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Sample records for pediatric acute leukemias

  1. The biology of pediatric acute megakaryoblastic leukemia

    PubMed Central

    Downing, James R.

    2015-01-01

    Acute megakaryoblastic leukemia (AMKL) comprises between 4% and 15% of newly diagnosed pediatric acute myeloid leukemia patients. AMKL in children with Down syndrome (DS) is characterized by a founding GATA1 mutation that cooperates with trisomy 21, followed by the acquisition of additional somatic mutations. In contrast, non–DS-AMKL is characterized by chimeric oncogenes consisting of genes known to play a role in normal hematopoiesis. CBFA2T3-GLIS2 is the most frequent chimeric oncogene identified to date in this subset of patients and confers a poor prognosis. PMID:26186939

  2. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    ERIC Educational Resources Information Center

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  3. Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells.

    PubMed

    Petrov, Ivan; Suntsova, Maria; Mutorova, Olga; Sorokin, Maxim; Garazha, Andrew; Ilnitskaya, Elena; Spirin, Pavel; Larin, Sergey; Kovalchuk, Olga; Prassolov, Vladimir; Zhavoronkov, Alex; Roumiantsev, Alexander; Buzdin, Anton

    2016-11-19

    Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies.

  4. Molecular pathway activation features of pediatric acute myeloid leukemia (AML) and acute lymphoblast leukemia (ALL) cells

    PubMed Central

    Petrov, Ivan; Suntsova, Maria; Mutorova, Olga; Sorokin, Maxim; Garazha, Andrew; Ilnitskaya, Elena; Spirin, Pavel; Larin, Sergey; Zhavoronkov, Alex; Kovalchuk, Olga; Prassolov, Vladimir; Roumiantsev, Alexander; Buzdin, Anton

    2016-01-01

    Acute lymphoblast leukemia (ALL) is characterized by overproduction of immature white blood cells in the bone marrow. ALL is most common in the childhood and has high (>80%) cure rate. In contrast, acute myeloid leukemia (AML) has far greater mortality rate than the ALL and is most commonly affecting older adults. However, AML is a leading cause of childhood cancer mortality. In this study, we compare gene expression and molecular pathway activation patterns in three normal blood, seven pediatric ALL and seven pediatric AML bone marrow samples. We identified 172/94 and 148/31 characteristic gene expression/pathway activation signatures, clearly distinguishing pediatric ALL and AML cells, respectively, from the normal blood. The pediatric AML and ALL cells differed by 139/34 gene expression/pathway activation biomarkers. For the adult 30 AML and 17 normal blood samples, we found 132/33 gene expression/pathway AML-specific features, of which only 7/2 were common for the adult and pediatric AML and, therefore, age-independent. At the pathway level, we found more differences than similarities between the adult and pediatric forms. These findings suggest that the adult and pediatric AMLs may require different treatment strategies. PMID:27870639

  5. Renal Presentation in Pediatric Acute Leukemia: Report of 2 Cases.

    PubMed

    Sherief, Laila M; Azab, Seham F; Zakaria, Marwa M; Kamal, Naglaa M; Abd Elbasset Aly, Maha; Ali, Adel; Abd Alhady, Mohamed

    2015-09-01

    Renal enlargement at time of diagnosis of acute leukemia is very unusual. We here in report 2 pediatric cases of acute leukemia who had their renal affection as the first presenting symptom with no evidences of blast cells in blood smear and none of classical presentation of acute leukemia. The first case is a 4-year-old girl who presented with pallor and abdominal enlargement. Magnetic resonance imaging showed bilateral symmetrical homogenous enlarged kidneys suggestive of infiltration. Complete blood picture (CBC) revealed white blood count 11 × 10⁹/L, hemoglobin 8.7 g/dL and platelet count 197 × 10⁹/L. Bone marrow aspiration was performed, and diagnosed precursor B-cell ALL was made. The child had an excellent response to modified CCG 1991 standard risk protocol of chemotherapy with sustained remission, but unfortunately relapsed 11 month after the end of therapy. The second child was 13-month old, presented with pallor, vomiting, abdominal enlargement, and oliguria 2 days before admission. Initial CBC showed bicytopenia, elevated blood urea, creatinine, and serum uric acid, while abdominal ultrasonography revealed bilateral renal enlargement. Bone marrow examination was done and showed 92% blast of biphenotypic nature. So, biphynotypic leukemia with bilateral renal enlargement and acute renal failure was subsequently diagnosed. The patients admitted to ICU and received supportive care and prednisolone. Renal function normalized and chemotherapy was started. The child achieved complete remission with marked reduction of kidney size but, unfortunately she died from sepsis in consolidation phase of therapy. This case demonstrates an unusual early renal enlargement in childhood acute leukemia. Renal involvement of acute leukemia should be considered in child presenting with unexplained bilateral renal enlargement with or without renal function abnormalities and bone marrow examination should be included in the workup.

