of ATN-224 required to induce cell death is proportional to SOD1 levels, but independent of Bcl-2 status. In combination with doxorubicin, ATN-224 enhances cell death. In primary B cell acute lymphoblastic leukemia (B-ALL) patient samples, ATN-224 decreases the viable cell number. Our findings suggest that ATN-224’s dual targeting of SOD1 and CcOX is a promising approach for treatment of hematological malignancies either as an adjuvant or as a single agent. PMID:23416365

  4. Next generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematologic malignancies

    PubMed Central

    Hing, Zachary A.; Fung, Ho Yee Joyce; Ranganathan, Parvathi; Mitchell, Shaneice; El-Gamal, Dalia; Woyach, Jennifer A.; Williams, Katie; Goettl, Virginia M.; Smith, Jordan; Yu, Xueyan; Meng, Xiaomei; Sun, Qingxiang; Cagatay, Tolga; Lehman, Amy M.; Lucas, David M.; Baloglu, Erkan; Shacham, Sharon; Kauffman, Michael G.; Byrd, John C.; Chook, Yuh Min; Garzon, Ramiro; Lapalombella, Rosa

    2016-01-01

    The nuclear export receptor, Exportin 1 (XPO1), mediates transport of growth-regulatory proteins including tumor suppressors and is overactive in many cancers, including chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and aggressive lymphomas. Oral Selective Inhibitor of Nuclear Export (SINE) compounds that block XPO1 function were recently identified and hold promise as a new therapeutic paradigm in many neoplasms. One of these compounds, KPT-330 (selinexor), has made progress in Phase I/II clinical trials, but systemic toxicities limit its administration to twice-per-week and requiring supportive care. We designed a new generation SINE compound, KPT-8602, with a similar mechanism of XPO1 inhibition and potency but considerably improved tolerability. Efficacy of KPT-8602 was evaluated in preclinical animal models of hematologic malignancies including CLL and AML. KPT-8602 shows similar in vitro potency compared to KPT-330 but lower central nervous system penetration which resulted in enhanced tolerability, even when dosed daily, and improved survival in CLL and AML murine models compared to KPT-330. KPT-8602 is a promising compound for further development in hematologic malignancies and other cancers in which upregulation of XPO1 is seen. The wider therapeutic window of KPT-8602 may also allow increased on-target efficacy leading to even more efficacious combinations with other targeted anticancer therapies. PMID:27323910

  5. From the Biology of PP2A to the PADs for Therapy of Hematologic Malignancies

    PubMed Central

    Ciccone, Maria; Calin, George A.; Perrotti, Danilo

    2015-01-01

    Over the past decades, an emerging role of phosphatases in the pathogenesis of hematologic malignancies and solid tumors has been established. The tumor-suppressor protein phosphatase 2A (PP2A) belongs to the serine–threonine phosphatases family and accounts for the majority of serine–threonine phosphatase activity in eukaryotic cells. Numerous studies have shown that inhibition of PP2A expression and/or function may contribute to leukemogenesis in several hematological malignancies. Likewise, overexpression or aberrant expression of physiologic PP2A inhibitory molecules (e.g., SET and its associated SETBP1 and CIP2A) may turn off PP2A function and participate to leukemic progression. The discovery of PP2A as tumor suppressor has prompted the evaluation of the safety and the efficacy of new compounds, which can restore PP2A activity in leukemic cells. Although further studies are needed to better understand how PP2A acts in the intricate phosphatases/kinases cancer network, the results reviewed herein strongly support the development on new PP2A-activating drugs and the immediate introduction of those available into clinical protocols for leukemia patients refractory or resistant to current available therapies. PMID:25763353

  6. High rate of TTV infection in multitransfused patients with pediatric malignancy and hematological disorders.

    PubMed

    Maeda, M; Hamada, H; Tsuda, A; Kaneko, K; Fukunaga, Y

    2000-09-01

    The prevalence of transfusion-transmitted virus (TTV) infection has not been known in patients suffering from pediatric malignancies and hematological disorders who receive blood transfusion and/or blood products during treatment. Blood samples were taken from 75 patients. TTV infection was identified when TTV DNA was detected in serum by a polymerase chain reaction (PCR) assay. Hepatitis C virus (HCV) and hepatitis G virus (HGV) RNA were also assayed by PCR. TTV DNA was detected in 38 of 75 patients (51%). In 4 of 38 patients, the amount of blood transfused was less than 3 units. By time since last transfusion, TTV DNA was detected in 12 of 35 patients after more than 4 years, 12 of 21 between 1 and 4 years, and 14 of 19 within 1 year. Six patients had mixed infection of TTV and HCV, and 12 patients had mixed infection of TTV and HGV. Three different kinds of virus were found simultaneously in serum from 3 patients. Eight out of 75 patients showed abnormal levels of alanine aminotransferase (ALT) (>40 IU/liter), and 3 of them had TTV DNA. All patients who had TTV DNA and elevated ALT levels also were positive for HCV RNA and HGV RNA. The prevalence of TTV infection is high in patients with pediatric malignancies and hematological disorders after episodes of blood transfusion. Transfusion is one of the most important risk factors for TTV infection regardless of the amount of blood transfused.

  7. SDF1-3′A polymorphism is associated with increased risk of hematological malignancy: a meta-analysis

    PubMed Central

    Zhang, Xiaowen; Fan, Yang; Li, Zhijie

    2017-01-01

    CXCL12 (also named SDF1), a member of the chemokine family, has been demonstrated to play an important role in the progression of multiple types of hematological malignancy. Several recent studies have shown that SDF1-3′A polymorphism (rs1801157) is associated with susceptibility to hematological malignancy, but published studies’ results are disputed. Therefore, we performed a meta-analysis to evaluate the relationship between SDF1-3′A polymorphism and the risk of hematological malignancy based on the existing literature. We carried out a comprehensive literature search using the Web of Science, PubMed, Cochrane Library, Chinese Wan Fang, and Chinese National Knowledge Infrastructure databases. And the raw data were extracted and calculated in standard steps of meta-analysis. Overall, nine qualified studies containing 1,576 cases and 1,674 controls were included in the ultimate meta-analysis. The pooled results displayed that AA genotype significantly increased the risk of hematological malignancy. The result of subgroup analysis further indicated that SDF1-3′A polymorphism was significantly associated with increased risk of chronic myeloid leukemia, Hodgkin’s lymphoma and multiple myeloma, but was not associated with increased risk of acute myeloid leukemia and non-Hodgkin’s lymphoma. In addition, SDF1-3′A polymorphism was associated with increased risk of hematological malignancy in Africans and Asians, but not in Caucasians. In conclusion, our meta-analysis firstly demonstrated that SDF1-3′A polymorphism may be associated with increased risk of hematological malignancy, especially for chronic myeloid leukemia, Hodgkin’s lymphoma, multiple myeloma and the non-Caucasian population. Nevertheless, these conclusions should be reconfirmed by more evidence from large sample sized studies. PMID:28352190

  8. Fulminant sepsis caused by Bacillus cereus in patients with hematologic malignancies: analysis of its prognosis and risk factors.

    PubMed

    Inoue, Daichi; Nagai, Yuya; Mori, Minako; Nagano, Seiji; Takiuchi, Yoko; Arima, Hiroshi; Kimura, Takaharu; Shimoji, Sonoko; Togami, Katsuhiro; Tabata, Sumie; Yanagita, Soshi; Matsushita, Akiko; Nagai, Kenichi; Imai, Yukihiro; Takegawa, Hiroshi; Takahashi, Takayuki

    2010-05-01

    Bacillus cereus is a growing concern as a cause of life-threatening infections in patients with hematologic malignancies. However, the risk factors for patients with unfavorable outcomes have not been fully elucidated. At our institution, we observed the growth of B. cereus in blood culture in 68 patients with (23) or without (45) hematologic malignancies treated from September 2002 to November 2009. We defined a case as having sepsis when more than two blood culture sets were positive for B. cereus or only a single set was positive in the absence of other microorganisms in patients who had definite infectious lesions. We determined 12 of 23 patients with hematologic malignancies as having sepsis, as well as 10 of 45 patients without hematologic malignancies (p = 0.012). Of the 12 patients with hematologic malignancies, four patients with acute leukemia died of B. cereus sepsis within a few days. In our cohort, risk factor analysis demonstrated that a neutrophil count of 0/mm(3), central venous (CV) catheter insertion, and the presence of central nervous system (CNS) symptoms were significantly associated with a fatal prognosis (p = 0.010, 0.010, and 0.010, respectively). Analysis of data from our cohort in conjunction with those from 46 previously reported patients with B. cereus sepsis identified similar risk factors, that is, acute leukemia, extremely low neutrophil count, and CNS symptoms (p = 0.044, 0.004, and 0.002, respectively). These results indicate that appropriate prophylaxis and early therapeutic intervention against possible B. cereus sepsis are crucially important in the treatment of hematologic malignancies.

  9. Utility of bronchoalveolar lavage in diagnosing respiratory tract infections in patients with hematological malignancies: are invasive diagnostics still needed?

    PubMed Central

    Svensson, Tobias; Lundström, Kristina Lamberg; Höglund, Martin; Cherif, Honar

    2017-01-01

    Background Patients treated for hematological malignancies have an increased risk of serious infections. Diagnosis and prompt initiation of therapy are essential. Bronchoalveolar lavage (BAL) is a well-established investigation for identifying the cause of pulmonary infiltrates in immunocompromised patients. The aim of the study was to determine the diagnostic yield of BAL in patients treated for hematological malignancies and how often it contributed to a modification of the anti-infectious therapy. Methods We reviewed records from 151 consecutive BAL procedures in 133 adult patients with hematological malignancies, treated at a tertiary hematology unit from 2004 to 2013. Extensive microbiological work-ups on BAL samples had been performed according to a standardized protocol. Results A microbiological finding causing the infectious episode could be identified in 59 (39%) cases. In 44 (29%) of the cases, results from BAL had an impact on clinical management either by contributing to a specific diagnosis (25%) or by leading to cessation of ongoing microbiological therapy. The most common diagnoses were invasive pulmonary aspergillosis (IPA) and Pneumocystis jirovecii pneumonia (PJP). Diagnoses of IPA and PJP were based on results from BAL in 65% and 93% of cases, respectively. Several microbiological tests on BAL samples rendered no positive results. Complications were few and mainly mild. Conclusion BAL is still important for either verifying or excluding some of the most important respiratory tract pathogens in patients with hematological malignancies, particularly IPA and PJP. Standardized procedures for BAL sampling should be continually revised to exclude unnecessary microbiological tests. PMID:27739337

  10. Liquid biopsies for liquid tumors: emerging potential of circulating free nucleic acid evaluation for the management of hematologic malignancies

    PubMed Central

    Hocking, Jay; Mithraprabhu, Sridurga; Kalff, Anna; Spencer, Andrew

    2016-01-01

    Circulating free nucleic acids; cell free DNA and circulating micro-RNA, are found in the plasma of patients with hematologic and solid malignancies at levels higher than that of healthy individuals. In patients with hematologic malignancy cell free DNA reflects the underlying tumor mutational profile, whilst micro-RNAs reflect genetic interference mechanisms within a tumor and potentially the surrounding microenvironment and immune effector cells. These circulating nucleic acids offer a potentially simple, non-invasive, repeatable analysis that can aid in diagnosis, prognosis and therapeutic decisions in cancer treatment. PMID:27458529

  11. Expression of p16INK4A and p14ARF in hematological malignancies.

    PubMed

    Taniguchi, T; Chikatsu, N; Takahashi, S; Fujita, A; Uchimaru, K; Asano, S; Fujita, T; Motokura, T

    1999-11-01

    The INK4A/ARF locus yields two tumor suppressors, p16INK4A and p14ARF, and is frequently deleted in human tumors. We studied their mRNA expressions in 41 hematopoietic cell lines and in 137 patients with hematological malignancies; we used a quantitative reverse transcription-PCR assay. Normal peripheral bloods, bone marrow and lymph nodes expressed little or undetectable p16INK4A and p14ARF mRNAs, which were readily detected in 12 and 17 of 41 cell lines, respectively. Patients with hematological malignancies frequently lacked p16INK4A expression (60/137) and lost p14ARF expression less frequently (19/137, 13.9%). Almost all patients without p14ARF expression lacked p16INK4A expression, which may correspond to deletions of the INK4A/ARF locus. Undetectable p16INK4A expression with p14ARF expression in 41 patients may correspond to p16INK4A promoter methylation or to normal expression status of the p16INK4A gene. All patients with follicular lymphoma (FL), myeloma or acute myeloid leukemia (AML) expressed p14ARF while nine of 23 patients with diffuse large B cell lymphoma (DLBCL) lost p14ARF expression. Patients with ALL, AML or blast crisis of chronic myelogenous leukemia expressed abundant p16INK4A mRNAs more frequently than patients with other diseases (12/33 vs 6/104, P < 0.01). Patients with FL and high p14ARF expression had a significantly shorter survival time while survival for patients with DLBCL and increased p14ARF expression tended to be longer. These observations indicate that p16INK4A and p14ARF expression is differentially affected among hemato- logical malignancies and that not only inactivation but also increased expression may have clinical significance.

  12. Ethical and Clinical Aspects of Intensive Care Unit Admission in Patients with Hematological Malignancies: Guidelines of the Ethics Commission of the French Society of Hematology

    PubMed Central

    Malak, Sandra; Sotto, Jean-Jacques; Ceccaldi, Joël; Colombat, Philippe; Casassus, Philippe; Jaulmes, Dominique; Rochant, Henri; Cheminant, Morgane; Beaussant, Yvan; Zittoun, Robert; Bordessoule, Dominique

    2014-01-01

    Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice. PMID:25349612

  13. Three cases of nephrotic syndrome associated with hematological malignancies characterized by glomerular endocapillary proliferation and massive inflammatory cel infiltration.

    PubMed

    Hanada, Ken; Shirai, Sayuri; Ito, Takafumi; Tanabe, Kazuaki; Kimura, Kenjiro

    2014-04-01

    Nephrotic syndrome often emerges with malignancy. Membranous nephropathy is generally associated with solid tumors, and minimal change disease is associated with Hodgkin's disease. However, the complication of malignancy cannot be predicted by simply using renal histological findings. We report here three cases of nephrotic syndrome associated with hematological malignancy. On histology, Cases 1 and 2 were membranous nephropathy, and Case 3 was minimal change disease. Cases 1 and 2 were found to have B-cell non-Hodgkin's lymphoma, while Case 3 had Hodgkin's lymphoma. In Cases 1 and 2, proteinuria diminished as chemotherapy was started. All three cases were characterized by glomerular endocapillary proliferation and massive glomerular infiltration of inflammatory cells. These three cases are reported because their histologically atypical findings might be a feature of hematological malignancy- associated nephrotic syndrome and of any help for diagnosis.

  14. Challenges in the Role of Gammaglobulin Replacement Therapy and Vaccination Strategies for Hematological Malignancy

    PubMed Central

    Sánchez-Ramón, Silvia; Dhalla, Fatima; Chapel, Helen

    2016-01-01

    Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are prone to present with antibody production deficits associated with recurrent or severe bacterial infections that might benefit from human immunoglobulin (Ig) (IVIg/SCIg) replacement therapy. However, the original IVIg trial data were done before modern therapies were available, and the current indications do not take into account the shift in the immune situation of current treatment combinations and changes in the spectrum of infections. Besides, patients affected by other B cell malignancies present with similar immunodeficiency and manifestations while they are not covered by the current IVIg indications. A potential beneficial strategy could be to vaccinate patients at monoclonal B lymphocytosis and monoclonal gammopathy of undetermined significance stages (for CLL and MM, respectively) or at B-cell malignancy diagnosis, when better antibody responses are attained. We have to re-emphasize the need for assessing and monitoring specific antibody responses; these are warranted to select adequately those patients for whom early intervention with prophylactic anti-infective therapy and/or IVIg is preferred. This review provides an overview of the current scenario, with a focus on prevention of infection in patients with hematological malignancies and the role of Ig replacement therapy. PMID:27597852

  15. Gene Expression Profiling Identifies IRF4-Associated Molecular Signatures in Hematological Malignancies

    PubMed Central

    Wang, Ling; Yao, Zhi Q.; Moorman, Jonathan P.; Xu, Yanji; Ning, Shunbin

    2014-01-01

    The lymphocyte-specific transcription factor Interferon (IFN) Regulatory Factor 4 (IRF4) is implicated in certain types of lymphoid and myeloid malignancies. However, the molecular mechanisms underlying its interactions with these malignancies are largely unknown. In this study, we have first profiled molecular signatures associated with IRF4 expression in associated cancers, by analyzing existing gene expression profiling datasets. Our results show that IRF4 is overexpressed in melanoma, in addition to previously reported contexts including leukemia, myeloma, and lymphoma, and that IRF4 is associated with a unique gene expression pattern in each context. A pool of important genes involved in B-cell development, oncogenesis, cell cycle regulation, and cell death including BATF, LIMD1, CFLAR, PIM2, and CCND2 are common signatures associated with IRF4 in non-Hodgkin B cell lymphomas. We confirmed the correlation of IRF4 with LIMD1 and CFLAR in a panel of cell lines derived from lymphomas. Moreover, we profiled the IRF4 transcriptome in the context of EBV latent infection, and confirmed several genes including IFI27, IFI44, GBP1, and ARHGAP18, as well as CFLAR as novel targets for IRF4. These results provide valuable information for understanding the IRF4 regulatory network, and improve our knowledge of the unique roles of IRF4 in different hematological malignancies. PMID:25207815

  16. 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

  17. The role of second-generation 5-HT3 receptor antagonists in managing chemotherapy-induced nausea and vomiting in hematological malignancies.

    PubMed

    Schwartzberg, Lee S; Jacobs, Peter; Matsouka, Panagiota; Azevedo, Wellington; Pinto, Antonio

    2012-07-01

    Compared with solid tumor patients, those with hematological malignancies are at particular risk of chemotherapy-induced nausea and vomiting (CINV) because of their young age, exposure to highly-emetogenic induction, consolidation and salvage regimens, the high-dose conditioning regimens used before stem cell transplantation (SCT), and the heavy psychological burden of such treatments. In the absence of prophylaxis, around 75% of patients undergoing SCT experience delayed CINV. With first-generation 5-HT(3) receptor antagonists, only about 20% are completely protected from nausea and vomiting, and this frequent and debilitating adverse event has not been fully addressed. In contrast to solid tumors, there are no internationally agreed guidelines for the prevention and treatment of CINV in hematological malignancies. Work on a consensus is urgently required. The second-generation 5-HT(3) antagonist palonosetron is highly effective in preventing CINV in patients with solid tumors. The extended half-life of this agent and its mechanisms of action including allosteric binding, positive cooperativity and 5-HT(3) receptor internalization, may make it particularly effective in controlling delayed CINV. Although controlled comparisons against first-generation 5HT(3) agents have not yet been conducted in the setting of SCT, available evidence suggests that palonosetron may prove beneficial in preventing CINV in high risk patients with hematological malignancies.

  18. 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

  19. The prognostic factors for patients with hematological malignancies admitted to the intensive care unit.

    PubMed

    Cheng, Qian; Tang, Yishu; Yang, Qing; Wang, Erhua; Liu, Jing; Li, Xin

    2016-01-01

    Owing to the nature of acute illness and adverse effects derived from intensive chemotherapy, patients with hematological malignancies (HM) who are admitted to the Intensive Care Unit (ICU) often present with poor prognosis. However, with advances in life-sustaining therapies and close collaborations between hematologists and intensive care specialists, the prognosis for these patients has improved substantially. Many studies from different countries have examined the prognostic factors of these critically ill HM patients. However, there has not been an up-to-date review on this subject, and very few studies have focused on the prognosis of patients with HM admitted to the ICU in Asian countries. Herein, we aim to explore the current situation and prognostic factors in patients with HM admitted to ICU, mainly focusing on studies published in the last 10 years.

  20. AZD5153: A Novel Bivalent BET Bromodomain Inhibitor Highly Active against Hematologic Malignancies.

    PubMed

    Rhyasen, Garrett W; Hattersley, Maureen M; Yao, Yi; Dulak, Austin; Wang, Wenxian; Petteruti, Philip; Dale, Ian L; Boiko, Scott; Cheung, Tony; Zhang, Jingwen; Wen, Shenghua; Castriotta, Lillian; Lawson, Deborah; Collins, Michael; Bao, Larry; Ahdesmaki, Miika J; Walker, Graeme; O'Connor, Greg; Yeh, Tammie C; Rabow, Alfred A; Dry, Jonathan R; Reimer, Corinne; Lyne, Paul; Mills, Gordon B; Fawell, Stephen E; Waring, Michael J; Zinda, Michael; Clark, Edwin; Chen, Huawei

    2016-11-01

    The bromodomain and extraterminal (BET) protein BRD4 regulates gene expression via recruitment of transcriptional regulatory complexes to acetylated chromatin. Pharmacological targeting of BRD4 bromodomains by small molecule inhibitors has proven to be an effective means to disrupt aberrant transcriptional programs critical for tumor growth and/or survival. Herein, we report AZD5153, a potent, selective, and orally available BET/BRD4 bromodomain inhibitor possessing a bivalent binding mode. Unlike previously described monovalent inhibitors, AZD5153 ligates two bromodomains in BRD4 simultaneously. The enhanced avidity afforded through bivalent binding translates into increased cellular and antitumor activity in preclinical hematologic tumor models. In vivo administration of AZD5153 led to tumor stasis or regression in multiple xenograft models of acute myeloid leukemia, multiple myeloma, and diffuse large B-cell lymphoma. The relationship between AZD5153 exposure and efficacy suggests that prolonged BRD4 target coverage is a primary efficacy driver. AZD5153 treatment markedly affects transcriptional programs of MYC, E2F, and mTOR. Of note, mTOR pathway modulation is associated with cell line sensitivity to AZD5153. Transcriptional modulation of MYC and HEXIM1 was confirmed in AZD5153-treated human whole blood, thus supporting their use as clinical pharmacodynamic biomarkers. This study establishes AZD5153 as a highly potent, orally available BET/BRD4 inhibitor and provides a rationale for clinical development in hematologic malignancies. Mol Cancer Ther; 15(11); 2563-74. ©2016 AACR.

  1. 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.

  2. Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy

    PubMed Central

    2013-01-01

    Introduction Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. Methods This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. Results We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1–1133 mg/L; minimum concentration, 0.47–37.65 mg/L; volume of distribution, 0.08–0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42–27.25 L/h (mean, 9.93 L/h); half-life (t1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L. Conclusion Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1/2 and decreased CL. PMID:24286231

  3. Identification of novel fusion genes with 28S ribosomal DNA in hematologic malignancies.

    PubMed

    Kobayashi, Satoru; Taki, Tomohiko; Nagoshi, Hisao; Chinen, Yoshiaki; Yokokawa, Yuichi; Kanegane, Hirokazu; Matsumoto, Yosuke; Kuroda, Junya; Horiike, Shigeo; Nishida, Kazuhiro; Taniwaki, Masafumi

    2014-04-01

    Fusion genes are frequently observed in hematologic malignancies and soft tissue sarcomas, and are usually associated with chromosome abnormalities. Many of these fusion genes create in-frame fusion transcripts that result in the production of fusion proteins, and some of which aid tumorigenesis. These fusion proteins are often associated with disease phenotype and clinical outcome, and act as markers for minimal residual disease and indicators of therapeutic targets. Here, we identified the 28S ribosomal DNA (RN28S1) gene as a novel fusion partner of the B-cell leukemia/lymphoma 11B gene (BCL11B), the immunoglobulin κ variable 3-20 gene (IGKV3-20) and the component of oligomeric Golgi complex 1 gene (COG1) in hematologic malignancies. The RN28S1-BCL11B fusion transcript was identified in a case with mixed-lineage (T/myeloid) acute leukemia having t(6;14)(q25;q32) by cDNA bubble PCR using BCL11B primers; however, the gene fused to BCL11B on 14q32 was not on 6q25. IGKV3-20-RN28S1 and COG1-RN28S1 fusion transcripts were identified in the Burkitt lymphoma cell line HBL-5, and the multiple myeloma cell line KMS-18. RN28S1 would not translate, and the breakpoints in partner genes of RN28S1 were within the coding exons, suggesting that disruption of fusion partners by fusion to RN28S1 is the possible mechanism of tumorigenesis. Although further analysis is needed to elucidate the mechanism(s) through which these RN28S1-related fusions play roles in tumorigenesis, our findings provide important insights into the role of rDNA function in human genomic architecture and tumorigenesis.

  4. 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.

  5. Stem cell transplant as an immunomodulatory tool for children with hematologic malignancies.

    PubMed

    LaBelle, James L; Cunningham, John M

    2013-01-01

    Allogeneic stem cell transplantation (alloHSCT) is the most common and effective form of immunotherapy used for treatment of pediatric leukemias. A combination of graft manipulation, donor selection, fine-tuning of conditioning regimens, and use of lower and novel forms of immunosuppression following transplant has maximized the tolerability of alloHSCT in children. This outcome has facilitated new advances in disease-specific transplant regimens that seek to amplify the antitumor effects of the allograft, while reducing transplant-related mortality. However, disease relapse remains the preeminent challenge to the success of transplantation as a modality for successful treatment of high-risk disease. Separating graft versus host disease (GVHD) from graft versus leukemia (GVL) remains the most significant obstacle to enhancing disease-free survival. However, with increased clarity and discrimination in the effector mechanisms responsible for GVHD and/or GVL in patients of all ages, a new wave of clinical trials has become feasible that harnesses GVL effects to treat patients with high-risk myeloid and lymphoid malignancies. Exciting progress is being made in the use of alloHSCT with donor lymphocyte infusions (DLIs) in almost all forms of pediatric hematologic malignancies. This advance sets the stage for the use of HSCT and/or DLI in conjunction with novel disease-specific post-transplant therapies using small molecule therapeutics, tumor vaccines, and novel antibody therapies.

  6. Cognitive function in the acute course of allogeneic hematopoietic stem cell transplantation for hematological malignancies.

    PubMed

    Schulz-Kindermann, F; Mehnert, A; Scherwath, A; Schirmer, L; Schleimer, B; Zander, A R; Koch, U

    2007-06-01

    The aim of the study was to assess cognitive performance in patients with hematological malignancies before, and 3 months after, allogeneic hematopoietic stem cell transplant (HSCT). A consecutive sample of 39 patients was assessed before admission with a comprehensive neuropsychological test battery and health-related quality-of-life (HRQoL) questionnaires; 19 of these patients were retested around 100 days post HSCT. Test results were compared with normative data and revealed minimal differences at both time points in the level of group-means. One parameter - simple reaction time - was significantly worse (prolonged) at second measurement after HSCT. According to the definition of an impairment score (more than three impaired functions), 26% of patients were classified as impaired before as well as after HSCT. Neuropsychological test results did not vary systematically according to medical variables such as extent of pretreatment, graft-versus-host-disease (GvHD) and kind of conditioning protocol. As a dimension of HRQoL, self-rated cognitive function was in the normal range before and after HSCT. Significant correlations between HRQoL and neuropsychological parameters were related to symptom scales. This study showed impairments of neuropsychological performance for a subgroup of patients before and after allogeneic HSCT. Systematic effects of conditioning, medical variables or self-rated HRQoL could not be observed.

  7. 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.

  8. Management of Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients and Patients With Hematologic Malignancies

    PubMed Central

    Chemaly, Roy F.; Shah, Dimpy P.; Boeckh, Michael J.

    2014-01-01

    Despite preventive strategies and increased awareness, a high incidence of respiratory viral infections still occur in patients with hematologic malignancies (HMs) and in recipients of hematopoietic cell transplant (HCT). Progression of these viral infections to lower respiratory tract may prove fatal, especially in HCT recipients. Increasing evidence on the successful use of ribavirin (alone or in combination with immunomodulators) for the treatment of respiratory syncytial virus infections in HM patients and HCT recipients is available from retrospective studies; however, prospective clinical trials are necessary to establish its efficacy with confidence. The impact on progression to pneumonitis and/or mortality of treating parainfluenza virus infections with available (ribavirin) or investigational (DAS181) antiviral agents still needs to be determined. Influenza infections have been successfully treated with neuraminidase inhibitors (oseltamivir or zanamivir); however, the efficacy of these agents for influenza pneumonia has not been established, and immunocompromised patients are highly susceptible to emergence of antiviral drug resistance, most probably due to prolonged viral shedding. Infection control measures and an appreciation of the complications following respiratory viral infections in immunocompromised patients remain crucial for reducing transmission. Future studies should focus on strategies to identify patients at high risk for increased morbidity and mortality from these infections and to determine the efficacy of novel or available antiviral drugs. PMID:25352629

  9. Primary Graft Failure after Myeloablative Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

    PubMed Central

    Olsson, Richard F.; Logan, Brent R.; Chaudhury, Sonali; Zhu, Xiaochun; Akpek, Görgün; Bolwell, Brian J.; Bredeson, Christopher N.; Dvorak, Christopher C.; Gupta, Vikas; Ho, Vincent T.; Lazarus, Hillard M.; Marks, David I.; Ringdén, Olle T.H.; Pasquini, Marcelo C.; Schriber, Jeffrey R.; Cooke, Kenneth R.

    2015-01-01

    Clinical outcomes after primary graft failure (PGF) remain poor. Here we present a large retrospective analysis (n=23,272) which investigates means to prevent PGF and early detection of patients at high risk. In patients with hematologic malignancies, who underwent their first myeloablative allogeneic hematopoietic cell transplantation, PGF was reported in 1,278 (5.5%), and there was a marked difference in PGFs using peripheral blood stem cell compared to bone marrow grafts (2.5 vs. 7.3%; P<0.001). A 4-fold increase of PGF was observed in myeloproliferative disorders compared to acute leukemia (P<0.001). Other risk factors for PGF included recipient age below 30, HLA-mismatch, male recipients of female donor grafts, ABO-incompatibility, busulfan/cyclophosphamide conditioning, and cryopreservation. In bone marrow transplants, total nucleated cell doses ≤2.4 × 108/kg were associated with PGF (OR 1.39; P<0.001). The use of tacrolimus-based immunosuppression and granulocyte colony-stimulating factor were associated with decreased PGF risk. These data, allow clinicians to do more informed choices with respect to graft source, donor selection, conditioning and immunosuppressive regimens to reduce the risk of PGF. Moreover, a novel risk score determined on day 21 post-transplant may provide the rationale for an early request for additional hematopoietic stem cells. PMID:25772027

  10. Integrated genomic DNA/RNA profiling of hematologic malignancies in the clinical setting

    PubMed Central

    He, Jie; Abdel-Wahab, Omar; Nahas, Michelle K.; Wang, Kai; Rampal, Raajit K.; Intlekofer, Andrew M.; Patel, Jay; Krivstov, Andrei; Frampton, Garrett M.; Young, Lauren E.; Zhong, Shan; Bailey, Mark; White, Jared R.; Roels, Steven; Deffenbaugh, Jason; Fichtenholtz, Alex; Brennan, Timothy; Rosenzweig, Mark; Pelak, Kimberly; Knapp, Kristina M.; Brennan, Kristina W.; Donahue, Amy L.; Young, Geneva; Garcia, Lazaro; Beckstrom, Selmira T.; Zhao, Mandy; White, Emily; Banning, Vera; Buell, Jamie; Iwanik, Kiel; Ross, Jeffrey S.; Morosini, Deborah; Younes, Anas; Hanash, Alan M.; Paietta, Elisabeth; Roberts, Kathryn; Mullighan, Charles; Dogan, Ahmet; Armstrong, Scott A.; Mughal, Tariq; Vergilio, Jo-Anne; Labrecque, Elaine; Erlich, Rachel; Vietz, Christine; Yelensky, Roman; Stephens, Philip J.; Miller, Vincent A.; van den Brink, Marcel R. M.; Otto, Geoff A.; Lipson, Doron

    2016-01-01

    The spectrum of somatic alterations in hematologic malignancies includes substitutions, insertions/deletions (indels), copy number alterations (CNAs), and a wide range of gene fusions; no current clinically available single assay captures the different types of alterations. We developed a novel next-generation sequencing-based assay to identify all classes of genomic alterations using archived formalin-fixed paraffin-embedded blood and bone marrow samples with high accuracy in a clinically relevant time frame, which is performed in our Clinical Laboratory Improvement Amendments–certified College of American Pathologists–accredited laboratory. Targeted capture of DNA/RNA and next-generation sequencing reliably identifies substitutions, indels, CNAs, and gene fusions, with similar accuracy to lower-throughput assays that focus on specific genes and types of genomic alterations. Profiling of 3696 samples identified recurrent somatic alterations that impact diagnosis, prognosis, and therapy selection. This comprehensive genomic profiling approach has proved effective in detecting all types of genomic alterations, including fusion transcripts, which increases the ability to identify clinically relevant genomic alterations with therapeutic relevance. PMID:26966091

  11. Hematologic malignancies in South Africa 2000-2006: analysis of data reported to the National Cancer Registry.

    PubMed

    Schonfeld, Sara J; Erdmann, Friederike; Wiggill, Tracey; Singh, Elvira; Kellett, Patricia; Babb, Chantal; Schüz, Joachim

    2016-04-01

    Little is known about the incidence patterns of hematologic malignancies in Sub-Saharan Africa, including South Africa. We estimated incidence rates of pathology-confirmed adult cases of leukemia, myeloma and related diseases (myeloma), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) reported to the National Cancer Registry of South Africa (NCR) between 2000 and 2006, by age, gender, and population group (Black, White, Coloured, Asian/Indian). Gender-specific age-standardized rates were calculated overall and by population group and incidence rate ratios (IRRs) were estimated using Poisson regression models. Between 2000 and 2006, there were 14662 cases of leukemia, myeloma, HL, and NHL reported to the registry. Incidence rates of reported hematologic malignancies were generally 20-50% higher among males than females. Our analyses suggested marked differences in the rates of reported hematologic malignancies by population group which were most pronounced when comparing the White versus Black population groups (IRRs ranging from 1.6 for myeloma to 3.8 for HL for males and females combined). Challenges related to diagnosis and reporting of cancers may play a role in the patterns observed by population group while the set-up of the NCR (pathology-based) could lead to some degree of under-ascertainment in all groups. This is the first country-wide report of the incidence of hematologic malignancies in South Africa. Despite challenges, it is important to analyze and report available national cancer incidence data to raise awareness of the cancer burden and to characterize patterns by demographic characteristics so as ultimately to improve the provision of cancer-related health care.

  12. Potential Factors for Inadequate Voriconazole Plasma Concentrations in Intensive Care Unit Patients and Patients with Hematological Malignancies

    PubMed Central

    Duettmann, Wiebke; Raggam, Reinhard B.; Seeber, Katharina; Troppan, Katharina; Fruhwald, Sonja; Prueller, Florian; Wagner, Jasmin; Valentin, Thomas; Zollner-Schwetz, Ines; Wölfler, Albert

    2013-01-01

    Voriconazole plasma concentrations (VPCs) vary widely, and concentrations outside the therapeutic range are associated with either worse outcome in invasive aspergillosis (IA) or increased toxicity. The primary goal of this cohort study conducted in a real-life setting was to identify potential factors associated with inadequate VPCs in ICU patients and patients with hematological malignancies. Within a period of 12 months, trough VPCs were obtained and analyzed with high-performance liquid chromatography, and the adequate range was defined as 1.5 to 5.5 mg/liter. VPCs of <1.5 mg/liter were defined as low, whereas VPCs of >5.5 mg/liter were defined as potentially toxic. A total of 221 trough VPCs were obtained in 61 patients receiving voriconazole, and 124/221 VPCs (56%) were found to be low. Multivariate analysis revealed that low VPCs were significantly associated with clinical failure of voriconazole, prophylactic use, younger age, underlying hematological malignancy, concomitant proton pump inhibitor (PPI) (pantoprazole was used in 88% of the patients), and absence of side effects. Low VPCs remained an independent predictor of clinical failure of voriconazole. The defined adequate range was reached in 79/221 (36%) VPCs. In 18 samples (8%), potentially toxic levels were measured. Multivariate analysis revealed higher body mass index (BMI), absence of hematological malignancy, therapeutic application, and diarrhea as factors associated with potentially toxic VPCs. Neurotoxic adverse events occurred in six patients and were mostly associated with VPCs in the upper quartile of our defined adequate range. In conclusion, potential factors like younger age, prophylaxis, underlying hematological malignancy, BMI, and concomitant PPI should be considered within the algorithm of voriconazole treatment. PMID:23629724

  13. Cytogenetics in the management of hematologic malignancies: an update by the Groupe francophone de cytogénétique hématologique (GFCH).

    PubMed

    Nguyen-Khac, Florence; Daudignon, Agnès; Eclache, Virginie; Lafage-Pochitaloff, Marina; Lefebvre, Christine; Luquet, Isabelle; Penther, Dominique

    2016-10-01

    Cytogenetic analysis is still important in the management of many hematological malignancies, despite the new techniques available such as the high-throughput sequencing analysis, and the discovery of many acquired gene mutations in these diseases. The Groupe francophone de cytogénétique hématologique (GFCH) published in 2004 the recommendations for the cytogenetic management of hematological malignancies. It reports here the update of these recommendations, with a review of the literature for each disease.

  14. (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.

  15. Associations between allergies and risk of hematologic malignancies: results from the VITamins and lifestyle cohort study.

    PubMed

    Shadman, Mazyar; White, Emily; De Roos, Anneclaire J; Walter, Roland B

    2013-12-01

    Immune dysregulations associated with allergies may affect cancer cell biology but studies on the relationship between allergies and risk of hematologic malignancies (HM) yielded inconsistent results. Herein, we used the vitamins and Lifestyle (VITAL) cohort to examine this association. From 2000 to 2002, 66,212 participants, aged 50-76, completed a baseline questionnaire on cancer risk factors, medical conditions, allergies, and asthma. Through 2009, incident HMs (n = 681) were identified via linkage to the surveillance, epidemiology, and end results cancer registry. After adjustment for factors possibly associated with HMs, a history of airborne allergy was associated with increased risk of HMs (hazard ratio [HR] = 1.19 [95% confidence interval: 1.01-1.41], P = 0.039) in Cox proportional hazards models. This association was limited to allergies to plants/grass/trees (HR = 1.26 [1.05-1.50], P = 0.011) and was strongest for some mature B-cell lymphomas (HR = 1.50 [1.14-2.00], P = 0.005). Gender-stratified analyses revealed that the associations between airborne allergies overall and those to plants, grass, and trees were only seen in women (HR = 1.47 [1.14-1.91], P = 0.004; and HR = 1.73 [1.32-2.25], P < 0.001) but not men (HR = 1.03 [0.82-1.29], P = 0.782; and HR = 0.99 [0.77-1.27], P = 0.960). Together, our study indicates a moderately increased risk of HMs in women but not men with a history of allergies to airborne allergens, especially to plant, grass, or trees.

  16. Targeting SAMHD1 with the Vpx protein to improve cytarabine therapy for hematological malignancies.

    PubMed

    Herold, Nikolas; Rudd, Sean G; Ljungblad, Linda; Sanjiv, Kumar; Myrberg, Ida Hed; Paulin, Cynthia B J; Heshmati, Yaser; Hagenkort, Anna; Kutzner, Juliane; Page, Brent D G; Calderón-Montaño, José M; Loseva, Olga; Jemth, Ann-Sofie; Bulli, Lorenzo; Axelsson, Hanna; Tesi, Bianca; Valerie, Nicholas C K; Höglund, Andreas; Bladh, Julia; Wiita, Elisée; Sundin, Mikael; Uhlin, Michael; Rassidakis, Georgios; Heyman, Mats; Tamm, Katja Pokrovskaja; Warpman-Berglund, Ulrika; Walfridsson, Julian; Lehmann, Sören; Grandér, Dan; Lundbäck, Thomas; Kogner, Per; Henter, Jan-Inge; Helleday, Thomas; Schaller, Torsten

    2017-02-01

    The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment. Here we demonstrate that the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 (SAMHD1) promotes the detoxification of intracellular ara-CTP pools. Recombinant SAMHD1 exhibited ara-CTPase activity in vitro, and cells in which SAMHD1 expression was transiently reduced by treatment with the simian immunodeficiency virus (SIV) protein Vpx were dramatically more sensitive to ara-C-induced cytotoxicity. CRISPR-Cas9-mediated disruption of the gene encoding SAMHD1 sensitized cells to ara-C, and this sensitivity could be abrogated by ectopic expression of wild-type (WT), but not dNTPase-deficient, SAMHD1. Mouse models of AML lacking SAMHD1 were hypersensitive to ara-C, and treatment ex vivo with Vpx sensitized primary patient-derived AML blasts to ara-C. Finally, we identified SAMHD1 as a risk factor in cohorts of both pediatric and adult patients with de novo AML who received ara-C treatment. Thus, SAMHD1 expression levels dictate patient sensitivity to ara-C, providing proof-of-concept that the targeting of SAMHD1 by Vpx could be an attractive therapeutic strategy for potentiating ara-C efficacy in hematological malignancies.

  17. Large-volume leukapheresis for peripheral blood stem cell collection in patients with hematologic malignancies.

    PubMed

    Malachowski, M E; Comenzo, R L; Hillyer, C D; Tiegerman, K O; Berkman, E M

    1992-10-01

    Large-volume leukapheresis (LVL, 15-35 L) was performed in two groups of patients (n = 10) with hematologic malignancies to obtain peripheral blood stem cells for bone marrow rescue following high-dose chemotherapy. The target cell count was 7 x 10(8) mononuclear cells (MNCs = lymphocytes and monocytes) per kg of body weight. Group A patients (n = 4) were studied on Day 1 of LVL, and components were collected from them as four sequential samples. Total MNCs collected averaged 1.29 x 10(10), total colony-forming-units granulocyte-macrophage (CFU-GM) averaged 12.1 x 10(6), and a 1.8-fold mobilization of CFU-GM was observed (p < 0.05, Sample 1 vs. Sample 4). Group B patients (n = 6) were studied throughout the three consecutive planned days of 5-hour LVL. An average of three LVL procedures per patient was performed (range, 1.25-4), and an average of 27 L (range, 24-33) of blood per LVL was processed. The blood:ACD-A ratio was 24:1 with 3000 units of heparin per 500 mL of ACD-A; heparin was also added to the collection bags. The component had an average hematocrit (Hct) of 0.02 and MNC content of 93 percent. The patients' pre-LVL and post-LVL average Hct varied significantly (before Day 1, 0.36 +/- 0.08; after Day 3, 0.28 +/- 0.06; p < 0.05). Platelet counts also decreased, with post-Day 3 counts averaging 19 percent of the average pre-Day 1 counts (p < 0.05). A decrease in the average MNC count after LVL was significant on Day 1 only (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies

    PubMed Central

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies. PMID:26029215

  19. The effect of donor characteristics on survival after unrelated donor transplantation for hematologic malignancy

    PubMed Central

    Kollman, Craig; Spellman, Stephen R.; Zhang, Mei-Jie; Hassebroek, Anna; Anasetti, Claudio; Antin, Joseph H.; Champlin, Richard E.; Confer, Dennis L.; DiPersio, John F.; Fernandez-Viña, Marcelo; Hartzman, Robert J.; Horowitz, Mary M.; Hurley, Carolyn K.; Karanes, Chatchada; Maiers, Martin; Mueller, Carlheinz R.; Perales, Miguel-Angel; Setterholm, Michelle; Woolfrey, Ann E.; Yu, Neng

    2016-01-01

    There are >24 million registered adult donors, and the numbers of unrelated donor transplantations are increasing. The optimal strategy for prioritizing among comparably HLA-matched potential donors has not been established. Therefore, the objective of the current analyses was to study the association between donor characteristics (age, sex, parity, cytomegalovirus serostatus, HLA match, and blood group ABO match) and survival after transplantation for hematologic malignancy. The association of donor characteristics with transplantation outcomes was examined using either logistic or Cox regression models, adjusting for patient disease and transplantation characteristics associated with outcomes in 2 independent datasets: 1988 to 2006 (N = 6349; training cohort) and 2007 to 2011 (N = 4690; validation cohort). All donor-recipient pairs had allele-level HLA typing at HLA-A, -B, -C, and -DRB1, which is the current standard for selecting donors. Adjusting for patient disease and transplantation characteristics, survival was better after transplantation of grafts from young donors (aged 18-32 years) who were HLA matched to recipients (P < .001). These findings were validated for transplantations that occurred between 2007 and 2011. For every 10-year increment in donor age, there is a 5.5% increase in the hazard ratio for overall mortality. Increasing HLA disparity was also associated with worsening survival. Donor age and donor-recipient HLA match are important when selecting adult unrelated donors. Other donor characteristics such as sex, parity, and cytomegalovirus serostatus were not associated with survival. The effect of ABO matching on survival is modest and must be studied further before definitive recommendations can be offered. PMID:26527675

  20. Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies.

    PubMed

    Shah, Gunjan L; Shune, Leyla; Purtill, Duncan; Devlin, Sean; Lauer, Emily; Lubin, Marissa; Bhatt, Valkal; McElrath, Courtney; Kernan, Nancy A; Scaradavou, Andromachi; Giralt, Sergio; Perales, Miguel A; Ponce, Doris M; Young, James W; Shah, Monica; Papanicolaou, Genovefa; Barker, Juliet N

    2015-12-01

    Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4(+)CD45RA(+) and CD19(+) cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients.

  1. Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies

    PubMed Central

    Shah, Gunjan L.; Shune, Leyla; Purtill, Duncan; Devlin, Sean; Lauer, Emily; Lubin, Marissa; Bhatt, Valkal; McElrath, Courtney; Kernan, Nancy A.; Scaradavou, Andromachi; Giralt, Sergio; Perales, Miguel A.; Ponce, Doris M.; Young, James W.; Shah, Monica; Papanicolaou, Genovefa; Barker, Juliet N.

    2015-01-01

    As cord blood (CB) lacks memory T- and B-cells, and recent decreases in herd immunity to vaccine preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five (63%) patients (engrafting units median HLA-allele match 5/8, range 2–7/8) received protein-conjugated vaccines, and 63 (median age 34 years, range 0.9–64) were evaluated for responses. Median vaccination time was 17 months (range 7–45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19f, 23f) were seen in children and adults (60% versus 49%, p = 0.555). Responses to tetanus, diphtheria, pertussis, H. influenzae, and polio were observed in children (86–100%) and adults (53–89%) even if patients had prior GVHD or rituximab. CD4+CD45RA+ and CD19+ cell recovery significantly influenced tetanus and polio responses. In a smaller cohort, responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side-effects were identified and all vaccinated patients survive (median follow-up 57 months). While GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients. PMID:26271191

  2. Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

    PubMed

    Pittari, Gianfranco; Filippini, Perla; Gentilcore, Giusy; Grivel, Jean-Charles; Rutella, Sergio

    2015-01-01

    Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL)-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols. Cytokine-induced killer (CIK) cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming. NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  3. Alcohol Consumption Has a Protective Effect against Hematological Malignancies: a Population-Based Study in Sweden Including 420,489 Individuals with Alcohol Use Disorders12345

    PubMed Central

    Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2014-01-01

    BACKGROUND: It has been suggested that alcohol consumption is associated with increased risk of a few solid cancers, although studies that examined the association with hematological malignancies have shown inconsistent results. In this study, we examined the risk of hematological malignancies among individuals who had alcohol use disorders (AUDs) in Sweden. METHODS: Individuals with AUDs were identified from the nationwide Swedish Hospital Discharge Register and Outpatient Register, the Crime Register, and the Prescription Drug Register, and they were linked to the Swedish Cancer Registry to calculate standardized incidence ratios (SIRs) of hematological malignancies, using those Swedes without AUDs as a reference. In addition, we used a quasi-experimental sibling design to investigate the odds ratios among sibling pairs who were discordant with AUDs. RESULTS: A total of 420,489 individuals were identified with AUDs. After more than 15 million person-years of follow-up, a total of 1755 individuals developed hematological malignancies demonstrating a low risk, i.e., SIR = 0.60 (95% confidence interval = 0.57-0.63). People with AUDs had low risks for developing specific types of malignancies. The lowest risk (0.51) was for leukemia, followed by myeloma (0.52), non-Hodgkin lymphoma (0.65), and Hodgkin disease (0.71). The risk was lower among AUDs identified at an older age. The low risks of hematological malignancies were also noted using sibling analysis. CONCLUSIONS: Our data suggest that alcohol consumption has a protective effect against hematological malignancies. However, further studies are needed to identity the underlying mechanisms of the protective effect of alcohol consumption against hematological malignancies. PMID:24783999

  4. Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.