  6. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia

    PubMed Central

    Zwaan, C. Michel; Kolb, Edward A.; Reinhardt, Dirk; Abrahamsson, Jonas; Adachi, Souichi; Aplenc, Richard; De Bont, Eveline S.J.M.; De Moerloose, Barbara; Dworzak, Michael; Gibson, Brenda E.S.; Hasle, Henrik; Leverger, Guy; Locatelli, Franco; Ragu, Christine; Ribeiro, Raul C.; Rizzari, Carmelo; Rubnitz, Jeffrey E.; Smith, Owen P.; Sung, Lillian; Tomizawa, Daisuke; van den Heuvel-Eibrink, Marry M.; Creutzig, Ursula; Kaspers, Gertjan J.L.

    2015-01-01

    Diagnosis, treatment, response monitoring, and outcome of pediatric acute myeloid leukemia (AML) have made enormous progress during the past decades. Because AML is a rare type of childhood cancer, with an incidence of approximately seven occurrences per 1 million children annually, national and international collaborative efforts have evolved. This overview describes these efforts and includes a summary of the history and contributions of each of the main collaborative pediatric AML groups worldwide. The focus is on translational and clinical research, which includes past, current, and future clinical trials. Separate sections concern acute promyelocytic leukemia, myeloid leukemia of Down syndrome, and relapsed AML. A plethora of novel antileukemic agents that have emerged, including new classes of drugs, are summarized as well. Finally, an important aspect of the treatment of pediatric AML—supportive care—and late effects are discussed. The future is bright, with a wide range of emerging innovative therapies and with more and more international collaboration that ultimately aim to cure all children with AML, with fewer adverse effects and without late effects. PMID:26304895

  7. Beginning treatment for pediatric acute myeloid leukemia: the family connection.

    PubMed

    McGrath, Pam; Paton, Mary Anne; Huff, Nicole

    2005-01-01

    There is a loud silence on psycho-oncology research in relation to pediatric Acute Myeloid Leukemia (AML). This article is part of a series that begins to address the psycho-social hiatus. The present article documents the less obvious, often hidden, aspect of beginning treatment for pediatric AML--the "behind the scenes" experience of the home and family connection. The findings are from the first stage of a five year longitudinal study that examines through qualitative research the experience of childhood leukemia from the perspective of the child, siblings and parents. Open-ended interviews, audio-recorded and transcribed verbatim, were thematically analyzed with the assistance of the Non-numerical Unstructured Data by processes of Indexing Searching and Theory-building (NUD*IST) computer program. The findings emphasize the disruption to normalcy in relation to home life, school, and work, which is exacerbated for families who relocate for specialist treatment. The findings emphasise the need for support for families coping with childhood AML.

  8. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. Elbow septic arthritis associated with pediatric acute leukemia: a case report and literature review.

    PubMed

    Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki

    2015-01-01

    Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.

  10. Pediatric Acute Lymphoblastic Leukemia and Exposure to Pesticides

    PubMed Central

    Soldin, Offie P.; Nsouly-Maktabi, Hala; Genkinger, Jeanine M.; Loffredo, Christopher A.; Ortega-Garcia, Juan Antonio; Colantino, Drew; Barr, Dana B.; Luban, Naomi L.; Shad, Aziza T.; Nelson, David

    2013-01-01

    Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case–control study of children newly diagnosed with ALL, and their mothers (n = 41 child–mother pairs) were recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography–high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association. PMID:19571777

  11. Pediatric acute lymphoblastic leukemia and exposure to pesticides.

    PubMed

    Soldin, Offie P; Nsouli-Maktabi, Hala; Nsouly-Maktabi, Hala; Genkinger, Jeanine M; Loffredo, Christopher A; Ortega-Garcia, Juan Antonio; Colantino, Drew; Barr, Dana B; Luban, Naomi L; Shad, Aziza T; Nelson, David

    2009-08-01

    Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

  12. Intracerebral metastasis in pediatric acute lymphoblastic leukemia: A rare presentation

    PubMed Central

    Gokce, Müge; Aytac, Selin; Altan, Ilhan; Unal, Sule; Tuncer, Murat; Gumruk, Fatma; Cetin, Mualla

    2012-01-01

    Central nervous system leukemia may present in different ways. However, intraparenchymal mass is extremely rare in childhood leukemia. Herein, we report a boy who presented with right hemiparesis and anisocoria 1 year after the cessation of the chemotherapy protocol for acute lymphoblastic leukemia. Cranial imaging demonstrated an extensive mass located in the anterior white matter of left frontal lobe, and cerebrospinal fluid examination revealed concomitant lymphoblasts. Immunohistochemical staining of the biopsy material showed neoplastic cells with positive CD10 and TdT. Complete remission was achieved with chemotherapy alone for a duration of 2 years. PMID:23560011

  13. AIEOP-BFM consensus guidelines 2016 for flow cytometric immunophenotyping of Pediatric acute lymphoblastic leukemia.

    PubMed

    Dworzak, Michael N; Buldini, Barbara; Gaipa, Giuseppe; Ratei, Richard; Hrusak, Ondrej; Luria, Drorit; Rosenthal, Eti; Bourquin, Jean-Pierre; Sartor, Mary; Schumich, Angela; Karawajew, Leonid; Mejstrikova, Ester; Maglia, Oscar; Mann, Georg; Ludwig, Wolf-Dieter; Biondi, Andrea; Schrappe, Martin; Basso, Giuseppe

    2017-02-10

    Immunophenotyping by flow cytometry (FCM) is a worldwide mainstay in leukemia diagnostics. For concordant multicentric application, however, a gap exists between available classification systems, technologic standardization, and clinical needs. The AIEOP-BFM consortium induced an extensive standardization and validation effort between its nine national reference laboratories collaborating in immunophenotyping of pediatric acute lymphoblastic leukemia (ALL). We elaborated common guidelines which take advantage of the possibilities of multi-color FCM: marker panel requirements, immunological blast gating, in-sample controls, tri-partite antigen expression rating (negative vs. weak or strong positive) with capturing of blast cell heterogeneities and subclone formation, refined ALL subclassification, and a dominant lineage assignment algorithm able to distinguish "simple" from bilineal/"complex" mixed phenotype acute leukemia (MPAL) cases, which is essential for choice of treatment. These guidelines are a first step toward necessary inter-laboratory standardization of pediatric leukemia immunophenotyping for a concordant multicentric application. © 2017 International Clinical Cytometry Society.

  14. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling.

    PubMed

    Yeoh, Eng-Juh; Ross, Mary E; Shurtleff, Sheila A; Williams, W Kent; Patel, Divyen; Mahfouz, Rami; Behm, Fred G; Raimondi, Susana C; Relling, Mary V; Patel, Anami; Cheng, Cheng; Campana, Dario; Wilkins, Dawn; Zhou, Xiaodong; Li, Jinyan; Liu, Huiqing; Pui, Ching-Hon; Evans, William E; Naeve, Clayton; Wong, Limsoon; Downing, James R

    2002-03-01

    Treatment of pediatric acute lymphoblastic leukemia (ALL) is based on the concept of tailoring the intensity of therapy to a patient's risk of relapse. To determine whether gene expression profiling could enhance risk assignment, we used oligonucleotide microarrays to analyze the pattern of genes expressed in leukemic blasts from 360 pediatric ALL patients. Distinct expression profiles identified each of the prognostically important leukemia subtypes, including T-ALL, E2A-PBX1, BCR-ABL, TEL-AML1, MLL rearrangement, and hyperdiploid >50 chromosomes. In addition, another ALL subgroup was identified based on its unique expression profile. Examination of the genes comprising the expression signatures provided important insights into the biology of these leukemia subgroups. Further, within some genetic subgroups, expression profiles identified those patients that would eventually fail therapy. Thus, the single platform of expression profiling should enhance the accurate risk stratification of pediatric ALL patients.

  15. Recognition of adult and pediatric acute lymphoblastic leukemia blasts by natural killer cells.

    PubMed

    Torelli, Giovanni F; Peragine, Nadia; Raponi, Sara; Pagliara, Daria; De Propris, Maria S; Vitale, Antonella; Bertaina, Alice; Barberi, Walter; Moretta, Lorenzo; Basso, Giuseppe; Santoni, Angela; Guarini, Anna; Locatelli, Franco; Foà, Robin

    2014-07-01

    In this study, we aimed to investigate the pathways of recognition of acute lymphoblastic leukemia blasts by natural killer cells and to verify whether differences in natural killer cell activating receptor ligand expression among groups defined by age of patients, or presence of cytogenetic/molecular aberrations correlate with the susceptibility to recognition and killing. We analyzed 103 newly diagnosed acute lymphoblastic leukemia patients: 46 adults and 57 children. Pediatric blasts showed a significantly higher expression of Nec-2 (P=0.03), ULBP-1 (P=0.01) and ULBP-3 (P=0.04) compared to adult cells. The differential expression of these ligands between adults and children was confined to B-lineage acute lymphoblastic leukemia with no known molecular alterations. Within molecularly defined subgroups of patients, a high surface expression of NKG2D and DNAM1 ligands was found on BCR-ABL(+) blasts, regardless of patient age. Accordingly, BCR-ABL(+) blasts proved to be significantly more susceptible to natural killer-dependent lysis than B-lineage blasts without molecular aberrations (P=0.03). Cytotoxic tests performed in the presence of neutralizing antibodies indicated a pathway of acute lymphoblastic leukemia cell recognition in the setting of the Nec-2/DNAM-1 interaction. These data provide a biological explanation of the different roles played by alloreactive natural killer cells in pediatric versus adult acute lymphoblastic leukemia and suggest that new natural killer-based strategies targeting specific subgroups of patients, particularly those BCR-ABL(+), are worth pursuing further.