    PubMed

    Howard, Scott C; Trifilio, Steven; Gregory, Tara K; Baxter, Nadine; McBride, Ali

    2016-03-01

    Effective new treatments are now available for patients with hematologic malignancies. However, their propensity to cause tumor lysis syndrome (TLS) has not been systematically examined. A literature search identified published Phase I-III clinical trials of monoclonal antibodies (otlertuzumab, brentuximab, obinutuzumab, ibritumomab, ofatumumab); tyrosine kinase inhibitors (alvocidib [flavopiridol], dinaciclib, ibrutinib, nilotinib, dasatinib, idelalisib, venetoclax [ABT-199]); proteasome inhibitors (oprozomib, carfilzomib); chimeric antigen receptor (CAR) T cells; and the proapoptotic agent lenalidomide. Abstracts from major congresses were also reviewed. Idelalisib and ofatumumab had no reported TLS. TLS incidence was ≤5 % with brentuximab vedotin (for anaplastic large-cell lymphoma), carfilzomib and lenalidomide (for multiple myeloma), dasatinib (for acute lymphoblastic leukemia), and oprozomib (for various hematologic malignancies). TLS incidences were 8.3 and 8.9 % in two trials of venetoclax (for chronic lymphocytic leukemia [CLL]) and 10 % in trials of CAR T cells (for B-cell malignancies) and obinutuzumab (for non-Hodgkin lymphoma). TLS rates of 15 % with dinaciclib and 42 and 53 % with alvocidib (with sequential cytarabine and mitoxantrone) were seen in trials of acute leukemias. TLS mitigation was employed routinely in clinical trials of alvocidib and lenalidomide. However, TLS mitigation strategies were not mentioned or stated only in general terms for many studies of other agents. The risk of TLS persists in the current era of novel and targeted therapy for hematologic malignancies and was seen to some extent with most agents. Our findings underscore the importance of continued awareness, risk assessment, and prevention to reduce this serious potential complication of effective anticancer therapy.

  5. 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

  6. Disseminated toxoplasmosis in non-allografted patients with hematologic malignancies: report of two cases and literature review.

    PubMed

    Scerra, S; Coignard-Biehler, H; Lanternier, F; Suarez, F; Charlier-Woerther, C; Bougnoux, M-E; Gilquin, J; Lecuit, M; Hermine, O; Lortholary, O

    2013-10-01

    Toxoplasmosis can be a severe opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), and also among solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) patients. Patients with low-grade or chronic hematologic malignancies are treated with increasing immunosuppressive regimens and, therefore, represent an emerging population at risk for opportunistic diseases. We report here two cases of disseminated toxoplasmosis occurring in non-allografted hematologic patients with chronic lymphoproliferations. A review of 44 cases from the literature reveals that toxoplasmosis occurs increasingly in indolent B cell lymphoproliferative disorders. Aggressive lymphoproliferations, adenosine analogs, autologous HSCT, and the absence of chemoprophylaxis are the main risk factors for opportunistic toxoplasmosis. The central nervous system is the main organ involved. Fever is only present in half of all cases. Latent Toxoplasma cysts reactivation (LTCR) is the most common, but primary infection occurs in about 20% of cases. Global mortality is over 50%.

  7. Microarray Gene Expression Analysis to Evaluate Cell Type Specific Expression of Targets Relevant for Immunotherapy of Hematological Malignancies.

    PubMed

    Pont, M J; Honders, M W; Kremer, A N; van Kooten, C; Out, C; Hiemstra, P S; de Boer, H C; Jager, M J; Schmelzer, E; Vries, R G; Al Hinai, A S; Kroes, W G; Monajemi, R; Goeman, J J; Böhringer, S; Marijt, W A F; Falkenburg, J H F; Griffioen, M

    2016-01-01

    Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate potential efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. We performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN-γ to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlations between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.

  8. Molecular Analysis and Risk Factors for Escherichia coli Producing Extended-Spectrum β-Lactamase Bloodstream Infection in Hematological Malignancies

    PubMed Central

    Cornejo-Juárez, Patricia; Pérez-Jiménez, Carolina; Silva-Sánchez, Jesús; Velázquez-Acosta, Consuelo; González-Lara, Fernanda; Reyna-Flores, Fernando; Sánchez-Pérez, Alejandro; Volkow-Fernández, Patricia

    2012-01-01

    Introduction Patients with hematologic malignancies have greater risk-factors for primary bloodstream infections (BSI). Methods From 2004–2009, we analyzed bacteremia caused by extended-spectrum beta-lactamase Escherichia coli (ESBL-EC) (n = 100) and we compared with bacteremia caused by cephalosporin-susceptible E. coli (n = 100) in patients with hematologic malignancies. Objective To assess the clinical features, risk factors, and outcome of ESBL-EC BSI in patients with hematologic malignancies, and to study the molecular epidemiology of ESBL-EC isolates. Results The main diagnosis was acute leukemia in 115 patients (57.5%). Death-related E. coli infection was significantly increased with ESBL-EC (34% vs. control group, 19%; p = 0.03). Treatment for BSI was considered appropriate in 64 patients with ESBL-EC (mean survival, 245±345 days), and in 45 control patients this was 443±613 (p = 0.03). In patients not receiving appropriate antimicrobial treatment, survival was significantly decreased in cases compared with controls (26±122 vs. 276±442; p = 0.001). Fifty six of the ESBL-EC isolates were characterized by molecular analysis: 47 (84%) expressed CTX-M-15, two (3.6%) SHV, and seven (12.5%) did not correspond to either of these two ESBL enzymes. No TLA-1 enzyme was detected. Conclusions Patients who had been previously hospitalized and who received cephalosporins during the previous month, have an increased risk of ESBL-EC bacteremia. Mortality was significantly increased in patients with ESBL-EC BSI. A polyclonal trend was detected, which reflects non-cross transmission of multiresistant E.coli isolates. PMID:22540004

  9. Integration of microarray analysis into the clinical diagnosis of hematological malignancies: How much can we improve cytogenetic testing?

    PubMed Central

    Peterson, Jess F.; Aggarwal, Nidhi; Smith, Clayton A.; Gollin, Susanne M.; Surti, Urvashi; Rajkovic, Aleksandar; Swerdlow, Steven H.; Yatsenko, Svetlana A.

    2015-01-01

    Purpose To evaluate the clinical utility, diagnostic yield and rationale of integrating microarray analysis in the clinical diagnosis of hematological malignancies in comparison with classical chromosome karyotyping/fluorescence in situ hybridization (FISH). Methods G-banded chromosome analysis, FISH and microarray studies using customized CGH and CGH+SNP designs were performed on 27 samples from patients with hematological malignancies. A comprehensive comparison of the results obtained by three methods was conducted to evaluate benefits and limitations of these techniques for clinical diagnosis. Results Overall, 89.7% of chromosomal abnormalities identified by karyotyping/FISH studies were also detectable by microarray. Among 183 acquired copy number alterations (CNAs) identified by microarray, 94 were additional findings revealed in 14 cases (52%), and at least 30% of CNAs were in genomic regions of diagnostic/prognostic significance. Approximately 30% of novel alterations detected by microarray were >20 Mb in size. Balanced abnormalities were not detected by microarray; however, of the 19 apparently “balanced” rearrangements, 55% (6/11) of recurrent and 13% (1/8) of non-recurrent translocations had alterations at the breakpoints discovered by microarray. Conclusion Microarray technology enables accurate, cost-effective and time-efficient whole-genome analysis at a resolution significantly higher than that of conventional karyotyping and FISH. Array-CGH showed advantage in identification of cryptic imbalances and detection of clonal aberrations in population of non-dividing cancer cells and samples with poor chromosome morphology. The integration of microarray analysis into the cytogenetic diagnosis of hematologic malignancies has the potential to improve patient management by providing clinicians with additional disease specific and potentially clinically actionable genomic alterations. PMID:26299921

  10. Emerging therapeutic paradigms to target the dysregulated Janus kinase/signal transducer and activator of transcription pathway in hematological malignancies.

    PubMed

    Mughal, Tariq I; Girnius, Saulius; Rosen, Steven T; Kumar, Shaji; Wiestner, Adrian; Abdel-Wahab, Omar; Kiladjian, Jean-Jacques; Wilson, Wyndham H; Van Etten, Richard A

    2014-09-01

    Over the past decade, there has been increasing biochemical evidence that the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is aberrantly activated in malignant cells from patients with a wide spectrum of cancers of the blood and immune systems. The emerging availability of small molecule inhibitors of JAK and other signaling molecules in the JAK/STAT pathway has allowed preclinical studies validating an important role of this pathway in the pathogenesis of many hematologic malignancies, and provided motivation for new strategies for treatment of these diseases. Here, a round-table panel of experts review the current preclinical and clinical landscape of the JAK/STAT pathway in acute lymphoid and myeloid leukemias, lymphomas and myeloma, and chronic myeloid neoplasms.

  11. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization.

    PubMed

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; van der Bom, Johanna G

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.

  12. Treatments for hematologic malignancies in contrast to those for solid cancers are associated with reduced red cell alloimmunization

    PubMed Central

    Evers, Dorothea; Zwaginga, Jaap Jan; Tijmensen, Janneke; Middelburg, Rutger A.; de Haas, Masja; de Vooght, Karen M.K.; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C.V.; Hudig, Francisca; van der Bom, Johanna G.

    2017-01-01

    Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19–0.68) and 0.30 (range 0.12–0.81). Associations were primarily explained by immunosuppressive treatments [RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09–0.83)]. Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16–0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization. PMID:27634204

  13. Risk of solid tumors and hematological malignancy in persons with Turner and Klinefelter syndromes: A national cohort study.

    PubMed

    Ji, Jianguang; Zöller, Bengt; Sundquist, Jan; Sundquist, Kristina

    2016-08-15

    The risk of solid and hematological malignancy in patients with Turner syndrome, characterized by X chromosome monosomy in women, and Klinefelter syndrome, characterized with two and more X chromosomes in men, is not well established, but such evidence may have etiological implications on cancer development. We identified a total of 1,409 women with Turner syndrome and 1,085 men with Klinefelter syndrome from the Swedish Hospital Discharge and Outpatient Register. These individuals were further linked to the Swedish Cancer Register to examine the standardized incidence ratios (SIRs) of cancer using the general population without Turner and Klinefelter syndromes as reference. The overall risk of cancer was 1.34 for women with Turner syndrome; it was increased only for solid tumors. For a specific type of tumor, the risk of melanoma and central nervous system tumor was significantly increased. For persons with Klinefelter syndrome, the risk of solid tumors was decreased (SIR = 0.66), whereas the risk of hematological malignancy was increased (SIR = 2.72). Non-Hodgkin lymphoma and leukemia showed an increased SIR of 3.02 and 3.62, respectively. Our study supported the hypothesis that X chromosome plays an important role in the etiology of solid tumors. The underlying mechanisms for the increased incidence of non-Hodgkin lymphoma and leukemia in persons with Klinefelter syndrome need to be investigated further.

  14. Three hematologic malignancies in the same patient: chronic lymphocytic leukemia, followed by chronic myeloid leukemia and acute myeloid leukemia.

    PubMed

    Fattizzo, Bruno; Radice, Tommaso; Cattaneo, Daniele; Pomati, Mauro; Barcellini, Wilma; Iurlo, Alessandra

    2014-01-01

    The co-existence of both chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) have been described in a few cases, either simultaneously or subsequently presenting. We report an unusual case of three he-matological malignancies in the same patient: CLL, CML, and acute myeloid leukemia (AML). None of the three malignancies shared the same origin, since the marrow sample was negative for BCR-ABL1 transcript at the time of CLL diagnosis, CLL was in remission at CML diagnosis, and CML was in complete cytogenetic response at AML onset, indicating that this was not a blast crisis. Background: Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common proliferative disorders in Western countries, with an incidence of 4.2/100,000/year and 1-1.5/100,000/year, respectively. The co-existence of both CML and CLL is an extremely rare event, even if it has been described in a few cases, either simultaneously or subsequently presenting. Above all, the presence of more than two different hematologic neoplasms has not been described in literature so far. In the present study we report a particular case of a CLL patient, who first developed CML and then acute myeloid leukemia (AML).

  15. Individuals with hematological malignancies before undergoing chemotherapy present oxidative stress parameters and acute phase proteins correlated with nutritional status.

    PubMed

    Camargo, Carolina de Quadros; Borges, Dayanne da Silva; de Oliveira, Paula Fernanda; Chagas, Thayz Rodrigues; Del Moral, Joanita Angela Gonzaga; Durigon, Giovanna Steffanello; Dias, Bruno Vieira; Vieira, André Guedes; Gaspareto, Patrick; Trindade, Erasmo Benício Santos de Moraes; Nunes, Everson Araújo

    2015-01-01

    Hematological malignancies present abnormal blood cells that may have altered functions. This study aimed to evaluate nutritional status, acute phase proteins, parameters of cell's functionality, and oxidative stress of patients with hematological malignancies, providing a representation of these variables at diagnosis, comparisons between leukemias and lymphomas and establishing correlations. Nutritional status, C-reactive protein (CRP), albumin, phagocytic capacity and superoxide anion production of mononuclear cells, lipid peroxidation and catalase activity in plasma were evaluated in 16 untreated subjects. Main diagnosis was acute leukemia (n = 9) and median body mass index (BMI) indicated overweight (25.6 kg/m(2)). Median albumin was below (3.2 g/dL) and CRP above (37.45 mg/L) the reference values. Albumin was inversely correlated with BMI (r = -0.53). Most patients were overweight before the beginning of treatment and had a high CRP/albumin ratio, which may indicate a nutrition inflammatory risk. BMI values correlated positively with lipid peroxidation and catalase activity. A strong correlation between catalase activity and lipid peroxidation was found (r = 0.75). Besides the elevated BMI, these patients also have elevated CRP values and unexpected relations between nutritional status and albumin, reinforcing the need for nutritional counseling during the course of chemotherapy, especially considering the correlations between oxidative stress parameters and nutritional status evidenced here.

  16. miR-29s: a family of epi-miRNAs with therapeutic implications in hematologic malignancies

    PubMed Central

    Amodio, Nicola; Rossi, Marco; Raimondi, Lavinia; Pitari, Maria Rita; Botta, Cirino; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2015-01-01

    A wealth of studies has highlighted the biological complexity of hematologic malignancies and the role of dysregulated signal transduction pathways. Along with the crucial role of genetic abnormalities, epigenetic aberrations are nowadays emerging as relevant players in cancer development, and significant research efforts are currently focusing on mechanisms by which histone post-translational modifications, DNA methylation and noncoding RNAs contribute to the pathobiology of cancer. As a consequence, these studies have provided the rationale for the development of epigenetic drugs, such as histone deacetylase inhibitors and demethylating compounds, some of which are currently in advanced phase of pre-clinical investigation or in clinical trials. In addition, a more recent body of evidence indicates that microRNAs (miRNAs) might target effectors of the epigenetic machinery, which are aberrantly expressed or active in cancers, thus reverting those epigenetic abnormalities driving tumor initiation and progression. This review will focus on the broad epigenetic activity triggered by members of the miR-29 family, which underlines the potential of miR-29s as candidate epi-therapeutics for the treatment of hematologic malignancies. PMID:25968566

  17. Current epidemiology and antimicrobial resistance data for bacterial bloodstream infections in patients with hematologic malignancies: an Italian multicentre prospective survey.

    PubMed

    Trecarichi, E M; Pagano, L; Candoni, A; Pastore, D; Cattaneo, C; Fanci, R; Nosari, A; Caira, M; Spadea, A; Busca, A; Vianelli, N; Tumbarello, M

    2015-04-01

    A prospective cohort study was conducted in nine hematology wards at tertiary care centres or at university hospitals located throughout Italy from January 2009 to December 2012. All of the cases of bacterial bloodstream infection (BBSI) occurring in adult patients with hematologic malignancies were included. A total of 668 bacterial isolates were recovered in 575 BBSI episodes. Overall, the susceptibility rates of Gram-negative bacteria were 59.1% to ceftazidime, 20.1% to ciprofloxacin, 79.1% to meropenem, 85.2% to amikacin, 69.2% to gentamicin and 69.8% to piperacillin/tazobactam. Resistance to third-generation cephalosporins was found in 98/265 (36.9%) of Enterobacteriaceae isolates. Among Klebsiella pneumoniae strains, 15/43 (34.9%) were resistant to carbapenems. Of 66 Pseudomonas aeruginosa isolates, 46 (69.7%) were multidrug resistant. Overall, the susceptibility rates of Gram-positive bacteria were 97.4% to vancomycin and 94.2% to teicoplanin. Among the monomicrobial cases of BBSI, the 21-day mortality rate was significantly higher for those caused by Gram-negative bacteria compared to those caused by Gram-positive bacteria (47/278, 16.9% vs. 12/212, 5.6%; p < 0.001). Among Gram-negative bacteria, the mortality rate was significantly higher for BBSI caused by K. pneumoniae, P. aeruginosa, and Acinetobacter baumannii. Our results confirm the recently reported shift of prevalence from Gram-positive to Gram-negative bacteria as causative agents of BBSIs among patients with hematologic malignancies and highlight a worrisome increasing frequency in antimicrobial resistance among Gram-negative bacteria.

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

    ClinicalTrials.gov

    2017-03-30

    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

  19. 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

  20. Radiation Therapy and Late Mortality From Second Sarcoma, Carcinoma, and Hematological Malignancies After a Solid Cancer in Childhood

    SciTech Connect

    Tukenova, Markhaba; Guibout, Catherine; Hawkins, Mike; Quiniou, Eric; Mousannif, Abddedahir; Pacquement, Helene; Winter, David; Bridier, Andre; Lefkopoulos, Dimitri; Oberlin, Odile; Diallo, Ibrahima; Vathaire, Florent de

    2011-06-01

    Purpose: To compare patterns of long-term deaths due to secondary carcinomas, sarcomas, and hematological malignancies occurring after childhood cancer in a cohort of patients followed over a median of 28 years. Methods and Materials: The study included 4,230 patients treated at eight institutions, who were at least 5-year survivors of a first cancer, representing 105,670 person-years of observation. Complete clinical, chemotherapeutic, and radiotherapeutic data were recorded, and the integral radiation dose was estimated for 2,701 of the 2,948 patients who had received radiotherapy. The integral dose was estimated for the volume inside the beam edges. The causes of death obtained from death certificates were validated. Results: In total, 134 events were due to second malignant neoplasm(s) (SMN). We found that the standardized mortality ratio decreased with increasing follow-up for second carcinomas and sarcomas, whereas the absolute excess risk (AER) increased for a second carcinoma but decreased for second sarcomas. There was no clear variation in SMN and AER for hematological malignancies. We found a significant dose-response relationship between the radiation dose received and the mortality rate due to a second sarcoma and carcinoma. The risk of death due to carcinoma and sarcoma as SMN was 5.2-fold and 12.5-fold higher, respectively, in patients who had received a radiation dose exceeding 150 joules. Conclusions: Among patients who had received radiotherapy, only those having received the highest integral radiation dose actually had a higher risk of dying of a second carcinoma or sarcoma.

  1. Aberrant overexpression of an epithelial marker, 14-3-3σ, in a subset of hematological malignancies

    PubMed Central

    Motokura, Toru; Nakamura, Yukari; Sato, Hiroyuki

    2007-01-01

    Background 14-3-3σ is a p53-mediated cell-cycle inhibitor in epithelial cells. The expression of 14-3-3σ is frequently altered in cancers of epithelial origin associated with altered DNA methylation. Since its involvement in a non-epithelial tumor is unknown, we examined 14-3-3σ expression in patients with haematological malignancies. Methods We analyzed 41 hematopoietic cell lines and 129 patients with a variety of hematological malignancies for 14-3-3σ expression with real-time RT-PCR. We also examined protein levels by Western blot analysis and DNA methylation status of the 14-3-3σ gene by methylation-specific PCR analysis of bisulfite-treated DNA. In addition, mutations of p53 gene were identified by RT-PCR-SSCP analysis and the expression levels of 14-3-3σ were compared with those of other cell-cycle inhibitor genes, CDKN2A and ARF. Results The expression levels of 14-3-3σ mRNA in almost all cell lines were low and comparable to those in normal hematopoietic cells except for 2 B-cell lines. On the contrary, 14-3-3σ mRNA was aberrantly overexpressed frequently in mature lymphoid malignancies (30 of 93, 32.3%) and rarely in acute leukemia (3 of 35, 8.6%). 14-3-3σ protein was readily detectable and roughly reflected the mRNA level. In contrast to epithelial tumors, methylation status of the 14-3-3σ gene was not associated with expression in hematological malignancies. Mutations of p53 were identified in 12 patients and associated with lower expression of 14-3-3σ. The expression levels of 14-3-3σ, CDKN2A and ARF were not correlated with but rather reciprocal to one another, suggesting that simultaneous overexpression of any two of them is incompatible with tumor growth. Conclusion 14-3-3σ, an epithelial cell marker, was overexpressed significantly in a subset of mature lymphoid malignancies. This is the first report of aberrant 14-3-3σ expression in non-epithelial tumors in vivo. Since the significance of 14-3-3σ overexpression is unknown even in

  2. Clinical characteristics and outcomes of varicella zoster virus infection in children with hematologic malignancies in the acyclovir era

    PubMed Central

    Kim, Seul-Ki; Kim, Min Chae; Han, Seung Beom; Lee, Jae Wook; Chung, Nack-Gyun; Cho, Bin; Jeong, Dae Chul; Kang, Jin Han; Kim, Hack-Ki

    2016-01-01

    Background Although intravenous acyclovir therapy is recommended for varicella zoster virus (VZV) infection in immunocompromised children, the clinical characteristics and outcomes of VZV infection in the acyclovir era have rarely been reported. Methods The medical records of children diagnosed with varicella or herpes zoster virus, who had underlying hematologic malignancies, were retrospectively reviewed, and the clinical characteristics and outcomes of VZV infection were evaluated. Results Seventy-six episodes of VZV infection (herpes zoster in 57 and varicella in 19) were identified in 73 children. The median age of children with VZV infection was 11 years (range, 1-17), and 35 (46.1%) episodes occurred in boys. Acute lymphoblastic leukemia was the most common underlying malignancy (57.9%), and 90.8% of the episodes occurred during complete remission of the underlying malignancy. Acyclovir was administered for a median of 10 days (range, 4-97). Severe VZV infection occurred in 16 (21.1%) episodes. Although the finding was not statistically significant, a previous history of hematopoietic cell transplantation (HCT) appeared to be associated with the development of more severe episodes of herpes zoster (P=0.075). Conclusion Clinical characteristics of VZV infection in immunocompromised children were not significantly different from those without it, and clinical outcomes improved after the introduction of acyclovir therapy. However, risk factors for severe VZV infection require further investigation in a larger population and a prospective setting. PMID:28090487

  3. Diagnostic strategies for invasive fungal infections in patients with hematologic malignancies and hematopoietic stem cell transplant recipients.

    PubMed

    Norkin, Maxim; Wingard, John R

    2013-08-01

    Invasive fungal infections (IFIs) frequently occur and are associated with high morbidity and mortality in patients with hematologic malignancies (HMs) and hematopoietic stem cell transplant (HSCT) recipients. Early diagnosis of IFI in these patients facilitates prompt institution of therapy and leads to improved clinical outcomes. This article reviews widely used methodologies for diagnosing IFIs in patients with HM and HSCT recipients. Advantages and limitations of radiologic studies; microbiologic and histopathologic techniques; fungal biomarker assays, including those for galactomannan antigen and β-(1-3)-D-glucan; and molecular assays that are available to establish an early diagnosis of clinically relevant invasive fungal infections are discussed. Recommendations are provided regarding effective use of these methodologies in clinical practice.

  4. Diagnosis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Turkish Expert Opinion (TEO-2)

    PubMed Central

    Arıkan Akdağlı, Sevtap; Azap, Alpay; Başaran Demirkazık, Figen; Ener, Beyza; Aşcıoğlu Hayran, Sibel; Özdemir Kumbasar, Özlem; Metan, Gökhan; Odabaşı, Zekaver; Uzun, Ömrüm; Akan, Hamdi

    2014-01-01

    One of the most problematic issues in hematological malignancies is the diagnosis of invasive fungal diseases. Especially, the difficulty of mycological diagnosis and the necessity of immediate intervention in molds have led to the adoption of “surrogate markers” that do not verify but rather strongly suggest fungal infection. The markers commonly used are galactomannan (GM), beta-glucan, and imaging methods. Although there are numerous studies on these diagnostic approaches, none of these markers serve as a support for the clinician, as is the case in human immunodeficiency virus (HIV) or cytomegalovirus (CMV) infections. This paper has been prepared to explain the diagnostic tests. As molecular tests have not been standardized and are not used routinely in the clinics, they will not be mentioned here. PMID:25541650

  5. Longitudinal Changes in Body Mass and Composition in Survivors of Childhood Hematologic Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation

    PubMed Central

    Inaba, Hiroto; Yang, Jie; Kaste, Sue C.; Hartford, Christine M.; Motosue, Megan S.; Chemaitilly, Wassim; Triplett, Brandon M.; Shook, David R.; Pui, Ching-Hon; Leung, Wing

    2012-01-01

    Purpose To measure longitudinal changes in body mass and composition in survivors of childhood hematologic malignancies after allogeneic hematopoietic stem-cell transplantation (HSCT). Patients and Methods Body mass index (BMI) was analyzed in 179 survivors by category (underweight, healthy-weight, overweight, and obese) and by z score. Fat and lean body mass measured by dual-energy x-ray absorptiometry was analyzed as z scores. Results Over a median 6.6 years of follow-up, BMI z scores diminished significantly (0.32 pre-HSCT v −0.60 at 10 years post-HSCT; P < .001). Mean z scores for fat mass stayed within population norms, but those for lean mass remained below normal levels and diminished significantly over time (P = .018). Pre-HSCT BMI category and/or z score were strongly predictive of post-HSCT BMI (P < .001) and of fat and lean mass z scores (both P < .001). Survivors with extensive chronic graft-versus-host disease were more likely than others to have low BMI (P = .004) and low lean mass (P < .001) post-HSCT. Older age at HSCT (P = .015) and T-cell–depleted graft (P = .018) were predictive of lower post-HSCT BMI. Female patients had higher body fat (P = .002) and lower lean mass (P = .013) z scores than male patients, and black patients had higher fat mass z scores than white patients (P = .026). Conclusion BMI declines significantly after allogeneic HSCT for childhood hematologic malignancies, reflecting primarily a substantial decrease in lean mass but not fat mass. Monitoring and preservation of BMI and lean mass are vital, especially in those with the identified risk factors. PMID:23032628

  6. A Randomized Study Comparing the Efficacy of Three Hepatitis B Vaccine Induction Regimens in Adult Patients with Hematological Malignancies

    PubMed Central

    Özkurt, Zübeyde Nur; Suyanı, Elif; Haznedar, Rauf; Yağcı, Münci

    2016-01-01

    Objective: Non-responsiveness to hepatitis B virus (HBV) vaccines is not rare in hemato-oncological patients due to disease-associated or treatment-induced immune suppression. Although different strategies have been employed to improve the response rates, to date there is not an approved schedule for HBV immunization in patients with hematological malignancies. We designed a prospective randomized study to evaluate the efficacy of 3 different induction regimens for HBV vaccination. Materials and Methods: In the standard-dose (SD) group, total vaccine dose delivered was 40 µg and patients were vaccinated with 20 µg at weeks 0 and 4. In the high-dose dose-intensive (HDDI) group, total vaccine dose delivered was 80 µg and patients were vaccinated with 40 µg at weeks 0 and 4. In the high-dose time-intensive (HDTI) group, total vaccine dose delivered was 80 µg and patients were vaccinated with 20 µg at weeks 0, 2, 4, and 6. Results: In a cohort of 114 patients, 38.6% responded to HBV vaccination. The response rate in the SD arm, HDDI arm, and HDTI arm was 26.2%, 29.7%, and 44.4%, respectively (p>0.05). Age was the only variable identified as having a negative impact on response. Conclusion: Short of achieving statistical significance, a higher response rate was observed in the HDTI arm. Therefore, this study supports a high-dose, time-intensive HBV vaccine induction regimen in patients with hematological malignancies who are not on chemotherapy. PMID:27094506

  7. 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

  8. 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

  9. Development of farnesyltransferase inhibitors for clinical cancer therapy: focus on hematologic malignancies.

    PubMed

    Karp, Judith E; Lancet, Jeffrey E

    2007-09-01

    Farnesyltransferase inhibitors (FTIs) target and inhibit the peptide prenylating enzyme farnesyltransferase. This new class of signal transduction inhibitors is being tested clinically in diverse malignancies, with encouraging results in hematololgic malignancies and breast cancer in particuarl. Critical questions have yet to be answered, for example, optimal dose and schedule, disease subgroups most likely to respond, and appropriate combinations with standard cytotoxics and new biologics. Gene profiling studies of malignant target cells obtained during FTI clinical trials will help to identify patients who are likely to respond to FTIs and to develop mechanisms for overcoming FTI resistance. Clinical trials and correlative laboratory studies in progress and under development will define the optimal roles of FTIs in cancer patients.

  10. 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.

  11. Interpreting outcome data in hematological malignancies: a paradigm for clinical studies.

    PubMed

    Rowe, Jacob M

    2013-01-01

    Results of clinical studies are often contradictory in real time, and in other instances therapies may be adopted due to information from clinical studies where the data may be premature or resulting from small studies. Much of the data may have inherent selection biases, and their interpretation may be confusing and difficult. The hematological literature is full of such examples, and this review will describe some such instances in the hope of introducing both a cautionary note and encouraging more precise description of study conditions as well as an appreciation of the importance of allowing data from clinical studies to mature. Several examples will be drawn from clinical studies in lymphomas, leukemia, and bone marrow transplantation.

  12. 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.

  13. Planes, Trains, and Automobiles: Perspectives on CAR T Cells and Other Cellular Therapies for Hematologic Malignancies.

    PubMed

    Gill, Saar

    2016-08-01

    Hematologic oncologists now have at their disposal (or a referral away) a myriad of new options to get from point A (a patient with relapsed or poor-risk disease) to point B (potential tumor eradication and long-term disease-free survival). In this perspective piece, we discuss the putative mechanisms of action and the relative strengths and weaknesses of currently available cellular therapy approaches. Notably, while many of these approaches have been published in high impact journals, with the exception of allogeneic stem cell transplantation and of checkpoint inhibitors (PD1/PDL1 or CTLA4 blockade), the published clinical trials have mostly been early phase, uncontrolled studies. Therefore, many of the new cellular therapy approaches have yet to demonstrate incontrovertible evidence of enhanced overall survival compared with controls. Nonetheless, the science behind these is sure to advance our understanding of cancer immunology and ultimately to bring us closer to our goal of curing cancer.

  14. Advanced mast cell disease: an Italian Hematological Multicenter experience.

    PubMed

    Pagano, Livio; Valentini, Caterina Giovanna; Caira, Morena; Rondoni, Michela; Van Lint, Maria Teresa; Candoni, Anna; Allione, Bernardino; Cattaneo, Chiara; Marbello, Laura; Caramatti, Cecilia; Pogliani, Enrico Maria; Iannitto, Emilio; Giona, Fiorina; Ferrara, Felicetto; Invernizzi, Rosangela; Fanci, Rosa; Lunghi, Monia; Fianchi, Luana; Sanpaolo, Grazia; Stefani, Pietro Maria; Pulsoni, Alessandro; Martinelli, Giovanni; Leone, Giuseppe; Musto, Pellegrino

    2008-12-01

    The aim of the study is to evaluate clinical features, treatments and outcome of patients with systemic mast cell disease (MCD) who arrived to the attention of hematologists. A retrospective study was conducted over 1995-2006 in patients admitted in 18 Italian hematological divisions. Twenty-four cases of advanced MCD were collected: 12 aggressive SM (50%), 8 mast cell leukemia (33%), 4 SM with associated clonal non-mast cell-lineage hematologic disease (17%). Spleen and liver were the principal extramedullary organ involved. The c-kit point mutation D816V was found in 13/18 patients in which molecular biology studies were performed (72%). Treatments were very heterogeneous: on the whole Imatinib was administered in 17 patients, alpha-Interferon in 8, 2-CdA in 3; 2 patients underwent allogeneic hematopoietic stem cell transplantation. The overall response rate to Imatinib, the most frequently employed drugs, was of 29%, registering one complete remission and four partial remission; all responsive patients did not present D816V c-kit mutation. Overall three patients (12%) died for progression of disease. We conclude that MCD is characterized by severe mediator-related symptoms but with a moderate mortality rate. D816V c-kit mutation is frequent and associated with resistance against Imatinib. Because of the rarity of these forms, an effective standard of care is lacking. More data are needed to find new and successful therapeutic strategies.

  15. Pharmacokinetics and Pharmacodynamics with Extended Dosing of CC-486 in Patients with Hematologic Malignancies

    PubMed Central

    Garcia-Manero, Guillermo; Cogle, Christopher R.; Gore, Steven D.; Hetzer, Joel; Kumar, Keshava; Skikne, Barry; MacBeth, Kyle J.

    2015-01-01

    CC-486 (oral azacitidine) is an epigenetic modifier in development for patients with myelodysplastic syndromes and acute myeloid leukemia. In part 1 of this two-part study, a 7-day CC-486 dosing schedule showed clinical activity, was generally well tolerated, and reduced DNA methylation. Extending dosing of CC-486 beyond 7 days would increase duration of azacitidine exposure. We hypothesized that extended dosing would therefore provide more sustained epigenetic activity. Reported here are the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of CC-486 extended dosing schedules in patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML) from part 2 of this study. PK and/or PD data were available for 59 patients who were sequentially assigned to 1 of 4 extended CC-486 dosing schedules: 300mg once-daily or 200mg twice-daily for 14 or 21 days per 28-day cycle. Both 300mg once-daily schedules and the 200mg twice-daily 21-day schedule significantly (all P < .05) reduced global DNA methylation in whole blood at all measured time points (days 15, 22, and 28 of the treatment cycle), with sustained hypomethylation at cycle end compared with baseline. CC-486 exposures and reduced DNA methylation were significantly correlated. Patients who had a hematologic response had significantly greater methylation reductions than non-responding patients. These data demonstrate that extended dosing of CC-486 sustains epigenetic effects through the treatment cycle. Trial Registration ClinicalTrials.gov NCT00528983 PMID:26296092

  16. Depression and anxiety in patients with hematological malignancies, prevalence, and associated factors

    PubMed Central

    Abuelgasim, Khadega A.; Ahmed, Gasmelseed Y.; Alqahtani, Jamilah A.; Alayed, Aseel M.; Alaskar, Ahmed S.; Malik, Mansoor A.

    2016-01-01

    Objectives: To study the prevalence and associated factors of depression and anxiety in hematological cancers (HC) patients. Methods: We conducted a cross-sectional survey in all HC patients at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia between March 2014 and June 2015. We excluded patients with depression, or generalized anxiety disorder. We conducted a structured face to face interview using an internally developed and validated questionnaire (Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 patient’s questionnaire with all participants). Results: Among 211 participants, depression was detected in 98 (46.5%) and anxiety was detected in 47 (22.3%). Thirty-eight (18.1%) had concurrent anxiety and depression. Multiple co-morbidities and tense home atmosphere were predictive for anxiety and depression. We found no association between gender, smoking, income, or being on active therapy and depression or anxiety. Conclusions: Depression and anxiety are highly prevalent in HC patients in KAMC. Health care providers should screen HC cancers for depression and anxiety; as early intervention possibly improve their disease outcome and will likely enhance their psychological wellbeing. PMID:27464865

  17. New Insight on Epidemiology and Management of Bacterial Bloodstream Infection in Patients with Hematological Malignancies

    PubMed Central

    Menzo, Sara Lo; la Martire, Giulia; Ceccarelli, Giancarlo; Venditti, Mario

    2015-01-01

    Bloodstream infections (BSI) are a significant cause of morbidity and mortality in onco-hematologic patients. The Gram-negative bacteria were the main responsible for the febrile neutropenia in the sixties; their impact declined due to the use of fluoroquinolone prophylaxis. This situation was followed by the gradual emergence of Gram-positive bacteria also following the increased use of intravascular devices and the introduction of new chemotherapeutic strategies. In the last decade, the Gram-negative etiology is raising again because of the emergence of resistant strains that make questionable the usefulness of current strategies for prophylaxis and empirical treatment. Gram-negative BSI attributable mortality is relevant, and the appropriate empirical treatment significantly improves the prognosis; on the other hand the adequate delayed treatment of Gram-positive BSI does not seem to have a high impact on survival. The clinician has to be aware of the epidemiology of his institution and colonizations of his patients to choose the most appropriate empiric therapy. In a setting of high endemicity of multidrug-resistant infections also the choice of targeted therapy can be a challenge, often requiring strategies based on off-label prescriptions and low grade evidence. In this review, we summarize the current evidence for the best targeted therapies for difficult to treat bacteria BSIs and future perspectives in this topic. We also provide a flow chart for a rational approach to the empirical treatment of febrile neutropenia in a multidrug resistant, high prevalence setting. PMID:26185609

  18. Gene expression profiling of hematologic malignant cell lines resistant to oncolytic virus treatment

    PubMed Central

    Lee, Nam Hee; Kim, Mikyung; Oh, Sung Yong; Kim, Seong-Geun; Kwon, Hyuk-Chan; Hwang, Tae-Ho

    2017-01-01

    Pexa-Vec (pexastimogene devacirpvec; JX-594) has emerged as an attractive tool in oncolytic virotherapy. Pexa-Vec demonstrates oncolytic and immunotherapeutic mechanisms of action. But the determinants of resistance to Pexa-Vec are mostly unknown. We treated hemoatologic malignant cells with Pexa-Vec and examined the gene-expression pattern of sensitive and resistant cells. Human myeloid malignant cell lines (RPMI-8226, IM-9, K562, THP-1) and lymphoid cancer cell lines (MOLT4, CCRF-CEM, Ramos, U937) were treated with Pexa-Vec. Pexa-Vec was cytotoxic on myeloid cell lines in a dose-dependent manner, and fluorescent imaging and qPCR revealed that Pexa-Vec expression was low in RAMOS than IM-9 after 24 hrs and 48 hrs of infection. Gene expression profiles between two groups were analyzed by microarray. Genes with at least 2-fold increase or decrease in their expression were identified. A total of 660 genes were up-regulated and 776 genes were down-regulated in lymphoid cancer cell lines. The up- and down-regulated genes were categorized into 319 functional gene clusters. We identified the top 10 up-regulated genes in lymphoid cells. Among them three human genes (LEF1, STAMBPL1, and SLFN11) strongly correlated with viral replication. Up-regulation of PVRIG, LPP, CECR1, Arhgef6, IRX3, IGFBP2, CD1d were related to resistant to Pexa-Vec. In conclusion, lymphoid malignant cells are resistant to Pexa-Vec and displayed up-regulated genes associated with resistance to oncolytic viral therapy. These data provide potential targets to overcome resistance, and suggest that molecular assays may be useful in selecting patients for further clinical trials with Pexa-Vec. PMID:27901484

  19. Relationship of body mass index and arm anthropometry to outcomes after pediatric allogeneic hematopoietic cell transplantation for hematologic malignancies.

    PubMed

    Hoffmeister, Paul A; Storer, Barry E; Macris, Paula Charuhas; Carpenter, Paul A; Baker, K Scott

    2013-07-01

    Although nutritional status may adversely affect various health outcomes, the relationship between anthropometry and outcomes after hematopoietic cell transplantation (HCT) has not been fully studied in children. We analyzed the impact of pre-HCT body mass index (BMI), arm muscle area, and arm fat area on outcomes in 733 patients age 2-18 years who underwent allogeneic HCT for a hematologic malignancy between 1985 and 2009. We evaluated these 3 variables according to patient group based on age- and sex-adjusted percentiles for BMI, arm muscle area (<5th, 5th-24th, 25th-94th, and ≥95th), and arm fat area (<25th, 25th-94th, and ≥95th). Cox proportional hazards regression models for event-free survival (EFS), relapse, and nonrelapse mortality (NRM) at 100 days and 3 years after HCT, as well as grade II-IV acute graft-versus-host disease (GVHD) and chronic GVHD, were performed using the 3 major variables and adjusted for covariates. BMI was <5th percentile in only 3% of patients and ≥95th percentile in 15% of patients, but outcomes for both groups were similar to those for the BMI 25th-94th percentile group. The BMI 5th-24th percentile group had lower EFS (P = .01) and higher relapse (P = .003) at day +100 post-HCT, but these associations did not hold at 3 years post-HCT. Arm muscle area was <5th percentile in 8% of patients, and arm fat area was <25th percentile in 10%. Analysis of arm muscle area showed that the <5th percentile group had lower EFS and higher NRM and relapse rate at day +100 (P = .002, .04, and .01, respectively) and 3 years (P = .0004, .008, and .01, respectively) post-HCT. Arm fat area <25th percentile was associated with lower EFS at day +100 (hazard ratio, 1.5; P = .05), but not at 3 years post-HCT. Anthropometry variables were not associated with acute or chronic GVHD. In conclusion, arm muscle area <5th percentile appears to be a stronger predictor than BMI of poor outcomes after HCT in children with hematologic malignancies.

  20. Long-term outcomes after allogeneic stem cell transplantation for children with hematological malignancies.

    PubMed

    Ferry, C; Gemayel, G; Rocha, V; Labopin, M; Esperou, H; Robin, M; de Latour, R P; Ribaud, P; Devergie, A; Leblanc, T; Gluckman, E; Baruchel, A; Socié, G

    2007-08-01

    We analyzed long-term outcomes and psycho-social aspects in 112 children with malignancies surviving 1 year after hematopoietic stem cell transplantation. At 10 years, overall survival was 75+/-5%, TRM 18+/-4% and relapse 14+/-3%; 10-year cumulative incidence of infections was 31+/-4%, cataract 44+/-4%, pulmonary dysfunction 20+/-4%, bone and joint complications 29+/-5%, hypothyroidism 36+/-4%, cardiac complications 11+/-3% and secondary malignancies 7+/-3%. Total body irradiation (TBI) was the most significant risk factor associated with cataract, pulmonary impairment, osteoarticular complications and hypothyroidism. Chronic graft-versus-host disease was associated with higher incidence of pulmonary dysfunction. The number of complications per patient increased with time. Half of the patients had psychological disturbance, 13 signs of depression and 16 a history of eating behavior disorders; 54% of patients with one or more long-term complications had psychological problems. Sixty-nine patients had learning difficulties and 36 achieved normal scholarship. With increased follow-up, development of late effects and of psycho-social disturbance are of major concern. While the use of single-dose TBI has now been abandoned, other risk factors are still of concern in the early 2000s.

  1. Splenectomy for hematologic disease. The UCLA experience with 306 patients.

    PubMed

    Musser, G; Lazar, G; Hocking, W; Busuttil, R W

    1984-07-01

    Between 1956 and 1981, 306 splenectomies for hematologic diseases were performed at the UCLA Medical Center. Of these operations, more than 75% were performed for therapeutic reasons to control anemia, thrombocytopenia, neutropenia, or painful symptoms of splenomegaly. Of the 65 patients who had idiopathic thrombocytopenic purpura, 77% showed an excellent response, and of the 39 patients who had hereditary spherocytosis, 90% responded. Other diseases with predictably good response rates were autoimmune hemolytic anemias, Felty's syndrome, and hairy cell leukemia. Forty patients with Hodgkin's disease had splenectomies for diagnostic purposes the last 10 years. The overall morbidity and mortality were 24% and 6%, respectively, the most common complications being pneumonia, wound infections, and local postoperative bleeding, and the most common cause of death being sepsis. The review supports the thesis that in carefully selected patients, therapeutic splenectomy can have desirable palliative effects and that diagnostic splenectomy has a sufficiently low risk to warrant its consideration in patients with Hodgkin's disease.

  2. Perceptions, attitudes, and experiences of hematology/oncology fellows toward incorporating geriatrics in their training.

    PubMed

    Maggiore, Ronald J; Gorawara-Bhat, Rita; Levine, Stacie K; Dale, William

    2014-01-01

    The aging of the U.S. population continues to highlight emerging issues in providing care generally for older adults and specifically for older adults with cancer. The majority of patients with cancer in the U.S. are currently 65 years of age or older; therefore, training and research in geriatrics and geriatric oncology are viewed to be integral in meeting the needs of this vulnerable population. Yet, the ways to develop and integrate best geriatrics training within the context of hematology/oncology fellowship remain unclear. Toward this end, the current study seeks to evaluate the prior and current geriatric experiences and perspectives of hematology/oncology fellows. To gain insight into these experiences, focus groups of hematology/oncology fellows were conducted. Emergent themes included: 1) perceived lack of formal geriatric oncology didactics among fellows; 2) a considerable amount of variability exists in pre-fellowship geriatric experiences; 3) shared desire to participate in a geriatric oncology-based clinic; 4) differences across training levels in confidence in managing older adults with cancer; and 5) identification of specific criteria on how best to approach older adults with cancer in a particular clinical scenario. The present findings will help guide future studies in evaluating geriatrics among hematology/oncology fellows across institutions. They will also have implications in the development of geriatrics curricula and competencies specific to hematology/oncology training.

  3. The kinetics of hematopoietic niche cytokines and their influence on mobilization efficacy and timing in patients with hematological malignancies.

    PubMed

    Szmigielska-Kaplon, Anna; Krawczynska, Anna; Czemerska, Magdalena; Pluta, Agnieszka; Cebula-Obrzut, Barbara; Robak, Marta; Grzybowska-Izydorczyk, Olga; Szmigielska, Katarzyna; Robak, Tadeusz; Wierzbowska, Agnieszka

    2015-08-01

    The bone marrow niche functions are modulated by complicated cytokines network. The aim of our study was to evaluate the levels of VCAM-1, VEGF, MMP-9 and SDF during mobilization of CD34+ cells in patients with hematological malignancies. Thirty four patients were enrolled to the study (19F, 15 M) at median age of 57 years. The group consisted of patients with multiple myeloma (26) and lymphoma (8). The mobilization procedures comprised chemotherapy and then G-CSF. Blood samples were collected before chemotherapy (N = 34) and on the day of the first apheresis (N = 26). Cytokines were evaluated with ELISA assay. We observed significant increase in VCAM-1 levels during mobilization. On contrary, VEGF and SDF levels decreased during mobilization procedure. The levels of MMP-9 were stable during mobilization. We divided patients according to baseline cytokines levels below and above median into "low" and "high" expressors. The group of VEGF "low" expressors had longer median time of G-CSF treatment before first apheresis than 'high' expressors. Baseline VEGF levels correlated adversely with duration of G-CSF treatment before first apheresis. Patients were also divided according to median cytokines levels at apheresis into "low" and "high" expressors. "High" VCAM-1 expressors had higher CD34+in peripheral blood as well as higher CD34+numbers collected during first apheresis than "low" expressors. In conclusion, the levels of niche cytokines change significantly during mobilization in patients with hematopoietic malignancies. Baseline VEGF can influence timing of mobilization. Higher VCAM-1 corresponds with higher mobilization efficacy.

  4. Overlapping SETBP1 gain-of-function mutations in Schinzel-Giedion syndrome and hematologic malignancies.

    PubMed

    Acuna-Hidalgo, Rocio; Deriziotis, Pelagia; Steehouwer, Marloes; Gilissen, Christian; Graham, Sarah A; van Dam, Sipko; Hoover-Fong, Julie; Telegrafi, Aida B; Destree, Anne; Smigiel, Robert; Lambie, Lindsday A; Kayserili, Hülya; Altunoglu, Umut; Lapi, Elisabetta; Uzielli, Maria Luisa; Aracena, Mariana; Nur, Banu G; Mihci, Ercan; Moreira, Lilia M A; Borges Ferreira, Viviane; Horovitz, Dafne D G; da Rocha, Katia M; Jezela-Stanek, Aleksandra; Brooks, Alice S; Reutter, Heiko; Cohen, Julie S; Fatemi, Ali; Smitka, Martin; Grebe, Theresa A; Di Donato, Nataliya; Deshpande, Charu; Vandersteen, Anthony; Marques Lourenço, Charles; Dufke, Andreas; Rossier, Eva; Andre, Gwenaelle; Baumer, Alessandra; Spencer, Careni; McGaughran, Julie; Franke, Lude; Veltman, Joris A; De Vries, Bert B A; Schinzel, Albert; Fisher, Simon E; Hoischen, Alexander; van Bon, Bregje W

    2017-03-01

    Schinzel-Giedion syndrome (SGS) is a rare developmental disorder characterized by multiple malformations, severe neurological alterations and increased risk of malignancy. SGS is caused by de novo germline mutations clustering to a 12bp hotspot in exon 4 of SETBP1. Mutations in this hotspot disrupt a degron, a signal for the regulation of protein degradation, and lead to the accumulation of SETBP1 protein. Overlapping SETBP1 hotspot mutations have been observed recurrently as somatic events in leukemia. We collected clinical information of 47 SGS patients (including 26 novel cases) with germline SETBP1 mutations and of four individuals with a milder phenotype caused by de novo germline mutations adjacent to the SETBP1 hotspot. Different mutations within and around the SETBP1 hotspot have varying effects on SETBP1 stability and protein levels in vitro and in in silico modeling. Substitutions in SETBP1 residue I871 result in a weak increase in protein levels and mutations affecting this residue are significantly more frequent in SGS than in leukemia. On the other hand, substitutions in residue D868 lead to the largest increase in protein levels. Individuals with germline mutations affecting D868 have enhanced cell proliferation in vitro and higher incidence of cancer compared to patients with other germline SETBP1 mutations. Our findings substantiate that, despite their overlap, somatic SETBP1 mutations driving malignancy are more disruptive to the degron than germline SETBP1 mutations causing SGS. Additionally, this suggests that the functional threshold for the development of cancer driven by the disruption of the SETBP1 degron is higher than for the alteration in prenatal development in SGS. Drawing on previous studies of somatic SETBP1 mutations in leukemia, our results reveal a genotype-phenotype correlation in germline SETBP1 mutations spanning a molecular, cellular and clinical phenotype.

  5. Identification of Novel HLA-A*24:02-Restricted Epitope Derived from a Homeobox Protein Expressed in Hematological Malignancies

    PubMed Central

    Matsushita, Maiko; Otsuka, Yohei; Tsutsumida, Naoya; Tanaka, Chiaki; Uchiumi, Akane; Ozawa, Koji; Suzuki, Takuma; Ichikawa, Daiju; Aburatani, Hiroyuki; Okamoto, Shinichiro; Kawakami, Yutaka; Hattori, Yutaka

    2016-01-01

    The homeobox protein, PEPP2 (RHOXF2), has been suggested as a cancer/testis (CT) antigen based on its expression pattern. However, the peptide epitope of PEPP2 that is recognized by cytotoxic T cells (CTLs) is unknown. In this study, we revealed that PEPP2 gene was highly expressed in myeloid leukemia cells and some other hematological malignancies. This gene was also expressed in leukemic stem-like cells. We next identified the first reported epitope peptide (PEPP2271-279). The CTLs induced by PEPP2271-279 recognized PEPP2-positive target cells in an HLA-A*24:02-restricted manner. We also found that a demethylating agent, 5-aza-2’-deoxycytidine, could enhance PEPP2 expression in leukemia cells but not in blood mononuclear cells from healthy donors. The cytotoxic activity of anti-PEPP2 CTL against leukemic cells treated with 5-aza-2’-deoxycytidine was higher than that directed against untreated cells. These results suggest a clinical rationale that combined treatment with this novel antigen-specific immunotherapy together with demethylating agents might be effective in therapy-resistant myeloid leukemia patients. PMID:26784514

  6. A Pyrazolo[3,4-d]pyrimidine Compound Reduces Cell Viability and Induces Apoptosis in Different Hematological Malignancies

    PubMed Central

    Laurenzana, Ilaria; Caivano, Antonella; La Rocca, Francesco; Trino, Stefania; De Luca, Luciana; D’Alessio, Francesca; Schenone, Silvia; Falco, Geppino; Botta, Maurizio; Del Vecchio, Luigi; Musto, Pellegrino

    2016-01-01

    Molecular targeted therapies are based upon drugs acting on tumors by interfering with specific targets involved in growth and spread of cancer. Many targeted therapies were approved by Food and Drug Administration as standard treatment, others were introduced into preclinical or clinical studies on hematological malignancies (HMs). The development of drug-resistance in some HMs and the lack of effective treatments in other ones emphasized the need for searching new molecular targets and therapeutic agents. The aim of this study was to evaluate the effects of 4c pyrazolo[3,4-d]pyrimidine compound, a Src inhibitor, on lymphoid and myeloid neoplasms. Here, we demonstrated its ability to reduce cell viability, induce apoptosis and cell cycle arrest in lymphoid cell lines such as Jurkat, SKMM1, Derl-2/7, and myeloid cell lines, such as Jurl-MK1. Moreover, we reported a high expression of a Src kinase, Fyn, in these cell lines compared to healthy subjects. This study was a starting point to investigate 4c pyrazolo[3,4-d]pyrimidine compound as a drug for HMs and Src kinases as its potential molecular targets. PMID:27872592

  7. American Society of Hematology

    MedlinePlus

    ... Meeting on Hematologic Malignancies September 8-9, 2017, Chicago, IL Join us in Chicago and gain knowledge that can help you make ... Meeting on Hematologic Malignancies September 8-9, 2017, Chicago, Illinois View all meetings May 1, 2017 Applications ...

  8. Recommendations for Risk Categorization and Prophylaxis of Invasive Fungal Diseases in Hematological Malignancies: A Critical Review of Evidence and Expert Opinion (TEO-4)

    PubMed Central

    Boğa, Can; Bolaman, Zahit; Çağırgan, Seçkin; Karadoğan, İhsan; Özcan, Mehmet Ali; Özkalemkaş, Fahir; Saba, Rabin; Sönmez, Mehmet; Şenol, Esin; Akan, Hamdi; Akova, Murat

    2015-01-01

    This is the last of a series of articles on invasive fungal infections prepared by opinion leaders in Turkey. The aim of these articles is to guide clinicians in managing invasive fungal diseases in hematological malignancies and stem cell transplantation based on the available best evidence in this field. The previous articles summarized the diagnosis and treatment of invasive fungal disease and this article aims to explain the risk categorization and guide the antifungal prophylaxis in invasive fungal disease. PMID:26316478

  9. Dendritic cell count in the graft predicts relapse in patients with hematologic malignancies undergoing an HLA-matched related allogeneic peripheral blood stem cell transplant.

    PubMed

    Rajasekar, Reena; Lakshmi, Kavitha M; George, Biju; Viswabandya, Auro; Thirugnanam, Rajasekar; Abraham, Aby; Chandy, Mammen; Srivastava, Alok; Mathews, Vikram

    2010-06-01

    We investigated the impact of the number of infused and reconstituted immunocompetent cells including dendritic cells (DCs) on clinical outcome of patients with hematologic malignancies undergoing an allogeneic peripheral blood stem cell transplantation. Sixty-nine consecutive patients with hematologic malignancies were included in the analysis. The median age of the cohort was 32 years (range: 2-62 years) and there were 39 (57%) males. Twenty-one (30%) patients relapsed with a cumulative incidence of 44 % +/- 14% at a median follow up of 28 months. On a multivariate analysis, a high plasmacytoid dendritic cell (PC) content in the graft was associated with higher risk of relapse. The patients were further categorized based on the median PC counts in the graft as high (> or =2.3 x 10(6)/kg) and low (<2.3 x 10(6)/kg) groups. The baseline characteristics of these 2 groups were comparable. The group that had a high PC content in the graft had significantly higher risk of relapse and lower overall survival (OS) and event-free survival (EFS). Our data suggests that PC content in the graft predicts clinical outcomes such as relapse and survival in patients with hematologic malignancies undergoing an allogeneic HLA matched related peripheral blood stem cell transplantation. There is potential for pretransplant manipulation of this cellular subset in the graft.

  10. Therapeutic Challenges of Hepatic Mucormycosis in Hematologic Malignancy: A Case Report and Review of the Literature

    PubMed Central

    Bernardo, Raffaele M.; Gurung, Ananta; Jain, Dhanpat; Malinis, Maricar F.

    2016-01-01

    Patient: Female, 58 Final Diagnosis: Hepatic mucormycosis Symptoms: Abdominal pain • fever Medication: Amphotericin • posaconazole Clinical Procedure: IR-guided aspiration Specialty: Infectious Diseases Objective: Rare disease Background: The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy-and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. Case Report: We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. Conclusions: Among patient with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy. PMID:27406045

  11. Therapeutic Challenges of Hepatic Mucormycosis in Hematologic Malignancy: A Case Report and Review of the Literature.

    PubMed

    Bernardo, Raffaele M; Gurung, Ananta; Jain, Dhanpat; Malinis, Maricar F

    2016-07-13

    BACKGROUND The clinical presentation of mucormycosis can vary widely based on various host factors. Among malignancy- and bone marrow transplant-associated infections, the lungs are the most common site of infection. Involvement of the gastrointestinal tract is less frequently encountered. The clinical presentation is often nonspecific, and cultures typically yield no growth, making the diagnosis challenging. CASE REPORT We present a case of isolated hepatic mucormycosis in the setting of neutropenic fever and abdominal pain following induction chemotherapy for the treatment of acute myeloid leukemia. The patient was treated with combination antifungal therapy with amphotericin and posaconazole without surgical resection, given the presence of multiple liver lesions. After a prolonged course of dual antifungal therapy, the size of her liver lesions improved. Unfortunately, her lymphoproliferative disorder proved fatal, following approximately 13 months of antifungal therapy. CONCLUSIONS Among patients with mucormycosis, mortality remains high, especially in the setting of gastrointestinal involvement. Although surgical resection along with dual antifungal therapy can improve outcomes, the high mortality rate necessitates further investigation into improved diagnostic and treatment strategies including optimal antifungal therapy.

  12. Evolved Cellular Mechanisms to Respond to Genotoxic Insults: Implications for Radiation-Induced Hematologic Malignancies

    PubMed Central

    Fleenor, Courtney J.; Higa, Kelly; Weil, Michael M.; DeGregori, James

    2015-01-01

    Human exposure to ionizing radiation is highly associated with adverse health effects, including reduced hematopoietic cell function and increased risk of carcinogenesis. The hematopoietic deficits manifest across blood cell types and persist for years after radiation exposure, suggesting a long-lived and multi-potent cellular reservoir for radiation-induced effects. As such, research has focused on identifying both the immediate and latent hematopoietic stem cell responses to radiation exposure. Radiation-associated effects on hematopoietic function and malignancy development have generally been attributed to the direct induction of mutations resulting from radiation-induced DNA damage. Other studies have illuminated the role of cellular programs that both limit and enhance radiation-induced tissue phenotypes and carcinogenesis. In this review, distinct but collaborative cellular responses to genotoxic insults are highlighted, with an emphasis on how these programmed responses impact hematopoietic cellular fitness and competition. These radiation-induced cellular programs include apoptosis, senescence and impaired self-renewal within the hematopoietic stem cell (HSC) pool. In the context of sporadic DNA damage to a cell, these cellular responses act in concert to restore tissue function and prevent selection for adaptive oncogenic mutations. But in the contexts of whole-tissue exposure or whole-body exposure to genotoxins, such as radiotherapy or chemotherapy, we propose that these programs can contribute to long-lasting tissue impairment and increased carcinogenesis. PMID:26414506

  13. Bcl-2-family proteins and hematologic malignancies: history and future prospects.

    PubMed

    Reed, John C

    2008-04-01

    BCL-2 was the first antideath gene discovered, a milestone that effectively launched a new era in cell death research. Since its discovery more than 2 decades ago, multiple members of the human Bcl-2 family of apoptosis-regulating proteins have been identified, including 6 antiapoptotic proteins, 3 structurally similar proapoptotic proteins, and several structurally diverse proapoptotic interacting proteins that operate as upstream agonists or antagonists. Bcl-2-family proteins regulate all major types of cell death, including apoptosis, necrosis, and autophagy. As such, they operate as nodal points at the convergence of multiple pathways with broad relevance to biology and medicine. Bcl-2 derives its name from its original discovery in the context of B-cell lymphomas, where chromosomal translocations commonly activate the BCL-2 protooncogene, endowing B cells with a selective survival advantage that promotes their neoplastic expansion. The concept that defective programmed cell death contributes to malignancy was established by studies of Bcl-2, representing a major step forward in current understanding of tumorigenesis. Experimental therapies targeting Bcl-2 family mRNAs or proteins are currently in clinical testing, raising hopes that a new class of anticancer drugs may be near.

  14. Phase I-II study of high-dose busulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation for hematological malignancies: toxicities and hematopoietic recovery.

    PubMed

    Ballester, O F; Agaliotis, D P; Hiemenz, J W; Janssen, W E; Fields, K K; Zorksy, P E; Goldstein, S C; Perkins, J B; Elfenbein, G J

    1996-07-01

    In a phase I-II study, we evaluated toxicities, tolerability, pace of engraftment, and tumor responses to high-dose bulsulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with hematological malignancies. We treated 51 patients with various hematological malignancies involving the bone marrow with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of autologous peripheral blood stem cells. Stem cells were previously collected during hematopoietic recovery after cyclophosphamide (100 mg/kg) and etoposide (600 mg/m2) followed by G-CSF (5 micrograms/kg/day). Neutrophil recovery (>0.5 x 10(9)/I) was rapid in the majority of patients (median 10 days after transplant, range 7-91 days), resulting in a low number of days with severe neutropenia (median 7 days, range 5-85 days) and with fever (median 5 days, range 1-13 days). Platelet recovery, however, was delayed in 60% of patients. There was one acute transplant-related death (2%). Four patients died of late, presumed infections, pulmonary complications (interstitial pneumonia). Tumor responses were documented in a significant proportion of these patients with high-risk hematological malignancies. We conclude that peripheral blood stem cell transplantation results in rapid recovery of neutrophils but variable recovery of platelets after high-dose busulfan and cyclophosphamide, when stem cells are harvested following priming with cyclophosphamide/etoposide and G-CSF. The regimen is well-tolerated with limited non-hematological toxicities and transplant-related mortality. While significant tumor responses were documented in this trial, the ultimate efficacy of the regimen needs to be further defined.

  15. Polymorphism of CD44 influences the efficacy of CD34(+) cells mobilization in patients with hematological malignancies.

    PubMed

    Szmigielska-Kaplon, Anna; Szemraj, Janusz; Hamara, Katarzyna; Robak, Marta; Wolska, Anna; Pluta, Agnieszka; Czemerska, Magdalena; Krawczynska, Anna; Jamroziak, Krzysztof; Szmigielska, Katarzyna; Robak, Tadeusz; Wierzbowska, Agnieszka

    2014-07-01

    In the last decade, peripheral blood was the main source of hematopoietic stem cells (HSC) for autologous and allogeneic transplantation. The exact mechanisms of HSC mobilization are still not clear and the efficacy of the procedure is hardly predictable. Ligand-receptor interactions of adhesion molecules, such as SDF1/CXCR4, VLA4/VCAM-1, or CD44/osteopontin, play an important role in homing of HSC in the hematopoietic niche. There is some evidence that disruption of the ligand-receptor complex leads to the egress of HSCs to the peripheral blood. The aim of the present study was the evaluation of constitutive polymorphism of genes encoding cytokines and receptors present in the HSC niche and their impact on the efficacy of mobilization of HSCs in patients with hematological malignancies. We enrolled 110 patients (60 females and 50 males) in the study. The median age of the patients was 55 (range, 22 to 69) years. The group consisted of patients with multiple myeloma (n = 74), non-Hodgkin lymphoma (n = 19), Hodgkin lymphoma (n = 15), or acute myeloid leukemia (n = 2). The mobilization procedures comprised chemotherapy and subsequent granulocyte-colony stimulating factor (G-CSF) at a dose of 10 μg/kg daily. The poor mobilizers group was defined according to Italian National Bone Marrow Transplant Registry criteria: patients with peak CD34(+) in the peripheral blood < 20/μL or total yield < 2 × 10(6) CD34(+) cells/kg body weight in maximum 3 aphereses. Genotyping was performed using standard PCR-based assays. The group of patients (N = 108) who achieved minimal threshold for collections (CD34(+) at least 10/μL) proceeded to apheresis. The median total yield of CD34(+) in this group was 5.6 × 10(6) cells/kg body weight, whereas the median number of cells collected during the first apheresis was 3.3 × 10(6) cells/kg body weight. Median number of days of G-CSF treatment before first apheresis was 10. Fifteen patients fulfilled the criteria for poor mobilizer. The

  16. Targeting STAT5 in Hematological Malignancies through Inhibition of the Bromodomain and Extra-Terminal (BET) Bromodomain Protein BRD2

    PubMed Central

    Liu, Suhu; Walker, Sarah R.; Nelson, Erik A.; Cerulli, Robert; Xiang, Michael; Toniolo, Patricia A.; Qi, Jun; Stone, Richard M.; Wadleigh, Martha; Bradner, James E.; Frank, David A.

    2014-01-01

    The transcription factor signal transducer and activator of transcription 5 (STAT5) is constitutively activated in a wide range of leukemias and lymphomas, and drives the expression of genes necessary for proliferation, survival, and self-renewal. Thus, targeting STAT5 is an appealing therapeutic strategy for hematological malignancies. Given the importance of bromodomain-containing proteins in transcriptional regulation, we considered the hypothesis that a pharmacological bromodomain inhibitor could inhibit STAT5-dependent gene expression. We found that the small molecule bromodomain and extra-terminal (BET) bromodomain inhibitor JQ1 decreases STAT5-dependent (but not STAT3-dependent) transcription of both heterologous reporter genes and endogenous STAT5 target genes. JQ1 reduces STAT5 function in leukemia and lymphoma cells with constitutive STAT5 activation, or inducibly activated by cytokine stimulation. Among the BET bromodomain sub-family of proteins, it appears that BRD2 is the critical mediator for STAT5 activity. In experimental models of acute T cell lymphoblastic leukemias, where activated STAT5 contributes to leukemia cell survival, Brd2 knock-down or JQ1 treatment shows strong synergy with tyrosine kinase inhibitors in inducing leukemia cells apoptosis. By contrast, mononuclear cells isolated form umbilical cord blood, which is enriched in normal hematopoietic precursor cells, were unaffected by these combinations. These findings indicate a unique functional association between BRD2 and STAT5, and suggest that combinations of JQ1 and tyrosine kinase inhibitors may be an important rational strategy for treating leukemias and lymphomas driven by constitutive STAT5 activation. PMID:24435449

  17. Prospective Study of Single vs. Two Unit Umbilical Cord Blood Transplantation Following Reduced Intensity Conditioning in Adults with Hematologic Malignancies

    PubMed Central

    Kindwall-Keller, Tamila L.; Hegerfeldt, Yael; Meyerson, Howard J.; Margevicius, Seunghee; Fu, Pingfu; van Heeckeren, Willem; Lazarus, Hillard M.; Cooper, Brenda W.; Gerson, Stanton L.; Barr, Paul; Tse, William W.; Curtis, Christine; Fanning, Laura R.; Creger, Richard J.; Carlson-Barko, Joanne M.; Laughlin, Mary J.

    2011-01-01

    As the threshold nucleated cell dose for single unit umbilical cord blood (UCB) in adults has not to date been firmly established, we prospectively compared single vs. 2-unit UCB transplantation after reduced intensity conditioning (RIC) in adult patients with hematologic malignancies. Study design specified one UCB unit if the cryopreserved total nucleated cell (TNC) dose was ≥2.5×107/kg recipient weight, otherwise 2-units matched at minimum 4/6 HLA loci to the patient and 3/6 to each other were infused. Twenty-seven patients received 1 unit; 23 patients received 2 units. Median time to absolute neutrophil count (ANC) >500/μL was 24 days (95% CI 22–28 days), 25 days for 1-unit and 23 days for 2-units (p=0.99). At day 100, ANC >500/μL was 88.4% and 91.3% in the 1 and 2-unit groups (p=0.99), respectively. Three-year event free survival (EFS) was 28.6% and 39.1% in the 1 and 2-unit groups (p=0.71), respectively. Infusion of 2 units was associated with significantly lower relapse risk, 30.4% vs. 59.3% (p=0.045). Infused cell doses (TNC, CD3+, CD34+, CD56+CD3neg) did not impact engraftment, overall survival (OS), or EFS. Taken together, single unit UCB transplantation with threshold cell dose ≥2.5×107/kg recipient weight after RIC is a viable option for adults, although infusion of 2 units confers a lower relapse incidence. PMID:22002488

  18. ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody-Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies.

    PubMed

    Flynn, Michael J; Zammarchi, Francesca; Tyrer, Peter C; Akarca, Ayse U; Janghra, Narinder; Britten, Charles E; Havenith, Carin E G; Levy, Jean-Noel; Tiberghien, Arnaud; Masterson, Luke A; Barry, Conor; D'Hooge, Francois; Marafioti, Teresa; Parren, Paul W H I; Williams, David G; Howard, Philip W; van Berkel, Patrick H; Hartley, John A

    2016-11-01

    Despite the many advances in the treatment of hematologic malignancies over the past decade, outcomes in refractory lymphomas remain poor. One potential strategy in this patient population is the specific targeting of IL2R-α (CD25), which is overexpressed on many lymphoma and leukemic cells, using antibody-drug conjugates (ADC). ADCT-301 is an ADC composed of human IgG1 HuMax-TAC against CD25, stochastically conjugated through a dipeptide cleavable linker to a pyrrolobenzodiazepine (PBD) dimer warhead with a drug-antibody ratio (DAR) of 2.3. ADCT-301 binds human CD25 with picomolar affinity. ADCT-301 has highly potent and selective cytotoxicity against a panel of CD25-expressing human lymphoma cell lines. Once internalized, the released warhead binds in the DNA minor groove and exerts its potent cytotoxic action via the formation of DNA interstrand cross-links. A strong correlation between loss of viability and DNA cross-link formation is demonstrated. DNA damage persists, resulting in phosphorylation of histone H2AX, cell-cycle arrest in G2-M, and apoptosis. Bystander killing of CD25-negative cells by ADCT-301 is also observed. In vivo, a single dose of ADCT-301 results in dose-dependent and targeted antitumor activity against both subcutaneous and disseminated CD25-positive lymphoma models. In xenografts of Karpas 299, which expressed both CD25 and CD30, marked superiority over brentuximab vedotin (Adcetris) is observed. Dose-dependent increases in DNA cross-linking, γ-H2AX, and PBD payload staining were observed in tumors in vivo indicating a role as relevant pharmacodynamic assays. Together, these data support the clinical testing of this novel ADC in patients with CD25-expressing tumors. Mol Cancer Ther; 15(11); 2709-21. ©2016 AACR.

  19. Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies.

    PubMed

    Gaudio, Eugenio; Spizzo, Riccardo; Paduano, Francesco; Luo, Zhenghua; Efanov, Alexey; Palamarchuk, Alexey; Leber, Amanda S; Kaou, Mohamed; Zanesi, Nicola; Bottoni, Arianna; Costinean, Stefan; Rassenti, Laura Z; Nakamura, Tatsuya; Kipps, Thomas J; Aqeilan, Rami I; Pekarsky, Yuri; Trapasso, Francesco; Croce, Carlo M

    2012-01-05

    The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangement in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced IκBα phosphorylation and ubiquitination and subsequent activation of the NF-κB pathway. Our findings reveal functional cross-talk between Atm and Tcl1 and provide evidence for a novel pathway that could be targeted in leukemias and lymphomas.

  20. Tcl1 interacts with Atm and enhances NF-κB activation in hematologic malignancies

    PubMed Central

    Gaudio, Eugenio; Spizzo, Riccardo; Paduano, Francesco; Luo, Zhenghua; Efanov, Alexey; Palamarchuk, Alexey; Leber, Amanda S.; Kaou, Mohamed; Zanesi, Nicola; Bottoni, Arianna; Costinean, Stefan; Rassenti, Laura Z.; Nakamura, Tatsuya; Kipps, Thomas J.; Aqeilan, Rami I.; Pekarsky, Yuri; Trapasso, Francesco

    2012-01-01

    The T-cell leukemia/lymphoma 1 (TCL1) oncogene is a target of chromosomal translocations and inversions at 14q31.2, and its rearrangement in T cells causes T-cell prolymphocytic leukemias. TCL1 dysregulation in B cells is responsible for the development of an aggressive form of chronic lymphocytic leukemia (CLL), the most common human leukemia. We have investigated the mechanisms underlying the oncogenic functions of Tcl1 protein using a mass spectrometry approach and have identified Atm (ataxia-telangiectasia mutated) as a candidate Tcl1-interacting protein. The Tcl1-Atm complex formation was validated by coimmunoprecipitation experiments. Importantly, we show that the association of Atm with Tcl1 leads to enhanced IκBα phosphorylation and ubiquitination and subsequent activation of the NF-κB pathway. Our findings reveal functional cross-talk between Atm and Tcl1 and provide evidence for a novel pathway that could be targeted in leukemias and lymphomas. PMID:22065599

  1. Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy.

    PubMed

    Phillips, G L; Shepherd, J D; Barnett, M J; Lansdorp, P M; Klingemann, H G; Spinelli, J J; Nevill, T J; Chan, K W; Reece, D E

    1991-10-01

    Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year

  2. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia.

    PubMed

    Styczynski, J; Reusser, P; Einsele, H; de la Camara, R; Cordonnier, C; Ward, K N; Ljungman, P; Engelhard, D

    2009-05-01

    These guidelines on the management of HSV, VZV and EBV infection in patients with hematological malignancies and after SCT were prepared by the European Conference on Infections in Leukemia following a predefined methodology. A PubMed search was conducted using the appropriate key words to identify studies pertinent to management of HSV, VZV and EBV infections. References of relevant articles and abstracts from recent hematology and SCT scientific meetings were also reviewed. Prospective and retrospective studies identified from the data sources were evaluated, and all data deemed relevant were included in this analysis. The clinical and scientific background was described and discussed, and the quality of evidence and level of recommendation were graded according to the Centers for Disease Control criteria.

  3. 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.

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

    SciTech Connect

    Kim, Min Soo; Kim, Gyoung Mi; Choi, Yun-Jeong; Kim, Hye Joung; Kim, Yoo-Jin; Jin, Wook

    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 TrkA 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.

  5. Noninvasive early detection of anthracycline-induced cardiotoxicity in patients with hematologic malignancies using the phased tracking method.

    PubMed

    Saito, Yoshiko; Susukida, Ikuko; Uzuka, Yoshiro; Kanai, Hiroshi

    2016-09-01

    Anthracyclines are among the most effective and widely used anticancer drugs; however, their use is limited by serious cardiotoxicity. Early detection is necessary to prevent the high mortality rate associated with heart failure (HF). We evaluated cardiac function in 142 patients using conventional echocardiography and the phased tracking method (PTM), which was measured using the minute vibration and the rapid motion components, neither of which is recognized in standard M-mode nor in tissue Doppler imaging. For systolic function comparison, we compared left ventricular ejection fraction (LVEF) in conventional echocardiography with the average velocity of ventricular septum myocytes (Vave ) in the PTM. The Vave of 12 healthy volunteers was 1.5 (m/s)/m or more. At baseline of 99 patients, there was a positive correlation between LVEF and Vave in all patients. There were no significant differences in baseline cardiac function between patients with and without HF. There was a negative correlation between the cumulative anthracycline dose and LVEF or Vave among all patients. We determined that Vave 1.5 (m/s)/m was equivalent to LVEF 60%, 1.25 (m/s)/m to 55%, and 1.0 (m/s)/m to 50%. During the follow-up period, there was a pathological decrease in LVEF (<55%) and Vave (<1.25 m/s/m) in patients with HF; decreases in Vave were detected significantly earlier than those in LVEF (P < 0.001). When Vave declined to 1.5 (m/s)/m or less, careful continuous observation and cardiac examination was required. When Vave further declined to 1.0 (m/s)/m or lower, chemotherapy was postponed or discontinued; thus, serious drug-induced cardiomyopathy was avoided in patients who did not relapse. The PTM was superior to echocardiography for early, noninvasive detection and intermediate-term monitoring of left ventricle systolic function associated with anthracycline chemotherapy, among patients with hematologic malignancies. The PTM was an effective laboratory procedure to avoid the

  6. 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

  7. CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies?

    PubMed Central

    Pegram, Hollie J; Smith, Eric L; Rafq, Sarwish

    2016-01-01

    Chimeric antigen receptor (CAR) T-cell therapy has recently come into the spotlight due to impressive results in patients with B-cell acute lymphoblastic leukemia. By targeting CD19, a marker expressed most B-cell tumors, as well as normal B cells, CAR T-cell therapy has been investigated as a treatment strategy for B-cell leukemia and lymphoma. This review will discuss the successes of this therapy for the treatment of B-cell acute lymphoblastic leukemia and the challenges to this therapeutic strategy. We will also discuss application of CAR T-cell therapy to chronic lymphocytic leukemia and other B-cell malignancies including a follicular lymphoma, diffuse large B-cell lymphoma, as well as acute and plasma cell malignancies. PMID:26065479

  8. 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

  9. Evaluation of a PCR method to determine the clinical significance of blood cultures with Staphylococcus epidermidis in patients with hematological malignancies.

    PubMed

    Ahlstrand, Erik; Bäckman, Anders; Persson, Lennart; Mölling, Paula; Tidefelt, Ulf; Söderquist, Bo

    2014-06-01

    The aim was to investigate whether the detection and quantification of Staphylococcus epidermidis DNA in blood could distinguish S. epidermidis blood stream infections (BSIs) from blood culture contaminations in patients with hematological malignancies. The hld gene was chosen to identify S. epidermidis DNA and DNA in blood samples was detected by real-time PCR. Blood samples were obtained simultaneously with blood cultures positive for S. epidermidis (n = 30), during blood culture-negative episodes (n = 10) and episodes of bacteremia with other bacteria than S. epidermidis (n = 4) and from healthy blood donors (n = 10). In addition, DNA from S. epidermidis and a selection of other bacterial species were analyzed. Three different sets of criteria were used to classify episodes with positive blood cultures with S. epidermidis as BSIs or contaminations. All DNA preparations from S. epidermidis (n = 48) were hld-positive, but other bacterial species (n = 13) were negative. Sixteen (53%) of 30 blood samples from patients with blood cultures positive for S. epidermidis were hld-positive, but none of the controls. There was no clear association between a positive hld PCR and episodes interpreted as BSIs. In conclusion, hld PCR failed to distinguish S. epidermidis BSIs from blood culture contaminations in patients with hematological malignancies.

  10. Pharmacoutilization of epoetins in naïve patients with hematological malignancies in an unselected Italian population under clinical practice setting: a comparative analysis between originator and biosimilars

    PubMed Central

    Perrone, Valentina; Saragoni, Stefania; Buda, Stefano; Broccoli, Alessandro; Degli Esposti, Luca

    2016-01-01

    Aim The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in naïve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (ΔHb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean ± standard deviation (SD) age was 62.5±14.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8±11.8 years). The mean ± SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6±1.1 g/dL) compared to those who started with a reference product (10.1±2.1 g/dL). No significant differences in ΔHb were observed between biosimilar and originator groups during the followup period. The mean ± SD cost per patient was €667.98±573.93 and €340.85±235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion Our study showed that the use of

  11. Diagnosis and treatment of mucormycosis in patients with hematological malignancies: guidelines from the 3rd European Conference on Infections in Leukemia (ECIL 3).

    PubMed

    Skiada, Anna; Lanternier, Fanny; Groll, Andreas H; Pagano, Livio; Zimmerli, Stephan; Herbrecht, Raoul; Lortholary, Olivier; Petrikkos, George L

    2013-04-01

    Mucormycosis is an emerging cause of infectious morbidity and mortality in patients with hematologic malignancies. However, there are no recommendations to guide diagnosis and management. The European Conference on Infections in Leukemia assigned experts in hematology and infectious diseases to develop evidence-based recommendations for the diagnosis and treatment of mucormycosis. The guidelines were developed using the evidence criteria set forth by the American Infectious Diseases Society and the key recommendations are summarized here. In the absence of validated biomarkers, the diagnosis of mucormycosis relies on histology and/or detection of the organism by culture from involved sites with identification of the isolate at the species level (no grading). Antifungal chemotherapy, control of the underlying predisposing condition, and surgery are the cornerstones of management (level A II). Options for first-line chemotherapy of mucormycosis include liposomal amphotericin B and amphotericin B lipid complex (level B II). Posaconazole and combination therapy of liposomal amphotericin B or amphotericin B lipid complex with caspofungin are the options for second line-treatment (level B II). Surgery is recommended for rhinocerebral and skin and soft tissue disease (level A II). Reversal of underlying risk factors (diabetes control, reversal of neutropenia, discontinuation/taper of glucocorticosteroids, reduction of immunosuppressants, discontinuation of deferroxamine) is important in the treatment of mucormycosis (level A II). The duration of antifungal chemotherapy is not defined but guided by the resolution of all associated symptoms and findings (no grading). Maintenance therapy/secondary prophylaxis must be considered in persistently immunocompromised patients (no grading).

  12. PROPOFOL-FENTANYL VERSUS PROPOFOL ALONE FOR LUMBAR PUNCTURE SEDATION IN CHILDREN WITH ACUTE HEMATOLOGIC MALIGNANCIES: PROPOFOL DOSING AND ADVERSE EVENTS

    PubMed Central

    Hollman, Gregory A.; Schultz, Meredith M; Eickhoff, Jens C; Christenson, Devon K

    2011-01-01

    Objective We sought to determine whether the combination of propofol and fentanyl results in lower propofol doses and fewer adverse cardiopulmonary events than propofol and placebo for lumbar puncture (LP) in children with acute hematologic malignancies. Design Randomized, controlled, double blind, crossover study. Setting Pediatric Sedation Program Patients Children with acute leukemia or lymphoma receiving sedation for LP. Interventions Each patient received two sedations in random order, one with propofol/placebo and one with propofol/fentanyl. The study investigator and patient/parent were blinded to placebo or fentanyl. Data collected included patient age and diagnosis, propofol dose and adverse events. Adverse events included oxygen saturation < 94%, airway obstruction, apnea, hypotension and bradycardia (< 5% mean for age). Logistic regression analysis was utilized to assess probability of adverse events and the Wilcoxon Signed Rank and McNemar’s tests were used for paired comparisons. Measurements and Main Results Twenty-two patients were enrolled. Fourteen patients were male and 8 were female. Each patient was studied twice for a total of 44 sedations. The median age was 5.0 years (range 2.2–17.2 years). All procedures were successfully completed. The median total dose of propofol was 5.05 mg/kg (range 2.4–10.2 mg/kg) for propofol/placebo versus 3.00 mg/kg (range 1.4–10.5 mg/kg) for propofol/fentanyl (p < 0.001). Twelve adverse events occurred in 11 of 22 patients (50.0%) propofol/placebo compared to 6 of 22 (18.2%) propofol/fentanyl (p= 0.02). The most common adverse event was hypotension. Conclusions The combination of propofol and fentanyl versus propofol alone for LP sedation in children with acute hematologic malignancies resulted in lower propofol doses and fewer adverse events. PMID:18838923

  13. 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

  14. Clinical impact of absolute lymphocyte count on day 30 after unmanipulated haploidentical blood and marrow transplantation for pediatric patients with hematological malignancies.

    PubMed

    Chang, Ying-Jun; Zhao, Xiang-Yu; Huo, Ming-Rui; Xu, Lan-Ping; Liu, Dai-Hong; Liu, Kai-Yan; Huang, Xiao-Jun

    2011-02-01

    Currently, limited information is available regarding the effects of early lymphocyte recovery on transplant outcomes in pediatric patients with hematological malignancies after unmanipulated haploidentical transplantation. In this study, we evaluated the association of Day 30 absolute lymphocyte count (ALC-30) with transplant outcomes in 60 consecutive pediatric patients with hematological malignancies receiving T-cell-repleted transplantation from an haploidentical related donors. After median follow-up of 36 months (range, 1.4-75 months), higher relapse rate was observed in patients with an ALC-30 < 300 cells/μL compared to patients with an ALC-30 ≥ 300 cells/μL (35.5% vs. 13.8%, P = 0.049). More patients died of infections in those with an ALC-30 < 300 cells/μL compared with patients with an ALC-30 ≥ 300 cells/μL (25.8% vs. 3.4%, P = 0.015). The ALC-30 above the cutoff value 300 cells/μL was associated with improved overall-survival (HR 0.301, 95% CI 0.117-0.771; P = 0.012), leukemia free survival (HR 0.195, 95% CI 0.078-0.498; P=0.002), less relapse (HR 0.224 95% CI 0.070-0.717; P = 0.012), and less transplant- related mortality (HR=0.166; 95%CI 0.037-0.750; P = 0.020). Our results suggest that a higher ALC-30 ≥ 300 cells/μL) could be a useful and simple tool to predict pediatric patients with a superior outcome after unmanipulated haploidentical transplantation.

  15. Molecular epidemiology of human respiratory syncytial virus subgroups A and B identified in adults with hematological malignancy attending an Irish hospital between 2004 and 2009.

    PubMed

    Salter, Aisling; Laoi, Bairbre Ni; Crowley, Brendan

    2011-02-01

    Human respiratory syncytial virus (HRSV) is an important cause of respiratory infection in patients with hematological malignancy, particularly hematopoietic stem cell transplant recipients. This study investigated the genetic variability of the attachment (G) protein gene among HRSV isolates collected from adult patients with hematological malignancy. Between December 2004 and March 2009, 60 samples collected from 58 adults attending an Irish hospital were positive for HRSV by direct immunofluorescence. Nucleotide sequence analysis of the G gene showed a slightly higher frequency of HRSV subgroup A (52%) than HRSV subgroup B (48%). Genetic variability was higher among subgroup A viruses (up to 13% at nucleotide level) than among subgroup B viruses (up to 4%). Phylogenetic analysis revealed two genotypes of HRSV subgroup A, GA2 and GA5, which cocirculated between 2004/2005 and 2007/2008, although GA2 alone was identified in season 2008/2009. Genotype BA was the only genotype of HRSV subgroup B identified. Genotype-specific amino acid substitutions were identified, with two and seven changes for GA2 and GA5, respectively. Furthermore, one to four potential N-glycosylation sites were found among HRSV subgroup A isolates while two to three were identified in HRSV B isolates. Predicted O-glycosylation sites included 25-34 and 40-43 in HRSV subgroups A and B, respectively. The average synonymous mutation-to-non-synonymous mutation ratios (dS/dN) implied neutral selection pressure on both HRSV subgroup isolates. This study provides data for the first time on the molecular epidemiology of HRSV isolates over five successive epidemic seasons among patients attending an Irish hospital.

  16. 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.

  17. 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

  18. Effects of teicoplanin and those of vancomycin in initial empirical antibiotic regimen for febrile, neutropenic patients with hematologic malignancies. Gimema Infection Program.

    PubMed

    Menichetti, F; Martino, P; Bucaneve, G; Gentile, G; D'Antonio, D; Liso, V; Ricci, P; Nosari, A M; Buelli, M; Carotenuto, M

    1994-09-01

    The efficacy and toxicity of teicoplanin and vancomycin in the initial empirical antibiotic regimen in febrile, neutropenic patients with hematologic malignancies were compared in a prospective, randomized, unblinded, multicenter trial in the setting of 29 hematologic units in tertiary-care or university hospitals. A total of 635 consecutive febrile patients with hematologic malignancies and chemotherapy-induced neutropenia were randomly assigned to receive intravenously amikacin plus ceftazidime plus either teicoplanin at 6 mg/kg of body weight once daily or vancomycin at 1 g twice daily. An efficacy analysis was done for 527 evaluable patients: 275 treated with teicoplanin and 252 treated with vancomycin. Overall, successful outcomes were recorded for 78% of patients who received teicoplanin and 75% of those who were randomized to vancomycin (difference, 3%; 95% confidence interval [CI], -10 to 4%; P = 0.33). A total of 102 patients presented with primary, single-agent, gram-positive bacteremia. Coagulase-negative staphylococci accounted for 42%, Staphylococcus aureus accounted for 27%, and streptococci accounted for 21% of all gram-positive blood isolates. The overall responses to therapy of gram-positive bacteremias were 92 and 87% for teicoplanin and vancomycin, respectively (difference, 5%; CI, -17 to 6%; P = 0.22). Side effects, mainly represented by skin rash, occurred in 3.2 and 8% of teicoplanin- and vancomycin-treated patients, respectively (difference, -4.8%; CI, 0.7 to 8%; P = 0.03); the rate of nephrotoxicity was 1.4 and 0.8% for the teicoplanin and vancomycin groups, respectively (difference, 0.6%; CI, -2 to 1%; P = 0.68). Further infections were caused by gram-positive organisms in two patients (0.7%) treated with teicoplanin and one patient (0.4%) who received vancomycin (difference, 0.3%; CI, -0.9 to 1.0%; P = 0.53). Overall mortalities were 8.5 and 11% for teicoplanin- and vancomycin-treated patients, respectively (difference, -2.5%; CI, - 2 to 7

  19. 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.

  20. Phenotype diversity in type 1 Gaucher disease: discovering the genetic basis of Gaucher disease/hematologic malignancy phenotype by individual genome analysis.

    PubMed

    Lo, Sarah M; Choi, Murim; Liu, Jun; Jain, Dhanpat; Boot, Rolf G; Kallemeijn, Wouter W; Aerts, Johannes M F G; Pashankar, Farzana; Kupfer, Gary M; Mane, Shrikant; Lifton, Richard P; Mistry, Pramod K

    2012-05-17

    Gaucher disease (GD), an inherited macrophage glycosphingolipidosis, manifests with an extraordinary variety of phenotypes that show imperfect correlation with mutations in the GBA gene. In addition to the classic manifestations, patients suffer from increased susceptibility to hematologic and nonhematologic malignancies. The mechanism(s) underlying malignancy in GD is not known, but is postulated to be secondary to macrophage dysfunction and immune dysregulation arising from lysosomal accumulation of glucocerebroside. However, there is weak correlation between GD/cancer phenotype and the systemic burden of glucocerebroside-laden macrophages. Therefore, we hypothesized that genetic modifier(s) may underlie the GD/cancer phenotype. In the present study, the genetic basis of GD/T-cell acute lymphoblastic lymphoma in 2 affected siblings was deciphered through genomic analysis. GBA gene sequencing revealed homozygosity for a novel mutation, D137N. Whole-exome capture and massively parallel sequencing combined with homozygosity mapping identified a homozygous novel mutation in the MSH6 gene that leads to constitutional mismatch repair deficiency syndrome and increased cancer risk. Enzyme studies demonstrated that the D137N mutation in GBA is a pathogenic mutation, and immunohistochemistry confirmed the absence of the MSH6 protein. Therefore, precise phenotype annotation followed by individual genome analysis has the potential to identify genetic modifiers of GD, facilitate personalized management, and provide novel insights into disease pathophysiology.

  1. Clinical experiences with microwave thermal ablation of lung malignancies.

    PubMed

    Sidoff, Luby; Dupuy, Damian E

    2017-02-01

    Approximately 30% of early stage lung cancer patients are not surgical candidates due to medical co-morbidities, poor cardiopulmonary function and advanced age. These patients are traditionally offered chemotherapy and radiation, which have shown relatively modest improvements in mortality. For over a decade, percutaneous image-guided ablation has emerged as a safe, cost-effective, minimally invasive treatment alternative for patients who would otherwise not qualify for surgery. Although radiofrequency ablation (RFA) is currently the most extensively studied and widely utilised technique in the treatment of lung malignancies, there is a growing body of evidence that microwave ablation (MWA) has several unique benefits over RFA and cryoablation in the lung. This article reviews our institution's clinical experiences in the treatment of lung malignancies with MWA including patient selection, procedural technique, imaging follow-up, treatment outcomes and comparison of ablation techniques.

  2. Detection of antibodies to Candida albicans germ tubes for diagnosis and therapeutic monitoring of invasive candidiasis in patients with hematologic malignancies.

    PubMed Central

    García-Ruiz, J C; del Carmen Arilla, M; Regúlez, P; Quindós, G; Alvarez, A; Pontón, J

    1997-01-01

    We prospectively investigated the ability of detection of antibodies to Candida albicans germ tubes (CAGT) to diagnose invasive candidiasis in 95 consecutive admissions of 73 patients with hematologic disorders undergoing intensive chemotherapy. The episodes were divided into three groups according to clinical and microbiological diagnosis. Group 1 comprised eight admissions of eight patients with invasive candidiasis. Group 2 comprised 42 admissions of 34 patients without evidence of invasive candidiasis. Group 3 comprised the remaining 45 admissions of 37 patients with febrile episodes which were not diagnosed by microbiological culture. Antibodies to CAGT were detected in 87.5% of group 1 patients. Detection of antibodies to CAGT in patients with Candida fungemia was delayed somewhat relative to the time the blood culture was positive, but antibodies to CAGT were detected earlier than a diagnosis was made in patients with deep-tissue candidiasis. Sera from 2 admissions in group 2 and 12 admissions in group 3 revealed antibodies to CAGT. At a titer of > or = 1:20, detection of antibodies to CAGT had a sensitivity of 87.5%, specificity of 95.2%, positive predictive value of 77.8%, and negative predictive value of 97.6%. Antibodies to CAGT were usually detected before beginning of empiric antifungal therapy. Titers of antibodies to CAGT were maintained in most patients who died but declined and eventually disappeared in the patients who survived. Since antibodies to CAGT were detected in all patients with tissue-proven invasive candidiasis but negative by blood culture, detection of antibodies to CAGT complemented blood cultures for diagnosis and therapeutic monitoring of patients with hematologic malignancies and invasive candidiasis. PMID:9399535

  3. Reduced-intensity conditioning followed by related allografts in hematologic malignancies: long-term outcomes most successful in indolent and aggressive non-Hodgkin lymphomas.

    PubMed

    Warlick, Erica D; Tomblyn, Marcie; Cao, Qing; Defor, Todd; Blazar, Bruce R; Macmillan, Margaret; Verneris, Michael; Wagner, John; Dusenbery, Kathryn; Aurora, Mukta; Bachanova, Veronika; Brunstein, Claudio; Burns, Linda; Cooley, Sarah; Kaufman, Dan; Majhail, Navneet S; McClune, Brian; McGlave, Philip; Miller, Jeffrey; Oran, Betul; Slungaard, Arne; Vercellotti, Gregory; Weisdorf, Daniel J

    2011-07-01

    Reduced-intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients (median age, 57 years; range, 23-70 years) with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total-body irradiation (200 cGy) with or without antithymocyte globulin followed by related donor allogeneic HCT at the University of Minnesota between 2002 and 2008. The cohort included 45 patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 with aggressive non-Hodgkin lymphoma (NHL), 8 with indolent NHL, 10 with Hodgkin lymphoma (HL), 10 with myeloma, and 23 with acute lymphocytic leukemia, chronic myelogenous leukemia, other leukemias, or myeloproliferative disorders. The probability of 4-year overall survival was 73% for patients with indolent NHL, 58% for those with aggressive NHL, 67% for those with HL, 30% for those with AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse in these patients were 0%, 32%, 50%, 33%, and 38%, and those for progression-free survival were 73%, 45%, 27%, 27%, and 10%. The incidence of treatment-related mortality was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease was 38% at day +100, and that of chronic graft-versus-host disease was 50% at 2 years. Multivariate analysis revealed superior overall survival and progression-free survival in patients with both indolent and aggressive NHL compared with those with AML/MDS, HL, or myeloma. Worse 1-year treatment-related mortality was observed in patients with a Hematopoietic Cell Transplantation Comorbidity Index score ≥ 3 and in cytomegalovirus-seropositive recipients. These results suggest that (1) RIC conditioning was well tolerated by an older, heavily pretreated

  4. REDUCED INTENSITY CONDITIONING FOLLOWED BY RELATED ALLOGRAFTS IN HEMATOLOGIC MALIGNANCIES: LONG TERM OUTCOMES MOST SUCCESSFUL IN INDOLENT AND AGGRESSIVE NON-HODGKINS LYMPHOMAS

    PubMed Central

    Warlick, Erica D; Tomblyn, Marcie; Cao, Qing; DeFor, Todd; Blazar, Bruce R; MacMillan, Margaret; Verneris, Michael; Wagner, John; Dusenbery, Kathryn; Aurora, Mukta; Bachanova, Veronika; Brunstein, Claudio; Burns, Linda; Cooley, Sarah; Kaufman, Dan; Majhail, Navneet S; McClune, Brian; McGlave, Philip; Miller, Jeffrey; Oran, Betul; Slungaard, Arne; Vercellotti, Gregory; Weisdorf, Daniel J

    2014-01-01

    Reduced intensity conditioning (RIC) extends the curative potential of allogeneic hematopoietic cell transplantation (HCT) to patients with hematologic malignancies unable to withstand myeloablative conditioning. We prospectively analyzed the outcomes of 123 patients, median age of 57 (range 23-70), with hematologic malignancies treated with a uniform RIC regimen of cyclophosphamide, fludarabine, and total body irradiation (200 cGy) with or without anti-thymocyte globulin (ATG) followed by related donor allogeneic HCT at the University of Minnesota from 2002-2008. Forty-five patients had acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), 27 patients had aggressive non-Hodgkin lymphoma (NHL), 8 indolent NHL, 10 Hodgkin Lymphoma (HL), 10 myeloma and the remaining 23 had acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), other leukemias, or myeloproliferative disorders. Probability of four year overall survival (OS) was 73% for patients with indolent NHL, 58% for aggressive NHL, 67% for HL, 30% for AML/MDS, and only 10% for those with myeloma. Corresponding outcomes for relapse were 0%, 32%, 50%, 33%, and 38% and for progression free survival (PFS) were 73%, 45%, 27%, 27%, and 10%, respectively. The incidence of treatment related mortality (TRM) was 14% at day +100 and 22% at 1 year. The incidence of grade II-IV acute graft-versus-host disease (aGVHD) at day +100 was 38% and chronic GVHD at 2 years was 50%. Multivariate analysis revealed superior OS and PFS in patients with both indolent and aggressive NHL compared with AML/MDS, HL, or myeloma. Worse 1 year TRM was observed with hematopoietic cell transplant comorbidity index (HCT-CI) score ≥ 3 and CMV seropositive recipients. These results suggest that: 1) RIC conditioning was well tolerated by an older, heavily pre-treated population; 2) indolent and aggressive NHLs respond well to RIC conditioning highlighting the importance of the graft versus lymphoma (GVL) effect; and 3

  5. Etiology, clinical course and outcome of healthcare-associated bloodstream infections in patients with hematological malignancies: a retrospective study of 350 patients in a Finnish tertiary care hospital.