  16. Acute Activation of Metabolic Syndrome Components in Pediatric Acute Lymphoblastic Leukemia Patients Treated with Dexamethasone

    PubMed Central

    Warris, Lidewij T.; van den Akker, Erica L. T.; Bierings, Marc B.; van den Bos, Cor; Zwaan, Christian M.; Sassen, Sebastiaan D. T.; Tissing, Wim J. E.; Veening, Margreet A.; Pieters, Rob; van den Heuvel-Eibrink, Marry M.

    2016-01-01

    Although dexamethasone is highly effective in the treatment of pediatric acute lymphoblastic leukemia (ALL), it can cause serious metabolic side effects. Because studies regarding the effects of dexamethasone are limited by their small scale, we prospectively studied the direct effects of treating pediatric ALL with dexamethasone administration with respect to activation of components of metabolic syndrome (MetS); in addition, we investigated whether these side effects were correlated with the level of dexamethasone. Fifty pediatric patients (3–16 years of age) with ALL were studied during a 5-day dexamethasone course during the maintenance phase of the Dutch Childhood Oncology Group ALL-10 and ALL-11 protocols. Fasting insulin, glucose, total cholesterol, HDL, LDL, and triglycerides levels were measured at baseline (before the start of dexamethasone; T1) and on the fifth day of treatment (T2). Dexamethasone trough levels were measured at T2. We found that dexamethasone treatment significantly increased the following fasting serum levels (P<0.05): HDL, LDL, total cholesterol, triglycerides, glucose, and insulin. In addition, dexamethasone increased insulin resistance (HOMA-IR>3.4) from 8% to 85% (P<0.01). Dexamethasone treatment also significantly increased the diastolic and systolic blood pressure. Lastly, dexamethasone trough levels (N = 24) were directly correlated with high glucose levels at T2, but not with other parameters. These results indicate that dexamethasone treatment acutely induces three components of the MetS. Together with the weight gain typically associated with dexamethasone treatment, these factors may contribute to the higher prevalence of MetS and cardiovascular risk among survivors of childhood leukemia who received dexamethasone treatment. PMID:27362350

  17. Bafilomycin A1 targets both autophagy and apoptosis pathways in pediatric B-cell acute lymphoblastic leukemia

    PubMed Central

    Yuan, Na; Song, Lin; Zhang, Suping; Lin, Weiwei; Cao, Yan; Xu, Fei; Fang, Yixuan; Wang, Zhen; Zhang, Han; Li, Xin; Wang, Zhijian; Cai, Jinyang; Wang, Jian; Zhang, Yi; Mao, Xinliang; Zhao, Wenli; Hu, Shaoyan; Chen, Suning; Wang, Jianrong

    2015-01-01

    B-cell acute lymphoblastic leukemia is the most common type of pediatric leukemia. Despite improved remission rates, current treatment regimens for pediatric B-cell acute lymphoblastic leukemia are often associated with adverse effects and central nervous system relapse, necessitating more effective and safer agents. Bafilomycin A1 is an inhibitor of vacuolar H+-ATPase that is frequently used at high concentration to block late-phase autophagy. Here, we show that bafilomycin A1 at a low concentration (1 nM) effectively and specifically inhibited and killed pediatric B-cell acute lymphoblastic leukemia cells. It targeted both early and late stages of the autophagy pathway by activating mammalian target of rapamycin signaling and by disassociating the Beclin 1-Vps34 complex, as well as by inhibiting the formation of autolysosomes, all of which attenuated functional autophagy. Bafilomycin A1 also targeted mitochondria and induced caspase-independent apoptosis by inducing the translocation of apoptosis-inducing factor from mitochondria to the nucleus. Moreover, bafilomycin A1 induced the binding of Beclin 1 to Bcl-2, which further inhibited autophagy and promoted apoptotic cell death. In primary cells from pediatric patients with B-cell acute lymphoblastic leukemia and a xenograft model, bafilomycin A1 specifically targeted leukemia cells while sparing normal cells. An in vivo mouse toxicity assay confirmed that bafilomycin A1 is safe. Our data thus suggest that bafilomycin A1 is a promising candidate drug for the treatment of pediatric B-cell acute lymphoblastic leukemia. PMID:25512644

  18. Cognitive reserve and brain volumes in pediatric acute lymphoblastic leukemia

    PubMed Central

    Kesler, Shelli R.; Tanaka, Hiroko; Koovakkattu, Della

    2011-01-01

    Acute lymphoblastic leukemia (ALL) is associated with long-term, progressive cognitive deficits and white matter injury. We measured global and regional white and gray matter as well as cognitive function and examined relationships between these variables and cognitive reserve, as indicated by maternal education level, in 28 young survivors of ALL and 31 healthy controls. Results indicated significantly reduced white matter volumes and cognitive testing scores in the ALL group compared to controls. Maternal education was inversely related to both global and regional white matter and directly related to gray matter in ALL and was directly related to both gray and white matter in controls, consistent with the cognitive reserve hypothesis. Cognitive performance was associated with different brain regions in ALL compared to controls. Maternal education was significantly positively correlated with working and verbal memory in ALL as well as processing speed and verbal memory in controls, improving models of cognitive outcome over medical and/or demographic predictors. Our findings suggest that cognitive reserve may be an important factor in brain injury and cognitive outcome in ALL. Additionally, children with ALL may experience some neural reorganization related to cognitive outcome. PMID:20814845

  19. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update

    PubMed Central

    Pui, Ching-Hon; Carroll, William L.; Meshinchi, Soheil; Arceci, Robert J.