    PubMed

    Åttman, Emilia; Aittoniemi, Janne; Sinisalo, Marjatta; Vuento, Risto; Lyytikäinen, Outi; Kärki, Tommi; Syrjänen, Jaana; Huttunen, Reetta

    2015-01-01

    This retrospectively collected laboratory-based surveillance data includes 575 healthcare-associated bloodstream infections (BSIs) in 350 patients with hematological malignancy in Tampere University Hospital, Finland, during 1999-2001 and 2005-2010. The most common underlying diseases were acute myelogenous leukemia (n=283, 49%), followed by myeloma (n=87, 15%) and acute lymphocytic leukemia (n=76, 13%). The overall rate was 9.1 BSIs per 1000 patient-days. Gram-positive BSIs predominated and the most common pathogens were coagulase-negative staphylococci (23%), viridans streptococci (11%), enterococci (9%) and Escherichia coli (9%). Fungi caused 2% of BSIs. The 7-day and 28-day case fatalities were 5% and 10% and were highest in BSIs caused by P. aeruginosa (19% and 34%, respectively). The median age of patients with BSI has increased; it was 55.0 years during 1999-2001, compared to 59.0 years in 2005-2007 and 59.0 years in 2008-2010 (p<0.0001). Gram-positive bacteria predominated in this material. Case fatalities were low as compared to previous reports although the median age of patients increased.

  6. 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.

  7. Molecular and clinical significance of fibroblast growth factor 2 (FGF2 /bFGF) in malignancies of solid and hematological cancers for personalized therapies

    PubMed Central

    Akl, Mohamed R.; Nagpal, Poonam; Ayoub, Nehad M.; Tai, Betty; Prabhu, Sathyen A.; Capac, Catherine M.; Gliksman, Matthew; Goy, Andre; Suh, K. Stephen

    2016-01-01

    Fibroblast growth factor (FGF) signaling is essential for normal and cancer biology. Mammalian FGF family members participate in multiple signaling pathways by binding to heparan sulfate and FGF receptors (FGFR) with varying affinities. FGF2 is the prototype member of the FGF family and interacts with its receptor to mediate receptor dimerization, phosphorylation, and activation of signaling pathways, such as Ras-MAPK and PI3K pathways. Excessive mitogenic signaling through the FGF/FGFR axis may induce carcinogenic effects by promoting cancer progression and increasing the angiogenic potential, which can lead to metastatic tumor phenotypes. Dysregulated FGF/FGFR signaling is associated with aggressive cancer phenotypes, enhanced chemotherapy resistance and poor clinical outcomes. In vitro experimental settings have indicated that extracellular FGF2 affects proliferation, drug sensitivity, and apoptosis of cancer cells. Therapeutically targeting FGF2 and FGFR has been extensively assessed in multiple preclinical studies and numerous drugs and treatment options have been tested in clinical trials. Diagnostic assays are used to quantify FGF2, FGFRs, and downstream signaling molecules to better select a target patient population for higher efficacy of cancer therapies. This review focuses on the prognostic significance of FGF2 in cancer with emphasis on therapeutic intervention strategies for solid and hematological malignancies. PMID:27007053

  8. Optimal Molecular Methods in Detecting p190BCR-ABL Fusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature

    PubMed Central

    Sonu, Rebecca J.; Jonas, Brian A.; Dwyre, Denis M.; Gregg, Jeffrey P.; Rashidi, Hooman H.

    2015-01-01

    Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR). A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS) based assay and identified as the rare fusion variant e1a3 of p190BCR-ABL. Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results. PMID:25949834

  9. Success rate and risk factors for failure of empirical antifungal therapy with itraconazole in patients with hematological malignancies: a multicenter, prospective, open-label, observational study in Korea.

    PubMed

    Kim, Soo-Jeong; Cheong, June-Won; Min, Yoo Hong; Choi, Young Jin; Lee, Dong-Gun; Lee, Je-Hwan; Yang, Deok-Hwan; Lee, Sang Min; Kim, Sung-Hyun; Kim, Yang Soo; Kwak, Jae-Yong; Park, Jinny; Kim, Jin Young; Kim, Hoon-Gu; Kim, Byung Soo; Ryoo, Hun-Mo; Jang, Jun Ho; Kim, Min Kyoung; Kang, Hye Jin; Cho, In Sung; Mun, Yeung Chul; Jo, Deog-Yeon; Kim, Ho Young; Park, Byeong-Bae; Kim, Jin Seok

    2014-01-01

    We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462).

  10. Clinical and molecular cytogenetic studies in ten patients with hematological malignancies characterized by t(20;21)(q11;q11) resulted from del(20q).

    PubMed

    Wu, Chunxiao; Zhang, Jun; Bai, Shuxiao; Yao, Jianxin; Qiu, Huiying; Xue, Yongquan; Chen, Suning; Wu, Yafang; Shen, Juan; Pan, Jinlan

    2016-10-01

    This study reports 10 patients with hematological malignances with t(20;21)(q11;q11) resulting from del(20q) (for example, der(20)del(20)(q11q13)t(20;21)(q11;q11) and der(21)t(20;21)(q11;q11)) and described their clinical features and the possible prognostic significance of this abnormality. The t(20;21)(q11;q11) was a rare but recurrent abnormality secondary to del(20q) besides i(20q-). The frequency of der(20)del(20)(q11q13)t(20;21)(q11;q11) among our patients with del(20q) was 2.4%. It was considered that the 20q deletion preceded translocation with chromosome 21. This abnormality is often cryptic, occurs predominantly in older men and is observed most often in myelodysplastic syndromes. Patients with this abnormality have an unfavorable prognosis, similar to patients with i(20q-). The molecular consequences of der(20)del(20)(q11q13)t(20;21)(q11;q11) may be different from patients with i(20q-). To the best of our knowledge this is the largest dataset published to date.

  11. Rapid Memory T-cell Reconstitution Recapitulating CD45RA-depleted Haploidentical Transplant Graft Content in Patients with Hematologic Malignancies

    PubMed Central

    Triplett, Brandon M; Shook, David R; Eldridge, Paul; Li, Ying; Kang, Guolian; Dallas, Mari; Hartford, Christine; Srinivasan, Ashok; Chan, Wing Keung; Suwannasaen, Duangchan; Inaba, Hiroto; Pui, Ching-Hon; Leung, Wing

    2015-01-01

    T-cell depletion of an HLA-haploidentical graft is often used to prevent graft-vs.-host disease (GvHD), but the procedure may lead to increased graft failure, relapse, and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GvHD through removal of naïve T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA– memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without total body irradiation or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post-transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vβ spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GvHD despite infusion of a median of >100 million per kilogram haploidentical T cells. PMID:25665048

  12. Pathogenic molds (including Aspergillus species) in hospital water distribution systems: a 3-year prospective study and clinical implications for patients with hematologic malignancies.

    PubMed

    Anaissie, Elias J; Stratton, Shawna L; Dignani, M Cecilia; Lee, Choon-kee; Summerbell, Richard C; Rex, John H; Monson, Thomas P; Walsh, Thomas J

    2003-04-01

    The incidence of mold infections in patients with hematologic malignancies continues to increase despite the widespread use of air filtration systems, suggesting the presence of other hospital sources for these molds. Water sources are known to harbor pathogenic molds. We examined samples from water, water surfaces, air, and other environment sources from a bone marrow transplantation unit with optimal air precautions. Molds (Aspergillus species, others) were recovered in 70% of 398 water samples, in 22% of 1311 swabs from plumbing structures and environmental surfaces, and in 83% of 274 indoor air samples. Microscopic examination of the water plumbing lines revealed hyphal forms compatible with molds. Four findings suggest that indoor airborne molds were aerosolized from the water: (1) higher mean airborne concentrations of molds in bathrooms (16.1 colony-forming units [CFU]/m(3)) than in patient rooms (7 CFU/m(3)) and hallways (8.6 CFU/m(3); P =.00005); (2) a strong type and rank correlation between molds isolated from hospital water and those recovered from indoor hospital; (3) lack of seasonal correlation between the airborne mold concentration in outdoor and indoor air; and (4) molecular relatedness between a clinical strain and a water-related strain (previously reported). Hospital water distribution systems may serve as a potential indoor reservoir of Aspergillus and other molds leading to aerosolization of fungal spores and potential exposure for patients.

  13. Association of mannose-binding lectin levels and invasive fungal disease in hematologic malignancy patients receiving myelosuppressive chemotherapy or allogeneic hematopoietic stem cell transplantation.

    PubMed

    Riwes, M M; Leather, H; Neal, D; Bennett, C; Sugrue, M; Cline, C; Stokes, J; Hiemenz, J; Hsu, J; Wingard, J R

    2016-09-01

    Several studies have suggested an association of mannose-binding lectin (MBL) deficiency with infections. In this study, we investigated the association between MBL deficiency and invasive fungal disease (IFD) in hematologic malignancy patients receiving myelosuppressive chemotherapy or hematopoietic stem cell transplant. MBL levels were quantified at the start of treatment in 152 patients who were followed for 6 months and scored as developing IFD or not. Forty-five patients (29.6%) developed IFD, of which 21 (46.7% of IFD cases and 13.8% of patients) were proven or probable IFD. Fifty-nine (38.8%) had MBL levels <1000 ng/mL. The rates of all IFD in patients with MBL levels below and above 1000 ng/mL were 33.9% and 26.9%, respectively (P=0.356). The rates of proven or probable IFD in patients with MBL levels below and above 1000 ng/mL were 11.9% and 15.1%, respectively (P=0.579). MBL levels <1000 ng/mL were not predictors of death (P=0.233). As expected, IFD was associated with death (P<0.0001). Our findings indicate that MBL levels <1000 ng/mL were not associated with an increased risk of developing IFD or overall survival.

  14. Discussing and managing hematologic germ line variants.

    PubMed

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-12-02

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  15. Discussing and managing hematologic germ line variants.

    PubMed

    Kohlmann, Wendy; Schiffman, Joshua D

    2016-11-24

    With the introduction of genomic technologies, more hereditary cancer syndromes with hematologic malignancies are being described. Up to 10% of hematologic malignancies in children and adults may be the result of an underlying inherited genetic risk. Managing these patients with hereditary hematologic malignancies, including familial leukemia, remains a clinical challenge because there is little information about these relatively rare disorders. This article covers some of the issues related to the diagnosis and interpretation of variants associated with hereditary hematologic malignancies, including the importance of an accurate family history in interpreting genetic variants associated with disease. The challenges of screening other family members and offering the most appropriate early malignancy detection is also discussed. We now have a good opportunity to better define hereditary cancer syndromes with associated hematologic malignancies and contribute to clinically effective guidelines.

  16. Encephalopathy is the dose-limiting toxicity of intravenous hepsulfam: results of a phase I trial in patients with advanced hematological malignancies.

    PubMed

    Larson, R A; Geller, R B; Janisch, L; Milton, J; Grochow, L B; Ratain, M J

    1995-01-01

    Hepsulfam is a bisulfamic ester which is similar in structure to busulfan and is believed to act as a bifunctional alkylator inducing both DNA-DNA and DNA-protein crosslinks. Prior studies in patients with refractory solid tumors have identified the dose-limiting toxicity of hepsulfam to be cumulative myelosuppression resulting in prolonged leukopenia and thrombocytopenia. This phase I trial was designed to determine the maximally tolerated dose of hepsulfam administered intravenously in patients with refractory leukemias and other advanced hematologic malignancies. Hepsulfam was administered as a 30-min or 2-h intravenous infusion to 21 patients with advanced leukemia or multiple myeloma. All patients had been extensively treated and had progressive disease. Cycles were repeated every 5 weeks. Cohorts of patients were treated at 360, 480, 640, and 800 mg/m2. The dose-limiting toxicity of intravenous hepsulfam was severe encephalopathy. The single patient treated at 800 mg/m2 became comatose within 48 h and required 3 weeks for his mental status to return to baseline. There were, however, no irreversible neurological sequelae. Several patients treated at 640 mg/m2 had clinical evidence of toxic deliriums and slowing of alpha rhythm waves on electroencephalograms indicative of a gray-matter encephalopathy. When hepsulfam was infused over 30 min, patients complained of uncomfortable parasthesias, but when the drug was administered over 2 h, these acute symptoms were less common. Myelosuppression was observed in most patients. Among those patients who had some suppression of their leukemia, peripheral blood counts recovered to pretreatment levels after 3-5 weeks. Apart from CNS toxicity, non-hematologic toxicity was minimal. Pharmacokinetic studies demonstrated rapid clearance of hepsulfam so that the drug was not reliably detected in the plasma after 24 h. The recommended phase II dose of hepsulfam as a single 2-h intravenous infusion is 480 mg/m2, but this dose

  17. Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow-Review of Published Literature.

    PubMed

    Farhan, Shatha; Peres, Edward; Janakiraman, Nalini

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting.

  18. Outcomes of critically ill patients with hematologic malignancies: prospective multicenter data from France and Belgium--a groupe de recherche respiratoire en réanimation onco-hématologique study.

    PubMed

    Azoulay, Elie; Mokart, Djamel; Pène, Frédéric; Lambert, Jérôme; Kouatchet, Achille; Mayaux, Julien; Vincent, François; Nyunga, Martine; Bruneel, Fabrice; Laisne, Louise-Marie; Rabbat, Antoine; Lebert, Christine; Perez, Pierre; Chaize, Marine; Renault, Anne; Meert, Anne-Pascale; Benoit, Dominique; Hamidfar, Rebecca; Jourdain, Mercé; Darmon, Michael; Schlemmer, Benoit; Chevret, Sylvie; Lemiale, Virginie

    2013-08-01

    PURPOSE Patients with hematologic malignancies are increasingly admitted to the intensive care unit (ICU) when life-threatening events occur. We sought to report outcomes and prognostic factors in these patients. PATIENTS AND METHODS Ours was a prospective, multicenter cohort study of critically ill patients with hematologic malignancies. Health-related quality of life (HRQOL) and disease status were collected after 3 to 6 months. Results Of the 1,011 patients, 38.2% had newly diagnosed malignancies, 23.1% were in remission, and 24.9% had received hematopoietic stem-cell transplantations (HSCT, including 145 allogeneic). ICU admission was mostly required for acute respiratory failure (62.5%) and/or shock (42.3%). On day1, 733 patients (72.5%) received life-supporting interventions. Hospital, day-90, and 1-year survival rates were 60.7%, 52.5%, and 43.3%, respectively. By multivariate analysis, cancer remission and time to ICU admission less than 24 hours were associated with better hospital survival. Poor performance status, Charlson comorbidity index, allogeneic HSCT, organ dysfunction score, cardiac arrest, acute respiratory failure, malignant organ infiltration, and invasive aspergillosis were associated with higher hospital mortality. Mechanical ventilation (47.9% of patients), vasoactive drugs (51.2%), and dialysis (25.9%) were associated with mortality rates of 60.5%, 57.5%, and 59.2%, respectively. On day 90, 80% of survivors had no HRQOL alterations (physical and mental health similar to that of the overall cancer population). After 6 months, 80% of survivors had no change in treatment intensity compared with similar patients not admitted to the ICU, and 80% were in remission. CONCLUSION Critically ill patients with hematologic malignancies have good survival, disease control, and post-ICU HRQOL. Earlier ICU admission is associated with better survival.

  19. Neuroleptic malignant syndrome in Malaysia: a university hospital experience.

    PubMed

    Lee, M K; Ong, S B; Tan, C T; Loh, T G

    1992-09-01

    The neuroleptic malignant syndrome (NMS) is a potentially fatal complication of antipsychotic therapy. A retrospective study of nine patients seen over six years at the University Hospital, Kuala Lumpur (UHKL), is described. The estimated annualised incidence was 1.2 per 1000 in-patients with psychosis. No ethnic difference was detected. Clinical features were similar to experiences elsewhere, with wide variability seen in the severity of illness. The neuroleptic drugs implicated were haloperidol, trifluoperazine, chlorpromazine, fluphenazine and clopenthixol. Treatment consisted of withdrawal of offending drugs and supportive measures. Specific therapy was given to five patients. There was one death. At follow-up no deterioration was detected. A different neuroleptic drug was successfully re-introduced in four patients. In view of the wide usage of major tranquillizers, a high degree of clinical awareness of this serious complication is necessary for early diagnosis to reduce morbidity and mortality.

  20. Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology.

    PubMed

    Cornely, Oliver A; Böhme, Angelika; Buchheidt, Dieter; Einsele, Hermann; Heinz, Werner J; Karthaus, Meinolf; Krause, Stefan W; Krüger, William; Maschmeyer, Georg; Penack, Olaf; Ritter, Jörg; Ruhnke, Markus; Sandherr, Michael; Sieniawski, Michal; Vehreschild, Jörg-Janne; Wolf, Hans-Heinrich; Ullmann, Andrew J

    2009-01-01

    There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

  1. Anti-Müllerian hormone and antral follicle count reveal a late impairment of ovarian reserve in patients undergoing low-gonadotoxic regimens for hematological malignancies.

    PubMed

    Di Paola, Rossana; Costantini, Claudio; Tecchio, Cristina; Salvagno, Gian Luca; Montemezzi, Rachele; Perandini, Alessio; Pizzolo, Giovanni; Zaffagnini, Stefano; Franchi, Massimo

    2013-01-01

    The impact of cancer therapy on the reproductive potential of patients is increasingly recognized because survival rates of patients have clearly improved in recent years. Different fertility preservation methods, either generally accepted or still experimental, are currently available, and counseling of patients requires a delicate balance between the efficacy and side effects of the proposed method and the characteristics of both the tumor and the therapy. Deeper knowledge of the effects of cancer therapy on the reproductive potential of patients over time is required to identify the most appropriate fertility preservation method. In this paper, we report a case-control study in which female patients who were diagnosed with hematological malignancies and treated with chemotherapy and/or radiotherapy were compared with age-matched controls in terms of ovarian reserve, as measured by ultrasound examination and hormonal status. By stratifying patients for gonadotoxicity of the therapy received and time elapsed from the end of the therapy, we report that patients treated with low gonadotoxic therapies, while being similar to age-matched controls in their ovarian reserve when evaluated within a few years from the end of the therapy, show a clear impairment over longer times. We also report that anti-Müllerian hormone is the most sensitive hormonal parameter in detecting changes in ovarian reserve when compared with follicle-stimulating hormone or inhibin-B. This study stresses the importance of accurate counseling at the time of diagnosis of cancer and emphasizes the risks of infertility with low gonadotoxic therapies that may reduce the reproductive window of survivors.

  2. A Phase I Study of the First-in-Class Anti-Mitochondrial Metabolism Agent, CPI-613, in Patients with Advanced Hematologic Malignancies

    PubMed Central

    Pardee, Timothy S.; Lee, King; Luddy, John; Maturo, Claudia; Rodriguez, Robert; Isom, Scott; Miller, Lance D.; Stadelman, Kristin M.; Levitan, Denise; Hurd, David; Ellis, Leslie R.; Harrelson, Robin; Manuel, Megan; Dralle, Sarah; Lyerly, Susan; Powell, Bayard L

    2014-01-01

    Purpose The lipoate derivative CPI-613 is a first-in-class agent that targets mitochondrial metabolism. This study determined the effects of CPI-613 on mitochondrial function and defined the maximally tolerated dose (MTD), pharmacokinetics (PKs), and safety in patients with relapsed or refractory hematologic malignancies. Experimental Design Human leukemia cell lines were exposed to CPI-613 and mitochondrial function was assayed. A phase I trial was conducted in which CPI-613 was given as a 2-hour infusion on days 1 and 4 for 3 weeks every 28 days. Results CPI-613 inhibited mitochondrial respiration of human leukemia cells consistent with the proposed mechanism of action. In the phase I trial, 26 patients were enrolled. CPI-613 was well tolerated with no marrow suppression observed. When the infusion time was shortened to 1 hour renal failure occurred in 2 patients. At 3780 mg/m2, there were 2 dose-limiting toxicities (DLTs). At a dose of 2940 mg/m2 over 2 hours, no DLTs were observed, establishing this as the MTD. Renal failure occurred in a total of 4 patients and resolved in all but 1, who chose hospice care. CPI-613 has a triphasic elimination with an alpha half-life of ~1.34 hours. Of 21 evaluable, heavily pretreated, patients, 4 achieved an objective response and 2 achieved prolonged stabilization of disease for a clinical benefit rate of 29%. Following drug exposure, gene expression profiles of peripheral blood mononuclear cells from responders demonstrated immune activation. Conclusion CPI-613 inhibits mitochondrial function and demonstrates activity in a heavily pretreated cohort of patients. PMID:25165100

  3. [North-South cooperation on transfusion and hematology teaching: A Benin experience].

    PubMed

    Lafia, E; Anani, L; Glitho, S; Bankole, C; Fachinan, H; Py, J-Y; Domenech, J; Martenot, B; Colombat, P; Chobli, M; Zohoun, I

    2015-06-01

    Hematologic diseases are a significant part of health disorders in Benin. As an example, anemia is the second cause of hospitalization, measuring up to 7.9% all over the country (National Plan of Sanitary Development, 2009-2018). By contrast, there is only one active hematologist in the country. Thanks to two partnerships, on one hand between the health sciences faculty in Cotonou (Benin) and the medicine one in Tours (France), and on the other hand between the Beninese Blood Transfusion National Agency and the French Blood Establishment, a first blood transfusion and hematology formation was held in Cotonou on December 2014. Among other benefits, was created an hematology-transfusion network in order to facilitate relations between Beninese hospital doctors, with the support of the two French partner institutions. The article describes this progress.

  4. Invasive infections caused by Trichosporon species and Geotrichum capitatum in patients with hematological malignancies: a retrospective multicenter study from Italy and review of the literature.

    PubMed

    Girmenia, Corrado; Pagano, Livio; Martino, Bruno; D'Antonio, Domenico; Fanci, Rosa; Specchia, Giorgina; Melillo, Lorella; Buelli, Massimo; Pizzarelli, Giampaolo; Venditti, Mario; Martino, Pietro

    2005-04-01

    Trichosporonosis is an uncommon but frequently fatal mycosis in immunocompromised patients. A multicenter retrospective study was conducted to characterize cases of proven or probable invasive trichosporonosis diagnosed over the past 20 years in Italian patients with hematological diseases. Of the 52 cases identified, 17 were classified as Trichosporon sp. infections and 35 were attributed to Geotrichum capitatum. Acute myeloid leukemia accounted for 65.4% of the cases. The incidence rates of Trichosporon sp. and G. capitatum infections in acute leukemia patients were 0.4 and 0.5%, respectively. Overall, 76.9% of cases had positive blood cultures. Pulmonary involvement was documented in 26.9% of cases. Death was reported for 57.1% of G. capitatum infections and for 64.7% of Trichosporon sp. infections. A literature review on trichosporonosis in patients with any underlying disease or condition reveals G. capitatum as a predominantly European pathogen, particularly in certain Mediterranean areas, while Trichosporon sp. infections are seen with similar frequencies on all continents. The majority of published Trichosporon sp. and G. capitatum infections occurred in patients with hematological diseases (62.8 and 91.7%, respectively). Well over half of these were suffering from acute leukemia (68 and 84% of patients with Trichosporon sp. and G. capitatum infections, respectively). Crude mortality rates were 77% for Trichosporon spp. and 55.7% for G. capitatum. The optimal therapy for trichosporonosis has yet to be identified; however, in vitro experiences are providing encouraging evidence of the potential role of the new triazoles, in particular, voriconazole.

  5. Immunotherapy in high-risk chemotherapy-resistant patients with metastatic solid tumors and hematological malignancies using intentionally mismatched donor lymphocytes activated with rIL-2: a phase I study.

    PubMed

    Slavin, Shimon; Ackerstein, Aliza; Or, Reuven; Shapira, Michael Y; Gesundheit, Benjamin; Askenasy, Nadir; Morecki, Shoshana

    2010-10-01

    The feasibility and safety of immunotherapy mediated by intentionally mismatched rIL-2 activated killer lymphocytes (IMAK) with no prior stem cell engraftment was investigated in patients with advanced chemotherapy-resistant hematological malignancies and metastatic solid tumors. Our goals were to maximize anti-cancer activity by using intentionally mismatched donor lymphocytes; amplify killing of target cancer cells by rIL-2 activation of killer cells in vitro and in vivo, and avoid the risk of graft-versus-host disease (GVHD) by anticipated rejection of alloreactive donor lymphocytes. Conditioning consisted of 5 days of fludarabine 25 mg/m(2) or a single dose of cyclophosphamide 1,000 mg/m(2), 2 subcutaneous injections of alpha interferon (IFN) 3 x 10(6) and COX2 inhibitors, followed by administration of IMAK (65 +/- 5 CD3(+)CD56(-); 17 +/- 5 CD3(-)CD56(+)) in conjunction with low dose subcutaneous rIL-2 (6 x 10(6) IU/m(2)/day) for 5 days for continuous activation of alloreactive donor lymphocytes prior to their anticipated rejection. Here, we present our phase 1 clinical study data in a cohort of 40 high-risk patients with metastatic solid tumors and hematological malignancies. Treatment was accompanied by some malaise and occasional self-limited fever but otherwise well tolerated on an outpatient basis. Transient engraftment of donor cells was documented in two patients and only one developed self-limited grade 1 GVHD. Among patients with chemotherapy-resistant disease, long-term progression-free survival was recorded in 5 of 21 evaluable patients with metastatic solid tumors and in four of five patients with hematological malignancies. We conclude that the proposed procedure is feasible, safe, and potentially effective, with some otherwise resistant cancer patients long-term disease-free, thus justifying larger Phase II studies in patients with hematological malignancies and metastatic solid tumors, preferably at a stage of minimal residual disease with the

  6. Improved radioimmunotherapy of hematologic malignancies

    SciTech Connect

    Press, O.W.

    1989-05-12

    In the seven months which have elapsed since initial funding of this project, considerable progress has been made towards achieving the objectives of this research. These objectives include: to study the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (mAbs) targeting tumor associated antigens; to examine the effects of lysomotropic amines (ammonium chloride, chloroquine, amantadine), carboxylic ionophores (monensin), and thionamides (propylthiouracil), on the retention of radiolabeled mAbs by tumor cells; to identify the subcellular site of radioimmunoconjugate degradation, and to quantify the sizes of the fragments generated by intracellular metabolism of radiolabeled mAbs; to examine the effects of lysomotropic agents on the quality of external gamma camera imaging and radiation dosimetry generated in tumor-bearing mice injected with radiolabeled mAbs; to examine the effects of lysomotropic agents on the radiotherapeutic efficacy of radiolabeled mAbs in murine tumors and human tumors xenografted to nude mice; and to compare the effects of lysomotropic agents on the degradation of radioimmunoconjugates made with different radionuclides and different conjugation methods.

  7. A Prospective Study of {sup 18}FDG-PET With CT Coregistration for Radiation Treatment Planning of Lymphomas and Other Hematologic Malignancies

    SciTech Connect

    Terezakis, Stephanie A.; Schöder, Heiko; Kowalski, Alexander; McCann, Patrick; Lim, Remy; Turlakov, Alla; Gonen, Mithat; Barker, Chris; Goenka, Anuj; Lovie, Shona; Yahalom, Joachim

    2014-06-01

    Purpose: This prospective single-institution study examined the impact of positron emission tomography (PET) with the use of 2-[{sup 18}F] fluoro-2-deoxyglucose and computed tomography (CT) scan radiation treatment planning (TP) on target volume definition in lymphoma. Methods and Materials: 118 patients underwent PET/CT TP during June 2007 to May 2009. Gross tumor volume (GTV) was contoured on CT-only and PET/CT studies by radiation oncologists (ROs) and nuclear medicine physicians (NMPs) for 95 patients with positive PET scans. Treatment plans and dose-volume histograms were generated for CT-only and PET/CT for 95 evaluable sites. Paired t test statistics and Pearson correlation coefficients were used for analysis. Results: 70 (74%) patients had non-Hodgkin lymphoma, 10 (11%) had Hodgkin lymphoma, 12 (10%) had plasma-cell neoplasm, and 3 (3%) had other hematologic malignancies. Forty-three (45%) presented with relapsed/refractory disease. Forty-five (47%) received no prior chemotherapy. The addition of PET increased GTV as defined by ROs in 38 patients (median, 27%; range, 5%-70%) and decreased GTV in 41 (median, 39.5%; range, 5%-80%). The addition of PET increased GTV as defined by NMPs in 27 patients (median, 26.5%; range, 5%-95%) and decreased GTV in 52 (median, 70%; range, 5%-99%). The intraobserver correlation between CT-GTV and PET-GTV was higher for ROs than for NMPs (0.94, P<.01 vs 0.89, P<.01). On the basis of Bland-Altman plots, the PET-GTVs defined by ROs were larger than those defined by NMPs. On evaluation of clinical TPs, only 4 (4%) patients had inadequate target coverage (D95 <95%) of the PET-GTV defined by NMPs. Conclusions: Significant differences between the RO and NMP volumes were identified when PET was coregistered to CT for radiation planning. Despite this, the PET-GTV defined by ROs and NMPs received acceptable prescription dose in nearly all patients. However, given the potential for a marginal miss, consultation with an experienced PET

  8. [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.

  9. 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

    SciTech Connect

    Taylor, R.P.; Horgan, C.; Buschbacher, R.; Brunner, C.M.; Hess, C.E.; O'Brien, W.M.; Wanebo, H.J.

    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.

  10. Experience of Peripherally Inserted Central Venous Catheter in Patients with Hematologic Diseases

    PubMed Central

    Hashimoto, Yoshinori; Fukuta, Takanori; Maruyama, Junko; Omura, Hiromi; Tanaka, Takayuki

    2017-01-01

    Objective Although use of the peripherally inserted central venous catheter (PICC) has become increasingly common, there are few reports of PICCs used for patients with hematologic diseases. In this study, we analyzed the safety of PICC placement in patients with hematologic diseases where PICCs had been placed to perform blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation. Methods This study included 142 PICCs placed in 95 patients managed at our department from November 2013 to December 2015. The PICCs used were the GroshongⓇ Catheter (NXT single-lumen; BARD Inc.). Results A total of 95 patients underwent the placement of 142 PICCs. The mean patient age was 65.5 years. The total duration of catheterization was 8,089 days, with a mean duration of 57.0 days. Chemotherapy was administered through 107 catheters. Stem cells were injected through 12 catheters. Although a fever was observed in association with 103 catheters, it was generally controlled by antimicrobial therapy. There were 18 catheter-related bloodstream infection (CRBSI) cases, an incidence equivalent to 2.1 cases per 1,000 catheter-days. Conclusion The present study demonstrated a low CRBSI incidence rate and found no evidence of serious complications with PICC placement. PICCs can be used for blood collection, blood transfusion, drug administration, and hematopoietic stem cell transplantation without problems. Thus, PICC placement appears to be a safe procedure for patients with hematologic diseases. Safe catheters are therefore urgently needed for these patients. We expect that PICCs will be widely adopted in Japan in the near future. PMID:28202859

  11. A pilot study of cytoreductive chemotherapy combined with infusion of additional peripheral blood stem cells reserved at time of harvest for transplantation in case of relapsed hematologic malignancies after allogeneic peripheral blood stem cell transplant.

    PubMed

    Kim, J G; Sohn, S K; Kim, D H; Lee, N Y; Suh, J S; Lee, K S; Lee, K B

    2004-01-01

    Reharvesting leukocytes from donors for a donor leukocyte infusion (DLI) is inconvenient and occasionally impossible in case of unrelated donors. It is well known that the effect of a growth factor-primed DLI is comparable to that of a nonprimed DLI. In total, 42 patients with hematologic malignancies and a high risk of relapse were allocated, on an intent-to-treat basis, a peripheral blood stem cell transplantation (PBSCT) from HLA-matched sibling donors, and then at the time of harvest, additional peripheral blood stem cells (PBSCs) were also reserved for a therapeutic primed DLI in case of relapse. In all, 12 patients who relapsed after allogeneic PBSCT were treated with mainly cytarabine-based chemotherapy followed by a cryopreserved PBSC infusion. The median dose of CD3+ and CD34+ cells for the primed DLIs was 1.43 x 10(8)/kg and 4.75 x 10(6)/kg, respectively. Six of the 12 relapsed patients exhibited a complete response after the primed DLI, plus their 1-year survival rate was 33%. The new development or progression of graft-versus-host disease after a primed DLI was observed in 50% of the patients. Overall, the survival at 1 year was 16.7%. Accordingly, the induction of a graft-versus-leukemia effect through a primed DLI, using additional PBSCs reserved at the original time of harvest, would appear to be feasible for patients with relapsed hematologic malignancies. Furthermore, this approach is also more convenient for donors.

  12. Palliative care in pediatric hematological oncology patients: experience of a tertiary hospital

    PubMed Central

    Valadares, Maria Thereza Macedo; Mota, Joaquim Antônio César; de Oliveira, Benigna Maria

    2014-01-01

    Objective To evaluate the approach to palliative care for hematological oncology patients in the pediatric ward of a tertiary hospital. Methods This was a retrospective, descriptive study of 29 hematological oncology patients who died between 2009 and 2011. Data regarding the approach and prevalence of pain, prevalence of other symptoms, multidisciplinary team participation, communication between staff and family and limited invasive therapy were collected from the medical records. Results Twenty-seven (93.1%) patients displayed disease progression unresponsive to curative treatment. The median age at death was ten years old. Pain was the most prevalent symptom with all patients who reported pain receiving analgesic medications. The majority took weak (55.2%) and/or strong (65.5%) opioids. The patients were followed by pediatricians and a pediatric hematologist/oncologist. Participation of other professionals was also documented: 86.2% were followed by social services and 69% by psychologists, among others. There were explicit descriptions of limitation of invasive therapy in the medical records of 26 patients who died with disease progression. All these decisions were shared with the families. Conclusion Although the hospital where this study was conducted does not have a specialized team in pediatric palliative care, it meets all the requirements for developing a specific program. The importance of approaching pain and other prevalent symptoms in children with cancer involving a comprehensive multidisciplinary team is evident. Discussions were had with most of the families on limiting invasive therapy, but no record of a well-defined and coordinated treatment plan for palliative care was found. PMID:25453649

  13. Umbilical cord blood transplantation in hematologic diseases in patients over 15 years old: long-term experience at the Pontificia Universidad Católica de Chile.

    PubMed

    Ramirez, P; Nervi, B; Bertin, P; Poggi, H; Lagos, M; Selman, C; Pizarro, I; Jara, V; Wiestruck, A; Barriga, F

    2013-01-01

    Most patients who require a sibling stem cell transplantation do not have a matched donor. In our experience, only 1/3 patients have a matched unrelated donor (MUD); therefore, the majority of the patients will require umbilical cord blood (UCB). Patients treated for hematologic diseases with UCB transplants were included. UCB selection and conditioning regimens were performed according to the Minnesota group. Graft-versus-host disease (GVHD) prophylaxis, infection prevention, and patient care were performed according to institutional guidelines. We analyzed patients and graft demography, neutrophil and platelet recovery, chimerism kinetics, GVHD incidence, overall (OS), progression-free survival (PFS) and transplant-related mortality (TRM). We included 29 patients with a median age of 34.8 years (range 15-55). Eighteen were male and the median weight was 72.6 kg (range 54-100). Nineteen patients had acute leukemia. Myeloablative (MA) conditioning was used in 27 patients. Seventeen received double UCB (DUCB) grafts. Median total nucleated cell (10(7)/kg) was 4.2 (range 3.9-4.9) and 4.4 (range 2.8-6.3) for single UCB (SUCB) and DUCB transplants, respectively. Median time for neutrophil engraftment was 24.7 (range 14-43) and 25.8 days (range 14-52) after SUCB and DUCB transplants, respectively. Median time for platelet engraftment was 147 (range 30-516) and 81 days (range 37-200) after SUCB and DUCB transplants, respectively. All the patients receiving MA conditioning had >95% chimerism shortly after transplant. Cumulative incidence of grades II-IV and III-IV acute GVHD was 41% and 20%, respectively. Localized chronic GVHD was seen in 14% of the patients. Median follow-up was 16.7 months (range 1-63). Five-year OS and PFS were 38% and 39%, respectively. One-year TRM was 42%. UCB transplantation is associated with potential cure of hematologic malignancies and our results are similar to other series. Studies are needed to decrease mortality and improve immune

  14. Hematology Glossary

    MedlinePlus

    ... includes neutrophils, eosinophils, and basophils back to top H hematocrit : the percentage of the whole blood volume ... hematology: the scientific study of blood and blood-forming tissues hematopoiesis: the process by which the body ...

  15. Malignant intraperitoneal mesothelioma-Başkent University experience

    PubMed Central

    Macuks, Ronalds; Özdemir, Halis; Dursun, Polat; Özen, Özlem Işıksaçan; Haberal, Nihan; Ayhan, Ali

    2011-01-01

    Objective To evaluate diagnostic and treatment results of malignant intraperitoneal mesothelioma in one setting. Materials and Method: 12 patients treated for malignant peritoneal mesothelioma from January 2007 to June 2009 in Başkent University Ankara Hospital, Department of Gynaecology and Obstetrics were evaluated. In a retrospective observational study design tumour stage, grade, differentiation, time from first symptoms, pleural involvement, peritoneal cancer index, surgical cytoreduction, chemotherapeutic regimen, number of cycles, disease free survival and overall survival were evaluated. Disease free survival, overall survival, time until first symptoms were researched. Results The main presenting symptom was abdominal distension. Primary cytoreductive surgery followed by chemotherapy was performed in 9 patients. In 6 patients completeness of cytoreductive score below 2 was achieved. As a first line chemotherapy the most often used was cisplatin in combination with pemetrexed. Themean time from first symptoms until the diagnosis was 1.9 months. Disease free survival of 4.4±1.0 months after completing particular treatment and overall 1-year survival of 85.7 % was observed. No correlations between first symptoms (0.27, p=0.52), time until the diagnosis (−0.29, p=0.44) and overall survival were observed. Similarly, correlations between peritoneal cancer index (0.25, p=0.67), prior surgical score (−.45, p=0.37), completeness of cytoreduction score (0.61, p=0.27) and overall survival were not observed. Conclusions Because of the low number of patients and different treatment approaches data from a particular patient setting are inconclusive, but from the literature there is evidence that patients with malignant intraperitoneal mesothelioma should undergo optimal cytoreduction and receive a combination of cisplatin and pemetrexed as a first line chemotherapy for intravenous or cisplatin in different chemotherapy regimens using the intraperitoneal

  16. 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.

  17. Second malignancies after Hodgkin's disease: the Munich experience.

    PubMed

    Munker, R; Grützner, S; Hiller, E; Aydemir, U; Enne, W; Dietzfelbinger, H; Busch, M; Haas, R; Emmerich, B; Schmidt, M; Dühmke, E; Hölzel, D; Wilmanns, W

    1999-12-01

    The occurrence of second malignancies (SM) is an important late event following the treatment of Hodgkin's disease (HD). We sought to determine the incidence, the risk factors, and the prognosis of SM in our population of patients with HD. A total of 1120 patients diagnosed with HD were registered at six participating institutions in Munich (calendar period 1974-1994). The mean follow-up for the development of SM was 9.1 years. A cumulative treatment score was calculated for both radio- and chemotherapy. The relative and absolute risks of SM were established. All SM were investigated for response to treatment and outcome. We observed 85 SM [eight leukemias, 22 non-Hodgkin's lymphomas (NHL), two plasma cell neoplasias, and 53 solid tumors]. Five patients developed third malignancies. The relative risk of developing a second neoplasm was compared with that within the normal population and was 3.1-fold. The risk varied according to the category of SM. Higher relative risks (20.5 and 25.9-fold), but lower absolute risks were observed for leukemias and non-Hodgkin's lymphomas. Solid tumors had lower relative risks (1.8-fold). Splenectomy increased the risk of SM (relative risk 4.4-fold versus 2.7-fold). The risk of SM did not correlate with the initial treatment (radio- or chemotherapy) and did not decrease with prolonged follow-up. The cumulative intensity of radiotherapy, chemotherapy, or the two modalities combined correlated with the risk of SM. Since some cases occurred early after diagnosis, not all second neoplasms can be considered treatment-associated. After 15 years, an actuarial risk of 11.7% was calculated for all SM, of 1.0% for leukemias, of 3.0% for NHL, and of 7.7% for solid tumors. The prognosis of SM varied between good (thyroid cancer, melanoma: median survival 5+ years), average (breast cancer, NHL), and poor (acute myeloid leukemias, lung cancers: median survival 9 months). With the exception of NHL, second cancers often occurred in topographic

  18. Autoimmune hematological diseases after allogeneic hematopoietic stem cell transplantation in children: an Italian multicenter experience.

    PubMed

    Faraci, Maura; Zecca, Marco; Pillon, Marta; Rovelli, Attilio; Menconi, Maria Cristina; Ripaldi, Mimmo; Fagioli, Franca; Rabusin, Marco; Ziino, Ottavio; Lanino, Edoardo; Locatelli, Franco; Daikeler, Thomas; Prete, Arcangelo

    2014-02-01

    Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab.

  19. Management of malignant pleural mesothelioma—The European experience

    PubMed Central

    2014-01-01

    Management of malignant pleural mesothelioma (MPM) remains a clinical challenge and the incidence of the disease will continue to increase worldwide. Several aspects of mesothelioma treatment are discussed controversially, in particular, regarding extent and best type of surgery, radiotherapy, and the role of neoadjuvant or adjuvant treatment. However, best survival data is reported from groups using multimodality treatment including macroscopic complete resection (MCR) achieved by either extrapleural pneumonectomy (EPP) or (extended) pleurectomy/decortication for patients qualifying from the tumor biology, stage, and patient’s performance status and comorbidities. Several aspects have to be considered during surgery but morbidity and mortality have been reduced at experienced centres. The final analysis of extended selection algorithms is pending. PMID:24868442

  20. An intense and unforgettable experience: the lived experience of malignant wounds from the perspectives of patients, caregivers and nurses.

    PubMed

    Alexander, Susan J

    2010-12-01

    Malignant wounds occur infrequently, but are typically described as devastating and overwhelming. However, there has been little formalised research, and the vast majority of existing malignant wound literature comprises reports of health care professionals from their management of the physical symptoms. Few studies have investigated the lived experience from the perspectives of patients and nurses and none have investigated the experiences of lay caregivers caring for a patient with a malignant wound. As a result, there has been little mention in existing literature of the non physical issues associated with malignant wounds or how they might be addressed. The purpose of this study was to address this gap in knowledge by investigating the lived experience of malignant wounds from the perspectives of those living it. In-depth interviews were conducted with patients, caregivers and nurses. The data were analysed thematically within a hermeneutic phenomenological methodology to show four themes: (i) malodour; (ii) new mode of being-in-the-world; (iii) still room for hope and (iv) enduring memories. Although this study confirmed previous findings that malodour was one of the worst aspects of malignant wounds, it was significant that the other three themes occurred in the previously largely overlooked psychosocial domain.

  1. Reptile hematology.

    PubMed

    Sykes, John M; Klaphake, Eric

    2015-01-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available.

  2. Reptile Hematology.

    PubMed

    Sykes, John M; Klaphake, Eric

    2015-09-01

    The basic principles of hematology used in mammalian medicine can be applied to reptiles. The appearances of the blood cells are significantly different from those seen in most mammals, and vary with taxa and staining method used. Many causes for abnormalities of the reptilian hemogram are similar to those for mammals, although additional factors such as venipuncture site, season, hibernation status, captivity status, and environmental factors can also affect values, making interpretation of hematologic results challenging. Values in an individual should be compared with reference ranges specific to that species, gender, and environmental conditions when available.

  3. Primary prophylaxis of bacterial infections and Pneumocystis jirovecii pneumonia in patients with hematological malignancies and solid tumors : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

    PubMed

    Neumann, S; Krause, S W; Maschmeyer, G; Schiel, X; von Lilienfeld-Toal, M

    2013-04-01

    Bacterial infections are the most common cause for treatment-related mortality in patients with neutropenia after chemotherapy. Here, we discuss the use of antibacterial prophylaxis against bacteria and Pneumocystis pneumonia (PCP) in neutropenic cancer patients and offer guidance towards the choice of drug. A literature search was performed to screen all articles published between September 2000 and January 2012 on antibiotic prophylaxis in neutropenic cancer patients. The authors assembled original reports and meta-analysis from the literature and drew conclusions, which were discussed and approved in a consensus conference of the Infectious Disease Working Party of the German Society of Hematology and Oncology (AGIHO). Antibacterial prophylaxis has led to a reduction of febrile events and infections. A significant reduction of overall mortality could only be shown in a meta-analysis. Fluoroquinolones are preferred for antibacterial and trimethoprim-sulfamethoxazole for PCP prophylaxis. Due to serious concerns about an increase of resistant pathogens, only patients at high risk of severe infections should be considered for antibiotic prophylaxis. Risk factors of individual patients and local resistance patterns must be taken into account. Risk factors, choice of drug for antibacterial and PCP prophylaxis and concerns regarding the use of prophylactic antibiotics are discussed in the review.

  4. Long-term experience with (laterally) extended endopelvic resection (LEER) in relapsed pelvic malignancies.

    PubMed

    Höckel, Michael

    2015-03-01

    Gynecologic cancers recurring in the pelvis are generally advanced in malignant progression limiting curative treatment approaches. The cancer field theory links cancer progression to reversed morphogenesis and allows the exact anatomical delineation of the cancer field, i.e., the tissue compartment of potential tumor infiltration related to the tumor's ontogenetic stage. Cancer surgery is redefined with the resection of ontogenetic stage-related cancer fields instead of the mere removal of the malignant tumor with an uninvolved tissue margin. Most gynecologic pelvic malignancies recurring in the pelvis represent ontogenetic stages 3 and 4. (Laterally) extended endopelvic resection ((L)EER) has been designed to resect the cancer fields of gynecologic tumors in these advanced ontogenetic stages. This paper reports long-term experience with (L)EER for relapsed pelvic malignancies strongly supporting the cancer field theory and the principle and practice of cancer field resection.

  5. Experiment M115: Special hematologic effects: Dynamic changes in red cell shape in response to the space-flight environment

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Burns, L. C.; Fischer, C. L.

    1974-01-01

    The significance of the transformations in red cell shape observed during the Skylab study must be considered relative to the limitation of man's participation in extended space flight missions. The results of this one study are not conclusive with respect to this question. Based on these examinations of red cells in normal, healthy men and based on other Skylab experiment data relative to the functional capacity of the red cells in vitro and the performance capacity of man as an integrated system, the changes observed would not appear to be the limiting factor in determining man's stay in space. However, the results of this experiment and the documented red cell mass loss during space flight raise serious questions at this time relative to the selection criteria utilized for passengers and crews of future space flights. Until the specific cause and impact of the red cell shape change on cell survival in vivo can be resolved, individuals with diagnosed hematologic abnormalities should not be considered as prime candidates for missions, especially those of longer duration.

  6. Comparison of the effects of Ficoll-Hypaque separation and whole blood lysis on results of immunophenotypic analysis of blood and bone marrow samples from patients with hematologic malignancies.

    PubMed Central

    Tamul, K R; Schmitz, J L; Kane, K; Folds, J D

    1995-01-01

    We compared flow cytometric immunophenotyping results obtained by using the lysed whole blood method of sample preparation with those obtained by using Ficoll-Hypaque-separated cells on 44 consecutive specimens from patients with various hematologic malignancies. When the samples were analyzed as a group, seven antigens (CD2, CD3, CD5, CD11c, CD20, CD22, and CD34) demonstrated significantly different percentages of positively staining cells. When the samples were grouped by disease, results for patients with acute lymphocytic leukemia were discordant for CD22 and HLA-DR and results for patients with hairy cell leukemia were discordant for CD34. Most of the differences, however, were not with antigens critical to the evaluation of the malignancy. Additionally, the most frequent reason for differences in the percentage of positive cells was due to isotype control-based placement of the quadrant markers and not an actual discrepancy in staining. However, analysis of the CD34 antigen yielded eight instances in which staining of Ficoll-Hypaque-separated cells was essentially negative, but a clearly positive population was evident with the lysed preparation. This finding has important implications because of the prognostic significance of this antigen. Further studies are needed to determine the cause of this phenomenon. PMID:7545079

  7. NCI First International Workshop on the Biology, Prevention and Treatment of Relapse after Allogeneic Hematopoietic Cell Transplantation: Report from the Committee on Prevention of Relapse Following Allogeneic Cell Transplantation for Hematological Malignancies

    PubMed Central

    Alyea, Edwin P.; DeAngelo, Daniel J.; Moldrem, Jeffrey; Pagel, John M.; Przepiorka, Donna; Riddell, Stan; Sadelin, Michel; Young, James W.; Giralt, Sergio; Bishop, Michael

    2011-01-01

    Prevention of relapse after allogeneic hematopoietic stem cell transplantation is the most likely approach to improve survival of patients treated for hematologic malignancies. Herein we review the limits of currently available transplant therapies and the innovative strategies being developed to overcome resistance to therapy or to fill therapeutic modalities not currently available. These novel strategies include nonimmunologic therapies, such as targeted preparative regimens and posttransplant drug therapy, as well as immunologic interventions, including graft engineering, donor lymphocyte infusions, T cell engineering, vaccination and dendritic cell-based approaches. Several aspects of the biology of the malignant cells as well as the host have been identified that obviate success of even these newer strategies. To maximize the potential for success, we recommend pursuing research to develop additional targeted therapies to be used in the preparative regimen or as maintenance post-transplant, better characterize the T-cell and dendritic cells subsets involved in graft-versus-host disease and the graft-versus-leukemia/tumor effect, identify strategies for timing immunologic or nonimmunologic therapies to eliminate the noncycling cancer stem cell, identify more targets for immunotherapies, develop new vaccines that will not be limited by HLA, and develop methods to identify population at very high risk for relapse in order to accelerate clinical development and avoid toxicity in patients not at risk for relapse. PMID:20580849

  8. Avian Hematology.

    PubMed

    Jones, Michael P

    2015-09-01

    Avian veterinarians often rely heavily on the results of various diagnostic tests, including hematology results. As such, cellular identification and evaluation of the cellular response are invaluable tools that help veterinarians understand the health or condition of their patient, as well as to monitor severity and clinical progression of disease and response to treatment. Therefore, it is important to thoroughly understand how to identify and evaluate changes in the avian erythron and leukon, as well as to interpret normal and abnormal results.

  9. Avian hematology.

    PubMed

    Jones, Michael P

    2015-01-01

    Avian veterinarians often rely heavily on the results of various diagnostic tests, including hematology results. As such, cellular identification and evaluation of the cellular response are invaluable tools that help veterinarians understand the health or condition of their patient, as well as to monitor severity and clinical progression of disease and response to treatment. Therefore, it is important to thoroughly understand how to identify and evaluate changes in the avian erythron and leukon, as well as to interpret normal and abnormal results.

  10. Spacelab 1 hematology experiment (INS103): Influence of space flight on erythrokinetics in man

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Chen, J. P.; Crosby, W.; Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.; Larkin, E.; Tavassoli, M.

    1985-01-01

    An experiment conducted on the 10-day Spacelab 1 mission aboard the ninth Space Shuttle flight in November to December 1983 was designed to measure factors involved in the control of erythrocyte turnover that might be altered during weightlessness. Blood samples were collected before, during, and after the flight. Immediately after landing, red cell mass showed a mean decrease of 9.3 percent in the four astronauts. Neither hyperoxia nor an increase in blood phosphate was a cause of the decrease. Red cell survival time and iron incorporation postflight were not significantly different from their preflight levels. Serum haptoglobin did not decrease, indicating that intravascular hemolysis was not a major cause of red cell mass change. An increase in serum ferritin after the second day of flight may have been caused by red cell breakdown early in flight. Erythropoietin levels decreased during and after flight, but preflight levels were high and the decrease was not significant. The space flight-induced decrease in red cell mass may result from a failure of erythropoiesis to replace cells destroyed by the spleen soon after weightlessness is attained.

  11. 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

    2017-03-21

    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.

  12. Allogeneic hematopoietic stem cell transplant for hematological malignancies from mismatched 9/10 human leukocyte antigen unrelated donors: comparison with transplants from 10/10 unrelated donors and human leukocyte antigen identical siblings.

    PubMed

    Michallet, Mauricette; Sobh, Mohamad; Serrier, Caroline; Morisset, Stéphane; Labussière, Hélène; Ducastelle, Sophie; Barraco, Fiorenza; Gilis, Lila; Thomas, Xavier; Nicolini, Franck E

    2015-04-01

    We studied the outcome of 213 patients who received allo-HSCT for hematological malignancies, 121 (57%) from HLA identical siblings, 63 (29%) from 10/10 HLA identical unrelated donors and 29 (14%) from 9/10 HLA mismatched unrelated donors. Engraftment was lower in the 9/10 HLA group (90%) than in the 10/10 HLA group (95%) than in the sibling group (99%); 3 months CI of aGVHD ≥ 2 was 32% (23-41), 20% (15-26) and 27% (23-32) respectively; the one year CI of extensive cGVHD was 21% (13-30), 9% (5-13) and 17% (14-21) respectively. The median OS was 10 months (5-21), 18 months (11-NR) and 60 months (31-NR) respectively with 2-years probability of 19% (8-44), 43% (31-59) and 63% (54-74) respectively. TRM was significantly higher in the 9/10 HLA group with 1 year CI of 45% (35-55), compared to 33% (27-39) in the unrelated 10/10 HLA group and 12% (9-15) in the identical siblings group (p < 0.001).

  13. Ethacrynic acid oxadiazole analogs induce apoptosis in malignant hematologic cells through downregulation of Mcl-1 and c-FLIP, which was attenuated by GSTP1-1.

    PubMed

    Liu, Guyue; Wang, Rui; Wang, Yuetong; Li, Pengzhan; Zhao, Guisen; Zhao, Linxiang; Jing, Yongkui

    2013-09-01

    Ethacrynic acid, a diuretic, inhibits glutathione S-transferase P1-1 (GSTP1-1) activity and induces cell death in malignant cells at high concentrations. To improve ethacrynic acid activity, ethacrynic acid oxadiazole analogs 6s and 6u were synthesized. Although both compounds have greater antiproliferative effects than ethacrynic acid in human HL-60 cells, 6u has a reduced ability to inhibit GSTP1-1 activity. The mechanisms of both 6s- and 6u-induced cell death as well as the role of GSTP1-1 in their actions were studied. Both 6s and 6u equally induced apoptosis in HL-60 cells due to the activation of caspase-3, -9, and -8, which was correlated with the downregulation of antiapoptotic proteins c-FLIP, Mcl-1, and XIAP. The caspase inhibitor Z-VAD-FMK blocked the reduction of XIAP, but not of c-FLIP and Mcl-1, in 6s-treated cells. The reduction of c-FLIP and Mcl-1 by 6s was not blocked by the proteasomal inhibitor MG132, but was correlated with inhibition of the phosphorylation of extracellular signal-regulated kinase (ERK) and eIF4E. Both 6s and 6u decreased the intracellular glutathione (GSH) levels. N-acetylcysteine blocked reduction in the levels of Mcl-1, c-FLIP, and intracellular GSH as well as apoptosis in HL-60 cells treated by either compound. Silencing of GSTP1-1 in K562 cells sensitized, but overexpression of GSTP1-1 in Raji cells blocked, apoptosis induction by either compound. GSH conjugation at the methylene group abrogated the ability of inducing apoptosis. These data suggest that the methylene group plays an important role in the downregulation of c-FLIP and Mcl-1 proteins and apoptosis induction, which is inactivated by GSTP1-1 by forming GSH conjugates.

  14. Fludarabine Phosphate and Total-Body Radiation Followed by Donor Peripheral Blood Stem Cell Transplant and Immunosuppression in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2016-11-28

    -cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies; Waldenström Macroglobulinemia

  15. A single-center analysis of chronic graft-versus-host disease-free, relapse-free survival after alternative donor stem cell transplantation in children with hematological malignancies.

    PubMed

    Inagaki, Jiro; Fukano, Reiji; Noguchi, Maiko; Okamura, Jun

    2017-02-15

    We assessed the clinical outcomes of allogeneic hematopoietic stem cell transplantation (SCT) from alternative donors for pediatric patients with hematological malignancies, defining graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) as a composite endpoint. We also defined chronic GVHD-free, relapse-free survival (cGRFS) as survival without severe chronic GVHD, relapse, or death. The probabilities of 2-year disease-free survival from a human leukocyte antigen (HLA) matched unrelated donor (n = 57), related donor with HLA-1 antigen mismatch in the graft-versus-host direction (1Ag-GvH-MMRD, n = 28), and unrelated umbilical cord blood (n = 35) were 52.2, 38.5, and 40.4%, respectively (P = 0.14), and for 2-year GRFS were 26.2, 13.4, and 30.4%, respectively (P = 0.089), and for 2-year cGRFS were 36.2, 16.7, and 40.4%, respectively (P = 0.015). Of the three groups, the 1Ag-GvH-MMRD group showed a significantly higher cumulative incidence of severe cGVHD, and was identified as a significant risk factor for worse cGRFS. These results suggest that intensification of GVHD prophylaxis may be needed for SCT from 1Ag-GvH-MMRD. As with GRFS, cGRFS should be used as an endpoint of the clinical study to predict long-term morbidity and mortality for patients who need longer follow-up such as pediatric SCT recipients.

  16. Analysis of memory-like natural killer cells in human cytomegalovirus-infected children undergoing αβ+T and B cell-depleted hematopoietic stem cell transplantation for hematological malignancies.

    PubMed

    Muccio, Letizia; Bertaina, Alice; Falco, Michela; Pende, Daniela; Meazza, Raffaella; Lopez-Botet, Miguel; Moretta, Lorenzo; Locatelli, Franco; Moretta, Alessandro; Della Chiesa, Mariella

    2016-03-01

    We analyzed the impact of human cytomegalovirus infection on the development of natural killer cells in 27 pediatric patients affected by hematological malignancies, who had received a HLA-haploidentical hematopoietic stem cell transplantation, depleted of both α/β+ T cells and B cells. In line with previous studies in adult recipients of umbilical cord blood transplantation, we found that human cytomegalovirus reactivation accelerated the emergence of mature natural killer cells. Thus, most children displayed a progressive expansion of a memory-like natural killer cell subset expressing NKG2C, a putative receptor for human cytomegalovirus, and CD57, a marker of terminal natural killer cell differentiation. NKG2C(+)CD57(+) natural killer cells were detectable by month 3 following hematopoietic stem cell transplantation and expanded until at least month 12. These cells were characterized by high killer Ig-like receptors (KIRs) and leukocyte inhibitory receptor 1 (LIR-1) and low Siglec-7, NKG2A and Interleukin-18Rα expression, killed tumor targets and responded to cells expressing HLA-E (a NKG2C ligand). In addition, they were poor Interferon-γ producers in response to Interleukin-12 and Interleukin-18. The impaired response to these cytokines, together with their highly differentiated profile, may reflect their skewing toward an adaptive condition specialized in controlling human cytomegalovirus. In conclusion, in pediatric patients receiving a type of allograft different from umbilical cord blood transplantation, human cytomegalovirus also induced memory-like natural killer cells, possibly contributing to controlling infections and reinforcing anti-leukemia effects.

  17. Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study.

    PubMed

    Berger, Massimo; Lanino, Edoardo; Cesaro, Simone; Zecca, Marco; Vassallo, Elena; Faraci, Maura; De Bortoli, Massimiliano; Barat, Veronica; Prete, Arcangelo; Fagioli, Franca

    2016-05-01

    Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high-risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients.

  18. Radiotherapy applications of patients with malignant mesothelioma: A single center experience

    PubMed Central

    Akmansu, Muge; Erpolat, Ozge Petek; Goksel, Fatih; Tunc, Evrim; Ozturk, Can

    2012-01-01

    Background In the management of malignant pleural mesothelioma, radiotherapy has been used for the purpose of prophylaxis to reduce the incidence of recurrence at surgical insertion sites or palliate the symptoms. Aim The purpose of the study was to evaluate the techniques and effectiveness of radiotherapy in malignant pleural mesothelioma. Materials and methods Forty-four (18 female, 26 male) patients diagnosed with malignant pleural mesothelioma were retrospectively evaluated. All patients had surgery or thoracoscopic biopsy for diagnosis, staging or treatment and all received palliative or prophylactic radiotherapy. Fifty-seven percent of the patients received chemotherapy. Results Prophylactic radiation was applied to 27 patients with 4–15 MeV electron energies. The median radiotherapy dose was 30 Gy with 3 Gy daily fraction dose. During treatment, 12 patients had grade 1 erythema according to the RTOG scale. In 3 (12%) patients, a local failure at treatment field was observed. Palliative radiotherapy was applied to 17 patients for pain palliation. The median radiation dose was 40 Gy with 2 Gy daily fraction dose by using 6–18 MV photon and/or 4–12 MeV electron energies. Two patients had grade 1 erythema and one patient had grade 2 odynophagy according to the RTOG scale. For 10 (59%) patients, palliation of chest pain was delivered. No late toxicity was observed for all cases. Conclusion Our experience showed that prophylactic and palliative radiotherapy are effective and safe therapy modalities in malignant pleural mesothelioma in preventing seeding metastasis at intervention sites or relieving pain. Prospective randomized studies are still needed to determine the benefits of radiotherapy application and to indicate optimum dose schemes. PMID:24416534

  19. Mycophenolate Mofetil and Cyclosporine in Reducing Graft-Versus-Host Disease in Patients With Hematologic Malignancies or Metastatic Kidney Cancer Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-02-27

    /Lymphoma; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Renal Cell Cancer; T-cell Large Granular Lymphocyte Leukemia; Type 1 Papillary Renal Cell Carcinoma; Type 2 Papillary Renal Cell Carcinoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies; Waldenström Macroglobulinemia

  20. Patients’ experiences of chronic non-malignant musculoskeletal pain: a qualitative systematic review

    PubMed Central

    Toye, Francine; Seers, Kate; Allcock, Nick; Briggs, Michelle; Carr, Eloise; Andrews, JoyAnn; Barker, Karen

    2013-01-01

    Background Musculoskeletal (MSK) pain is one of the most predominant types of pain and accounts for a large portion of the primary care workload. Aim To systematically review and integrate the findings of qualitative research to increase understanding of patients’ experiences of chronic non-malignant MSK pain. Design and setting Synthesis of qualitative research using meta-ethnography using six electronic databases up until February 2012 (Medline, Embase, Cinahl, Psychinfo, Amed and HMIC). Method Databases were searched from their inception until February 2012, supplemented by hand-searching contents lists of specific journals for 2001–2011 and citation tracking. Full published reports of qualitative studies exploring adults’ own experience of chronic non-malignant MSK pain were eligible for inclusion. Results Out of 24 992 titles, 676 abstracts, and 321 full texts were screened, 77 papers reporting 60 individual studies were included. A new concept of pain as an adversarial struggle emerged. This adversarial struggle was to: 1) affirm self; 2) reconstruct self in time; 3) construct an explanation for suffering; 4) negotiate the healthcare system; and 5) prove legitimacy. However, despite this struggle there is also a sense for some patients of 6) moving forward alongside pain. Conclusions This review provides a theoretical underpinning for improving patient experience and facilitating a therapeutic collaborative partnership. A conceptual model is presented, which offers opportunities for improvement by involving patients, showing them their pain is understood, and forming the basis to help patients move forward alongside their pain. PMID:24351499

  1. End of life care in hematology: still a challenging concern.

    PubMed

    Niscola, Pasquale; Tendas, Andrea; Scaramucci, Laura; Giovannini, Marco

    2014-01-01

    The majority of patients with hematological malignancies (HM) may experience troublesome symptoms and complicating clinical syndromes throughout all phases of disease. Therefore, among the current concepts concerning the comprehensive management of hematological patients, palliative care should exert a more ever expanding role, in particular in the advanced phases of disease, as there are special clinical needs (such as blood transfusions and anti-infective treatments), presented by this peculiar category of cancer patients. However, reported experiences on advanced HM patients claimed a too intensive level of medical care during the last week of life for which the needs of future and collaborative researches in order to set a proper allocation of medical resources and the optimal end-of-life care in the hematologic setting are highly awaited. Indeed, the most important aspect of caring for these suffering patients is to ameliorate or restore their quality of life (QoL) though a highly humanized approach, whereas technological and pharmacological measures should be limited enough to control the symptoms burden and the several kinds of sufferance that may complicate the final phase of disease course.

  2. Zebrafish in hematology: sushi or science?

    PubMed Central

    Carradice, Duncan

    2008-01-01

    After a decade of the “modern era” of zebrafish hematology research, what have been their major contributions to hematology and what challenges does the model face? This review argues that, in hematology, zebrafish have demonstrated their suitability, are proving their utility, have supplied timely and novel discoveries, and are poised for further significant contributions. It presents an overview of the anatomy, physiology, and genetics of zebrafish hematopoiesis underpinning their use in hematology research. Whereas reverse genetic techniques enable functional studies of particular genes of interest, forward genetics remains zebrafish's particular strength. Mutants with diverse and interesting hematopoietic defects are emerging from multiple genetic screens. Some mutants model hereditary blood diseases, occasionally leading to disease genes first; others provide insights into developmental hematology. Models of malignant hematologic disorders provide tools for drug-target and pharmaceutics discovery. Numerous transgenic zebrafish with fluorescently marked blood cells enable live-cell imaging of inflammatory responses and host-pathogen interactions previously inaccessible to direct observation in vivo, revealing unexpected aspects of leukocyte behavior. Zebrafish disease models almost uniquely provide a basis for efficient whole animal chemical library screens for new therapeutics. Despite some limitations and challenges, their successes and discovery potential mean that zebrafish are here to stay in hematology research. PMID:18182572

  3. OPSI threat in hematological patients

    PubMed Central

    Serio, B; Pezzullo, L; Giudice, V; Fontana, R; Annunziata, S; Ferrara, I; Rosamilio, R; De Luca, C; Rocco, M; Montuori, N; Selleri, C

    Overwhelming post-splenectomy infection (OPSI) is a rare medical emergency, mainly caused by encapsulated bacteria, shortly progressing from a mild flu-like syndrome to a fulminant, potentially fatal, sepsis. The risk of OPSI is higher in children and in patients with underlying benign or malignant hematological disorders. We retrospectively assessed OPSI magnitude in a high risk cohort of 162 adult splenectomized patients with malignant (19%) and non malignant (81%) hematological diseases, over a 25-year period: 59 of them splenectomized after immunization against encapsulated bacteria, and 103, splenectomized in the previous 12-year study, receiving only life-long oral penicillin prophylaxis. The influence of splenectomy on the immune system, as well as the incidence, diagnosis, risk factors, preventive measures and management of OPSI are also outlined. OPSI occurred in 7 patients (4%) with a median age of 37 years at time interval from splenectomy ranging from 10 days to 12 years. All OPSIs occurred in non immunized patients, except one fatal Staphylococcus aureus -mediated OPSI in a patient adequately immunized before splenectomy. Our analysis further provides evidence that OPSI is a lifelong risk and that current immune prophylaxis significantly decreases OPSI development. Improvement in patients’ education about long-term risk of OPSI and increased physician awareness to face a potentially lethal medical emergency, according to the current surviving sepsis guidelines, represent mandatory strategies for preventing and managing OPSI appropriately. PMID:24251241

  4. Artificial intelligence in hematology.

    PubMed

    Zini, Gina

    2005-10-01

    Artificial intelligence (AI) is a computer based science which aims to simulate human brain faculties using a computational system. A brief history of this new science goes from the creation of the first artificial neuron in 1943 to the first artificial neural network application to genetic algorithms. The potential for a similar technology in medicine has immediately been identified by scientists and researchers. The possibility to store and process all medical knowledge has made this technology very attractive to assist or even surpass clinicians in reaching a diagnosis. Applications of AI in medicine include devices applied to clinical diagnosis in neurology and cardiopulmonary diseases, as well as the use of expert or knowledge-based systems in routine clinical use for diagnosis, therapeutic management and for prognostic evaluation. Biological applications include genome sequencing or DNA gene expression microarrays, modeling gene networks, analysis and clustering of gene expression data, pattern recognition in DNA and proteins, protein structure prediction. In the field of hematology the first devices based on AI have been applied to the routine laboratory data management. New tools concern the differential diagnosis in specific diseases such as anemias, thalassemias and leukemias, based on neural networks trained with data from peripheral blood analysis. A revolution in cancer diagnosis, including the diagnosis of hematological malignancies, has been the introduction of the first microarray based and bioinformatic approach for molecular diagnosis: a systematic approach based on the monitoring of simultaneous expression of thousands of genes using DNA microarray, independently of previous biological knowledge, analysed using AI devices. Using gene profiling, the traditional diagnostic pathways move from clinical to molecular based diagnostic systems.

  5. A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies

    PubMed Central

    Chen, Ping; Yuan, Xiaohong; Luo, Xiaofeng; Liu, Tingbo; Zheng, Jing; Zheng, Zhihong; Zheng, Xiaoyun; Chen, Xinji; Zhang, Langhui; Zheng, Hao; Chen, Zaisheng; Hua, Xueling; Le, Shaohua; Li, Jian; Chen, Zhizhe; Hu, Jianda

    2016-01-01

    Haplo-HSCT has been used when HLA-matched siblings are not available. Conditioning regimens aim to reduce tumor burden prior to HSCT and provide sufficient immunoablation. We report the outcome of haplo-HSCT in 63 consecutive patients from 2/2013 to 12/2015 (19 females/44 males) with high-risk or relapsed/refractory hematological malignancies (n=29-AML; 8-sAML; 19-ALL; 5-advanced-MDS; 2-CML-BC). Median age was 20 years (range: 1.1-49). Twenty-one patients achieved remission prior to transplant, while 42 did not. Patients received FA5-BUCY, i.e., 5-day salvage chemotherapy (Fludarabine/Ara-C) and conditioning (Busulfan/Cyclophosphamide). GvHD prophylaxis included ATG, CsA, MMF and short-term MTX. All patients received stem cells from bone marrow and peripheral blood, and achieved successful engraftment, except two who died before. With a median follow-up of 269 days (120-1081), 42/63 patients are still alive and disease-free. Two-year OS and RFS were similar in patients not in remission and in those in complete remission (61.3% vs 56.3%, p=0.88; 58.3% vs 56.3%, p=0.991). Non-relapse mortality and relapse incidence were 22.2% and 11.1%, respectively. Severe acute-GvHD occurred in 4/63 patients. Transplant-related mortality was low at day+100 (17.5%) and for the entire study period (20.6%). Unexpectedly, few patients experienced mild-to-moderate toxicity, and main causes of death were infection and GvHD. BM blast counts, age, and donor-recipient gender-pairs did not affect the outcome. Less chemotherapy cycles prior to HSCT might result in more favorable outcome. Thus, haplo-HSCT with FA5-BUCY appears promising for advanced disease, especially when TBI and amsacrine, used for FLAMSA, are not available and in pediatric patients for whom TBI is not recommended. PMID:27705929

  6. Filgrastim-Stimulated Bone Marrow Compared with Filgrastim-Mobilized Peripheral Blood in Myeloablative Sibling Allografting for Patients with Hematologic Malignancies: A Randomized Canadian Blood and Marrow Transplant Group Study.

    PubMed

    Couban, Stephen; Aljurf, Mahmoud; Lachance, Sylvie; Walker, Irwin; Toze, Cynthia; Rubinger, Morel; Lipton, Jeffrey H; Lee, Stephanie J; Szer, Richard; Doocey, R; Lewis, Ian D; Huebsch, Lothar; Howson-Jan, Kang; Lalancette, Michel; Almohareb, Fahad; Chaudhri, Nadeem; Ivison, Sabine; Broady, Raewyn; Levings, Megan; Fairclough, Diane; Devins, Gerald; Szwajcer, David; Foley, Ronan; Smith, Clayton; Panzarella, Tony; Kerr, Holly; Kariminia, Amina; Schultz, Kirk R

    2016-08-01

    In adult hematopoietic cell transplantation (HCT), filgrastim-mobilized peripheral blood (G-PB) has largely replaced unstimulated marrow for allografting. Although the use of G-PB results in faster hematopoietic recovery, it is also associated with more chronic graft-versus-host disease (cGVHD). A potential alternative allograft is filgrastim-stimulated marrow (G-BM), which we hypothesized may be associated with prompt hematopoietic recovery but with less cGVHD. We conducted a phase 3, open-label, multicenter randomized trial of 230 adults with hematologic malignancies receiving allografts from siblings after myeloablative conditioning to compare G-PB with G-BM. The primary endpoint was time to treatment failure, defined as a composite of extensive cGVHD, relapse/disease progression, and death. With a median follow-up of 36 months (range, 9.6 to 48), comparing G-BM with G-PB, there was no difference between the 2 arms with respect to the primary outcome of this study (hazard ratio [HR], .91; 95% confidence interval [CI], .68 to 1.22; P = .52). However, the cumulative incidence of overall cGVHD was lower with G-BM (HR, .66; 95% CI, .46 to .95; P = .007) and there was no difference in the risk of relapse or progression (P = .35). The median times to neutrophil recovery (P = .0004) and platelet recovery (P = .012) were 3 days shorter for recipients allocated to G-PB compared with those allocated to G-BM, but there were no differences in secondary engraftment-related outcomes, such as time to first hospital discharge (P = .17). In addition, there were no graft failures in either arm. This trial demonstrates that, compared with G-PB, the use of G-BM allografts leads to a significantly lower rate of overall cGVHD without a loss of the graft-versus-tumor effect and comparable overall survival. Our findings suggest that further study of this type of allograft is warranted.

  7. Surgery for massive malignant tumors of the left atrium – one center’s experience

    PubMed Central

    Andrushchuk, Uladzimir; Ostrovsky, Youry; Zharkov, Vladimir; Krutau, Valery; Yudina, Olga; Ilyina, Tatsiana; Grinchuk, Irina

    2016-01-01

    Introduction Surgery for primary non-resectable malignant tumors of the left atrium is controversial. Today heart autotransplantation as a method of surgical treatment for patients suffering primary massive malignant tumors of the left atrium is still not sufficiently studied. Material and methods We provide information on our single-center 5-year experience in performing surgical interventions for massive malignant tumors of the left atrium and including cases of 5 patients (3 males – 60%, 2 females – 40%). One case (1/5, 20%) involved debulking surgery with partial resection of the left atrial (LA) wall and its reconstruction using a xenopericardium patch. Orthotopic heart transplantation was performed in 1 patient (1/5, 20%) and heart autotransplantation (HA) in the 3 other cases (3/5, 60%). Results Mean myocardial ischemia duration was 165.6 ±12.0 minutes (range: 137–198), cardiopulmonary bypass (CPB) duration was 248.6 ±36.6 minutes (range: 188–392), and intervention duration was 498.0 ±77.4 minutes (range: 330–780). Mean total blood loss was estimated to be 2432 ±616.5 ml (range: 1610–4880). Major in-hospital complications were registered in 4 patients (4/5, 80%). In-hospital mortality was registered in 3 patients (3/5, 60%). Survival time in 2 (2/5, 40%) patients discharged from the hospital was 29 and 9 months, respectively. Both died because of disease progression. Conclusions Surgery in patients with massive resectable primary malignant tumor of the left atrium is associated with high incidence of major hospital complications and mortality. Heart autotransplantation with radical tumor resection is the treatment of choice for these cases. The surgical approach implies thorough primary hemostasis and selection of a proper surgical approach, allowing revision of all the regions of intervention during each step. The possibility of excessive tension and bleeding in the area of bicaval anastomosis should be considered when performing heart

  8. Photodynamic Therapy in Gynecologic Malignancies: A Review of the Roswell Park Cancer Institute Experience

    PubMed Central

    Mayor, Paul C.; Lele, Shashikant

    2016-01-01

    Photodynamic therapy (PDT) is a treatment modality used in the management of solid tumor malignancies that employs the use of a photosensitizing agent, a light source and oxygen in order to illicit a direct cytotoxic effect. Its use in gynecologic malignancies is somewhat novel and has been used for palliative and curative intent. At the Roswell Park Cancer Institute, the use of PDT in the management of gynecologic cancers began in the mid 1980s and since that time 35 patients have received PDT as a treatment for recurrent or metastatic cutaneous and vulvar, vaginal, anal, and cervical recurrences. In our experience, 85% patients with metastatic cutaneous lesions had a complete response. Twenty-seven percent of patients with metastatic vaginal, cervical or anal recurrences had a complete response to therapy with a median response time of 28 months. Side effects from the treatment included moderate to severe burning sensation, pain and edema at the treatment site requiring narcotic pain medication for symptom management in patients who underwent treatment to cutaneous lesions as well as lower genital tract recurrences. PDT should be considered an option in patients who are too frail to undergo the standard of care or decline the standard of care in lieu of a less invasive treatment modality. PMID:27669307

  9. Vasculitis associated with malignancy.

    PubMed

    Mertz, L E; Conn, D L

    1992-02-01

    A large variety of vasculopathic syndromes are uncommonly associated with malignancies. Vasculitis is usually manifested by skin lesions and is generally associated with hematologic malignancies rather than solid tumors. Evidence of autoantibodies, immune complexes, and complement consumption is typically absent. Myelodysplastic syndromes can be confidently linked to vasculitis on the basis of recent literature. The temporal relationship of malignancy to vasculitis development is variable except that vasculitis generally follows the discovery of hairy cell leukemia and splenectomy. Vasculitis may occasionally be a complication of chemotherapy, radiation therapy, and bone marrow transplantation. Occasionally, malignant disorders may mimic vasculitic syndromes. The etiopathogenesis of vasculitis in patients with malignant disorders is unknown. The recent literature on vasculitis and malignancy addresses predominantly case reports and small patient cohorts and identifies clinical characteristics rather than pathogenic mechanisms.

  10. 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.

  11. 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

  12. Parainfluenza virus type 3 infections in a hematology unit.

    PubMed

    Hohenthal, U; Nikoskelainen, J; Vainionpää, R; Peltonen, R; Routamaa, M; Itälä, M; Kotilainen, P

    2001-02-01

    Parainfluenza virus type 3 (PIV3) is associated with a high mortality rate in BMT recipients with lower respiratory tract infections. We describe nine patients with hematological malignancies (five having undergone either allogeneic or autologous stem cell transplantation) identified as having PIV3 infection during a 2-month period in a Hematology Unit. Four patients with infiltrates on chest radiograph received intravenous ribavirin therapy; all survived. The infection was community-acquired in two patients, while nosocomial origin of the disease was evident, or presumed, in the remaining seven. The policy implemented to control the spread of PIV3 was as follows: (1) nasopharyngeal samples for antigen detection were obtained from all patients presenting with respiratory symptoms; (2) all diagnosed (or suspected) PIV3-positive hematological patients were nursed following contact isolation precautions, preferably in the Infectious Diseases Unit; and (3) staff were given further education on hospital hygiene. Our experience shows that it may be possible to avoid mortality for PIV3 lower respiratory tract infection in immunocompromised patients by early commencement of intravenous ribavirin. It is also possible, even without closing the ward, to contain nosocomial spread of PIV3 by implementing systematic nasopharyngeal sampling for rapid diagnostics, and by strict adherence to cohorting and contact isolation precautions.

  13. The Psychosocial Experience of Adolescents with Haematological Malignancies in Jordan: An Interpretive Phenomenological Analysis Study

    PubMed Central

    2014-01-01

    The qualitative research method of interpretive phenomenological analysis was used to explore the lived experience of 14 Jordanian adolescents with haematological malignancies. They were admitted to two hospitals in Jordan and were interviewed for this study twice during the first six months after receiving their diagnosis. The results of this study revealed three themes: (1) Being in hospital, (2) The changing self, and (3) Fearing the unknown. When the participants were hospitalised due to their illness they were removed from their families and friends and prevented from engaging in their normal daily routine. Participants also reported receiving limited emotional and psychological support from health team members during hospitalisation. From the onset of cancer treatments, the bio-psychosocial side effects of the chemotherapy became one of the most distressing factors for participants affecting all aspects of their life and generated uncertainty about their future. The findings add to existing understanding of the lived experiences of cancer patients and in particular Jordanian adolescents. They provide a valuable insight for clinicians into improvements in service delivery to this group of patients. PMID:24550700

  14. Neonatal hematologic disorders.

    PubMed

    Purves, Erica

    2005-01-01

    Neonatal hematology is a complex subspecialty of pediatric hematology, combining the unique aspects of the maternal/fetal relationship, the delicate balance of coagulation factors, and the distinctive physiologic conditions of the newborn period. The objective of this article is to briefly review specific hematologic disorders that commonly present in the newborn period. Alloimmune cytopenias, polycythemia, thrombosis and bleeding associated with vitamin K deficiency will be discussed through a focus on pathophysiology, signs and symptoms, current treatment strategies, and implications for nursing care.

  15. Hematologic disorders of fish.

    PubMed

    Clauss, Tonya M; Dove, Alistair D M; Arnold, Jill E

    2008-09-01

    Hematology can be a useful tool for monitoring health status, detecting illness, and following the progress of disease and response to therapy. Despite advances in fish medicine in recent years, interpretation of fish hematology often is hampered by a lack of meaningful reference values and the bewildering diversity of fish species. A multitude of intrinsic and extrinsic factors cause normal and abnormal variation in hematologic data. This article provides an overview of some of the hematologic abnormalities in fish induced by infectious agents and environmental, husbandry, and nutritional issues.

  16. Malignancies in a renal transplant population: The St. Michael's Hospital experience

    PubMed Central

    Saleeb, R.; Faragalla, H.; Yousef, G. M.; Stewart, R.; Streutker, C. J.

    2016-01-01

    Introduction: Previous publications have shown an increased incidence of various malignancies amongst renal transplant populations. The objective of this study was to analyze the rate and types of malignancies occurring in the St. Michael's Hospital renal transplant population and to determine whether our results were comparable to those previously published. Methods: After approval by the hospital's research ethic board, review of the records and pathology of the 1584 patients in the renal transplant clinic database patients was performed. The reports dated back to the year 1970. Results: Amongst the 1584 renal transplant patients, 106 patients with 132 dysplastic and malignant posttransplant lesions were identified. The highest incidence amid the malignancies was in nonmelanoma skin malignancies squamous cell carcinoma (SCC), basal cell carcinoma, and Kaposi sarcoma, with a total of 32 patients having 54 separate tumors (2.02% of all patients, 43.2% of tumors). Following skin tumors in incidence were genitourinary (28 tumors), gastrointestinal tract (GIT) lesions (8 adenocarcinomas, 14 dysplastic lesions, 1 low grade neuroendocrine tumor/carcinoid), posttransplant lymphoproliferative disorders (PTLDs) (10 cases), gynecologic (6 carcinomas), cervical/anal/vulvar dysplasia and invasive (SCCs) (4), and thyroid (3 papillary tumors). Nine patients had tumors of multiple sites/types. With respect to outcome, 14 patients died of malignancy, with the highest mortality being in the GIT malignancies (six patients). Second in mortality were the PTLD and skin tumor groups. Discussion: Information on the incidence and outcome of various malignancies in renal transplant patients is important in designing guidelines for the follow-up of these patients regarding tumor screening and prevention. The rate of malignancies in our group is comparable to that reported in other centers. PMID:27141185

  17. Thiopurines related malignancies in inflammatory bowel disease: Local experience in Granada, Spain

    PubMed Central

    Gómez-García, María; Cabello-Tapia, Maria José; Sánchez-Capilla, Antonio Damián; De Teresa-Galván, Javier; Redondo-Cerezo, Eduardo

    2013-01-01

    , 27.27% (112 patients) and 11.66% (50 patients) received treatment with Infliximab and Adalimumab respectively, but only 1.83% (7 patients) and 0.78% (3 patients) received these drugs in the group of patients who did not received thiopurines (P < 0.001 and P < 0.001 respectively). Finally, 6.8% (29 patients) among those treated with thiopurines have received other immunesupresants (Methotrexate, Tacrolimus, Cyclosporin), compare to 1% (4 patients) of patients not treated with thiopurines (P < 0.001). Among patients treated with thiopurines, 3.97% developed a malignancy, and among those not treated neoplasms presented in 8.1% (P = 0.013). The most frequent neoplasms were colorectal ones (12 cases in patients not treated with thiopurines but none in treated, P < 0.001) followed by non-melanoma skin cancer (8 patients in treated with thiopurines and 6 in not treated, P > 0.05). CONCLUSION: In our experience, thiopurine therapy did not increase malignancies development in IBD patients, and was an efective and safe treatment for these diseases. PMID:23946592

  18. Clinical development of demethylating agents in hematology

    PubMed Central

    Navada, Shyamala C.; Steinmann, Juliane; Lübbert, Michael; Silverman, Lewis R.

    2014-01-01

    The term epigenetics refers to the heritable changes in gene expression that are not associated with a change in the actual DNA sequence. Epigenetic dysregulation is linked to the pathogenesis of a number of malignancies and has been studied extensively in myelodysplastic syndromes and acute myeloid leukemia. DNA methylation is frequently altered in cancerous cells and likely results in transcriptional silencing of tumor suppressor genes. Re-expression of these genes by inhibition of the DNA methyltransferases has been successful in the treatment of benign and malignant disease. In this Review, we discuss the clinical development of demethylating agents in hematology, with a focus on azacitidine and decitabine. PMID:24382388

  19. Primary-to-secondary care referral experience of suspected colorectal malignancy in young adults

    PubMed Central

    Patel, K; Doulias, T; Hoad, T; Lee, C; Alberts, JC

    2016-01-01

    Introduction Colorectal cancer in patients younger than 50 years of age is increasing steadily in the UK with limited guidelines available indicating need for secondary care referral. The aims of this study were to report the cancer incidence in those aged under 50 years referred to secondary care with suspected colorectal malignancy and also to analyse the quality of those referrals. Methods A total of 197 primary care referrals made between 2008 and 2014 to a UK district general hospital for suspected colorectal malignancy were analysed. All confirmed cancers were further evaluated regarding presenting symptoms, tumour characteristics and clinical outcomes. Each referral was given a referral performance score (out of 9) dependant on relevant information documented. Results The overall malignancy rate was 9.1% (11 male and 7 female patients). The median age in this cohort was 41.5 years (interquartile range [IQR]: 37–49 years). Abdominal pain was the only presenting symptom to differ significantly when comparing malignant with non-malignant patients (44.4% vs 21.8% respectively, p=0.042). The median time period between referral date and colorectal specialist consultation was 11 days (IQR: 7–13 days) and the median referral performance score was 5 (range: 3–9). Conclusions Malignancy is prevalent in patients under 50 years of age who are referred to secondary care for suspected colorectal cancer. Those referred with abdominal pain in the presence of other high risk lower gastrointestinal symptoms are at significant risk of having a malignancy. Major deficiencies are apparent in urgent primary care referrals, highlighting the need for further national guidance to aid early diagnosis of colorectal cancer in the young. PMID:27023637

  20. Managing critically Ill hematology patients: Time to think differently.

    PubMed

    Azoulay, Elie; Pène, Frédéric; Darmon, Michael; Lengliné, Etienne; Benoit, Dominique; Soares, Marcio; Vincent, Francois; Bruneel, Fabrice; Perez, Pierre; Lemiale, Virginie; Mokart, Djamel

    2015-11-01

    The number of patients living with hematological malignancies (HMs) has increased steadily over time. This is the result of intensive and effective treatments that also increase the probability of infiltrative, infectious or toxic life threatening event. Over the last two decades, the number of patients with HMs admitted to the ICU increased and their mortality has dropped sharply. ICU patients with HMs require an extensive diagnostic workup and the optimal use of ICU treatments to identify the reason for ICU admission and the nature of the complication that explains organ dysfunctions. Mortality of ARDS or septic shock is up to 50%, respectively. In this review, the authors share their experience with managing critically ill patients with HMs. They discuss the main aspects of the diagnostic and therapeutic management of critically ill patients with HMs and argue that outcomes have improved over time and that many classic determinants of mortality have become irrelevant.

  1. Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience.

    PubMed

    Zilinska, Z; Sersenova, M; Chrastina, M; Sr, J Breza; Bena, L; Baltesova, T; Jurcina, A; Roland, R; Lackova, E; Cellar, M; Laca, L; Dedinska, I

    2017-01-05

    Malignancies are one of the three major causes of renal recipient´s death with a functioning graft after cardiovascular diseases and infections. Among the variety of risk factors, including conventional and specific to transplant recipients, the duration of immunosuppressive therapy, the intensity of therapy, and the type of immunosuppressive agent all have an impact on development of post-transplant malignancy. The aim of our retrospective study was to document the incidence, the type of malignancies, the patient/graft survival in the group of kidney transplant recipients in Slovak Republic, and to identify the factors which influenced the outcome. We analyzed the data of 1421 patients who underwent renal transplantation from deceased or living donors in the period from 2007 to 2015 in the Slovak transplant centers. The incidence of malignant tumors was 6%, the malignancy was diagnosed in 85 patients at the age of 54.1 ± 9.8 years, more frequently in men (68.2 %; P < 0.0001). The mean time of malignancy occurrence was 45 months after transplantation. The most frequent malignancies were skin cancers- basal cell carcinoma (BCC) in 17.6%, squamous cell carcinoma (SCC) in 8.2%, and malignant melanoma (MM) in 2.4% of patients, followed by non-skin tumors such as renal cell carcinoma (RCC) in 16.5%, cancer of colon in 12.9%, prostatic cancer in 9.4%, breast cancer in 9.4%, cancer of lung in 7.1%, post-transplant lymphoproliferative disease (PTLD) in 2.4%, cancer of urine bladder in 2.4%, and cancer of sublingual gland in 1.17% of patients. Surgical treatment was used in 40% of patients, chemotherapy in 7.1%, radiotherapy in 2.4%, treatment with biological agents in 15.3%, combined therapy in 29.4% and palliative treatment in 5.9% of patients. 55.3% of patients underwent conversion from other immunosuppressive agents into mTORi at the time of malignancy occurrence. The remission was achieved in 48.2% of patients, 28.2% of patients were in the oncology treatment in the

  2. Predictors of malignancy in patients with pheochromocytomas/paragangliomas: Asian Indian experience

    PubMed Central

    Sarathi, Vijaya; Kasaliwal, Rajeev; Pandit, Reshma; Goroshi, Manjunath; Malhotra, Gaurav; Dalvi, Abhay; Bakshi, Ganesh; Bhansali, Anil; Rajput, Rajesh; Shivane, Vyankatesh; Lila, Anurag; Bandgar, Tushar; Shah, Nalini S

    2016-01-01

    Background and aims Malignant transformation of pheochromocytomas/paragangliomas (PCC/PGL) is a rare occurrence, and predictive factors for the same are not well understood. This study aims to identify the predictors of malignancy in patients with PCC/PGL. Materials and methods We performed a retrospective analysis of 142 patients with either PCC or PGL registered at our institute between 2000 and 2015. Records were evaluated for clinical parameters like age, gender, familial/syndromic presentation, symptomatic presentation, biochemistry, size, number and location of tumours and presence of metastases and mode of its diagnosis. Results Twenty patients were found to have metastases; 13 had metastases at diagnosis and seven during follow-up. Metastases were detected by radiology (CT-neck to pelvis) in 11/20 patients (5/13 synchronous and 6/7 metachronous), 131I-metaiodobenzylguanidine in five (2/12 synchronous and 3/6 metachronous) patients and 18F-flurodeoxyglucose PET/CT in 15 (12/12 synchronous and 3/3 metachronous) patients. Malignant tumours were significantly larger than benign tumours (8.3 ± 4.1 cm, range: 3–22 cm vs 5.7 ± 2.3 cm, range: 2–14 cm, P = 0.0001) and less frequently metanephrine secreting. On linear regression analysis, tumour size and lack of metanephrine secretion were the independent predictors of malignancy. Conclusions Patients with primary tumour size >5.7 cm and lack of metanephrine secretory status should be evaluated for possible malignancy not only at diagnosis but also in the postoperative period. As compared to CT and 131I-MIBG scan, 18F-flurodeoxyglucose PET/CT analyses are better (sensitivity: 100%) for the diagnosis of metastases in our study. PMID:27852633

  3. Incidences of malignancy in chronic burn scar ulcers: experience from Bangladesh.

    PubMed

    Das, Kishore Kumar; Chakaraborty, Anjana; Rahman, Ashrafur; Khandkar, Sazzad

    2015-09-01

    Malignant transformation on any scar tissue is known as Marjolin's ulcer. Most cases of Marjolin's ulcer reported so far occur in post-burn scars but not all ulcers that occur in post-burn scar are malignant. One hundred and forty cases of chronic non-healing ulcers in post-burn scar were included in this prospective observational study. The study was conducted in the Department of Burn and Plastic Surgery Unit of Dhaka Medical College Hospital. Mean age of the patients was 40.63±18.44 with a range from 12 to 75 years. Two third of the patients were male. All patients underwent excision biopsy and coverage with either split thickness skin graft or flap. Histopathological analysis of the resected specimen revealed malignancy in 46 cases and pseudoepitheliomatous hyperplasia in four cases and verruca plantaris in one case. The rest of the cases were chronic non-healing benign ulcers. All 46 cases of Marjolin's ulcer were squamous cell carcinoma with a mean latency period of 26.73 years. The commonest site of chronic ulcer was in the lower extremities (n-80, 57%), and malignancy was also found to be more common there (n-18). The most common type of burn was flame burn (68.57%). The Marjolin's ulcers were significantly larger in size than benign ulcers, and were mostly exophytic or ulcerative in appearance whereas benign ulcers were mostly flat. A non-healing ulcer in a post-burn scar should be addressed promptly because of its potential to develop into a malignant ulcer. Emphasis should be given to early surgical treatment of deep partial to full thickness burns to prevent scar formation, particularly over joints, and thus reduce the risk of development of Marjolin's ulcer.

  4. Hyperthermic intraperitoneal chemotherapy as palliative treatment for malignant ascites A single-center experience and a review of the literature.

    PubMed

    Graziosi, Luigina; Marino, Elisabetta; De Angelis, Verena; Rebonato, Alberto; Donini, Annibale

    Malignant ascites is an abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal cancer dissemination. This clinical condition could represent the terminal evolution of a lethal disease and could influence the prognosis, severely impairing the patients' quality of life. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk; diuretics, paracentesis, peritoneo-venous shunts and intraperitoneal biologic agents like anti-VEGF molecules, metalloproteinase inhibitors and immunomodulators are included. None of these approaches have been established as a standard of care because of their low efficacy or severe side effects. The last two decades saw the emergence of cytoreductive surgery with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) as a viable therapeutic approach resulting in an effective cure against refractory malignant ascites. The following describes our experiences with 3 cases together with a literature review.

  5. Waldenström's macroglobulinemia: clinical course and prognostic factors in 60 patients. Experience from a single hematology unit.

    PubMed

    Kyrtsonis, M C; Vassilakopoulos, T P; Angelopoulou, M K; Siakantaris, P; Kontopidou, F N; Dimopoulou, M N; Boussiotis, V; Gribabis, A; Konstantopoulos, K; Vaiopoulos, G A; Fessas, P; Kittas, C; Pangalis, G A

    2001-12-01

    Waldenström's macroglobulinemia (WM) is a lymphoplasmacytic lymphoma characterized by the presence in patients' serum of an IgM monoclonal component. We report on our experience with 60 WM patients, focusing on their clinical findings, response to treatment, and the possible identification of prognostic factors. Of these patients, 70% presented with fatigue, and lymphadenopathy was observed in 22%, splenomegaly in 18%, hepatomegaly in 13%, and extranodal site of involvement in 6%. Bleeding tendency was seen in 17%, infections in 17%, hyperviscosity syndrome in 12%, and cardiac failure in 25% of the patients. The median of IgM levels was 30 g/l with hypoalbuminemia in 20% of cases, hypogammaglobulinemia in 27%, polyclonal hypergammaglobulinemia in 15%, kappa light-chain restriction in 78%, and Bence-Jones proteinuria in 54%. Anemia was frequent (85%), followed by leukocytosis (18%), lymphocytosis (12%), leukopenia (10%), and thrombocytopenia (10%). Cryoglobulinemia and autoimmune hemolytic anemia were encountered in 5%. In all cases but two, bone marrow was involved. Of 50 patients initially treated with intermittent oral chlorambucil, 46 (92%) responded. Median overall survival was 108 months. Factors associated with adverse prognosis were age > or =65 years (p=0.06), presence of lymphadenopathy (p=0.06), bone marrow infiltration > or =50% (p=0.007), international prognostic index (IPI) > or =3 (p=0.0001), and Morel's scoring system (p=0.04). Concluding, we found in this series of WM patients that chlorambucil is an effective treatment and that the parameters of age, lymphadenopathy, percentage of bone marrow infiltration, IPI, and Morel's scoring system carry prognostic significance.

  6. 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.

  7. Double-Layered PTFE-Covered Nitinol Stents: Experience in 32 Patients with Malignant Esophageal Strictures

    SciTech Connect

    Park, Jung Gu; Jung, Gyoo-Sik Oh, Kyung Seung; Park, Seon-Ja

    2010-08-15

    We evaluated the effectiveness of a double-layered polytetrafluoroethylene (PTFE)-covered nitinol stent in the palliative treatment of malignant esophageal strictures. A double-layered PTFE-covered nitinol stent was designed to reduce the propensity to migration of conventional covered stent. The stent consists of an inner PTFE-covered stent and an outer uncovered nitinol stent tube. With fluoroscopic guidance, the stent was placed in 32 consecutive patients with malignant esophageal strictures. During the follow-up period, the technical and clinical success rates, complications, and cumulative patient survival and stent patency were evaluated. Stent placement was technically successful in all patients, and no procedural complications occurred. After stent placement, the symptoms of 30 patients (94%) showed improvement. During the mean follow-up of 103 days (range, 9-348 days), 11 (34%) of 32 patients developed recurrent symptoms due to tumor overgrowth in five patients (16%), tumor ingrowth owing to detachment of the covering material (PTFE) apart from the stent wire in 3 (9%), mucosal hyperplasia in 2 (6%), and stent migration in 1 (3%). Ten of these 11 patients were treated by means of placing a second covered stent. Thirty patients died, 29 as a result of disease progression and 1 from aspiration pneumonia. The median survival period was 92 days. The median period of primary stent patency was 190 days. The double-layered PTFE-covered nitinol stent seems to be effective for the palliative treatment of malignant esophageal strictures. We believe that the double-layer configuration of this stent can contribute to decreasing the stent's migration rate.

  8. [Managing of platelet transfusion refractoriness of haematological malignancies. Experience IPC-EFSAM].