    2011-01-01

    Purpose We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research. Methods A review of English literature on childhood acute leukemias from the past 5 years was performed. Results Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients. Conclusion The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade. PMID:21220611

  20. Genomic Profiling of Adult and Pediatric B-cell Acute Lymphoblastic Leukemia.

    PubMed

    Liu, Yuan-Fang; Wang, Bai-Yan; Zhang, Wei-Na; Huang, Jin-Yan; Li, Ben-Shang; Zhang, Ming; Jiang, Lu; Li, Jian-Feng; Wang, Ming-Jie; Dai, Yu-Jun; Zhang, Zi-Guan; Wang, Qiang; Kong, Jie; Chen, Bing; Zhu, Yong-Mei; Weng, Xiang-Qin; Shen, Zhi-Xiang; Li, Jun-Min; Wang, Jin; Yan, Xiao-Jing; Li, Yan; Liang, Ying-Min; Liu, Li; Chen, Xie-Qun; Zhang, Wang-Gang; Yan, Jin-Song; Hu, Jian-Da; Shen, Shu-Hong; Chen, Jing; Gu, Long-Jun; Pei, Deqing; Li, Yongjin; Wu, Gang; Zhou, Xin; Ren, Rui-Bao; Cheng, Cheng; Yang, Jun J; Wang, Kan-Kan; Wang, Sheng-Yue; Zhang, Jinghui; Mi, Jian-Qing; Pui, Ching-Hon; Tang, Jing-Yan; Chen, Zhu; Chen, Sai-Juan

    2016-06-01

    Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

  1. [Results of the treatment of nonlymphoblastic acute leukemia in a pediatric population].

    PubMed

    Rivera Luna, R; Ajuria Gottwald, E; Silva Sosa, M; González Chirinos, P

    1977-01-01

    On a prospective fashion during approximately two years, 22 pediatric patients with acute non lymphocytic leukemia were evaluated. Of this population the majority had acute mielocytic leukemia, followed by acute myelomonocytic leukemia. Absolutely all patients at the time of diagnosis and subsequently every 4 to 6 weeks had a bone marrow aspiration test. When the patients were first seen, 54% of them presented fever; lymph node enlargement was not a common finding. Only few of this patients presented splenomegaly and/or hepatomegaly. In regards to complete blood counts the most outstanding of its was the presence of leukocyte count above 20000/mm.3 in 8 of this patients. From the 22 patients studied only 21 are evaluable. All 21 patients were treated with a 4 drug combination (modified COAP). Sixteen patients (76%) achieved bone marrow remission, of which only 15 patients (71%) achieved complete remission. The median duration remission was of 9.2 months with a range of 2 to 26 months. At the present time only 7 patients (33%) are alive and on remission. Two more patients are alive but in full relapse. The mortality rate of this study is of 59%. The review of recent chemotherapy reports is presented and the need for further trials is emphasized especially in view of recent papers published in which it appears that better results are being obtained at last in children's acute non lymphocitic leukemia.

  2. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    PubMed Central

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID:26137238

  3. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia.

    PubMed

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; Dabaghi, Mohammad; Nadimi, Motahareh

    2015-05-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

  4. Use of gemtuzumab ozogamicin in the treatment of pediatric relapsed/ refractory Acute Myeloid Leukemia.

    PubMed

    Ünal, Elif; Sahdev, Indira

    2008-03-05

    Gemtuzumab ozogamicin (GO, MylotargTM) is an antibody-targeted chemotherapy agent that has been studied in acute myeloid leukemia (AML) at first relapse in adults. There is limited experience in pediatric patients. We report six patients with refractory/relapsed CD33+AML who were treated with GO on compassionate-use basis. One patient attained remission. One patient is still alive following hematopoietic stem cell transplantation (HSCT), and one patient died in remission. Two patients were refractory and three patients had a response with <5% blasts in the bone marrow. Fever and chills, hypotension and hypoxia were observed as side effects. Three patients developed veno-occlusive disease (VOD) of the liver. Two of these three patients had persistence of VOD at the time of their deaths. One patient treated postSCT had bone marrow response without VOD. GO should be used cautiously in chemotherapy-refractory AML pediatric patients due to the high incidence of VOD.