    PubMed

    Dettori, I; Ladaique, P

    2014-11-01

    The platelet refractoriness is a complication of transfusion treatments potentially dramatic in onco-haematology. Chemo-treatment of haematological malignancies or packs of allogeneic bone marrow transplants require iterative platelet transfusion requirements. The discovery of a platelet refractoriness along with its support should be the most reactive as possible but also adapted to the cause. In the case of allo-immunization, it may be expected. The purpose of this presentation is to recall the different etiologies and perform a feedback on the support transfusion platelet of onco-haematology adult patients at Institut Paoli-Calmettes (IPC) in partnership with the EFSAM.

  9. Management of bilateral malignant ovarian germ cell tumors: Experience of a single institute

    PubMed Central

    Zhao, Ting; Liu, Yan; Jiang, Hongyuan; Zhang, Hao; Lu, Yuan

    2016-01-01

    Bilateral malignant ovarian germ cell tumors (MOGCTs) are rare. Determination of the optimal treatment modalities is crucial, as these malignancies mainly affect girls and young women who may wish to preserve their fertility. In order to review the prevalence, clinical characteristics, treatment and outcome of bilateral MOGCTs, we performed a retrospective review of patients who were diagnosed with bilateral MOGCTs and underwent primary surgery at the Obstetrics and Gynecology Hospital of Fudan University (Shanghai, China) between January, 2001 and December, 2014. Of the 130 patients investigated, 8 were diagnosed with bilateral disease, most of whom were International Federation of Gynecology and Obstetrics stage I. There was no significant difference in overall and disease-free survival between patients with unilateral and those with bilateral disease. Cases with dysgerminoma, dysgerminoma coexisting with gonadoblastoma, yolk sac tumor and ovarian primary choriocarcinoma were included in this study. Fertility was spared in 2 patients (1 with dysgerminoma and 1 with ovarian primary choriocarcinoma). The patient with ovarian choriocarcinoma experienced relapse and was finally salvaged by radical surgery and adjuvant chemotherapy. According to our results and the published data, patients affected by bilateral MOGCTs have a satisfactory prognosis. The treatment modalities largely depend on the histological type of the tumor. Fertility-sparing surgery may be safe for patients affected by dysgerminoma, but should be considered with caution in patients with ovarian primary choriocarcinoma. PMID:27446585

  10. Local Control of Perivascular Malignant Liver Lesions Using Percutaneous Irreversible Electroporation: Initial Experiences

    SciTech Connect

    Eller, Achim Schmid, Axel; Schmidt, Joachim; May, Matthias Brand, Michael Saake, Marc Uder, Michael Lell, Michael

    2015-02-15

    PurposeThis study was designed to assess efficacy and safety in the treatment of perivascular malignant liver lesions using percutaneous, computed tomography (CT)-guided irreversible electroporation (IRE).MethodsFourteen patients (mean age 58 ± 11 years) with 18 malignant liver lesions were consecutively enrolled in this study. IRE was performed in patients not eligible for surgery and lesions abutting large vessels or bile ducts. Follow-up exams were performed using multislice-CT (MS-CT) or MRI.ResultsMedium lesion diameter was 20 ± 5 mm. Ten of 14 (71 %) were successfully treated with no local recurrence to date (mean follow-up 388 ± 160 days). One case left initial tumor control unclear and additional RFA was performed 4 weeks after IRE. Complications occurred in 4 of 14 (29 %) cases. In one case, intervention was terminated and abdominal bleeding required laparotomy. In two cases, a postinterventional hematothorax required intervention. In another case, abdominal bleeding could be managed conservatively. No complications related to the bile ducts occurred.ConclusionsPercutaneous IRE seems to be effective in perivascular lesions but is associated with a higher complication rate compared with thermoablative techniques.

  11. Probe-based confocal laser endomicroscopy in head and neck malignancies: early preclinical experience

    NASA Astrophysics Data System (ADS)

    Englhard, Anna; Girschick, Susanne; Mack, Brigitte; Volgger, Veronika; Gires, Oliver; Conderman, Christian; Stepp, Herbert; Betz, Christian Stephan

    2013-06-01

    Background: Malignancies of the upper aerodigestive tract (UADT) are conventionally diagnosed by white light endoscopy, biopsy and histopathology. Probe-based Confocal Laser Endomicroscopy (pCLE) is a novel non-invasive technique which offers in vivo surface and sub-surface imaging of tissue. It produces pictures of cellular architecture comparable to histology without the need for biopsy. It has already been successfully used in different clinical subspecialties to help in the diagnosis and treatment planning of inflammatory and neoplastic diseases. PCLE needs to be used in combination with specific or non-specific contrast agents. In this study we evaluated the potential use of pCLE in combination with non-specific and specific contrast agents to distinguish between healthy mucosa and invasive carcinoma. Methods: Tissue samples from healthy mucosa and squamous cell carcinoma of the head and neck were taken during surgery. After topical application of three different contrast agents, samples were examined using different pCLE-probes and a Confocal Laser Scanning Microscope (CLSM). Images were then compared to the corresponding histological slides and cryosections. Results: Initial results show that pCLE in combination with fluorophores allows visualization of cellular and structural components. Imaging of different layers was possible using three distinct pCLEprobes. Conclusion: pCLE is a promising non-invasive technique that may be a useful adjunct in the evaluation, diagnosis and treatment planning of head and neck malignancies.

  12. Diagnostic hematology of reptiles.

    PubMed

    Stacy, Nicole I; Alleman, A Rick; Sayler, Katherine A

    2011-03-01

    The hematologic evaluation of reptiles is an indispensable diagnostic tool in exotic veterinary practice. The diversity of reptile species, their characteristic physiologic features, and effects of intrinsic and extrinsic factors present unique challenges for accurate interpretation of the hemogram. Combining the clinical presentation with hematologic findings provides valuable information in the diagnosis and monitoring of disease and helps guide the clinician toward therapy and further diagnostic testing. This article outlines the normal and pathologic morphology of blood cells of reptile species. The specific comparative aspects of reptiles are emphasized, and structural and functional abnormalities in the reptilian hemogram are described.

  13. Malignant pleural effusion in the presence of trapped lung. Five-year experience of PleurX tunnelled catheters.

    PubMed

    Efthymiou, Christopher Andrew; Masudi, Tahir; Thorpe, James Andrew Charles; Papagiannopoulos, Kostas

    2009-12-01

    Malignant pleural effusions in the presence of trapped lung remain notoriously difficult to treat. Various methods exist ranging from minimally invasive procedures including repeated needle thoracocentesis to the need for a formal surgical procedure such as placement of a pleuroperitoneal shunt and even thoracotomy and decortication. Controversy exists as to what is the optimum treatment for this condition. Any planned treatment should balance the therapeutic benefit provided against convalesce for a disease with a limited life expectancy. Patients should not spend a significant proportion of their remaining life span recovering from palliative procedures. In a series of patients with malignant pleural effusion the medial survival time was 20 weeks, with 30 days and 1 year mortality rates of 12.8% and 83.6%, respectively. We describe our five-year experience with the use of indwelling PleurX catheters in patients with malignant pleural effusions in the presence of confirmed trapped lung on radiological or VATS investigation. Patient health related quality of life was investigated by telephone questionnaire. The parameters analysed were symptomatic relief, mobility and ease of management following insertion. One hundred and sixteen patients underwent PleurX catheter insertion by a single operator, 48 questionnaires were completed. Of the 48 cases analysed, improvement in all three quality of life indices was recorded following catheter insertion. Ease of mobility was recorded as moderately satisfied and very satisfied in 50% and 15% of patients, respectively. Symptomatic improvement was found to have been increased with 42% and 6% of patients responding to moderately satisfied and very satisfied, respectively. Ease of management was recorded as 'slightly satisfied' and moderately satisfied in 50% and 33% of patients, respectively, demonstrating a high satisfaction index in patients with chronic progressively debilitating malignancies. Complications were either

  14. Overview of Local Flaps of the Face for Reconstruction of Cutaneous Malignancies: Single Institutional Experience of Seventy Cases

    PubMed Central

    Rao, Jagdeep K; Shende, Kaustubh Sharad

    2016-01-01

    Context: The most common malignant tumours of the face are basal cell carcinoma, squamous cell carcinoma and melanoma. While the results of skin graft are less than satisfactory for large areas to cover, distant flaps are bulky with a poor colour match. Local fasciocutaneous flaps provide reasonable option for reconstruction of facial defects with good colour and texture match and good success rate. Aims: This study aimed to analyse the various modalities of reconstruction after resection of facial malignancies and their advantages and disadvantages. Settings and Design: This was a retrospective study. Materials and Methods: Of 70 patients, 34 were managed with V-Y advancement flap, 24 with nasolabial flap, 8 with median forehead flap and 4 with standard forehead flap cover. The duration of follow-up ranged from 6 months to 2 years. Statistical Analysis Used: Nil. Results: Of 34 V-Y advancement flaps, 2 showed suture dehiscence at the apex of triangle which was allowed to heal secondarily with regular dressings. All the 24 nasolabial flaps were healthy without any complication. All patients had satisfactory functional and cosmetic outcomes. Conclusions: In our experience, local flaps give the best results and are the first choice for reconstruction of the face. Most defects can be best closed by nasolabial, V-Y advancement and forehead flap. Outstanding functional and cosmetic results can be achieved. Proper execution requires considerable technical skill and experience. PMID:28163451

  15. Long Term Incidence of Secondary Malignancies Following Allogeneic Hematopoietic Cell Transplantation: a Single Center Experience.

    PubMed

    Michelis, Fotios V; Kotchetkov, Rouslan; Grunwald, Rebecca M; Azeem, Aamir; Atenafu, Eshetu G; Lipton, Jeffrey H; Loach, David; Gupta, Vikas; Kuruvilla, John; Kim, Dennis D; Viswabandya, Auro; Deotare, Uday; Messner, Hans A

    2017-02-27

    To review the emergence of secondary malignancies (SM) in recipients of allogeneic hematopoietic cell transplantation (HCT). We documented the occurrence of SM in 2415 allogeneic HCT recipients, ages 18-71, in a single center over four decades. SM was seen in 209 patients, including 58 with non-metastatic squamous cell (SCC) and basal cell carcinoma (BCC) of the skin. Cumulative incidence of SM was 6.3% at 10 years, 13.5% at 20 years and 17.6% at 30 years post-HCT. Median age at diagnosis of SM was 61 years (range 21-85). By multivariable analysis, older age at HCT was the only independent prognostic factor for SM (HR=1.39 for age 41-55 and HR=1.92 for age >55 compared to age ≤40, p=0.001). The rate of SM (excluding non-metastatic SCC/BCC of skin) after HCT was 2.07 times higher (p=0.01) compared to the general population. Overall survival (OS) following diagnosis of SM (excluding non-metastatic SCC/BCC of skin) was 58% at 5 years and 50% at 10 years post-diagnosis. ECOG score was the only independent predictor of OS on multivariable analysis, with over 2 fold increased risk of death for patients with an ECOG score of 1 and over 6 fold for ECOG 2-4, compared to ECOG score 0 (p<0.0001). Forty (19%) of the 209 patients diagnosed with SM subsequently developed another new malignancy. OS was 68% and 51% at 5 and 10 years, respectively. The survival of SM patients post-HCT is favorable, thus warranting diligent long-term cancer screening and standard of care treatment. ECOG status of these patients is a predominant prognostic factor.

  16. Hematologic Complications of Pregnancy

    PubMed Central

    Townsley, Danielle M.

    2013-01-01

    Pregnancy induces a number of physiologic changes that affect the hematologic indices, either directly or indirectly. Recognizing and treating hematologic disorders that occur during pregnancy is difficult owing to the paucity of evidence available to guide consultants. This paper specifically reviews the diagnosis and management of benign hematologic disorders occurring during pregnancy. Anemia secondary to iron deficiency is the most frequent hematologic complication and is easily treated with oral iron formulations,; however care must be taken not to miss other causes of anemia, such as sickle cell disease. Thrombocytopenia is also a common reason for consulting the hematologist and distinguishing gestational thrombocytopenia from immune thrombocytopenia (ITP), preeclampsia, HELLP syndrome, or thrombotic thrombocytopenic purpura (TTP) is essential since the treatment differs widely. Occasionally the management of mother and infant involves the expeditious recognition of neonatal alloimmune thrombocytopenia (NAIT), a condition that is responsible for severe life-threatening bleeding of the newborn. Additionally, inherited and acquired bleeding disorders affect pregnant women disproportionately and often require careful monitoring of coagulation parameters in order to prevent bleeding in the puerperium. Finally, venous thromboembolism (VTE) during pregnancy is still largely responsible for mortality during pregnancy and the diagnosis, treatment options and guidelines for prevention of VTE during pregnancy are explored. PMID:23953339

  17. Spray cryotherapy (SCT): institutional evolution of techniques and clinical practice from early experience in the treatment of malignant airway disease

    PubMed Central

    Turner, J. Francis; Parrish, Scott

    2015-01-01

    Background Spray cryotherapy (SCT) was initially developed for gastroenterology (GI) endoscopic use in the esophagus. In some institutions where a device has been utilized by GI, transition to use in the airways by pulmonologists and thoracic surgeons occurred. Significant differences exist, however, in the techniques for safely using SCT in the airways. Methods We describe the early experience at Walter Reed National Military Medical Center from 2011 to 2013 using SCT in patients with malignant airway disease and the evolution of our current techniques and clinical practice patterns for SCT use in patients. In November 2013 enrollment began in a multi-institutional prospective SCT registry in which we are still enrolling and will be reported on separately. Results Twenty-seven patients that underwent 80 procedures (2.96 procedures/patient). The average age was 63 years with a range of 20 to 87 years old. The average Eastern Cooperative Oncology Group (ECOG) status was 1.26. All malignancies were advanced stage disease. All procedures were performed in the central airways. Other modalities were used in combination with SCT in 31 (39%) of procedures. Additionally 45 of the 80 (56%) procedures were performed in proximity to a silicone, hybrid, or metal stent. Three complications occurred out of the 80 procedures. All three were transient hypoxia that limited continued SCT treatments. These patients were all discharged from the bronchoscopy recovery room to their pre-surgical state. Conclusions SCT can be safely used for treatment of malignant airway tumor (MAT) in the airways. Understanding passive venting of the nitrogen gas produced as the liquid nitrogen changes to gas is important for safe use of the device. Complications can be minimized by adopting strict protocols to maximize passive venting and to allow for adequate oxygenation in between sprays. PMID:26807288

  18. Malignant transformation in non-recurrent peritoneal cystic mesothelioma Our experience and review of the literature.

    PubMed

    Santangelo, Giuseppe; Accardo, Marina; De Vita, Ferdinando; Del Giudice, Santolo; Gallucci, Federica; Fabozzi, Alessio; De Falco, Massimo

    2016-01-29

    Il mesotelioma peritoneale cistico è un tumore raro. Si tratta di un tumore benigno, che tuttavia va incontro a recidive locali post-chirurgiche in oltre il 50% dei casi. È proprio a seguito di recidive ricorrenti che si possono determinare trasformazioni maligne di questa neoplasia, come descritto in Letteratura. Nel Giugno del 2004 un paziente di 73 anni è giunto presso la nostra struttura con una tumefazione addominale causa di dolore gravativo: si trattava di una massa di 16 cm, la cui struttura, agli esami strumentali (ecografia, TC con m.d.c. e RMN), appariva pluricistica. Attraverso una laparotomia mediana si è provveduto alla sua rimozione e il paziente è stato dimesso in VIII giornata post-operatoria senza complicanze. L’esame istologico, corredato da studio immunoistochimico e di microscopia elettronica, ha consentito di porre diagnosi di mesotelioma peritoneale pluricistico in trasformazione maligna. D’accordo con gli oncologi, in considerazione della scarsa efficacia dei trattamenti adiuvanti e della scarsità dei dati riportati in Letteratura sull’argomento, si è deciso di sottoporre il paziente unicamente ad uno stretto follow-up, con esecuzione di ecografia addominale ogni sei mesi e TC addominale ogni anno. Ad oggi, dieci anni dopo il trattamento, il paziente, di 83 anni, gode di un discreto stato di salute e non si sono verificate riprese o recidive di malattia, né locali, né a distanza. Oltre al fatto di essere risultato maligno alla sua prima manifestazione e non dopo ripetute recidive, il caso presenta altre particolarità: il mesotelioma peritoneale cistico, infatti, solitamente colpisce soggetti di sesso femminile (con un rapporto F:M di 4,5:1) ad un’età media di 60 anni, mentre il caso descritto riguarda un soggetto di sesso maschile di 73 anni. La nostra osservazione dimostra la possibilità che il mesotelioma peritoneale vada incontro a trasformazioni maligne già alla sua prima manifestazione e non esclusivamente dopo

  19. Hematologic manifestations of Helicobacter pylori infection

    PubMed Central

    Campuzano-Maya, Germán

    2014-01-01

    Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases. PMID:25278680

  20. Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience

    PubMed Central

    Mannu, Claudia; Gazzola, Anna; Bacci, Francesco; Sabattini, Elena; Sagramoso, Carlo; Roncolato, Fernando; Rossi, Maura; Laginestra, Maria Antonella; Sapienza, Maria Rosaria; Agostinelli, Claudio; De Leo, Antonio; Piccioli, Milena; Righi, Simona; Artioli, Patrizia; Chilli, Luigi; Da Pozzo, Gianpaolo; De Biase, Giuseppe; Sandri, Federica; Pileri, Stefano A; Piccaluga, Pier Paolo

    2011-01-01

    Diagnosis of B-non Hodgkin lymphomas (NHLs) is based on clinical, morphological and immunohistochemi-cal features. However, in up to 10-15% of cases, analysis of immunoglobulin heavy (IGH) or light (IGK/IGL) chains genes is required to discriminate between malignant and reactive lymphoid proliferations. In this study, we evaluated the feasibility and efficiency of IGK analysis in the routine diagnostic of B-cell lymphoproliferative disorders (B-LD) when applied to formalin-fixed paraffin-embedded (FFPE) tissues. Clonality patterns were studied in 59 B-LD using the BIOMED-2 protocol for IGK assays, after failure of the IGH assay. PCR products were evaluated by both heterodu-plex and GeneScan analysis. IGK analysis was technically successful in all cases. Overall, it supported the histopa-thological suspicion in 52/59 cases (88%), the sensitivity and specificity being 83% and 80%, respectively. Further, positive and negative predictive values were 95% and 50%, respectively. Interestingly, among various lymphoma subtypes, marginal zone lymphoma and follicular lymphoma most frequently required IGK analysis. In conclusion, IGK study according to the BIOMED-2 protocol resulted feasible and extremely useful in supporting challenging diagnosis of B-LD even if applied on FFPE samples. Accordingly, when NHL is suspected, negative results at IGH analysis should not be considered as conclusive and further investigation of IGK is appropriate. PMID:22432078

  1. Second malignant neoplasms complicating Hodgkin's disease: the National Cancer Institute experience

    SciTech Connect

    Tester, W.J.; Kinsella, T.J.; Waller, B.; Makuch, R.W.; Kelley, P.A.; Glatstein, E.; DeVita, V.T.

    1984-07-01

    The medical records of all patients treated for Hodgkin's disease during the years 1964-1981 were reviewed. Four hundred seventy-three previously untreated patients were analyzed. Thirty-four subsequent second malignant neoplasms were observed in 33 patients among those treated for Hodgkin's disease. Eight cases of acute nonlymphocyctic leukemia, one case of chronic myeloid leukemia, three cases of non-Hodgkin's lymphoma, three cases of sarcoma, and 19 other tumors were identified. The ten-year estimated risk of leukemia by treatment was the following: radiotherapy only (0), chemotherapy only (0.02), initial combined radiotherapy-chemotherapy (0.06), and salvage combined radiotherapy-chemotherapy (0.09). The ten-year estimated risk of solid tumors was 0.07 overall, with all treatment groups associated with similar risks. Unlike some other reports, a greater risk of leukemia in patients who began treatment for Hodgkin's disease at age 40 or older was not found. However, a positive association was noted between increasing risk of solid tumors and increasing patient age.

  2. Initial experience with full-length metal stent to relieve malignant ureteral obstruction.

    PubMed

    Borin, James F; Melamud, Ori; Clayman, Ralph V

    2006-05-01

    Ureteral obstruction caused by extrinsic compression by a malignancy generally can be overcome initially with a ureteral stent. However, the long-term failure rate is high, usually necessitating placement of a nephrostomy tube. Herein, we present the initial case, in this country, of intractable ureteral obstruction managed successfully with the newly developed all-metal Resonance stent (Cook Ireland Ltd., Limerick, Ireland) constructed of MP35N alloy, a composite of nonmagnetic nickel-cobalt-chromium-molybdenum. The patient is a 64-year-old woman with metastatic breast cancer causing retroperitoneal fibrosis and ureteral obstruction diagnosed laparoscopically. The obstruction failed to respond to placement of a single 7F double-J stent and then of two 6F double-J stents in the left ureter. As a last resort, in order to avoid nephrostomy-tube placement, the 6F metal stent was placed; this provided unobstructed flow of urine, as documented on a subsequent Whitaker test and, most recently, on a renal scan, 4 months after initial stent placement.

  3. Personalized Oncogenomics: Clinical Experience with Malignant Peritoneal Mesothelioma Using Whole Genome Sequencing

    PubMed Central

    Sheffield, Brandon S.; Tinker, Anna V.; Shen, Yaoqing; Hwang, Harry; Li-Chang, Hector H.; Pleasance, Erin; Ch’ng, Carolyn; Lum, Amy; Lorette, Julie; McConnell, Yarrow J.; Sun, Sophie; Jones, Steven J. M.; Gown, Allen M.; Huntsman, David G.; Schaeffer, David F.; Churg, Andrew; Yip, Stephen; Laskin, Janessa; Marra, Marco A.

    2015-01-01

    Peritoneal mesothelioma is a rare and sometimes lethal malignancy that presents a clinical challenge for both diagnosis and management. Recent studies have led to a better understanding of the molecular biology of peritoneal mesothelioma. Translation of the emerging data into better treatments and outcome is needed. From two patients with peritoneal mesothelioma, we derived whole genome sequences, RNA expression profiles, and targeted deep sequencing data. Molecular data were made available for translation into a clinical treatment plan. Treatment responses and outcomes were later examined in the context of molecular findings. Molecular studies presented here provide the first reported whole genome sequences of peritoneal mesothelioma. Mutations in known mesothelioma-related genes NF2, CDKN2A, LATS2, amongst others, were identified. Activation of MET-related signaling pathways was demonstrated in both cases. A hypermutated phenotype was observed in one case (434 vs. 18 single nucleotide variants) and was associated with a favourable outcome despite sarcomatoid histology and multifocal disease. This study represents the first report of whole genome analyses of peritoneal mesothelioma, a key step in the understanding and treatment of this disease. PMID:25798586

  4. Multiscale Modeling of Hematologic Disorders

    SciTech Connect

    Fedosov, Dmitry A.; Pivkin, Igor; Pan, Wenxiao; Dao, Ming; Caswell, Bruce; Karniadakis, George E.

    2012-01-28

    Parasitic infectious diseases and other hereditary hematologic disorders are often associated with major changes in the shape and viscoelastic properties of red blood cells (RBCs). Such changes can disrupt blood flow and even brain perfusion, as in the case of cerebral malaria. Modeling of these hematologic disorders requires a seamless multiscale approach, where blood cells and blood flow in the entire arterial tree are represented accurately using physiologically consistent parameters. In this chapter, we present a computational methodology based on dissipative particle dynamics (DPD) which models RBCs as well as whole blood in health and disease. DPD is a Lagrangian method that can be derived from systematic coarse-graining of molecular dynamics but can scale efficiently up to small arteries and can also be used to model RBCs down to spectrin level. To this end, we present two complementary mathematical models for RBCs and describe a systematic procedure on extracting the relevant input parameters from optical tweezers and microfluidic experiments for single RBCs. We then use these validated RBC models to predict the behavior of whole healthy blood and compare with experimental results. The same procedure is applied to modeling malaria, and results for infected single RBCs and whole blood are presented.

  5. Predictive factors for outcomes after reduced intensity conditioning hematopoietic stem cell transplantation for hematological malignancies: a 10-year retrospective analysis from the Société Française de Greffe de Moelle et de Thérapie Cellulaire.

    PubMed

    Michallet, Mauricette; Le, Quoc-Hung; Mohty, Mohamad; Prébet, Thomas; Nicolini, Franck; Boiron, Jean Michel; Esperou, Hélène; Attal, Michel; Milpied, Noel; Lioure, Bruno; Bordigoni, Pierre; Yakoub-Agha, Ibrahim; Bourhis, Jean-Henri; Rio, Bernard; Deconinck, Eric; Renaud, Marc; Chir, Zina; Blaise, Didier

    2008-05-01

    This retrospective study analyzed the impact of demographic and transplantation variables on outcomes of 1108 patients who have undergone allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning (RIC HSCT) for hematological malignancies and were reported to the Société Française de Greffe de Moelle et de Thérapie Cellulaire registry between November 1994 and December 2004. Only 442 patients (40%) were in complete remission (CR) at time of transplantation. Peripheral blood stem cells were used in the majority of patients (n = 878; 79%), 255 patients received fludarabine and low-dose total body irradiation, while 465 patients (42%) fludarabine and busulfan with rabbit anti-thymocyte globulins (ATG). The impact of demographic and transplant variables was studied on overall (OS) and event-free survival (EFS) in univariate and multivariate analysis. With a median follow-up of 21 months, 3-year probability of OS and EFS was 42% and 30%, respectively, and treatment-related mortality was 15% at 2 years. The multivariate analysis showed a significant negative impact on OS and EFS of the absence of CR status before transplantation; conditioning regimen, including >10 mg/kg ATG; and minor ABO incompatibility. In conclusion, this study highlights the major impact on RIC HSCT outcome of disease status before transplantation, ATG dose and ABO incompatibility.

  6. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.; Fischer, C. L.; Johnson, P. C.; Ritzmann, S. E.; Mengel, C. E.

    1975-01-01

    The hematology and immunology program conducted in support of the Apollo missions was designed to acquire specific laboratory data relative to the assessment of the health status of the astronauts prior to their commitment to space flight. A second objective was to detect and identify any alterations in the normal functions of the immunohematologic systems which could be attributed to space flight exposure, and to evaluate the significance of these changes relative to man's continuing participation in space flight missions. Specific changes observed during the Gemini Program formed the basis for the major portion of the hematology-immunology test schedule. Additional measurements were included when their contribution to the overall interpretation of the flight data base became apparent.

  7. Hematology of camelids.

    PubMed

    Vap, Linda; Bohn, Andrea A

    2015-01-01

    Interpretation of camelid hematology results is similar to that of other mammals. Obtaining accurate results and using appropriate reference intervals can be a bit problematic, particularly when evaluating the erythron. Camelid erythrocytes vary from other mammals in that they are small, flat, and elliptical. This variation makes data obtained from samples collected from these species prone to error when using some automated instruments. Normal and abnormal findings in camelid blood are reviewed as well as how to ensure accurate results.

  8. Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Patients with Hematologic Malignancies Who Relapse following Autologous Transplantation: A Multi-Institutional Prospective Study from the Cancer and Leukemia Group B (CALGB trial 100002)

    PubMed Central

    Bashey, Asad; Owzar, Kouros; Johnson, Jeffrey L.; Edwards, Peggy S.; Kelly, Michael; Baxter-Lowe, Lee-Ann; Devine, Steven; Farag, Sherif; Hurd, David; Ball, Edward; McCarthy, Philip; Lister, John; Shea, Thomas C.; Linker, Charles

    2013-01-01

    We prospectively treated 80 patients with relapse of malignancy or secondary myelodysplasia after autologous hematopoietic cell transplantation (AHCT) with allogeneic hematopoietic cell transplantation (allo-HCT) using a reduced-intensity conditioning (RIC) regimen of fludarabine 150 mg/m2 plus intravenous busulfan 6.4 mg/kg. Both sibling (MSD) and unrelated donors (MUD) were allowed. Patients transplanted from MUD donors received more intensive graft-versus-host disease (GVHD) prophylaxis, including rabbit anti-thymocyte globulin 10 mg/kg, mycophenolate mofetil, and an extended schedule of tacrolimus. With a median follow-up of 3.1 years (0.9 to 5.8), TRM at 6 months and 2 years was 8% and 23% respectively. Neither TRM nor the rates of acute GVHD were different in those with sibling or MUD donors. Donor CD3 cell chimerism > 90% at day +30 was achieved more often in patients with MUD than with MSD donors, 70% versus 23% (p<0.0001). Median EFS was higher in patients who achieved early full donor chimerism (14.2 versus 8 mo, p = 0.0395). Allo-HCT using this RIC regimen can be performed with low TRM in patients who have received a prior AHCT. Efforts to improve early donor CD3 chimerism may improve EFS. PMID:20674758

  9. Drug-Induced Hematologic Syndromes

    PubMed Central

    Mintzer, David M.; Billet, Shira N.; Chmielewski, Lauren

    2009-01-01

    Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications. PMID:19960059

  10. JAK3: a two-faced player in hematological disorders.

    PubMed

    Cornejo, Melanie G; Boggon, Titus J; Mercher, Thomas

    2009-12-01

    JAK3 is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells and that has been implicated in the signal transduction of the common gamma chain subfamily of cytokine receptors. As a result, JAK3 plays an essential role in hematopoieisis during T cell development. JAK3 inactivating mutations result in immunodeficiency syndromes (SCID) in both humans and mice. Recent data indicate that abnormal activation of JAK3 due to activating mutations is also found in human hematological malignancies, including acute megakaryoblastic leukemia (AMKL) and cutaneous T cell lymphoma (CTCL). After a brief summary of the JAK3 structure and function, we will review the evidence on the emerging role of JAK3 activation in hematological malignancies that warrant further studies to test the relevance of specific inhibition of JAK3 as a therapeutic approach to these challenging clinical entities.

  11. Hematologic and oncologic complications in the critically ill child.

    PubMed Central

    McIntosh, S.

    1984-01-01

    Admission of a patient to an intensive care unit for management of direct consequences of a hematologic or oncologic disease is occasionally necessary. Such problems included exchange transfusion, sepsis, compression of vital structures by malignant tumor, metabolic derangements, leukostasis, post-operative care, major sickling episodes in vital organs, and disseminated coagulopathy. More often, however, hematologic complications arise in the child critically ill from other causes, such as trauma or infections. The first two sections of this review address blood transfusion and hemostasis, topics likely to have wide application in the care of critically ill children. The last portion discusses problems unique to patients with sickling or malignant disease. Images FIG. 3 FIG. 4 FIG. 5 FIG. 6 PMID:6382836

  12. Radiotherapy for malignancy in patients with scleroderma: The Mayo Clinic experience

    SciTech Connect

    Gold, Douglas G.; Miller, Robert C.; Petersen, Ivy A.; Osborn, Thomas G.

    2007-02-01

    Purpose: To determine the frequency of acute and chronic adverse effects in patients with scleroderma who receive radiotherapy for treatment of cancer. Methods and Materials: Records were reviewed of 20 patients with scleroderma who received radiotherapy. Acute and chronic toxic effects attributable to radiotherapy were analyzed, and freedom from radiation-related toxicity was calculated. Results: Of the 20 patients, 15 had acute toxic effects, with Grade 3 or higher toxicity for 3 patients. Seven patients had self-limited Grade 1 or 2 radiation dermatitis, and no patient had Grade 3 or higher radiation dermatitis. Thirteen patients had chronic toxic effects, with Grade 3 or higher chronic toxicity for 3 patients. The median estimated time to any grade chronic toxicity was 0.4 years, and the median estimated time to Grade 3 or higher chronic toxicity has not been reached. Conclusions: The results suggest that although some patients with scleroderma treated with radiation experience considerable toxic effects, the occurrence of Grade 3 or higher toxicity may be less than previously anticipated.

  13. Outcomes of adults with active or progressive hematological malignancies at the time of allo-SCT: a survey from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

    PubMed

    Chevallier, P; Labopin, M; Milpied, N; Bilger, K; Socié, G; Yakoub-Agha, I; Michallet, M; Bulabois, C-E; Maury, S; Beguin, Y; Bay, J-O; Blaise, D; Maillard, N; Guillerm, G; Daguindeau, E; Raus, N; Mohty, M

    2014-03-01

    Previous data suggested that allo-SCT might be an effective therapy in the setting of chemo-refractory/relapsed diseases because of the potent long-term immune-mediated tumor control. This retrospective study aimed to analyze the outcome of adult patients who received allo-SCT in a chemo-refractory/relapsed status. The series included 840 patients with active or progressive disease at the time of transplant. Median age was 50 years. With a median follow-up of 40 months, 3-year OS, disease-free survival (DFS), and non-relapse mortality rates were 29±2, 23±2, and 30±2%, respectively. At the last follow-up, 252 patients (30%) were still alive (of whom 201 were in CR (24%). In a Cox multivariate analysis, the use of a reduced-intensity conditioning (RIC) before allo-SCT and use of an HLA-identical sibling donor remained independently associated with a better OS (hazard ratio (HR)=0.82; 95% confidence interval (CI), 0.69-0.98, P=0.03; and HR=0.79; 95% CI, 0.66-0.93, P=0.006, respectively). Also, a diagnosis of myelodysplastic syndrome/myeloproliferative disorder, Hodgkin lymphoma and non-Hodgkin lymphoma compared with acute leukemia had a favorable impact on OS (HR=0.55; 95% CI, 0.45-0.68, P<0.0001; HR=0.49; 95% CI, 0.31-0.75, P=0.001; and HR=0.47; 95% CI, 0.35-0.63, P<0.0001, respectively). In conclusion, this study suggests that allo-SCT may be of benefit in some subgroups of patients with active or progressive hematological malignancies at the time of allo-SCT.

  14. [Epidemiological, clinical, cytologic and immunophenotypic aspects of acute leukemia in children: the experience at the hematology laboratory of IBN SINA University Hospital Center].

    PubMed

    Doumbia, Mariam; Uwingabiye, Jean; Bissan, Aboubacar; Rachid, Razine; Benkirane, Souad; Masrar, Azlarab

    2016-01-01

    The aim of this study was to describe epidemiological, cytologic and immunophenotypic aspects of acute leukemias (AL) in children diagnosed at IBN SINA University Hospital Center and to determine the concordance between cytology and immunophenotyping results. This is a cross-sectional study conducted in the hematology laboratory of IBN SINA University Hospital Center between June 2012 and May 2014. Among the 104 cases with diagnosed AL, 52% were boys with a sex-ratio H/F= 1.32, the average age was 5.7 years. The distribution of different types of AL was: lymphoid AL (LAL) (74%), myeloid (AML) (20.2%), biphenotypic AL (BAL) (65.8%). Among the LALs, 78% were classified as B LAL and 22% as T LAL. Clinical signs were mainly presented with tumor syndrome (73.1%), fever (61%) and hemorrhagic syndrome (50%). The most common blood count abnormalities were: thrombopenia (89.4%), anemia (86.5%), hyperleukocytosis (79.8%). The rate of peripheral and bone marrow blasts was statistically higher for LAL than for AML and BAL (p <0.001). The rate of relapse and mortality was 21.2% and 16. 3% respectively. Concordance rate between the results of cytology and of immunophenotyping was 92.7% for LAL and 82.6% for AML. Diagnosis of AL is always based primarily on cytology. Immunophenotyping allowed us to make a better distinction between acute leukemias. The management of paediatric AL is a major health problem which requires specialized care centers.

  15. Unexpected Second Primary Malignancies Detected by F-18 FDG PET/CT During Follow-up for Primary Malignancy: Two Case Reports.

    PubMed

    Bang, Ji-In; Lee, Eun Seong; Kim, Tae-Sung; Kim, Seok-Ki

    2015-03-01

    As the survival rate of cancer patients has increased over the last few decades, the risk of cancer survivors developing second primary malignancies has gained attention. We report two rare cases of second primary hematologic malignancy detected by (18)F-fluorodeoxyglucose (F-18 FDG) positron emission tomography/computed tomography (PET/CT) during follow-up for primary solid malignancies. Acute lymphoblastic leukemia developed in a breast cancer patient and non-Hodgkin lymphoma in an anal cancer patient. F-18 FDG PET/CT findings led to the diagnosis of unexpected second primary hematologic malignancy in cancer survivors in these two cases.

  16. 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

  17. Improved radioimmunotherapy of hematologic malignancies. Progress report, 1988--1991

    SciTech Connect

    Press, O.W.; Barofsky, D.F.

    1991-12-31

    This progress report describes accomplishments under four headings, namely: The study of the relative rates of metabolic degradation of radiolabeled monoclonal antibodies (MAb) targeting tumor associated antigens; Effects of lysosomotropic amines, carboxylic ionophores, and thioamides on the retention of radiolabeled MAbs by tumor cells; Subcellular site of radioimmunoconjugate degradation and the sizes of fragments generated by intracellular metabolism of radiolabeled antibodies; and Patterns of metabolic degradation of radioimmunoconjugates made with different techniques and with different radionuclides.

  18. The molecular mechanism of thalidomide analogs in hematologic malignancies.

    PubMed

    Lindner, Stefanie; Krönke, Jan

    2016-12-01

    Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells. The underlying molecular mechanisms for these pleiotropic effects remained obscure until the identification of the cereblon (CRBN) E3 ubiquitin ligase as the primary target of thalidomide and its analogs in 2010. Binding of thalidomide or lenalidomide increases the affinity of CRBN to the transcription factors IKZF1 and IKZF3 and casein kinase 1α (CK1α). Ubiquitination and degradation of these neo-substrates results in IL-2 release and growth arrest of multiple myeloma and MDS cells. The discovery of this previously undescribed mechanism for an approved drug provides a proof-of-concept for the development of new therapeutics that exploit ubiquitin ligases for specific degradation of disease-associated proteins.

  19. 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)

  20. 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

  1. 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

  2. Study of MLN8237 in Participants With Advanced Hematological Malignancies

    ClinicalTrials.gov

    2017-03-29

    B-cell Follicular Lymphoma; B-cell Marginal Zone Lymphoma; Diffuse Large B-cell Lymphoma; B-cell Mantle Cell Lymphoma; B-cell Small Lymphocytic Lymphoma (SLL); B-Cell Chronic Lymphocytic Leukemia (B-CLL); Multiple Myeloma; Waldenstrom's Macroglobulinemia; Noncutaneous Peripheral T-cell Lymphoma Not Otherwise Specified (PTCL-NOS); Angioimmunoblastic T-cell Lymphoma (AITL); Anaplastic Large Cell Lymphoma; Enteropathy Associated T-cell Lymphoma (EATCL); NK Lymphoma (NKL)

  3. Rasburicase and Allopurinol in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2015-05-28

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; de Novo Myelodysplastic Syndromes; Noncontiguous Stage II Adult Burkitt Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Stage I Adult Burkitt Lymphoma; Stage III Adult Burkitt Lymphoma; Stage IV Adult Burkitt Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Pleural malignancies.

    PubMed

    Friedberg, Joseph S; Cengel, Keith A

    2010-07-01

    Pleural malignancies, primary or metastatic, portend a grim prognosis. In addition to the serious oncologic implications of a pleural malignancy, these tumors can be highly symptomatic. A malignant pleural effusion can cause dyspnea, secondary to lung compression, or even tension physiology from a hydrothorax under pressure. The need to palliate these effusions is a seemingly straightforward clinical scenario, but with nuances that can result in disastrous complications for the patient if not attended to appropriately. Solid pleural malignancies can cause great pain from chest wall invasion or can cause a myriad of morbid symptoms because of the invasion of thoracic structures, such as the heart, lungs, or esophagus. This article reviews pleural malignancies, the purely palliative treatments, and the treatments that are performed with definitive (curative) intent.

  5. Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST) in 17 patients: the Institut Curie experience.

    PubMed

    Klijanienko, Jerzy; Caillaud, Jean-Michel; Lagacé, Réal; Vielh, Philippe

    2002-08-01

    Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are insufficiently documented in the literature. Cytological and histological specimens in 24 tumors in 17 patients were correlated. The review of the original cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma, and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma. At the review tumors were histologically reclassified as well-differentiated MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well-differentiated MPNST were composed of polymorphous oval to round cells, small spindle-shaped cells with wavy and comma-like naked nuclei, and a fibrillary, delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant and polymorphous cells. The malignant Triton tumor was composed of oval to round rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of polymorphous and round, epithelial-like cells. The cytological diagnosis of MPNST may be difficult, especially in anaplastic tumors. The correlation between the cytological features and the clinical information--origin of the tumor from a nerve trunk, a preexisting neurofibroma, patients with known history of neurofibromatosis 1--could be indicative of an MPNST diagnosis.

  6. Unexpected ovarian malignancy found after laparoscopic surgery in patients with adnexal masses--a single institutional experience.

    PubMed

    Saito, Shigeko; Kajiyama, Hiroaki; Miwa, Yoko; Mizuno, Mika; Kikkawa, Fumitaka; Tanaka, Shiho; Okamoto, Tomomitsu

    2014-02-01

    Laparoscopy has become the standard surgery for the treatment of benign ovarian tumors. The aim of this study was to evaluate the appropriateness of laparoscopy for ovarian tumors, including those with malignant potential. A total of 487 patients with adnexal masses underwent laparoscopic surgery in Social Insurance Chukyo Hospital from January 2000 to December 2012. We reviewed 471 cases that fulfilled the criteria set for this study, and examined 10 cases with unexpected ovarian malignancy to analyze their preoperative diagnosis, second surgery, postoperative chemotherapy, and prognosis. The ages of the 471 patients ranged from 13 to 50 years, with a median of 31. Nulliparous patients numbered 321(68.1%). Of all, 436 patients mostly consisted of those with endometrioma, benign ovarian neoplasm or functional cyst. In all, we histologically identified 10 women with malignancy: 6 with borderline ovarian tumors (BOT), 2 with ovarian cancer, and 2 with histologically rare tumors (immature teratoma and granulosa cell tumor). All patients with BOT were diagnosed with a mucinous histology. Two patients underwent both second radical surgery (hysterectomy and contra- or bilateral salpingo-oophorectomy) and chemotherapies that consisted of CBDCA and PTX or DTX. Thus, 2 patients underwent staging procedures, but the remaining 8 cases did not. None of them had evidence of recurrences. With accurate staging and careful postoperative follow-up, laparoscopic surgery could be a feasible initial operation for patients with adnexal masses including early-stage ovarian malignancy.

  7. Understanding Drug Resistance to Targeted Therapeutics in Malignant B-Cell Lymphoproliferative Disorders (B-LPDs)

    DTIC Science & Technology

    2014-10-01

    Ibrutinib for Frontline CLL Therapy? The Duke Debates in Hematological Malignancies, regional Duke CME activity. The Mills House, Charleston, SC, March 14...Hematological Malignancies: Ibrutinib for Frontline CLL Therapy? The Mills House, Charleston, SC, March 14-16th, 2014. Grand Rounds and Institutional...18451242 8. David A. Rizzieri, Robert Storms, Dong-Feng Chen, Gwynn Long, Daniel A. Nikcevich, Cristina Gasparetto, Mitchell Horwitz, John Chute, Keith

  8. Our experience in the treatment of Malignant Fibrous Hystiocytoma of the larynx: clinical diagnosis, therapeutic approach and review of literature

    PubMed Central

    Motta, Sergio; Marcuccio, Giuseppina; Paccone, Marianna; Rocca, Aldo; Ilardi, Gennaro; Tafuri, Domenico; Mesolella, Massimo; Motta, Gaetano

    2016-01-01

    Abstract Hereditary spherocytosis (HS) and Chronic myelocytic leukemia (CML) are both life threatening hemotologic diseases. They are rarely seen to occur simultaneously in one individual patient. Here we demonstrate a case of HS associated with CML in this study. The patient is a young female, diagnosed with HS in 2005, and was given partial embolization of the splenic artery. She got significant remission after the procedure. In 2008, she was found abnormal in blood routine test, after bone marrow routine, chromosome and fusion gene tests, she was diagnosed with CML (chronic phase). She did not receive regular treatment until 3 months prior, and is currently being treated with Dasatimib. She achieved hematological remission, but had no significant improvement in chromosome and fusion gene figures. Due to her severe condition of hemolysis, a splenectomy or an allogeneic hematopoietic stem cell transplantation is considered.

  9. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    PubMed Central

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  10. [Clinical relevance of immunotyping of oncologic and hematologic diseases].

    PubMed

    Diehl, V; Pfreundschuh, M

    1987-06-01

    Progress in immunology and molecular biology have provided a better understanding of etiology, pathogenesis and biology of many oncological and hematological diseases. In clinical practice, certain new methods of immunotyping (IT) are of diagnostic importance in assigning undifferentiated tumors to lymphoid, epithelial or mesenchymal origin and in defining subgroups of leukemias and lymphomas. The demonstration of rearrangements of gene coding for immunoglobulins or T-cell receptors assigns hematological malignancies of early differentiation to the B- or T-cell lineage, discriminates between reactive lymphoid changes and clonal lymphoid expansion and detects persistent clonal growth after therapy. In certain clinical entities (e.g. ALL) the immunological subtypes are of importance for differential therapy. By means of IT new clinical entities have been defined (Ki-1-lymphoma, T gamma-lymphoproliferative, LFA-1-deficiency) and the pathomechanisms of others have been elucidated (Bernard-Soulier-disease Syndrome, Glanzmann-Nägeli thrombasthenia). Of immediate therapeutic importance is the identification by IT of receptors for specific hormones or biological response modifiers on malignant cells. In-vivo diagnosis by monoclonal antibodies opens a way to define more exactly the extent of malignant disease by scintigrams or NMR.

  11. The New Nitinol Conformable Self-Expandable Metal Stents for Malignant Colonic Obstruction: A Pilot Experience as Bridge to Surgery Treatment

    PubMed Central

    2014-01-01

    Introduction. Self-expandable metal stents (SEMS) are a nonsurgical option for treatment of malignant colorectal obstruction also as a bridge to surgery approach. The new nitinol conformable stent has improved clinical outcomes in these kinds of patients. We report a pilot experience with nitinol conformable SEMS placement as bridge to surgery treatment in patients with colorectal obstruction. Materials and Methods. Between April and August 2012, we collected data on colonic nitinol conformable SEMS placement in a cohort of consecutive symptomatic patients, with malignant colorectal obstruction, who were treated as a bridge to surgery. Technical success, clinical success, and adverse events were recorded. Results. Ten patients (7 male (70%)), with a mean age of 69.2 ± 10.1, were evaluated. The mean length of the stenosis was 3.6 ± 0.6 cm. Five patients (50%) were treated on an emergency basis. The median time from stent placement to surgery was 16 days (interquartile range 7–21). Technical and clinical success was achieved in all patients with a significant early improvement of symptoms. No adverse events due to the SEMS placement were observed. Conclusion. This pilot study confirmed the important role of nitinol conformable SEMS as a bridge to surgery option in the treatment of symptomatic malignant colorectal obstruction. PMID:24526914

  12. MicroRNA-155 and Its Role in Malignant Hematopoiesis

    PubMed Central

    Ranganath, Prajnya

    2015-01-01

    MicroRNA-155 (miR-155) is a multifunctional molecule involved in both normal and malignant hematopoiesis. It has been found to be involved in the pathogenesis of many different hematological malignancies with either an oncogenic or a tumor-repressor effect, depending on the nature of the cell and the type of malignancy. In particular, it has been strongly implicated in the causation of diffuse large B-cell lymphomas. This review focuses on the molecular interactions of miR-155, its oncogenic mechanisms, and its potential as an effective therapeutic target for the associated malignancies. PMID:26523117

  13. Role of Craniofacial Resection for Malignant Tumors Involving the Anterior Skull Base: Surgical Experience in a Single Institution

    PubMed Central

    Kim, You-Sub; Kim, Gun-Woo; Lim, Sang Chul; Lee, Kyung-Hwa; Jang, Woo-Youl; Jung, Tae-Young; Kim, In-Young; Jung, Shin

    2015-01-01

    Background Craniofacial resection (CFR) has been regarded as a standard treatment for various tumors involving the anterior skull base. The purpose of this study was to evaluate the results of CFR for the patients with anterior skull base malignancies in our hospital. Methods We retrospectively analyzed 17 patients with anterior skull base malignancies treated with CFR between 2001 and 2012. Mean follow-up duration was 41 months (range, 2-103 months). Results Intracranial involvement was found in 11 patients (65%) and orbital extension in 6 patients (35%). Classical bifrontal craniotomy was combined with endoscopic endonasal approach in 14 patients and external approach in 3 patients. Vascularized flap was used for reconstruction of the anterior fossa floor in 16 patients (94%). The most common pathological type was squamous cell carcinoma (6 patients). Gross total resection was achieved in all cases. Postoperative complications developed in 4 patients (24%) and included local wound problem and brain abscess. One patient with liver cirrhosis died from unexpected varix bleeding after the operation. Although postoperative treatment, such as radiotherapy or chemotherapy, was performed in 14 patients, local recurrence was seen in 6 patients. The mean overall survival time after the operation was 69.0 months (95% confidence interval: 47.5-90.5 months) with a 1-, 2-, and 5-year survival rate of 82.3%, 76.5%, and 64.7%, respectively. Postoperative radiotherapy was found to be the powerful prognostic factor for favorable survival. Conclusion Considering the higher local control rate and acceptable complication or mortality rate, CFR with adjuvant radiotherapy is a gold standard treatment option for malignant tumors involving anterior skull base, especially with extensive intracranial involvement. PMID:26605262

  14. First Experiences in Percutaneous Arterial Chemoembolization of Malignant Liver Lesions by Means of Real-Time CT Fluoroscopy

    SciTech Connect

    Kirchner, Johannes; Laufer, Ulf; Kickuth, Ralph; Schilling, Esther M.; Scherf, Claudia; Liermann, Dieter

    1999-11-15

    Computed tomography fluoroscopy (CTF) allows real-time display (continuous imaging) and has been increasingly used in interventional procedures. We wished to demonstrate the usefulness of CTF in chemoembolization of the liver. Twenty-one patients with primary or secondary malignant lesions of the liver underwent CTF-guided chemoembolization after angiographic positioning of a catheter in the hepatic artery. Embolization materials such as Lipiodol and mitomycin C were administered under continuous CT scanning. CTF led to a change of the method (correction of catheter position, application of norepinephrine) in nine of 21 cases. There were no fatal complications.

  15. Therapeutic drug monitoring of monoclonal antibodies in inflammatory and malignant disease: Translating TNF-α experience to oncology.

    PubMed

    Oude Munnink, T H; Henstra, M J; Segerink, L I; Movig, K L L; Brummelhuis-Visser, P

    2016-04-01

    Lack of response to monoclonal antibodies (mAbs) has been associated with inadequate mAb serum concentrations. Therapeutic drug monitoring (TDM) of mAbs has the potential to guide to more effective dosing in individual patients. This review discusses the mechanisms responsible for interpatient variability of mAb pharmacokinetics, summarizes exposure-response data of mAbs used in inflammatory and malignant disease, presents current evidence of mAb-TDM in inflammatory disease, and provides hurdles and required future steps for further implementing mAb-TDM.

  16. 42 CFR 493.849 - Condition: Hematology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Hematology. 493.849 Section 493.849 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.849 Condition: Hematology. The specialty of hematology, for the purpose of...

  17. 42 CFR 493.1215 - Condition: Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.1215 Section 493.1215 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1215 Condition: Hematology. If the laboratory provides services in the specialty of Hematology,...

  18. 42 CFR 493.1215 - Condition: Hematology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Hematology. 493.1215 Section 493.1215 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1215 Condition: Hematology. If the laboratory provides services in the specialty of Hematology,...

  19. 42 CFR 493.849 - Condition: Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Hematology. 493.849 Section 493.849 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.849 Condition: Hematology. The specialty of hematology, for the purpose of...

  20. Hematological disorders and pulmonary hypertension

    PubMed Central

    Mathew, Rajamma; Huang, Jing; Wu, Joseph M; Fallon, John T; Gewitz, Michael H

    2016-01-01

    Pulmonary hypertension (PH), a serious disorder with a high morbidity and mortality rate, is known to occur in a number of unrelated systemic diseases. Several hematological disorders such as sickle cell disease, thalassemia and myeloproliferative diseases develop PH which worsens the prognosis. Associated oxidant injury and vascular inflammation cause endothelial damage and dysfunction. Pulmonary vascular endothelial damage/dysfunction is an early event in PH resulting in the loss of vascular reactivity, activation of proliferative and antiapoptotic pathways leading to vascular remodeling, elevated pulmonary artery pressure, right ventricular hypertrophy and premature death. Hemolysis observed in hematological disorders leads to free hemoglobin which rapidly scavenges nitric oxide (NO), limiting its bioavailability, and leading to endothelial dysfunction. In addition, hemolysis releases arginase into the circulation which converts L-arginine to ornithine, thus bypassing NO production. Furthermore, treatments for hematological disorders such as immunosuppressive therapy, splenectomy, bone marrow transplantation, and radiation have been shown to contribute to the development of PH. Recent studies have shown deregulated iron homeostasis in patients with cardiopulmonary diseases including pulmonary arterial hypertension (PAH). Several studies have reported low iron levels in patients with idiopathic PAH, and iron deficiency is an important risk factor. This article reviews PH associated with hematological disorders and its mechanism; and iron homeostasis and its relevance to PH. PMID:28070238

  1. Malignancies and anti-TNF therapy in rheumatoid arthritis: a single-center observational cohort study.

    PubMed

    Berghen, Nathalie; Teuwen, Laure-Anne; Westhovens, Rene; Verschueren, Patrick

    2015-10-01

    Inhibitors of tumor necrosing factor alpha (TNF-a) have proven to be highly effective in the treatment of rheumatoid arthritis (RA). Concerns, however, are raised about the possible association between these treatments and an increased development of malignancies. The objective of this paper was to compare the risk of hematologic and solid malignancies in patients treated for RA with anti-TNF therapy, with the risk in the general population. From January 2000 until January 2012, all RA patients that started treatment with anti-TNF agents were included in this single-center cohort study. The primary outcome of this study was the incidence of malignancy after starting anti-TNF treatment. In our cohort of 365 patients, 34 malignancies were discovered in 30 patients after the start of anti-TNF treatment; 20 patients developed a solid malignancy, 6 a hematologic, 2 a solid and a hematologic malignancy, and 2 patients developed 2 solid malignancies. The overall incidence rate (IR) of malignancy was 1379.1 per 100.000 patient years. The risk or standardized incidence ratio (SIR) of solid malignancy, calculated by comparison with the age-adjusted population in Flanders, was 120.1 in female and 136.7 in male patients. The calculated SIR of hematologic malignancy was 450.8 for women and 473.9 for men. Some immune modulation-related lymphoproliferative disorders regressed spontaneously when stopping TNF blockers. Overall, the malignancy risk in our rheumatoid arthritis patients treated with anti-TNF therapy was slightly higher than in the normal population; the risk of hematologic malignancies was more important.

  2. Malignant mesothelioma

    PubMed Central

    Moore, Alastair J; Parker, Robert J; Wiggins, John

    2008-01-01

    Malignant mesothelioma is a fatal asbestos-associated malignancy originating from the lining cells (mesothelium) of the pleural and peritoneal cavities, as well as the pericardium and the tunica vaginalis. The exact prevalence is unknown but it is estimated that mesotheliomas represent less than 1% of all cancers. Its incidence is increasing, with an expected peak in the next 10–20 years. Pleural malignant mesothelioma is the most common form of mesothelioma. Typical presenting features are those of chest pain and dyspnoea. Breathlessness due to a pleural effusion without chest pain is reported in about 30% of patients. A chest wall mass, weight loss, sweating, abdominal pain and ascites (due to peritoneal involvement) are less common presentations. Mesothelioma is directly attributable to occupational asbestos exposure with a history of exposure in over 90% of cases. There is also evidence that mesothelioma may result from both para-occupational exposure and non-occupational "environmental" exposure. Idiopathic or spontaneous mesothelioma can also occur in the absence of any exposure to asbestos, with a spontaneous rate in humans of around one per million. A combination of accurate exposure history, along with examination radiology and pathology are essential to make the diagnosis. Distinguishing malignant from benign pleural disease can be challenging. The most helpful CT findings suggesting malignant pleural disease are 1) a circumferential pleural rind, 2) nodular pleural thickening, 3) pleural thickening of > 1 cm and 4) mediastinal pleural involvement. Involvement of a multidisciplinary team is recommended to ensure prompt and appropriate management, using a framework of radiotherapy, chemotherapy, surgery and symptom palliation with end of life care. Compensation issues must also be considered. Life expectancy in malignant mesothelioma is poor, with a median survival of about one year following diagnosis. PMID:19099560

  3. P06.13OUTCOME AND PROGNOSTIC FACTORS IN ATYPICAL AND MALIGNANT MENINGIOMA: UNIVERSITY OF FLORENCE EXPERIENCE

    PubMed Central

    Detti, B.; Scoccianti, S.; Greto, D.; Cassani, S.; Cappelli, S.; Giacomelli, I.; Bordi, L.; Di cataldo, V.; Monteleone, E.; Livi, L.

    2014-01-01

    AIM: This study aim to retrospectively assess prognostic factors and outcome in 68 patients with atypical and malignant meningiomas. MATERIAL AND METHODS: Data of 68 patients affected by meningioma between january 1993 and december 2011 were retrospective analyzed. In 80 % of the patients surgical resection was macroscopical; in 51 patients histology resulted atypical and in 17 malignant. All patients performed radiation treatment, of them 56% after surgical resection, 26% at the first relapse and 18% at the secon relapse, mean dose delivered was 54.6 Gy. RESULTS: Median follow-up was 6.7 years, (range 1.5-19.9 years). The actuarial overall survival rates at 5- and 10-year were 74.1 and 45.6 %, respectively. At univariate analysis age >60 years and radiotherapy dose >52 Gy showed statistical significance, (p = 0.04 and p = 0.03, respectively). At the multivariate analysis only radiotherapy dose >52 Gy maintained the statistical significance, (p = 0.037). The 5- and 10-year disease-free survival rates were 76.5 and 69.5 % respectively, on univariate analysis they were significantly influenced by size >5 cm (p = 0.04) and grading (p = 0.003), both still remained significant prognostic factors at multivariate analysis (p = 0.044 and p = 0.0006, respectively). Treatment related toxicities were limited: 16 % of the patients experienced grade ≤ 2 acute side effects, no ≥ grade 3 acute toxicity was exeperienced. CONCLUSIONS: In study, age and radiotherapy dose were associated with a longer overall survival, while disease free survival was influenced by preoperative size and grading of the tumor . Although there were some advantages in terms of overall survival for patients treated with postoperative radiotherapy, the benefit did not reach the significance. Multicenter prospective studies are necessary to clarify the management and the correct timing of radiotherapy in such a rare disease.

  4. Acute megakaryoblastic leukemia (acute 'malignant' myelofibrosis): An unusual cause of osteosclerosis

    SciTech Connect

    Karasick, S.; Karasick, D.; Schilling, J.

    1982-11-01

    Acute megakaryoblastic leukemia or acute 'malignant' myelosclerosis is an acute and rapidly progressive myeloproliferative syndrome characterized by minimal or absent splenomegaly, pancytopenia, diffuse marrow fibrosis, and circulating blasts of megakaryocytic origin. The disease must be differentiated from other hematologic malignancies especially myelofibrosis with myeloid metaplasia. The radiographic changes of osteosclerosis in our patient have not been previously reported in the literature.

  5. Hematology and immunology studies

    NASA Technical Reports Server (NTRS)

    Kimzey, S. L.

    1977-01-01

    A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.

  6. Hematological complications in anorexia nervosa

    PubMed Central

    De Filippo, E; Marra, M; Alfinito, F; Di Guglielmo, M L; Majorano, P; Cerciello, G; De Caprio, C; Contaldo, F; Pasanisi, F

    2016-01-01

    Background/objectives: Anemia, leukopenia and, although less frequently, thrombocytopenia are possible hematological complications of anorexia nervosa considered strictly secondary to chronic malnutrition. This is a retrospective study on the prevalence of these disorders in a large cohort of 318 female patients with AN (20.4±5.6 years, body mass index (BMI) 15.9±1.6 kg/m2), recruited in the Outpatient Unit for Malnutrition secondary to Eating Disorders at the Department of Clinical Medicine and Surgery, Federico II University Hospital, since February 1991 to December 2012. Subjects/methods: Patients were studied on an outpatient basis after obtaining medical history, clinical examination, routine hematobiochemical and endocrine tests, electrocardiography, psychiatric interview and bioelectrical impedance analysis and, in particular, phase angle determination. All patients with other comorbidities, in particular with mean corpuscular volume <80 fl, were excluded for suspected genetic alteration in the synthesis of hemoglobin. Results: Hematologic data showed that 16.7% of patients had anemia, 7.9% neutropenia and 8.9% thrombocytopenia. These abnormalities were strictly related to the duration of illness (P=0.028), and to protein energy malnutrition, in particular, BMI and phase angle (P<0.001). Conclusions: Our study offers description of the incidence of hematologic defects in a selected and large sample of AN female patients, suggesting that its incidence is related to the degree and duration of protein energy malnutrition. PMID:27436150

  7. Survival of hematological patients after discharge from the intensive care unit: a prospective observational study

    PubMed Central

    2013-01-01

    Introduction Although the survival rates of hematological patients admitted to the ICU are improving, little is known about the long-term outcome. Our objective was to identify factors related to long-term outcome in hematological patients after ICU discharge. Methods A prospective, observational study was carried out in seven centers in Spain. From an initial sample of 161 hematological patients admitted to one of the participating ICUs during the study period, 62 were discharged alive and followed for a median time of 23 (1 to 54) months. Univariate and multivariate analysis were performed to identify the factors related to long term-survival. Finally, variables that influence the continuation of the scheduled therapy for the hematological disease were studied. Results Mortality after ICU discharge was 61%, with a median survival of 18 (1 to 54) months. In the multivariate analysis, an Eastern Cooperative Oncology Group score (ECOG) >2 at ICU discharge (Hazard ratio 11.15 (4.626 to 26.872)), relapse of the hematological disease (Hazard ratio 9.738 (3.804 to 24.93)) and discontinuation of the planned treatment for the hematological disease (Hazard ratio 4.349 (1.286 to 14.705)) were independently related to mortality. Absence of stem cell transplantation, high ECOG and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores decreased the probability of receiving the planned therapy for the hematological malignancy. Conclusions Both ICU care and post-ICU management determine the long-term outcome of hematological patients who are discharged alive from the ICU. PMID:24377481

  8. A "bone marrow score" for predicting hematological disease in immunocompetent patients with fevers of unknown origin.

    PubMed

    Wang, Hao-Yuan; Yang, Ching-Fen; Chiou, Tzeon-Jye; Yang, Sheng-Hsiang; Gau, Jyh-Pyng; Yu, Yuan-Bin; Liu, Chun-Yu; Liu, Jin-Hwang; Chen, Po-Min; Hsu, Hui-Chi; Fung, Chang-Phone; Tzeng, Cheng-Hwai; Hsiao, Liang-Tsai

    2014-12-01

    Delayed diagnosis of hematological malignancies in immunocompetent patients with fever of unknown origin (FUO) remains an exhausting challenge for non-hematologist physicians. This retrospective cohort study aimed to establish a scoring system, "bone marrow (BM) score", to identify FUO patients who require early bone marrow biopsy (BMB) to diagnose hematological disease. Two cohorts, comprising 85 (training) and 20 (validation) eligible immunocompetent patients, with FUOs diagnosed between January 1, 2006 and July 31, 2013, underwent BMBs and were enrolled in the study. Demographic, laboratory, imaging, diagnostic, and outcome data were collected and retrospectively analyzed. Factors associated with hematological etiologies diagnosed using BMBs in the training cohort were identified and scored according to the relative hazards. These were further validated using the validation cohort. For the training cohort, 29 of 85 (34.1%) patients had hematological etiologies diagnosed using BMB. Seven factors significantly predicted the diagnostic yield of hematological diseases in the BM and were scored, with the 6 points for leucoerythroblastic changes in peripheral blood smears, 5.5 for elevated ferritin level (>1000 ng/mL), 4 for splenomegaly, 2 for thrombocytopenia, 1.5 for each of elevated lactate dehydrogenase levels and anemia, and 1 for neutropenia. When the cut-off value of the scoring system was set to 6, its sensitivity and specificity to diagnose hematological diseases in the BM of immunocompetent FUO patients were 93% and 58%, respectively. For the validation cohort, 7 of 20 (35%) patients had hematological disease, and all had BM scores higher than the cut-off, with the sensitivity and specificity at 100% and 77%, respectively. As immunocompetent FUO patients with hematological disease have poor prognoses, the "BM score" is valuable for non-hematologist physicians to identify immunocompetent FUO patients requiring early BMB.

  9. TET proteins and 5-methylcytosine oxidation in hematological cancers

    PubMed Central

    An, Jungeun; Pastor, William A.; Ko, Myunggon; Rao, Anjana

    2015-01-01

    Summary DNA methylation has pivotal regulatory roles in mammalian development, retrotransposon silencing, genomic imprinting and X-chromosome inactivation. Cancer cells display highly dysregulated DNA methylation profiles characterized by global hypomethylation in conjunction with hypermethylation of promoter CpG islands (CGIs) that presumably lead to genome instability and aberrant expression of tumor suppressor genes or oncogenes. The recent discovery of Ten-Eleven-Translocation (TET) family dioxygenases that oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in DNA has led to profound progress in understanding the mechanism underlying DNA demethylation. Among the three TET genes, TET2 recurrently undergoes inactivating mutations in a wide range of myeloid and lymphoid malignancies. TET2 functions as a bona fide tumor suppressor particularly in the pathogenesis of myeloid malignancies resembling chronic myelomoncytic leukemia (CMML) and myelodysplastic syndromes (MDS) in human. Here we review diverse functions of TET proteins and the novel epigenetic marks that they generate in DNA methylation/demethylation dynamics and normal and malignant hematopoietic differentiation. The impact of TET2 inactivation in hematopoiesis and various mechanisms modulating the expression or activity of TET proteins are also discussed. Furthermore, we also present evidence that TET2 and TET3 collaborate to suppress aberrant hematopoiesis and hematopoietic transformation. A detailed understanding of the normal and pathological functions of TET proteins may provide new avenues to develop novel epigenetic therapies for treating hematological malignancies. PMID:25510268

  10. Triaging referrals as part of hematology/oncology fellowship training.

    PubMed

    Kyei, Mark; Lavelle, Ellen; Kyasa, Jameel; Safar, Mazin; Makhoul, Issam; Mehta, Paulette

    2010-09-01

    We developed an integrative component of the consult rotation for fellows training in hematology/oncology. This component consisted of triaging all consults to the hematology/oncology service of the CAVHS during a 1-year period of time. The goals of the rotation were to improve timeliness of response to consultation requests, to gain experience in differential diagnosis of patients with potential hematologic/oncologic disorders through of such patients, review of decisions with attending physicians, and communication of such with the referring physician. The major benefits were that fellows integrated didactic learning into real-life clinical cases, selected patients for their continuity clinic to assure sufficient variety and complexity of cases, honed their communication skills, learned about referring and attending physicians' styles, and gained practice in clinical vignettes representative of cases they would be expected to see in clinical practice. Disadvantages were time involvement (approximately 2 h/day) and risks of over- or under-referrals. Administratively, there was a significant decline in the wait time for patients to be seen in the hematology/oncology service. In all, this elective is a valuable integrative experience of senior fellows, but may have less value for first year fellows.

  11. Palliation of Obstructing Malignant Colonic Lesions Using Self-Expanding Metal Stents: A Single-Center Experience

    SciTech Connect

    Shrivastava, Vivek; Tariq, Omar; Tiam, ReeNee; Nyhsen, Christiane; Marsh, Ralph

    2008-09-15

    To evaluate the efficacy, risks, and survival after palliative colorectal stenting at a single center, we conducted a retrospective review of consecutive patients who had colorectal self-expanding metal stents (SEMSs) inserted over an 8-year period (September 1998 to September 2006) to relieve an obstructing colorectal tumor. All patients either had proven distant metastases or were unfit for surgical decompression. A single interventional radiologist (R.M.) inserted the stents, which were either Memotherm or WallFlex. Ninety-one patients with a median age of 73 years had a colorectal stent inserted for palliation of an obstructing colorectal malignancy. Technical success was achieved in 81 of 91 (89%) patients, and clinical success in 80 of 81 (99%). At the time of analysis (December 2006), 13 of 91 (14.2%) patients were alive. The patients who died had a median survival of 59 days, IQR 17-181 days. Seven (7/81) patients suffered stent migration, which occurred 10.3 days (IQR, 5-14 days) after the procedure. Three patients (3/81) re-presented with intestinal obstruction secondary to tumor ingrowth and 10 (10.9%) patients suffered bowel perforation. Ten patients (10.9%) had two stents inserted coaxially and overlapping in one procedure. This was performed in cases where the stricture was too long to be easily crossed by a single stent. We conclude that colorectal SEMS is a safe and effective mode of treatment for the palliation of obstructing colorectal cancers, which avoids high-risk surgery.

  12. Malignant hyperthermia.

    PubMed

    Cantin, R Y; Poole, A; Ryan, J F

    1986-10-01

    The increasing use of intravenous and inhalation sedation in the dental office has the potential of increasing the incidence of malignant hyperthermia (MH) in susceptible subjects. The object of this article is to present two cases of MH and to discuss its pathophysiology, its clinical picture, and its management in the light of the current literature. Stringent screening procedures should be adopted and maintained in order to channel suspected cases to appropriate centers for expert consultation and management. It is further advocated that a program of education for patients and their families be instituted, as it is an essential prerequisite of effective prophylaxis.

  13. Hematological manifestations of nephropathic cystinosis.

    PubMed

    Emadi, Ashkan; Burns, Kathleen H; Confer, Bradley; Borowitz, Michael J; Streiff, Michael B

    2008-01-01

    Pancytopenia is an uncommon manifestation of cystinosis, a congenital lysosomal storage disease. We describe a 34-year-old patient with nephropathic cystinosis with multisystem involvement who developed progressive bone marrow failure after renal transplantation. Bone marrow examination demonstrated widespread deposition of cystine crystals in histiocytes and in the background. We review the literature on the hematologic manifestations of cystinosis and discuss the available treatment options for patients with bone marrow failure secondary to cystine accumulation. The availability of effective oral therapy and the limited activity of hematopoietic growth factors in these patients highlight the importance of bone marrow examination early in the evaluation of cystinosis patients with abnormal blood counts.

  14. Circulating endothelial cells: a new biomarker of endothelial dysfunction in hematological diseases.

    PubMed

    Gendron, Nicolas; Smadja, David M

    2016-08-01

    The endothelium and its integrity are in the center of numerous cardiovascular, pulmonary and tumoral diseases. Several studies identified different circulating cellular sub-populations, which allow a noninvasive exploration of endothelial dysfunction. Furthermore, angiogenesis plays a major role in the biology of benign and malignant hematologic diseases. Among these biomarkers, circulating endothelial cells could be considered as a marker of endothelial injury and/or endothelial activation as well as vascular remodeling, whereas circulating endothelial progenitor cells would be only involved in the vascular regeneration. In the future, the quantification of circulating endothelial cells in many diseases could be a noninvasive biomarker used in diagnosis, prognostic and therapeutic follow-up of lung vasculopathy and/or residual disease of hematological malignancies.

  15. Hematology of infancy and childhood: Third edition

    SciTech Connect

    Nathan, D.G.; Oski, F.A.

    1987-01-01

    These two volumes consist of 14 sections, each containing several chapters. The section titles are: History, Neonatal Hematology, Bone Marrow Failure, Disorders of Erythrocyte Production, Hemolytic Anemias, Disorders of Hemoglobin, The Phagocyte System, The Immune System, Oncology, Storage Disease, Coagulation, Genetics, Transfusion Therapy, and Hematologic Manifestations of Systemic Diseases.

  16. 42 CFR 493.851 - Standard; Hematology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Hematology. 493.851 Section 493.851 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.851 Standard; Hematology. (a) Failure to attain a score of at least 80 percent...

  17. 42 CFR 493.1269 - Standard: Hematology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard: Hematology. 493.1269 Section 493.1269 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1269 Standard: Hematology. (a) For manual cell counts performed using a hemocytometer—...

  18. 42 CFR 493.851 - Standard; Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Hematology. 493.851 Section 493.851 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.851 Standard; Hematology. (a) Failure to attain a score of at least 80 percent...

  19. 42 CFR 493.1269 - Standard: Hematology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Hematology. 493.1269 Section 493.1269 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1269 Standard: Hematology. (a) For manual cell counts performed using a hemocytometer—...

  20. 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

  1. Panobinostat (LBH589): a potent pan-deacetylase inhibitor with promising activity against hematologic and solid tumors.

    PubMed

    Prince, H Miles; Bishton, Mark J; Johnstone, Ricky W

    2009-06-01

    The deacetylase inhibitors are a structurally diverse class of targeted antineoplastic agents that have demonstrated in vitro and in vivo preclinical activity in a wide range of malignancies. Based on this preclinical activity, several deacetylase inhibitors have undergone rapid clinical development in recent years. Among these, the deacetylase inhibitor panobinostat is one of the most widely studied, with extensive pharmacokinetic, pharmacodynamic and dose-finding data available across a wide variety of hematologic and solid tumors. Furthermore, panobinostat has demonstrated favorable clinical activity against various hematologic malignancies, most notably lymphomas and myeloid malignancies in Phase I and II studies. In this article, we discuss the preclinical data on panobinostat and emerging data from Phase I and II studies in cancer patients.

  2. Pleiotropic roles of Notch signaling in normal, malignant, and developmental hematopoiesis in the human

    PubMed Central

    Kushwah, Rahul; Guezguez, Borhane; Lee, Jung Bok; Hopkins, Claudia I; Bhatia, Mickie

    2014-01-01

    The Notch signaling pathway is evolutionarily conserved across species and plays an important role in regulating cell differentiation, proliferation, and survival. It has been implicated in several different hematopoietic processes including early hematopoietic development as well as adult hematological malignancies in humans. This review focuses on recent developments in understanding the role of Notch signaling in the human hematopoietic system with an emphasis on hematopoietic initiation from human pluripotent stem cells and regulation within the bone marrow. Based on recent insights, we summarize potential strategies for treatment of human hematological malignancies toward the concept of targeting Notch signaling for fate regulation. PMID:25252682

  3. Effect of Increasing Experience on Dosimetric and Clinical Outcomes in the Management of Malignant Pleural Mesothelioma With Intensity-Modulated Radiation Therapy

    SciTech Connect

    Patel, Pretesh R.; Yoo, Sua; Broadwater, Gloria; Marks, Lawrence B.; Miles, Edward F.; D'Amico, Thomas A.; Harpole, David; Kelsey, Chris R.

    2012-05-01

    Purpose: To assess the impact of increasing experience with intensity-modulated radiation therapy (IMRT) after extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM). Methods and Materials: The records of all patients who received IMRT following EPP at Duke University Medical Center between 2005 and 2010 were reviewed. Target volumes included the preoperative extent of the pleural space, chest wall incisions, involved nodal stations, and a boost to close/positive surgical margins if applicable. Patients were typically treated with 9-11 beams with gantry angles, collimator rotations, and beam apertures manually fixed to avoid the contalateral lung and to optimize target coverage. Toxicity was graded retrospectively using National Cancer Institute common toxicity criteria version 4.0. Target coverage and contralateral lung irradiation were evaluated over time by using linear regression. Local control, disease-free survival, and overall survival rates were estimated using the Kaplan-Meier method. Results: Thirty patients received IMRT following EPP; 21 patients also received systemic chemotherapy. Median follow-up was 15 months. The median dose prescribed to the entire ipsilateral hemithorax was 45 Gy (range, 40-50.4 Gy) with a boost of 8-25 Gy in 9 patients. Median survival was 23.2 months. Two-year local control, disease-free survival, and overall survival rates were 47%, 34%, and 50%, respectively. Increasing experience planning MPM cases was associated with improved coverage of planning target volumes (P=.04). Similarly, mean lung dose (P<.01) and lung V5 (volume receiving 5 Gy or more; P<.01) values decreased with increasing experience. Lung toxicity developed after IMRT in 4 (13%) patients at a median of 2.2 months after RT (three grade 3-4 and one grade 5). Lung toxicity developed in 4 of the initial 15 patients vs none of the last 15 patients treated. Conclusions: With increasing experience, target volume coverage improved and dose to the

  4. Malignant hyperthermia

    PubMed Central

    Rosenberg, Henry; Davis, Mark; James, Danielle; Pollock, Neil; Stowell, Kathryn

    2007-01-01

    Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000–100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as one in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The classic signs of MH include hyperthermia to marked degree, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity, and rhabdomyolysis, all related to a hypermetabolic response. The syndrome is likely to be fatal if untreated. Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. In humans the syndrome is inherited in autosomal dominant pattern, while in pigs in autosomal recessive. The pathophysiologic changes of MH are due to uncontrolled rise of myoplasmic calcium, which activates biochemical processes related to muscle activation. Due to ATP depletion, the muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene located on chromosome 19q13.1, and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be used for identifying those at risk with greater frequency. Dantrolene

  5. Supernumerary nipples in children with hematologic disorders.

    PubMed

    Aslan, D; Gürsel, T; Kaya, Z

    2004-01-01

    The authors report on supernumerary nipples and various hematologic disorders in 7 patients [factor X deficiency (n = 1), factor XI deficiency (n = 2), acute lymphoblastic leukemia (n = 3), and acute myeloblastic leukemia (n = 1)]. They would like to draw attention to the association of supernumerary nipples with hematological disorders, which has not been published before and is considered to be added to the anomalies associated with supernumerary nipples.

  6. Hematologic Disorders in the Elderly

    PubMed Central

    Walsh, John R.

    1981-01-01

    Management of hematologic disorders in older patients must often be weighed in a setting of decreased physiological reserves and concurrent illnesses. Anemia in the elderly should never be attributed to old age. Even a mild anemia in collusion with multiple physical and mental problems may tip the balance for those previously able to cope with their disabilities. Iron deficiency anemia and the anemia of chronic disease are the most common types of anemia in the elderly. Nutritional anemias due to folate or vitamin B12 deficiency are treatable and should not be overlooked. Newer chemotherapy regimens for acute nonlymphocytic leukemia have been effective in many older patients. Decisions to treat are sometimes difficult, often depending on the aggregate of coexistent physical and mental disorders. The most prevalent type of leukemia in the elderly is chronic lymphocytic leukemia. A benign asymptomatic course requires no therapy, but aggressive disease requires treatment. Multiple myeloma should be suspected in an elderly person who has both unexplained anemia and bone pain. After definitive diagnosis, phlebotomy therapy should be considered for both polycythemia vera and secondary erythrocytosis to reduce blood viscosity and increase cerebral blood flow. PMID:6801866

  7. Ventilatory support in critically ill hematology patients with respiratory failure

    PubMed Central

    2012-01-01

    Introduction Hematology patients admitted to the ICU frequently experience respiratory failure and require mechanical ventilation. Noninvasive mechanical ventilation (NIMV) may decrease the risk of intubation, but NIMV failure poses its own risks. Methods To establish the impact of ventilatory management and NIMV failure on outcome, data from a prospective, multicenter, observational study were analyzed. All hematology patients admitted to one of the 34 participating ICUs in a 17-month period were followed up. Data on demographics, diagnosis, severity, organ failure, and supportive therapies were recorded. A logistic regression analysis was done to evaluate the risk factors associated with death and NIVM failure. Results Of 450 patients, 300 required ventilatory support. A diagnosis of congestive heart failure and the initial use of NIMV significantly improved survival, whereas APACHE II score, allogeneic transplantation, and NIMV failure increased the risk of death. The risk factors associated with NIMV success were age, congestive heart failure, and bacteremia. Patients with NIMV failure experienced a more severe respiratory impairment than did those electively intubated. Conclusions NIMV improves the outcome of hematology patients with respiratory insufficiency, but NIMV failure may have the opposite effect. A careful selection of patients with rapidly reversible causes of respiratory failure may increase NIMV success. PMID:22827955

  8. Seronegative and occult hepatitis C virus infections in patients with hematological disorders.

    PubMed

    Helaly, Ghada Fahmy; Elsheredy, Amel Gaber; El Basset Mousa, Adel Abd; Ahmed, Hayat Khalifa Fadlalla; Oluyemi, Abd El-Gaffar Sabry

    2017-01-01

    Studies of the association between seronegative or occult (OCI) hepatitis C virus (HCV) infection, and hematological disorders have yielded controversial results. The aim of this study was to investigate seronegative and OCI HCV infections in among patients with different hematological disorders. This study included 90 anti-HCV-negative patients with either benign or malignant hematological disorders (group I), along with 20 age- and sex-matched apparently healthy subjects, who served as controls (group II). We tested for HCV RNA in sera and PBMCs by RT-nested PCR and for liver enzyme activity. Seronegativity and OCI were detected in 66.7 % and 20 % respectively, of the studied cases (group I). OCI was more evident in Hodgkin lymphoma and thalassemia. A significant increase in AST activity was observed in the seronegative and OCI groups and in ALT and AST in HCV-seronegative or OCI and negative HCV patients (p ≤ 0.05). Seronegativity and OCI are a significant clinical problem in patients with hematological disorders, warranting wider use of molecular tests combined with periodic evaluations of liver functions for diagnostic purposes.

  9. Labeled cells in patients with malignancy

    SciTech Connect

    Dutcher, J.P.

    1984-07-01

    Recently, new approaches for radiosotopic cell labeling have gained prominence in the investigation of various aspects of malignant diseases and in the clinical care of such patients. Isotopes such as indium-111 can be visualized with standard scanning techniques providing further information about the migration of normal and malignant cells has been discovered. In vivo studies have been performed with indium-111 in animals and humans, including comparisons of the migration of abnormal cells (malignant) and of lymphocytes to abnormal nodes. Evaluation and comparison of the migration of carcinoma cells, normal lymphoid cells, and malignant lymphoid cells in animals show markedly different patterns of distribution, which could have bearing on investigations of mechanisms of metastasis. In vivo human studies also have evaluated the migration patterns of lymphoid cells from patients with chronic lymphocytic leukemia and well-differentiated lymphoma, showing very different migrating behavior between these two polarities of a similar diseases. There are concerns about the use of an isotope such as indium-111 for the labeling of long-lived cells such as lymphocytes. Laboratory studies have demonstrated impaired cell function at high concentrations of radioactivity. Some workers have expressed concern about long-term changes in cells that recirculate. Others cite precedents of other long-term uses of isotopes, therapeutically, without detrimental effects. These concerns continue to be investigated. Finally, an area of much interest in the use of indium-111 is the labeling of granulocytes. This technique has been useful diagnostically, to localize infections. The major value in patients with malignancy, primarily with hematologic malignancies, is to evaluate the potential benefit of granulocyte transfusions. Many of these patients develop prolonged granulocytopenia and become infected, and granulocyte transfusions may become a therapeutic consideration.

  10. Effect of electroconvulsive therapy on hematological parameters.

    PubMed

    Chaturvedi, S; Chadda, R K; Rusia, U; Jain, N

    2001-11-30

    Although a complete blood count is part of the evaluation before the use of electroconvulsive therapy (ECT), there are no known hematological contraindications for the procedure. A preliminary study was done on 31 randomly selected psychiatric patients (chronic schizophrenia, n=10; acute depression, n=8; acute mania, n=6; acute psychosis, n=6; delusional disorder, n=1) receiving ECT to study its hematological effects. Blood samples were drawn just before and 0, 1 and 2 h after ECT. Hemoglobin (Hb%), total and differential leukocyte count (TLC and DLC), red blood cell (RBC) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and platelet count were measured on a fully automated hematology analyzer (Sysmex K-1000). Significant changes were found in TLC, percentage of polymorphs and lymphocytes, and Hb%. Changes in other parameters were not statistically significant. More such studies are needed to substantiate these observations and to understand the mechanism and implication of these effects.

  11. Time trend of multiple myeloma and associated secondary primary malignancies in Asian patients: a Taiwan population-based study.

    PubMed

    Tzeng, Huey-En; Lin, Cheng-Li; Tsai, Chun-Hao; Tang, Chih-Hsin; Hwang, Wen-Li; Cheng, Ya-Wen; Sung, Fung-Chang; Chung, Chi-Jung

    2013-01-01

    Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78-1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79-21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.

  12. Telomeres, stem cells, and hematology

    PubMed Central

    2008-01-01

    Telomeres are highly dynamic structures that adjust the cellular response to stress and growth stimulation based on previous cell divisions. This critical function is accomplished by progressive telomere shortening and DNA damage responses activated by chromosome ends without sufficient telomere repeats. Repair of critically short telomeres by telomerase or recombination is limited in most somatic cells, and apoptosis or cellular senescence is triggered when too many uncapped telomeres accumulate. The chance of the latter increases as the average telomere length decreases. The average telomere length is set and maintained in cells of the germ line that typically express high levels of telomerase. In somatic cells, the telomere length typically declines with age, posing a barrier to tumor growth but also contributing to loss of cells with age. Loss of (stem) cells via telomere attrition provides strong selection for abnormal cells in which malignant progression is facilitated by genome instability resulting from uncapped telomeres. The critical role of telomeres in cell proliferation and aging is illustrated in patients with 50% of normal telomerase levels resulting from a mutation in one of the telomerase genes. Here, the role of telomeres and telomerase in human biology is reviewed from a personal historical perspective. PMID:18263784

  13. Precursors to Lymphoproliferative Malignancies

    PubMed Central

    Goldin, Lynn R.; McMaster, Mary L.; Caporaso, Neil E.

    2013-01-01

    We review monoclonal B-cell lymphocytosis (MBL) as a precursor to chronic lymphocytic leukemia and monoclonal gammopathy of undetermined significance (MGUS) as a precursor to plasma cell disorders. These conditions are present in the general population and increase with age. These precursors aggregate with lymphoproliferative malignancies in families suggesting shared inheritance. MBL and MGUS may share some of the same risk factors as their related malignancies but data are limited. While these conditions are characterized by enhanced risk for the associated malignancy, the majority of individuals with these conditions do not progress to malignancy. A key focus for current work is to identify markers that predict progression to malignancy. PMID:23549397

  14. Clinical experience of the use of voriconazole, caspofungin or the combination in primary and salvage therapy of invasive aspergillosis in haematological malignancies.

    PubMed

    Raad, Issam I; Zakhem, Aline El; Helou, Gilbert El; Jiang, Ying; Kontoyiannis, Dimitrios P; Hachem, Ray

    2015-03-01

    Invasive aspergillosis (IA) is a life-threatening infection in severely immunocompromised haematological malignancy patients. In this study, the efficacy and safety of caspofungin, voriconazole or the combination as primary and salvage therapy in patients with IA were compared. The study included 181 patients with haematological malignancies and IA who received primary or salvage therapy with caspofungin, voriconazole or the combination. In total, 138 patients who received treatment for ≥7 days were analysed; 86 underwent primary antifungal therapy (15 with caspofungin, 38 with voriconazole and 33 with both). Among the salvage therapy patients, 17 received caspofungin, 24 received voriconazole and 35 received both. In the primary therapy group, no difference in therapy response was found, but caspofungin was associated with higher IA mortality rates. A multivariate competing risk analysis of primary antifungal therapy revealed that voriconazole was independently associated with lower IA-associated mortality rates than caspofungin (hazard ratio=0.2, 95% confidence interval 0.06-0.96; P=0.04). In the salvage therapy group, the three treatment groups had similar responses and IA-associated mortality rates. The combination of voriconazole and caspofungin did not result in better outcomes compared with voriconazole alone, as primary or salvage therapy, in haematological malignancy patients. However, voriconazole was associated with a lower Aspergillus-associated mortality rate compared with caspofungin monotherapy.

  15. 42 CFR 493.1269 - Standard: Hematology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard: Hematology. 493.1269 Section 493.1269 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION LABORATORY REQUIREMENTS Quality System for Nonwaived Testing...

  16. Beyond the bloody mess: hematologic assessment.

    PubMed

    Rauen, Carol A

    2012-10-01

    Hematologic assessment is part of the routine assessment of acute and critically ill patients. Nurses must be aware of the reference ranges for complete blood cell counts and common coagulation profiles. A case study is presented of an elderly patient, taking warfarin for atrial fibrillation, who falls and sustains a head laceration. The subsequent assessment, hospital course, and treatments required are outlined.

  17. A hematologic survey of captive waterfowl

    USGS Publications Warehouse

    Shave, H.J.; Howard, V.

    1976-01-01

    Hematologic parameters were studied in giant Canada geese (Branta canadensis maxima), mallard ducks (Anas platyrhynchos platyrhynchos) and various species of diving ducks at seasonal intervals throughout the year. Highest values for packed cell volume, hemoglobin content and erythrocyte counts were found in the winter and pre-nesting periods. Mean corpuscular volume and mean corpuscular hemoglobin varied inversely with these values.

  18. Allo HSCT Using RIC for Hematological Diseases

    ClinicalTrials.gov

    2017-03-09

    Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Plasma Cell Leukemia; Myelodysplastic Syndromes; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; B-Cell Lymphoma; Follicular Lymphoma; Lymphoplasmacytic Lymphoma; Mantle-Cell Lymphoma; Prolymphocytic Leukemia; Lymphoblastic Lymphoma; Burkitt's Lymphoma; Non-Hodgkin's Lymphoma; Multiple Myeloma; Myeloproliferative Syndromes; Hematological Diseases

  19. Primary malignant neoplasms associated with chronic lymphocytic leukaemia.

    PubMed Central

    Lishner, M.; Prokocimer, M.; Ron, E.; Shaklai, M.

    1987-01-01

    The relationship between chronic lymphocytic leukaemia (CLL) and primary malignant neoplasms was evaluated using data from the Hematology Division in Beilinson Medical Center and the Israel Cancer Registry. The study population consisted of 81 patients diagnosed between 1962 and 1984. A total of 16 patients were found to have 21 malignant neoplasms in addition to their CLL. Excluding patients with nonmelanoma skin tumours, a 1.7 increased risk (statistically not significant) for developing second malignant neoplasms in CLL patients was detected. The only tumour which occurred significantly more than expected subsequent to CLL diagnosis was brain cancer. The coexistence of multiple cancers in the same patient was diagnosed in four of the patients. The results of this study further support the hypothesis that patients with CLL are prone to develop second neoplasms. PMID:3684832

  20. Combined loss of Tet1 and Tet2 promotes B-cell, but not myeloid malignancies in mice

    PubMed Central

    Zhao, Zhigang; Chen, Li; Dawlaty, Meelad M.; Pan, Feng; Weeks, Ophelia; Zhou, Yuan; Cao, Zeng; Shi, Hui; Wang, Jiapeng; Lin, Li; Chen, Shi; Yuan, Weiping; Qin, Zhaohui; Ni, Hongyu; Nimer, Stephen D.; Yang, Feng-Chun; Jaenisch, Rudolf; Jin, Peng; Xu, Mingjiang

    2016-01-01

    Summary TET1/2/3 are methylcytosine dioxygenases that regulate cytosine hydroxymethylation. Tet1/2 are abundantly expressed in HSC/HPCs and are implicated in hematological malignancies. Tet2-deletion in mice causes myeloid malignancies, while Tet1-null mice develop B-cell lymphoma after an extended period of latency. Interestingly, TET1/2 are often concomitantly downregulated in acute B-lymphocytic leukemia. Here, we investigated the overlapping and non-redundant functions of Tet1/2 in HSC maintenance and development of hematological malignancies using Tet1/2 double knockout (DKO) mice. DKO and Tet2−/− HSC/HPCs showed overlapping and unique 5hmC and 5mC profiles, and behaved differently. DKO mice exhibited strikingly decreased incidence and delayed-onset of myeloid malignancies compared to Tet2−/− mice, and in contrast developed lethal B-cell malignancies. Transcriptome analysis of DKO tumors revealed expression changes in many genes dysregulated in human B-cell malignancies, such as LMO2, BCL6 and MYC. These results highlight the critical roles of TET1/2 individually and together via communication in the pathogenesis of hematological malignancies. PMID:26586431

  1. Simulating Four Essential Conversations with Hematology/Oncology Trainees: a Qualitative Evaluation.

    PubMed

    Arnaoutakis, Konstantinos; Anders, Michael; Berry, Katherine

    2016-03-01

    Hematologists/oncologists have a crucial responsibility to effectively communicate with patients. However, they have been criticized for ineffective communication with patients. To develop effective communication behaviors that meet the needs of patients and families, trainees need practice and feedback about their performance. Medical faculties frequently teach communication skills using simulation-based curricula; however, they often include only general communication skills, without tailored approaches for specialties. This study examined Hematology/Oncology trainees' qualitative perceptions about the value of and techniques used for simulations of specialty specific, essential conversations with patients and families, and debriefing sessions. Results demonstrate a highly effective curriculum and positive learner experiences. While most reports on this topic take place within major academic cancer centers, outcomes from a mid-sized Hematology/Oncology training program are unknown. The study confirms feasibility for implementing a simulation-based communications program in a mid-sized Hematology/Oncology program and describes simulation techniques that were effective.

  2. Hematology/immunology (M110 series). [human hemodynamic response to weightlessness simulation

    NASA Technical Reports Server (NTRS)

    1973-01-01

    The hematology/immunology experiments in the Skylab mission study various aspects of the red blood cell, including its metabolism and life span, and blood volume changes under zero gravity conditions to determine the precise mechanism of the transient changes which have been seen on the relatively brief missions of the past.

  3. Proceedings from the 1st Insights in Hematology Symposium, Cluj-Napoca, Romania March 11-12, 2016.

    PubMed

    Bojan, Anca; Berindan-Neagoe, Ioana; Ciurea, S; Dima, Delia; Fuji, Shigeo; Ghiaur, G; Grewal, Ravnit; Mccormack, Emmet; Tanase, Alina; Trifa, A; Tomuleasa, Ciprian

    2016-09-01

    In the March 2016 issue of the Lancet Haematology, the editorial office published a paper stating the roadmap for European research in hematology, based on the European Hematology Association (EHA) consensus document that outlines the directions in hematology for the following years across the continent. The meeting entitled "Insights in hematology" is organized a support for the initiative of a roadmap for European hematologists regarding research, may it be basic research or clinical research, but this consensus should not be focused mainly on European institutions, but rather form the backbone of global research between Europe and the United States, Japan or any other country. This will allow Europeans to learn as well as to share their experience with the rest of the scientific and medical community. And the Cluj-Napoca meeting should be followed by other such meetings all across the EU.

  4. Determination of hematopoietic stem cells in peripheral blood by an automated hematology analyzer (SE-9000).

    PubMed

    Takekawa, K; Yamane, T; Hino, M; Tatsumi, N

    1998-12-01

    We evaluated the usefulness of an automated hematology analyzer (SE-9000) for the identification and counting of peripheral blood stem cells (PBSCs). The samples tested were from 14 patients with hematological malignancies. Peripheral blood samples were collected from the subjects before and after a course of chemotherapy. From the leukapheresis sample, CD34+ cells, assumed to be hematopoietic stem cells, were obtained with an immunomagnetic cell separator. The CD34+ cells obtained accumulated in the gate corresponding to low recurrent frequencies of the automated hematology analyzer. This gate shows results of the 'immature information' (IMI) channel. Software for detection of only the cells that accumulated in this gate was therefore developed. With this trial program, the regression coefficient between the percentage of leukocytes from the blood samples that were CD34+ and the percentage of such leukocytes that appeared on the IMI channel was 0.79. With this analyzer, the number of PBSC could be counted in about 80 s. The identification and counting of cells picked up by the IMI channel should be clinically useful for the monitoring of changes in PBSC after chemotherapy for mobilization.

  5. Malignant Vagal Paraganglioma.

    PubMed

    Hamersley, Erin R S; Barrows, Amy; Perez, Angel; Schroeder, Ashley; Castle, James T

    2016-06-01

    Paragangliomas are rare, typically benign neuroendocrine tumors that represent a small portion of head and neck tumors. A small percentage of these are known to have malignant potential. They arise from the carotid body, jugular bulb or vagus nerves. There is limited literature discussing the management of malignant vagal paragangliomas. We present a case of a 25 year old female with a left malignant vagal paraganglioma. The following case presentation will describe the presentation, classic radiologic findings, and management of a malignant vagal paraganglioma along with a review of the literature.

  6. Rheumatic Diseases and Malignancies

    PubMed Central

    BOJINCA, Violeta; JANTA, Iustina

    2012-01-01

    ABSTRACT There are many studies which demonstrate a higher risk for malignancy in patients with rheumatic diseases. There have been a number of possible explanations for the differences in the risk of certain malignancies in patients with rheumatic disease, compared with general population, but a clear mechanism is difficult to identify. Rheumatoid syndromes may be associated with malignancy as paraneoplastic conditions, which can antedate the neoplasm diagnosis. On the other hand, autoimmune rheumatic diseases have a higher risk of malignancy by themselves or because of the immunosuppressant treatments. PMID:23482881

  7. [Hematological variations with submaximal long-term physical exercise].

    PubMed

    Vogelaere, P; Brasseur, M; Leclercq, R; Quirion, A

    1988-03-01

    The purpose of this study was to determine the effects of cold stress on routine hematologic parameters when subjects are submitted on long-lasting exercise. Eight male subjects, aged 22.7 +/- 1.3 years with a peak oxygen consumption of 54.3 +/- 5.2 mL/kg/min performed, respectively at 20 degrees C and 0 degrees C, a two-hour submaximal cyclergometry at an intensity of 40% of that performed during a previous exhaustive test. A 21-gauge catheter was inserted into an ante cubital vein for collection of the blood samples. Platelets and WBC count was significantly (p less than 0.05) increased during exercise in both 20 degrees C and 0 degrees C environmental temperatures. A slight but not statistically significant increase of RBC, Hb and Hct and a plasma concentration during cold exposure was observed. Indices are unchanged in both experiments. The findings of this study suggest that physical exercise is a major factor inducing hypervolemia and that low thermal environment does not appear to be an effective factor influencing hematologic variables during exercise.