  5. Oral Microbiota Distinguishes Acute Lymphoblastic Leukemia Pediatric Hosts from Healthy Populations

    PubMed Central

    Zhou, Xuedong; You, Meng; Du, Qin; Yang, Xue; He, Jingzhi; Zou, Jing; Cheng, Lei; Li, Mingyun; Li, Yuqing; Zhu, Yiping; Li, Jiyao; Shi, Wenyuan; Xu, Xin

    2014-01-01

    In leukemia, oral manifestations indicate aberrations in oral microbiota. Microbiota structure is determined by both host and environmental factors. In human hosts, how health status shapes the composition of oral microbiota is largely unknown. Taking advantage of advances in high-throughput sequencing, we compared the composition of supragingival plaque microbiota of acute lymphoblastic leukemia (ALL) pediatric patients with healthy controls. The oral microbiota of leukemia patients had lower richness and less diversity compared to healthy controls. Microbial samples clustered into two major groups, one of ALL patients and another of healthy children, with different structure and composition. Abundance changes of certain taxa including the Phylum Firmicutes, the Class Bacilli, the Order Lactobacillales, the Family Aerococcaceae and Carnobacteriaceae, as well as the Genus Abiotrophia and Granulicatella were associated with leukemia status. ALL patients demonstrated a structural imbalance of the oral microbiota, characterized by reduced diversity and abundance alterations, possibly involved in systemic infections, indicating the importance of immune status in shaping the structure of oral microbiota. PMID:25025462

  6. Oral microbiota distinguishes acute lymphoblastic leukemia pediatric hosts from healthy populations.

    PubMed

    Wang, Yan; Xue, Jing; Zhou, Xuedong; You, Meng; Du, Qin; Yang, Xue; He, Jinzhi; He, Jingzhi; Zou, Jing; Cheng, Lei; Li, Mingyun; Li, Yuqing; Zhu, Yiping; Li, Jiyao; Shi, Wenyuan; Xu, Xin

    2014-01-01

    In leukemia, oral manifestations indicate aberrations in oral microbiota. Microbiota structure is determined by both host and environmental factors. In human hosts, how health status shapes the composition of oral microbiota is largely unknown. Taking advantage of advances in high-throughput sequencing, we compared the composition of supragingival plaque microbiota of acute lymphoblastic leukemia (ALL) pediatric patients with healthy controls. The oral microbiota of leukemia patients had lower richness and less diversity compared to healthy controls. Microbial samples clustered into two major groups, one of ALL patients and another of healthy children, with different structure and composition. Abundance changes of certain taxa including the Phylum Firmicutes, the Class Bacilli, the Order Lactobacillales, the Family Aerococcaceae and Carnobacteriaceae, as well as the Genus Abiotrophia and Granulicatella were associated with leukemia status. ALL patients demonstrated a structural imbalance of the oral microbiota, characterized by reduced diversity and abundance alterations, possibly involved in systemic infections, indicating the importance of immune status in shaping the structure of oral microbiota.

  7. Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia.

    PubMed

    Wang, Zhengyan; Hong, Ze; Gao, Feng; Feng, Weijing

    2013-11-01

    A genome-wide serum miRNA expression analysis previously showed the upregulation of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with healthy controls. The aim of this study was to investigate the expression patterns and the prognostic relevance of miR-375 in pediatric AML. Expression levels of miR-375 in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. Expression levels of miR-375 in the bone marrow of pediatric AML patients were significantly higher than those in normal controls (P < 0.001). Then, miR-375 upregulation occurred more frequently in French-American-British classification subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the expression levels of miR-375 in pediatric AML patients with unfavorable karyotypes were dramatically higher than those in intermediate and favorable groups (P = 0.002). Moreover, high miR-375 expression was significantly associated with shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001) in pediatric AML patients. Multivariate analysis further identified miR-375 expression and cytogenetics risk as independent prognostic factors for both relapse-free survival and overall survival. In particular, the prognostic relevance of miR-375 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our findings suggest for the first time that the upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric AML. Since its correlation with poor relapse-free survival and overall survival, miR-375 may be a novel biomarker to improve the management of pediatric AML patients.

  8. The promoter of miR-663 is hypermethylated in Chinese pediatric acute myeloid leukemia (AML)

    PubMed Central

    2013-01-01

    Background There is growing evidence supporting a role for microRNAs (miRNA) as targets in aberrant mechanisms of DNA hypermethylation. Epigenetic silencing of tumor suppressor miRNAs, including miR-663, which has recently been reported to be inactivated by hypermethylation in several cancers, may play important roles in pediatric acute myeloid leukemia (AML). However, expression of miR-663 and its promoter methylation remain status unclear in childhood leukemia. Methods Promoter methylation status of miR-663 was investigated by methylation specific PCR (MSP) and bisulfate genomic sequencing (BGS). Transcriptional expression of miR-663 was evaluated by semi-quantitative and real-time PCR, and the relationship between expression of miR-663 and promoter methylation was confirmed using 5-aza-2’-deoxycytidine (5-Aza) demethylation reagent. Results MiR-663 was aberrantly methylated in 45.5% (5/11) leukemia cell lines; BGS showed that the promoter was significantly methylated in three AML cell lines; methylation of miR-663 was significantly higher in Chinese pediatric AML patients [41.4% (29/70)] compared to normal bone marrow (NBM) control samples [10.0% (3/30)]. These results were confirmed by both BGS and 5-Aza demethylation analysis. In addition, miR-663 transcript expression was significantly lower in AML patients, both with and without miR-663 methylation, compared to controls; however, there were no significant differences in clinical features or French-American-British (FAB) classification between patients with and without miR-663 methylation. Conclusions Expression of miR-663 was significantly lower in pediatric AML cells compared to NBM controls; furthermore, a high frequency of miR-663 promoter hypermethylation was observed in both AML cell lines and pediatric AML samples. Inactivation of miR-663 by promoter hypermethylation could be affected by 5-Aza demethylation. These findings suggest that hypermethylation of the miR-663 promoter may be an early event in

  9. Methylation level of CpG islands in GGH gene promoter in pediatric acute leukemia

    PubMed Central

    Wang, Huihui; Mai, Huirong; Yuan, Xiuli; Li, Changgang; Wen, Feiqiu

    2017-01-01

    Background γ-Glutamyl hydrolase (GGH) regulates intracellular folates and antifolates such as methotrexate (MTX) for proper nucleotide biosynthesis and antifolate-induced cytotoxicity, respectively. In addition to genetic polymorphism and karyotypic abnormalities, methylation of CpG island 1 (CpG1) in the promoter region is found to modulate GGH activity by reducing GGH mRNA expression in acute lymphoblastic leukemia (ALL) cells. We aim to investigate methylation status of two CpG islands (CpG1 and CpG2) in the GGH promoter region in pediatric patients with ALL and acute myelogenous leukemia (AML). Methods 70B-ALL, 29 AML, 10 ITP (idiopathic thrombocytopenic purpura) and 40 healthy children are recruited in the present study. MS-HRM (methylation-sensitive high-resolution melting) and bisulfite sequencing PCR (BSP) are used to detect methylation change and its level in CpG1 and CpG2 in the GGH promoter region. GGH mRNA expression is quantified by real-time PCR. Correlation between CpG island methylation and GGH mRNA expression is assessed by statistical software. Results Methylations of CpG1 are detected in leukemia cells samples obtained from 30.9% (21/68) of patients with ALL and 20.7% (6/29) of patients with AML. These methylations are not detected in the controls. Methylations of CpG2 are detected in leukemia cell samples obtained from 44.1% (30/68) of the ALL patients and 37.9% (11/29) of the AML patients. These percentages are significantly higher than that observed in the control cell samples: 6.0% (3/50) (Fisher's exact test, P = 0.000). The abundance of CpG1 methylation in all leukemia cell samples is classified as Grade I (methylation level is less than 10%) and the abundance of CpG2 methylation in leukemia cell samples is classified in separate grades. Our results indicate that methylation of CpG1 or hypermethylation (the methylation level is greater than 10%) of CpG2 could significantly reduce GGH mRNA expression in leukemia cells from the ALL and AML

  10. Identification of mutant alleles of JAK3 in pediatric patients with acute lymphoblastic leukemia.

    PubMed

    Yin, Changhong; Sandoval, Claudio; Baeg, Gyeong-Hun

    2015-05-01

    Children with acute lymphoblastic leukemia (ALL) have an 80% chance of long-term survival. Despite the high rate of cure, children relapse, and recurrent ALL is difficult to cure with chemotherapeutic regimens. Therefore, improved biological understanding of ALL and the development of rationally designed therapeutics targeting molecules associated with the pathogenesis of ALL are essential. We identified missense and synonymous JAK3 mutations in 16 of 91 pediatric patients with ALL. The expression of JAK3(V722I) mutant caused the cytokine-independent activation of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling and conferred the factor-independent growth of murine interleukin-3 (IL-3)-dependent pro-B Ba/F3 cells. Importantly, inhibition of JAK3 by the known JAK3 inhibitor CP-690 550 converted the Ba/F3-JAK3(V722I) cells back to factor-dependent growth. These observations suggest that JAK3 may contribute to the pathogenesis of pediatric ALL and serve as an important therapeutic target which can be leveraged to improve outcomes for pediatric patients with ALL.