  8. Regulating hematology/oncology research involving human participants.

    PubMed

    Kapp, Marshall B

    2002-12-01

    The conduct of hematology/oncology research, particularly clinical trials involving human participants, is an extensively regulated enterprise. Professionals in the specialty of hematology/oncology have important stakes in the success of biomedical research endeavors. Knowledge about and compliance strategies regarding the pertinent regulatory parameters are essential for avoiding negative legal repercussions for involved professionals. At the same time, there is a need to be aware of and actively resist the danger that strong [legal] protectionism might inadvertently result in undermining physician investigators' sense of personal moral responsibility in the conduct of human experiments. For all the limitations of that virtue in the protection of human subjects, it is surely not one that we would want medical scientists to be without [47]. Members of the potential participant pool, financial sponsors, and the general public must be convinced that everyone involved in the research enterprise is committed to operating within acceptable legal and ethical boundaries if the atmosphere of confidence and trust that is indispensable to the continued process and progress of investigation aimed at extending and improving quality of life for all of us in the future is to continue and flourish [48].

  9. Hedgehog signaling in cancer stem cells: a focus on hematological cancers

    PubMed Central

    Campbell, Victoria; Copland, Mhairi

    2015-01-01

    The stem cell paradigm was first demonstrated in hematopoietic stem cells. Whilst classically it was cytokines and chemokines which were believed to control stem cell fate, more recently it has become apparent that the stem cell niche and highly conserved embryonic pathways play a key role in governing stem cell behavior. One of these pathways, the hedgehog signaling pathway, found in all organisms, is vitally important in embryogenesis, performing the function of patterning through early stages of development, and in adulthood, through the control of somatic stem cell numbers. In addition to these roles in health however, it has been found to be deregulated in a number of solid and hematological malignancies, components of the hedgehog pathway being associated with a poor prognosis. Further, these components represent viable therapeutic targets, with inhibition from a drug development perspective being readily achieved, making the hedgehog pathway an attractive potential therapeutic target. However, although the concept of cancer stem cells is well established, how these cells arise and the factors which influence their behavior are not yet fully understood. The role of the hedgehog signaling pathway and its potential as a therapeutic target in hematological malignancies is the focus of this review. PMID:25691811

  10. Hematological manifestations of primary mitochondrial disorders.

    PubMed

    Finsterer, Josef

    2007-01-01

    At onset mitochondrial disorders (MID) frequently manifest as a mono-organic problem but turn into multisystem disease during the disease course in most of the cases. Organs/tissues most frequently affected in MID are the cerebrum, peripheral nerves, and the skeletal muscle. Additionally, most of the inner organs may be affected alone or in combination. Hematological manifestations of MID include aplastic, megaloblastic, or sideroblastic anemia, leukopenia, neutropenia, thrombocytopenia, or pancytopenia. In single cases either permanent or recurrent eosinophilia has been observed. Hematological abnormalities may occur together with syndromic or nonsyndromic MIDs. Syndromic MIDs, in which hematological manifestations predominate, are the Pearson syndrome (pancytopenia), Kearns-Sayre syndrome (anemia), Barth syndrome (neutropenia), and the autosomal recessive mitochondrial myopathy, lactic acidosis and sideroblastic anemia syndrome. In single cases with Leigh's syndrome, MERRF (myoclonic epilepsy and ragged-red fiber) syndrome, Leber's hereditary optic neuropathy, and Friedreich's ataxia anemia has been described. Anemia, leukopenia, thrombocytopenia, eosinophilia, or pancytopenia can frequently also be found in nonsyndromic MIDs with or without involvement of other tissues. Therapy of blood cell involvement in MID comprises application of antioxidants, vitamins, iron, bone marrow-stimulating factors, or substitution of cells.

  11. Bronchial malignant melanoma.

    PubMed

    Weshler, Z; Sulkes, A; Kopolovitch, J; Leviatan, A; Shifrin, E

    1980-01-01

    We describe a case of malignant melanoma presenting initially as an endobronchial lesion located in the left main bronchus causing total atelectasis. This resolved with radiation therapy. Widespread metastases developed shortly thereafter. The differential diagnosis of primary and metastatic bronchial malignant melanoma is discussed. Other isolated case reports are reviewed.

  12. Percutaneous Vertebroplasty and Bone Cement Leakage: Clinical Experience with a New High-Viscosity Bone Cement and Delivery System for Vertebral Augmentation in Benign and Malignant Compression Fractures

    SciTech Connect

    Anselmetti, Giovanni Carlo; Zoarski, Gregg; Manca, Antonio; Masala, Salvatore; Eminefendic, Haris; Russo, Filippo; Regge, Daniele

    2008-09-15

    The aim of this study was to assess the feasibility of and venous leakage reduction in percutaneous vertebroplasty (PV) using a new high-viscosity bone cement (PMMA). PV has been used effectively for pain relief in osteoporotic and malignant vertebral fractures. Cement extrusion is a common problem and can lead to complications. Sixty patients (52 female; mean age, 72.2 {+-} 7.2) suffering from osteoporosis (46), malignancy (12), and angiomas (2), divided into two groups (A and B), underwent PV on 190 vertebrae (86 dorsal, 104 lumbar). In Group A, PV with high-viscosity PMMA (Confidence, Disc-O-Tech, Israel) was used. This PMMA was injected by a proprietary delivery system, a hydraulic saline-filled screw injector. In Group B, a standard low-viscosity PMMA was used. Postprocedural CT was carried out to detect PMMA leakages and complications. Fisher's exact test and Wilcoxon rank test were used to assess significant differences (p < 0.05) in leakages and to evaluate the clinical outcome. PV was feasible, achieving good clinical outcome (p < 0.0001) without major complications. In Group A, postprocedural CT showed an asymptomatic leak in the venous structures of 8 of 98 (8.2%) treated vertebrae; a discoidal leak occurred in 6 of 98 (6.1%). In Group B, a venous leak was seen in 38 of 92 (41.3%) and a discoidal leak in 12 of 92 (13.0%). Reduction of venous leak obtained by high-viscosity PMMA was highly significant (p < 0.0001), whereas this result was not significant (p = 0.14) related to the disc. The high-viscosity PMMA system is safe and effective for clinical use, allowing a significant reduction of extravasation rate and, thus, leakage-related complications.

  13. The effects of feeding clinoptilolite on hematology, performance, and health of newborn lambs.

    PubMed

    Norouzian, M A; Valizadeh, R; Khadem, A A; Afzalzadeh, A; Nabipour, A

    2010-11-01

    The effects of feeding clinoptilolite on hematology, performance, and health of newborn Balouchi lambs were evaluated in this experiment. In a completely randomized design, 30 newborn lambs were allocated to three groups and fed by basal diet (C0; without clinoptilolite) and C1 and C2 (the basal diet plus 1.5% and 3% clinoptilolite, respectively, for 6 weeks (3 weeks before and 3 weeks after weaning)). Blood samples were taken from all lambs, at the time when the animals were allocated to the experimental diet and at the end of each week of experiment, and analyzed for hematology, plasma fibrinogen, and total protein. Performance and health of all lambs were measured. Fecal consistency score and diarrhea severity were evaluated. There was no difference between lambs in case of hematological parameters. Lambs fecal consistency score and severity of diarrhea were lowest (P < 0.05) for lambs on C1 and C2 and highest for lambs on C0. Dry matter intake and feed conservation ratio were similar between the groups of lambs fed by different diets, but daily gain of lambs differed significantly (P < 0.05) and was higher in C2. It was concluded that addition of 3% clinoptilolite to starter diet of newborn lamb can reduce incidence and severity of diarrhea, although its effect on hematology and performance was negligible.

  14. The influence of multiple liver biopsies on hematologic and serum biochemical values of sheep.

    PubMed

    Harvey, R B; Lovering, S L; Bailey, E M; Norman, J O

    1984-10-01

    A rapid, simple liver biopsy technique for sheep was developed to obtain in situ liver samples for evaluation of histological tissue, enzyme assay, and ultrastructural changes that might occur during toxicological testing. The study was designed because repeated biopsies in the same individual could induce bias in hematologic, histological or serum biochemical parameters caused by the trauma of the biopsy procedure. In Experiment I, sheep were divided into a biopsied group (B), sham-operated group (SO), and a nonsurgical, untreated control group (C). Three liver biopsy samples per week were removed from each subject in Group B for five weeks. Biweekly blood samples were drawn for evaluation of hematologic and serum biochemical parameters. In Experiment II, Groups B and SO were dosed with CCl4 in order to validate the applicability of the biopsy procedure. Weekly biopsies were continued in Group B. Biweekly blood samples were evaluated for any hematologic or serum biochemical variations. Significant elevations of enzyme activities confirmed CCl4 hepatotoxicity in treated groups (B and SO) versus C group. Histological lesions in biopsy samples correlated closely with serum biochemical data in treated groups. It was concluded that the serial liver biopsy procedure causes negligible alterations in the hematologic, histological or serum biochemical parameters measured; is simple and rapid to perform, and provides a method for possible early detection of liver disease.

  15. Teaching hematology to second year medical students: results of a national survey of hematology course directors.

    PubMed

    Broudy, Virginia C; Hickman, Scot

    2007-04-01

    Increasing clinical productivity expectations at academic medical centers and new faculty effort reporting requirements for NIH-supported investigators challenge the tradition of faculty volunteerism for medical student teaching. To better define the structure, content, and financial support of second year medical school hematology courses nationwide, we mailed a survey to the hematology course directors at 85 of the 125 accredited US medical schools. The 58 course directors who returned the survey represent all regions of the US and both public and private medical schools. Median class size was 150 students (range 40-200), and some courses included a substantial proportion (up to 33%) of other types of students. The median number of hours per course was 33 h (range 8 to 74). Approximately 50% of the total teaching time was devoted to lecture (range 5 to 100%). Web-based teaching was used by 62% of course directors. The median number of faculty responsible for teaching the second year hematology course was 12 (range 1-36). The hematology course directors identified a number of obstacles, including difficulty in recruiting teachers, the lack of well-defined content, and the very modest budget (less than $1,500 for most courses). Only three of the course directors indicated that they received salary support for this role. These findings suggest that a national effort to define learning objectives for the hematology courses and to share teaching materials among medical schools is warranted. Little financial support is provided for the hematology course, and these findings compel the identification of resources to pay faculty for teaching medical student required courses.

  16. Magnesium homeostasis and hypomagnesemia in children with malignancy.

    PubMed

    Kaplinsky, Chaim; Alon, Uri S

    2013-05-01

    Hypomagnesemia is not uncommon among children with malignancies. It is especially seen in association with certain medications and can be further complicated by the presence of diarrhea and malnutrition. Severe hypomagnesemia may cause disturbances in the neuromuscular and cardiovascular systems. All patients with hypomagnesemia should be supplemented with the mineral, and urgent treatment is indicated when serum magnesium decreases below 1.0 mg/dl, a level under which symptoms may develop. This review addresses the essentials of magnesium physiology, and pathophysiology of hypomagnesemia, its etiologies, clinical manifestations and ways to treat it, with an emphasis on the child with hematologic/oncologic disorders.

  17. Verification and quality control of routine hematology analyzers.

    PubMed

    Vis, J Y; Huisman, A

    2016-05-01

    Verification of hematology analyzers (automated blood cell counters) is mandatory before new hematology analyzers may be used in routine clinical care. The verification process consists of several items which comprise among others: precision, accuracy, comparability, carryover, background and linearity throughout the expected range of results. Yet, which standard should be met or which verification limit be used is at the discretion of the laboratory specialist. This paper offers practical guidance on verification and quality control of automated hematology analyzers and provides an expert opinion on the performance standard that should be met by the contemporary generation of hematology analyzers. Therefore (i) the state-of-the-art performance of hematology analyzers for complete blood count parameters is summarized, (ii) considerations, challenges, and pitfalls concerning the development of a verification plan are discussed, (iii) guidance is given regarding the establishment of reference intervals, and (iv) different methods on quality control of hematology analyzers are reviewed.

  18. Optical digital microscopy for cyto- and hematological studies in vitro

    NASA Astrophysics Data System (ADS)

    Ganilova, Yu. A.; Dolmashkin, A. A.; Doubrovski, V. A.; Yanina, I. Yu.; Tuchin, V. V.

    2013-08-01

    The dependence of the spatial resolution and field of view of an optical microscope equipped with a CCD camera on the objective magnification has been experimentally investigated. Measurement of these characteristics has shown that a spatial resolution of 20-25 px/μm at a field of view of about 110 μm is quite realistic; this resolution is acceptable for a detailed study of the processes occurring in cell. It is proposed to expand the dynamic range of digital camera by measuring and approximating its light characteristics with subsequent plotting of the corresponding calibration curve. The biological objects of study were human adipose tissue cells, as well as erythrocytes and their immune complexes in human blood; both objects have been investigated in vitro. Application of optical digital microscopy for solving specific problems of cytology and hematology can be useful in both biomedical studies in experiments with objects of nonbiological origin.

  19. Hypercalcemia of Malignancy: An Update on Pathogenesis and Management

    PubMed Central

    Mirrakhimov, Aibek E.

    2015-01-01

    Hypercalcemia of malignancy is a common finding typically found in patients with advanced stage cancers. We aimed to provide an updated review on the etiology, pathogenesis, clinical presentation, and management of malignancy-related hypercalcemia. We searched PubMed/Medline, Scopus, Embase, and Web of Science for original articles, case reports, and case series articles focused on hypercalcemia of malignancy published from 1950 to December 2014. Hypercalcemia of malignancy usually presents with markedly elevated calcium levels and therefore, usually severely symptomatic. Several major mechanisms are responsible for the development of hypercalcemia of malignancy including parathyroid hormone-related peptide-mediated humoral hypercalcemia, osteolytic metastases-related hypercalcemia, 1,25 Vitamin D-mediated hypercalcemia, and parathyroid hormone-mediated hypercalcemia in patients with parathyroid carcinoma and extra parathyroid cancers. Diagnosis should include the history and physical examination as well as measurement of the above mediators of hypercalcemia. Management includes hydration, calcitonin, bisphosphonates, denosumab, and in certain patients, prednisone and cinacalcet. Patients with advanced underlying kidney disease and refractory severe hypercalcemia should be considered for hemodialysis. Hematology or oncology and palliative care specialists should be involved early to guide the options of cancer targeted therapies and help the patients and their closed ones with the discussion of comfort-oriented care. PMID:26713296

  20. Blood at 70: its roots in the history of hematology and its birth.

    PubMed

    Coller, Barry S

    2015-12-10

    This year we celebrate Blood's 70th year of publication. Created from the partnership of the book publisher Henry M. Stratton and the prominent hematologist Dr William Dameshek of Tufts School of Medicine, Blood has published many papers describing major advances in the science and clinical practice of hematology. Blood's founding antedated that of the American Society of Hematology (ASH) by more than 11 years and Stratton and Dameshek helped galvanize support for the creation of ASH. In this review, I place the birth of Blood in the context of the history of hematology before 1946, emphasizing the American experience from which it emerged, and focusing on research conducted during World War II. I also provide a few milestones along Blood's 70 years of publication, including: the growth in Blood's publications, the evolution of its appearance, the countries of submission of Blood papers, current subscriptions to Blood, and the evolution of topics reported in Blood's papers. The latter provides a snapshot of the evolution of hematology as a scientific and clinical discipline and the introduction of new technology to study blood and bone marrow. Detailed descriptions of the landmark discoveries reported in Blood will appear in later papers celebrating Blood's birthday authored by past Editors-in-Chief.

  1. Blood at 70: its roots in the history of hematology and its birth

    PubMed Central

    2015-01-01

    This year we celebrate Blood's 70th year of publication. Created from the partnership of the book publisher Henry M. Stratton and the prominent hematologist Dr William Dameshek of Tufts School of Medicine, Blood has published many papers describing major advances in the science and clinical practice of hematology. Blood's founding antedated that of the American Society of Hematology (ASH) by more than 11 years and Stratton and Dameshek helped galvanize support for the creation of ASH. In this review, I place the birth of Blood in the context of the history of hematology before 1946, emphasizing the American experience from which it emerged, and focusing on research conducted during World War II. I also provide a few milestones along Blood's 70 years of publication, including: the growth in Blood's publications, the evolution of its appearance, the countries of submission of Blood papers, current subscriptions to Blood, and the evolution of topics reported in Blood's papers. The latter provides a snapshot of the evolution of hematology as a scientific and clinical discipline and the introduction of new technology to study blood and bone marrow. Detailed descriptions of the landmark discoveries reported in Blood will appear in later papers celebrating Blood's birthday authored by past Editors-in-Chief. PMID:26631112

  2. Hematology of healthy Florida manatees (Trichechus manatus)

    USGS Publications Warehouse

    Harvey, J.W.; Harr, K.E.; Murphy, D.; Walsh, M.T.; Nolan, E.C.; Bonde, R.K.; Pate, M.G.; Deutsch, C.J.; Edwards, H.H.; Clapp, W.L.

    2009-01-01

    Background: Hematologic analysis is an important tool in evaluating the general health status of free-ranging manatees and in the diagnosis and monitoring of rehabilitating animals. Objectives: The purpose of this study was to evaluate diagnostically important hematologic analytes in healthy manatees (Trichechus manatus) and to assess variations with respect to location (free ranging vs captive), age class (small calves, large calves, subadults, and adults), and gender. Methods: Blood was collected from 55 free-ranging and 63 captive healthy manatees. Most analytes were measured using a CELL-DYN 3500R; automated reticulocytes were measured with an ADVIA 120. Standard manual methods were used for differential leukocyte counts, reticulocyte and Heinz body counts, and plasma protein and fibrinogen concentrations. Results: Rouleaux, slight polychromasia, stomatocytosis, and low numbers of schistocytes and nucleated RBCs (NRBCs) were seen often in stained blood films. Manual reticulocyte counts were higher than automated reticulocyte counts. Heinz bodies were present in erythrocytes of most manatees. Compared with free-ranging manatees, captive animals had slightly lower MCV, MCH, and eosinophil counts and slightly higher heterophil and NRBC counts, and fibrinogen concentration. Total leukocyte, heterophil, and monocyte counts tended to be lower in adults than in younger animals. Small calves tended to have higher reticulocyte counts and NRBC counts than older animals. Conclusions: Hematologic findings were generally similar between captive and free-ranging manatees. Higher manual reticulocyte counts suggest the ADVIA detects only reticulocytes containing large amounts of RNA. Higher reticulocyte and NRBC counts in young calves probably reflect an increased rate of erythropoiesis compared with older animals. ?? 2009 American Society for Veterinary Clinical Pathology.

  3. Stages of Malignant Mesothelioma

    MedlinePlus

    ... wall, abdomen, heart, or testicles. Being exposed to asbestos can affect the risk of malignant mesothelioma. Anything ... lived in places where they inhaled or swallowed asbestos . After being exposed to asbestos, it usually takes ...

  4. What Is Malignant Mesothelioma?

    MedlinePlus

    ... you learn about the treatment options and possible side effects, and point you to information and services to help you in your cancer journey. ... free PDFs of our malignant mesothelioma information ...

  5. Asbestos-related malignancy

    SciTech Connect

    Antmann, K.; Aisner, J.

    1986-01-01

    This book contains 20 chapters. Some of the chapter titles are: The Radiology of Asbestosis and Related Neoplasms; Computed Tomography and Malignant Mesothelioma; Radiation Therapy for Pleural Mesothelioma; and Radiation Therapy of Peritoneal Mesothelioma.

  6. Nanopharmacology in translational hematology and oncology

    PubMed Central

    Tomuleasa, Ciprian; Braicu, Cornelia; Irimie, Alexandra; Craciun, Lucian; Berindan-Neagoe, Ioana

    2014-01-01

    Nanoparticles have displayed considerable promise for safely delivering therapeutic agents with miscellaneous therapeutic properties. Current progress in nanotechnology has put forward, in the last few years, several therapeutic strategies that could be integrated into clinical use by using constructs for molecular diagnosis, disease detection, cytostatic drug delivery, and nanoscale immunotherapy. In the hope of bringing the concept of nanopharmacology toward a viable and feasible clinical reality in a cancer center, the present report attempts to present the grounds for the use of cell-free nanoscale structures for molecular therapy in experimental hematology and oncology. PMID:25092977

  7. Splenectomy in hematologic disorders. The ever-changing indications.

    PubMed Central

    Wilhelm, M C; Jones, R E; McGehee, R; Mitchener, J S; Sandusky, W R; Hess, C E

    1988-01-01

    A comparison between a series of splenectomies performed at the University of Virginia Medical Center for hematologic disorders between 1946 and 1962 (Series I) and 1963 and 1982 (Series II) is presented. Four hundred splenectomies (20 per year) were performed between 1963 and 1982 compared with 94 (5.5 per year) between 1946 and 1962. Also noted in Series II was a sharp decline in the number performed each year between 1974 and 1983. The major factor responsible for these observations was the evolution of the staging laparotomy for malignant lymphomas, particularly Hodgkin's disease, and the decline in the average annual incidence of staging laparotomies since 1974. Staging laparotomy currently is rarely done for non-Hodgkin's lymphomas. Also contributing to the changes noted was an increase in the total number but subsequent fall in the annual incidence of splenectomy for hereditary spherocytosis, idiopathic hypersplenism, and myeloproliferative disorders in Series II. The average number of splenectomies for idiopathic thrombocytopenic purpura increased from 1.1 per year in Series I to 3.6 per year in Series II; the annual incidence during the study period of Series II, however, remained constant. The total number of splenectomies for hairy cell leukemia and Felty's syndrome increased from zero in Series I to 12 and 17, respectively, in Series II, whereas the number of miscellaneous reasons dropped from 29 (1.7 per year) in Series I to 15 (0.75 per year) in Series II. The mortality rate in Series I was 6.3% compared with 4.0% in Series II. No deaths occurred in Series II after 1979. Indications for splenectomy in Series II were for diagnostic purposes in 3.2%, therapeutic in 56.5%, staging in 39.5%, and restaging in 0.8%. Accessory spleens were found in 49 (12.5%) in Series II. PMID:3377568

  8. [Recurrent cellulitis due to Helicobacter cinaedi after chemotherapy for malignant lymphoma].

    PubMed

    Ishizawa, Jo; Mori, Takehiko; Tsukada, Yuiko; Matsuki, Eri; Yokoyama, Kenji; Shimizu, Takayuki; Sugita, Kayoko; Murata, Mitsuru; Iwata, Satoshi; Okamoto, Shinichiro

    2012-06-01

    A 62-year-old man with diffuse large B-cell lymphoma received five courses of R-CHOP chemotherapy. The patient developed cellulitis in the bilateral lower extremities without fever, and blood culture yielded Helicobacter cinaedi after five-day culture. Although the response to tazobactam/piperacillin (TAZ/PIPC) was prompt, cellulitis recurred immediately after discontinuation of the drug. Even after two months of treatment with PIPC plus amikacin followed by amoxicillin, it recurred again soon after stopping the antibiotics. H. cinaedi reportedly causes bacteremia and cellulitis in immunocompromised patients mostly in patients with acquired immunodeficiency syndrome. Only sporadic cases have been reported in association with hematological malignancies. Physicians should be aware of H. cinaedi as one of the causative pathogens of bacteremia and cellulitis in patients with hematological malignancies. Longer incubation period of blood culture is needed to detect the microbe and long-term use of antimicrobials is required to prevent recurrent cellulitis.

  9. Implementing a clinical pharmacy service in hematology

    PubMed Central

    Farias, Tatiane Fernandes; Aguiar, Karina da Silva; Rotta, Inajara; Belletti, Klezia Morais da Silva; Carlotto, Juliane

    2016-01-01

    ABSTRACT Objective: To implement a clinical pharmacy service focused on the comprehensive review of antineoplastic drugs used in therapy of hematological diseases. Methods: An interventional study was conducted in a Brazilian tertiary teaching hospital in two different periods, with and without a clinical pharmacy service, respectively. This service consisted of an antineoplastic prescription validation (analysis of patients' characteristics, laboratory tests, compliance with the therapeutic protocol and with pharmacotechnical parameters). When problems were detected, the pharmacist intervened with the physician or another health professional responsible for the patient. Inpatients and outpatients with hematological diseases were included. Results: We found an increased detection of drug-related problem by 106.5% after implementing the service. Comparing the two periods, an increase in patients' age (26.7 years versus 17.6 years), a predominance of outpatients (54% versus 38%), and an increase in multiple myeloma (13% versus 4%) and non-Hodgkin lymphoma (16% versus 3%) was noted. The most commonly found problems were related to dose (33% versus 25%) and cycle day (14% versus 30%). With regard to clinical impact, the majority had a significant impact (71% versus 58%), and in one patient from the second period could have been fatal. The main pharmaceutical interventions were dose adjustment (35% versus 25%) and drug withdrawal (33% versus 40%). Conclusion: The pharmacy service contributed to increase the detection and resolution of drug-related problems, and it was an effective method to promote the safe and rational use of antineoplastic drugs. PMID:27759828

  10. Retreatment with brentuximab vedotin in patients with CD30-positive hematologic malignancies

    PubMed Central

    2014-01-01

    Background Brentuximab vedotin is a CD30-directed antibody-drug conjugate. Retreatment with brentuximab vedotin monotherapy was investigated in patients with CD30-positive Hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (ALCL) who relapsed after achieving complete or partial remission (CR or PR) with initial brentuximab vedotin therapy in a previous study (ClinicalTrials.gov NCT00947856). Methods Twenty-one patients with HL and 8 patients with systemic ALCL were retreated; 3 patients with systemic ALCL were retreated twice. Patients generally received brentuximab vedotin 1.8 mg/kg intravenously approximately every 3 weeks over 30 minutes as an outpatient infusion. The primary objectives of this study were to assess safety and to estimate antitumor activity of brentuximab vedotin retreatment. Results The objective response rate was 60% (30% CR) in HL patients and 88% (63% CR) in systemic ALCL patients. The estimated median duration of response for patients with an objective response was 9.5 months (range, 0.0+ to 28.0+ months) at the time of study closure. Of the 19 patients with objective response, 7 patients had not had an event of disease progression or death at the time of study closure; duration of response for these patients ranged from 3.5 to 28 months. Of the 11 patients with CR, 45% had response durations of over 1 year. Adverse events (AEs) occurring in ≥25% of patients during the retreatment period were generally similar in type and frequency to those observed in the pivotal trials of brentuximab vedotin monotherapy, with the exception of peripheral neuropathy, which is known to have a cumulative effect. Grade 3 or higher events were observed in 48% of patients; these were generally transient and managed by dose modifications or delays. Deaths due to AEs occurred in 3 HL patients; none were considered to be related to brentuximab vedotin retreatment. Discussion With the exception of a higher rate of peripheral motor neuropathy, retreatment with brentuximab vedotin was associated with similar side effects seen in the pivotal trials. Conclusions Retreatment with brentuximab vedotin monotherapy is associated with response rates in 68% (39% CR) of patients with relapsed HL and systemic ALCL. Trial registration United States registry and results database ClinicalTrials.gov NCT00947856. PMID:24642247

  11. Improved radioimmunotherapy of hematologic malignancies. Progress report, November 1, 1993--October 31, 1994

    SciTech Connect

    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.

  12. Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

    ClinicalTrials.gov

    2016-11-02

    Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myeloid Sarcoma; Chronic Myelogenous Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Myelodysplastic Syndrome (MDS); Non-Hodgkin Lymphoma (NHL)

  13. Rechallenging With Intrathecal Methotrexate After Developing Subacute Neurotoxicity in Children With Hematologic Malignancies.

    PubMed

    Badke, Colleen; Fleming, Amy; Iqbal, Asneha; Khilji, Ohmed; Parhas, Sophia; Weinstein, Joanna; Morgan, Elaine; Hijiya, Nobuko

    2016-04-01

    Methotrexate is associated with neurologic side effects. It is recommended that patients who developed neurotoxicity be rechallenged with methotrexate, but little is known about the safety of this approach. We performed a chart review to identify patients who received high-dose or intrathecal (IT) methotrexate. Twenty-one of 298 patients (7%) experienced neurologic symptoms attributed to methotrexate treatment in the premaintenance phase. Seventeen of these patients were rechallenged with IT methotrexate and 13 (76%) had no further neurotoxic events. No patients rechallenged during maintenance (n = 9) experienced recurrence of neurotoxic events. It is safe to rechallenge with IT methotrexate in maintenance.

  14. 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... leukemia (CLL); (3) Third-party flow cytometry data analysis software; and (4) Overview of FDA regulation... (77 FR 76051, December 26, 2012). An FDA workshop for acute lymphocytic leukemia (ALL) MRD was...

  15. Enigmatic Inv(9): A Case Report on Rare Findings in Hematological Malignancies

    PubMed Central

    Vijay, Sangeetha; Narayanan, Geetha; Sarojam, Santhi; Raveendran, Suresh Kumar; Hariharan, Sreedharan

    2016-01-01

    Introduction Inversion of chromosome 9 had been widely discussed among geneticists and evolutionary biologists because of its significant impact on various hereditary disorders and in the evolution of man. The role of such inversions in human disease evolution is an area hitherto unclear. Case Presentation We present the case of a chronic myeloid leukemia (CML) patient who showed intermittent relapse on treatment, with a rare appearance of clones with dual inversion (9) breakpoints [inv(9)(p22q34); inv(9)(p11q21)]. We also present the first report of inv(9)(p11,q13) as the sole abnormality in a patient with chronic myeloproliferative disorder(CMPD). Both the patients registered in 2012 and were from Kerala, India. Conclusions Both the cases discussed in our study have inv(9) as the sole abnormality and are found to confer a relatively poor prognosis. PMID:27280043

  16. 3-AP and High-Dose Cytarabine in Treating Patients With Advanced Hematologic Malignancies

    ClinicalTrials.gov

    2013-01-23

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  17. Bioengineering targeted nanodrugs for hematologic malignancies: An innovation in pediatric oncology

    NASA Astrophysics Data System (ADS)

    Krishnan, Vinu

    Chemotherapy for pediatric cancers employs combinations of highly toxic drugs. This has achieved 5-year survival rates exceeding 90% in children treated for leukemia -- the most prominent form of pediatric cancer. However, delayed onset of harmful side effects in more than 60% of survivors result in death or low quality of life post therapy. This is primarily due to the non-specific effect of drugs on healthy dividing cells in a growing child. Nanomedicine has advanced tremendously to improve adult cancer therapy, but as yet has had minimal impact in pediatric oncology. There is a pressing need for innovative therapeutic strategies that can reduce life-threatening side effects caused by conventional chemotherapy in the clinic. Targeting chemotherapeutic agents specifically to leukemia cells may alleviate treatment-related toxicity in children. The research objective of this dissertation is to bioengineer and advance preclinically a novel nanotherapeutic approach that can specifically target and deliver drugs into leukemic cells. Dexamethasone (Dex) is one of the most commonly used chemotherapeutic drugs in treating pediatric leukemia. For the first part in this study, we encapsulated Dex in polymeric NPs and validated its anti-leukemic potential in vitro and in vivo. NPs with an average diameter of 110 nm were assembled from an amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly-caprolactone (PCL) bearing pendant cyclic ketals (ECT2). The blank NPs were nontoxic to cultured cells in vitro and to mice in vivo. Encapsulation of Dex into the NPs (Dex-NP) did not compromise the bioactivity of the drug. Dex-NPs induced glucocorticoid phosphorylation and showed cytotoxicity similar to free drug when treated with leukemic cells. Studies using NPs labeled with fluorescent dyes revealed leukemic cell surface binding and internalization. In vivo biodistribution studies showed NP accumulation in the liver and spleen with subsequent clearance of particles with time. In a preclinical model of leukemia, Dex-NPs significantly improved the quality of life and survival of mice compared to the group treated with free Dex. In the second section, we demonstrate, that doxorubicin (DOX, an anthracycline commonly used in pediatric leukemia therapy) when encapsulated within 80 nm sized NPs and modified with targeting ligands against CD19 (a B-lymbhoblast antigen, CD19-DOX-NPs) can be delivered in a CD19-specific manner to leukemic cells. The CD19-DOX-NPs were internalized via receptor-mediated endocytosis and imparted cytotoxicity in a CD19-dependent manner in CD19 positive (CD19+) leukemic cells. Leukemic mice treated with CD19-DOX-NPs survived significantly longer and manifested a higher degree of agility indicating reduced apparent systemic toxicity during treatment compared to mice treated with free DOX. This study for the first time shows the efficacy of polymeric NPs to target and deliver chemotherapeutic drugs in pediatric oncology and suggests that targeted nanotherapy can potentially improve the therapeutic efficacy of conventional chemotherapy and reduce treatment-related side effects in children.

  18. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy.

    PubMed

    Ammann, Eric M; Jones, Michael P; Link, Brian K; Carnahan, Ryan M; Winiecki, Scott K; Torner, James C; McDowell, Bradley D; Fireman, Bruce H; Chrischilles, Elizabeth A

    2016-01-14

    In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications.

  19. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy

    PubMed Central

    Jones, Michael P.; Link, Brian K.; Carnahan, Ryan M.; Winiecki, Scott K.; Torner, James C.; McDowell, Bradley D.; Fireman, Bruce H.; Chrischilles, Elizabeth A.

    2016-01-01

    In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: −0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: −0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications. PMID:26443622

  20. Ipilimumab or Nivolumab in Treating Patients With Relapsed Hematologic Malignancies After Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-04-04

    Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma

  1. A Two-Step Approach to Reduced Intensity Bone Marrow Transplant for Patients With Hematological Malignancies

    ClinicalTrials.gov

    2016-10-18

    Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Aplastic Anemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Mastocytosis; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Anemia; Refractory Anemia With Ringed Sideroblasts; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Waldenström Macroglobulinemia

  2. Deferasirox in Treating Iron Overload Caused By Blood Transfusions in Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2017-01-17

    Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; Adult Langerhans Cell Histiocytosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Mast Cell Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Myeloid/NK-cell Acute Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelofibrosis; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia; Waldenstrom Macroglobulinemia

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

    ClinicalTrials.gov

    2013-08-09

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

  4. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-11-23

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Isolated Plasmacytoma of Bone; Monoclonal Gammopathy of Undetermined Significance; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Primary Myelofibrosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Adult T-cell Leukemia/Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Multiple Myeloma; Stage I Small Lymphocytic Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Adult Hodgkin Lymphoma; Stage II Adult T-cell Leukemia/Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Multiple Myeloma; Stage III Small Lymphocytic Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Hairy Cell Leukemia; Waldenström Macroglobulinemia

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

    ClinicalTrials.gov

    2016-05-03

    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)

  6. Methoxyamine and Fludarabine Phosphate in Treating Patients With Relapsed or Refractory Hematologic Malignancies

    ClinicalTrials.gov

    2015-08-12

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Chronic Lymphocytic Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  7. Analysis of non-clonal chromosome abnormalities observed in hematologic malignancies among Southwest Oncology Group patients

    SciTech Connect

    McConnell, T.S.; Dobin, S.M.

    1994-09-01

    From 1987-1994, the Southwest Oncology Group Cytogenetics Committee reviewed 1571 studies in 590 adult patient cases with ALL, AML, CML or CLL. These were analyzed for the presence of clinically important non-clonal abnormalities (NCA). Abnormalities were defined as non-clonal if one metaphase had a structural abnormality or an extra chromosome. Chromosome loss was not analyzed due to the possibility of random loss. In 72 cases (12%) comprising 136 studies, at least one NCA was observed. In 21 of these cases (29%), NCAs consisted of obvious clonal evolution or instability, and thus were not included in the analysis. At least one structural NCA was observed in which the abnormality differed from the mainline in 36 (50%) patients. Seventeen of the 36 cases had a normal mode. Nineteen of the 36 patients had an abnormal or normal/abnormal mode. At least one numerical NCA was found in 15 cases (21%). Fifteen cases (21%) contained at least one marker chromosome. Several cases involved NCA in more than one of the above divisions. NCAs could be classified into several categories: (1){open_quotes}the clone to come{close_quotes}, (2) evolving clones which then disappeared, (3) NCAs with putative clinical importance that never became clonal, (4) NCAs during remission identical to the preceding clonal abnormality, (5) NCAs which indicated clonal evolution or instability. Examples include one metaphase with t(9;22) or del(20q) or inv(16) or +8 which either preceded or followed clonal findings of the same aberration. Such findings should be communicated to the clinician.

  8. Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2015-12-18

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia

  9. Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2016-07-20

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

  10. Vorinostat, Tacrolimus, and Methotrexate in Preventing GVHD After Stem Cell Transplant in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2015-10-13

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Intraocular Lymphoma; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Chronic Lymphocytic Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Central Nervous System Hodgkin Lymphoma; Secondary Central Nervous System Non-Hodgkin Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Diffuse Small Cleaved Cell Lymphoma; Stage I Adult Hodgkin Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Marginal Zone Lymphoma; Stage I Small Lymphocytic Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

  11. Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

    ClinicalTrials.gov

    2017-01-09

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia in Remission; Acute Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Inv(3)(q21q26.2); RPN1-EVI1; Acute Myeloid Leukemia With Multilineage Dysplasia; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Complete Remission; B Acute Lymphoblastic Leukemia With t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Complete Remission; DS Stage II Plasma Cell Myeloma; DS Stage III Plasma Cell Myeloma; Myelodysplastic Syndrome; Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma; Secondary Acute Myeloid Leukemia; T Lymphoblastic Lymphoma

  12. Questionnaire survey on current status of home care and support for patients with hematological diseases.

    PubMed

    Adachi, Akiko; Tsukada, Yuiko; Kondo, Sakiko; Asakura, Keiko; Matsuki, Eri; Kawagoe, Shohei; Hashiguchi, Saori; Nonaka, Hiroshi; Takeda, Junzo; Okamoto, Shinichiro

    2014-11-01

    In order to survey the current status of home care and support for patients with hematological diseases, questionnaires were sent to 3,591 hospitals and home care facilities in Tokyo and surrounding prefectures. The first survey showed that 81.7% of medical staff members at hospitals reported that they had experience with home care and support, but only 24.9% of home care facility staff members had such experience. The second questionnaire, surveying 1,202 personnel, identified four factors hampering successful establishment of home care and support networks for hematological diseases. These included insufficient familial support for patients, difficulty making end of life decisions by family members and patients, limited access to transfusion support, and financial problems.

  13. 78 FR 69324 - Revised Medical Criteria for Evaluating Hematological Disorders

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-19

    ... limitations associated with hematological disorders. Why are we proposing to make these changes? We last... transplantation. We are also proposing changes to the current listings to reflect the considerable adjudicative... changes are we proposing? We propose to use only broad categories of hematological disorders in...

  14. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used...

  15. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used...

  16. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used...

  17. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used...

  18. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used...

  19. A Different Perspective on Evaluating the Malignancy Rate of the Non-Diagnostic Category of the Bethesda System for Reporting Thyroid Cytopathology: A Single Institute Experience and Review of the Literature

    PubMed Central

    Onenerk, Mine; Erkan, Murat; Gursan, Nilufer; Kilinc, Emine; Kilicoglu, Gamze Zeynep

    2016-01-01

    Objective To determine the malignancy rate in the non-diagnostic (ND) category of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) based on a different approach in relation to histopathology diagnoses. Study Design All ND fine needle aspirations (FNAs) that were performed under ultrasound guidance by an interventional radiologist with rapid on-site evaluation were included in the study. Slides were reevaluated to identify the cause of inadequacy as “qualitative” or “quantitative.” The malignancy rate of the ND category was assessed. Nodule/patient characteristics were compared between benign and malignant cases within the study cohort. Results The study cohort consisted of 192 ND aspirations. Overall there were 156 (81.3%) women and 36 (18.7%) men with a mean age of 50.6 years (range 24–82 years). The malignancy rate was 4.7%. None of the nodules (size, consistency, and number) or patient characteristics (gender and age) were found to be predictive of malignancy. Conclusion The malignancy rate of the ND category was high when compared to BSRTC predictions, but at the low end of the reported malignancy rates in the literature. Our results revealed that cyto-histopathologic correlation and method of malignancy rate estimation could have an effect on a wide range of reported malignancy rates. Furthermore, patient/nodule dependent factors were not statistically found to be predictive of malignancy. PMID:27627674

  20. Functional-genetic dissection of HDAC dependencies in mouse lymphoid and myeloid malignancies

    PubMed Central

    Matthews, Geoffrey M.; Mehdipour, Parinaz; Cluse, Leonie A.; Falkenberg, Katrina J.; Wang, Eric; Roth, Mareike; Santoro, Fabio; Vidacs, Eva; Stanley, Kym; House, Colin M.; Rusche, James R.; Vakoc, Christopher R.; Zuber, Johannes; Minucci, Saverio

    2015-01-01

    Histone deacetylase (HDAC) inhibitors (HDACis) have demonstrated activity in hematological and solid malignancies. Vorinostat, romidepsin, belinostat, and panobinostat are Food and Drug Administration–approved for hematological malignancies and inhibit class II and/or class I HDACs, including HDAC1, 2, 3, and 6. We combined genetic and pharmacological approaches to investigate whether suppression of individual or multiple Hdacs phenocopied broad-acting HDACis in 3 genetically distinct leukemias and lymphomas. Individual Hdacs were depleted in murine acute myeloid leukemias (MLL-AF9;NrasG12D; PML-RARα acute promyelocytic leukemia [APL] cells) and Eµ-Myc lymphoma in vitro and in vivo. Strikingly, Hdac3-depleted cells were selected against in competitive assays for all 3 tumor types. Decreased proliferation following Hdac3 knockdown was not prevented by BCL-2 overexpression, caspase inhibition, or knockout of Cdkn1a in Eµ-Myc lymphoma, and depletion of Hdac3 in vivo significantly reduced tumor burden. Interestingly, APL cells depleted of Hdac3 demonstrated a more differentiated phenotype. Consistent with these genetic studies, the HDAC3 inhibitor RGFP966 reduced proliferation of Eµ-Myc lymphoma and induced differentiation in APL. Genetic codepletion of Hdac1 with Hdac2 was pro-apoptotic in Eµ-Myc lymphoma in vitro and in vivo and was phenocopied by the HDAC1/2-specific agent RGFP233. This study demonstrates the importance of HDAC3 for the proliferation of leukemia and lymphoma cells, suggesting that HDAC3-selective inhibitors could prove useful for the treatment of hematological malignancies. Moreover, our results demonstrate that codepletion of Hdac1 with Hdac2 mediates a robust pro-apoptotic response. Our integrated genetic and pharmacological approach provides important insights into the individual or combinations of HDACs that could be prioritized for targeting in a range of hematological malignancies. PMID:26447190

  1. Whole Pelvic Intensity-modulated Radiotherapy for Gynecological Malignancies: A Review of the Literature

    PubMed Central

    Hymel, Rockne; Jones, Guy C.; Simone, Charles B.

    2015-01-01

    Radiation therapy has long played a major role in the treatment of gynecological malignancies. There is increasing interest in the utility of intensity-modulated radiotherapy (IMRT) and its application to treat gynecological malignancies. Herein, we review the state-of-the-art use of IMRT for gynecological malignancies and report how it is being used alone as well as in combination with chemotherapy in both the adjuvant and definitive settings. Based on dosimetric and clinical evidence, IMRT can reduce gastrointestinal, genitourinary, and hematological toxicities compared with 3D conformal radiotherapy for gynecologic malignancies. We discuss how these attributes of IMRT may lead to improvements in disease outcomes by allowing for dose escalation of radiation therapy, intensification of chemotherapy, and limiting toxicity-related treatment breaks. Currently accruing trials investigating pelvic IMRT for cervical and endometrial cancers are discussed. PMID:25600840

  2. Malignant peritoneal mesothelioma

    PubMed Central

    Munkholm-Larsen, Stine; Cao, Christopher Q; Yan, Tristan D

    2009-01-01

    Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM) represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. The great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated a median survival of 40 to 90 mo and 5-year survival of 30% to 60% after combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This remarkable improvement in survival has prompted new search into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade. PMID:21160794

  3. Malignant Vestibular Schwannoma

    PubMed Central

    Gruber, B.; Petchenik, L.; Williams, M.; Thomas, C.; Luken, M.G.

    1994-01-01

    A 61-year-old woman underwent a translabyrinthine resection of a right intracanulicular acoustic neuroma, which had been detected in the work-up of sudden hearing loss. At the time of surgery, the tumor was roughly twice as large as indicated by the magnetic resonance scan taken only 2 months previously. The tumor eroded the vertical and transverse crests and extended well into the cerebellopontine angle. It was impossible to distinguish the facial nerve proximal to the geniculate ganglion. All visible tumor was resected, along with the facial nerve. Histological evaluation showed a highly cellular tumor, with many mitoses and areas of necrosis, meeting the criteria for malignant schwannoma. The patient has no stigmata of neurofibromatosis, and has no known relatives with that condition. This case is only the fourth reported of a malignant vestibular schwannoma. The relationships between vestibular schwannoma, neurofibromatosis, and malignancy are discussed. ImagesFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:17171176

  4. [Peripherally inserted central catheters (PICC) in onco-hematology. PICC line in onco-hematology].

    PubMed

    Kabsy, Y; Baudin, G; Vinti, H; Novellas, S; Mannone, L; Chevallier, P; Mounier, N

    2010-09-01

    Peripherally inserted central catheters (PICC) have the advantage of limiting the risk of accidents during installation and are easy to remove. Its use in oncology remains debated because of possible infectious complications. We analyzed 52 PICC in patients with hematological tumor from Nice Hospital. An installation failure was noted in 5.8% of cases. After a follow-up of 15 months, the complication rate was 26.9%, mainly mechanical complications: obstruction (13.5%) or accidental removal (9.6%). The organic complications such as infection or thrombophlebitis represented 3.8%. The median duration was 26 days [2-291]. The longest duration was associated with PICC for chemotherapy (median: 58 days). Frequent blood samples (above: 2 week) were associated with lower duration (median: 23 days). In conclusion, PICC represent a simple and effective alternative to intra-venous central devices in onco-hematology. However, physicians have to focus on short-course treatment.

  5. Giant malignant insulinoma

    PubMed Central

    Karavias, Dimitrios; Habeos, Ioannis; Maroulis, Ioannis; Kalogeropoulou, Christina; Tsamandas, Athanasios; Chaveles, Ioannis

    2015-01-01

    Insulinomas are the most common pancreatic neuroendocrine tumors. Most insulinomas are benign, small, intrapancreatic solid tumors and only large tumors have a tendency for malignancy. Most patients present with symptoms of hypoglycemia that are relieved with the administration of glucose. We herein present the case of a 75-year-old woman who presented with an acute hypoglycemic episode. Subsequent laboratory and radiological studies established the diagnosis of a 17-cm malignant insulinoma, with local invasion to the left kidney, lymph node metastasis, and hepatic metastases. Patient symptoms, diagnostic and imaging work-up and surgical management of both the primary and the metastatic disease are reviewed. PMID:25960993

  6. A hostel for the hostile: the bone marrow niche in hematologic neoplasms

    PubMed Central

    Krause, Daniela S.; Scadden, David T.

    2015-01-01

    Our understanding of the biology of the normal hematopoietic stem cell niche has increased steadily due to improved murine models and sophisticated imaging tools. Less well understood, but of growing interest, is the interaction between cells in the bone marrow during the initiation, maintenance and treatment of hematologic neoplasms. This review summarizes the emerging concepts of the normal and leukemic hematopoietic bone marrow niche. Furthermore, it reviews current models of how the microenvironment of the bone marrow may contribute to or be modified by leukemogenesis. Finally, it provides the rationale for a “two-pronged” approach, directly targeting cancer cells themselves while also targeting the bone microenvironment to make it inhospitable to malignant cells and, ultimately, eradicating cancer stem-like cells. PMID:26521296

  7. Nurses’ Health Study Contributions on the Epidemiology of Less Common Cancers: Endometrial, Ovarian, Pancreatic, and Hematologic

    PubMed Central

    Barnard, Mollie E.; Bertrand, Kimberly A.; Bao, Ying; Crous-Bou, Marta; Wolpin, Brian M.; De Vivo, Immaculata; Tworoger, Shelley S.

    2016-01-01

    Objectives. To review the contributions of the Nurses’ Health Study (NHS) to epidemiologic knowledge of endometrial, ovarian, pancreatic, and hematologic cancers. Methods. We reviewed selected NHS publications from 1976 to 2016, including publications from consortia and other pooled studies. Results. NHS studies on less common cancers have identified novel risk factors, such as a reduced risk of endometrial cancer in women of advanced age at last birth, and have clarified or prospectively confirmed previously reported associations, including an inverse association between tubal ligation and ovarian cancer. Through biomarker research, the NHS has furthered understanding of the pathogenesis of rare cancers, such as the role of altered metabolism in pancreatic cancer risk and survival. NHS investigations have also demonstrated the importance of the timing of exposure, such as the finding of a positive association of early life body fatness, but not of usual adult body mass index, with non-Hodgkin lymphoma risk. Conclusions. Evidence from the NHS has informed prevention strategies and contributed to improved survival from less common but often lethal malignancies, including endometrial, ovarian, pancreatic, and hematologic cancers. PMID:27459458

  8. Hematologic diseases: High risk of Clostridium difficile associated diarrhea

    PubMed Central

    Gweon, Tae-Geun; Choi, Myung-Gyu; Baeg, Myong Ki; Lim, Chul-Hyun; Park, Jae Myung; Lee, In Seok; Kim, Sang Woo; Lee, Dong-Gun; Park, Yeon Joon; Lee, Jong Wook

    2014-01-01

    AIM: To investigate the incidence and clinical outcome of Clostridium difficile (C. difficile) associated diarrhea (CDAD) in patients with hematologic disease. METHODS: We retrospectively reviewed the medical records of patients who underwent C. difficile testing in a tertiar