  11. Pharmacogenetics of microRNAs and microRNAs biogenesis machinery in pediatric acute lymphoblastic leukemia.

    PubMed

    López-López, Elixabet; Gutiérrez-Camino, Ángela; Piñán, Maria Ángeles; Sánchez-Toledo, José; Uriz, Jose Javier; Ballesteros, Javier; García-Miguel, Purificación; Navajas, Aurora; García-Orad, África

    2014-01-01

    Despite the clinical success of acute lymphoblastic leukemia (ALL) therapy, toxicity is frequent. Therefore, it would be useful to identify predictors of adverse effects. In the last years, several studies have investigated the relationship between genetic variation and treatment-related toxicity. However, most of these studies are focused in coding regions. Nowadays, it is known that regions that do not codify proteins, such as microRNAs (miRNAs), may have an important regulatory function. MiRNAs can regulate the expression of genes affecting drug response. In fact, the expression of some of those miRNAs has been associated with drug response. Genetic variations affecting miRNAs can modify their function, which may lead to drug sensitivity. The aim of this study was to detect new toxicity markers in pediatric B-ALL, studying miRNA-related polymorphisms, which can affect miRNA levels and function. We analyzed 118 SNPs in pre-miRNAs and miRNA processing genes in association with toxicity in 152 pediatric B-ALL patients all treated with the same protocol (LAL/SHOP). Among the results found, we detected for the first time an association between rs639174 in DROSHA and vomits that remained statistically significant after FDR correction. DROSHA had been associated with alterations in miRNAs expression, which could affect genes involved in drug transport. This suggests that miRNA-related SNPs could be a useful tool for toxicity prediction in pediatric B-ALL.

  12. Pediatric Medical Care System in China Has Significantly Reduced Abandonment of Acute Lymphoblastic Leukemia Treatment

    PubMed Central

    Zhou, Qi; Hong, Dan; Lu, Jun; Zheng, Defei; Ashwani, Neetica

    2015-01-01

    In this study, we have analyzed both administrative and clinical data from our hospital during 2002 to 2012 to evaluate the influence of government medical policies on reducing abandonment treatment in pediatric patients with acute lymphoblastic leukemia. Two policies funding for the catastrophic diseases and the new rural cooperative medical care system (NRCMS) were initiated in 2005 and 2011, respectively. About 1151 children diagnosed with acute lymphoblastic leukemia were enrolled in our study during this period and 316 cases abandoned treatment. Statistical differences in sex, age, number of children in the family, and family financial status were observed. Of most importance, the medical insurance coverage was critical for reducing abandonment treatment. However, 92 cases abandoning treatment after relapse did not show significant difference either in medical insurance coverage or in duration from first complete remission. In conclusion, financial crisis was the main reason for abandoning treatment. Government-funded health care expenditure programs reduced families’ economic burden and thereby reduced the abandonment rate with resultant increased overall survival. PMID:25393454

  13. Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations

    PubMed Central

    Spinella, Jean-François; Cassart, Pauline; Richer, Chantal; Saillour, Virginie; Ouimet, Manon; Langlois, Sylvie; St-Onge, Pascal; Sontag, Thomas; Healy, Jasmine; Minden, Mark D.; Sinnett, Daniel

    2016-01-01

    T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with variable prognosis. It represents 15% of diagnosed pediatric ALL cases and has a threefold higher incidence among males. Many recurrent alterations have been identified and help define molecular subgroups of T-ALL, however the full range of events involved in driving transformation remain to be defined. Using an integrative approach combining genomic and transcriptomic data, we molecularly characterized 30 pediatric T-ALLs and identified common recurrent T-ALL targets such as FBXW7, JAK1, JAK3, PHF6, KDM6A and NOTCH1 as well as novel candidate T-ALL driver mutations including the p.R35L missense mutation in splicesome factor U2AF1 found in 3 patients and loss of function mutations in the X-linked tumor suppressor genes MED12 (frameshit mutation p.V167fs, splice site mutation g.chrX:70339329T>C, missense mutation p.R1989H) and USP9X (nonsense mutation p.Q117*). In vitro functional studies further supported the putative role of these novel T-ALL genes in driving transformation. U2AF1 p.R35L was shown to induce aberrant splicing of downstream target genes, and shRNA knockdown of MED12 and USP9X was shown to confer resistance to apoptosis following T-ALL relevant chemotherapy drug treatment in Jurkat leukemia cells. Interestingly, nearly 60% of novel candidate driver events were identified among immature T-ALL cases, highlighting the underlying genomic complexity of pediatric T-ALL, and the need for larger integrative studies to decipher the mechanisms that contribute to its various subtypes and provide opportunities to refine patient stratification and treatment. PMID:27602765

  14. Asparaginase Therapy in Pediatric Acute Lymphoblastic Leukemia: A Focus on the Mode of Drug Resistance.

    PubMed

    Chen, Shih-Hsiang

    2015-10-01

    Asparaginase is one of the most important chemotherapeutic agents against pediatric acute lymphoblastic leukemia (ALL), the most common form of childhood cancer. The therapeutic efficacy (e.g., chemoresistance) and adverse effects of asparaginase (e.g., hypersensivity and pancreatitis) have been investigated over the past four decades. It was suggested early on that leukemic cells are resistant to asparaginase because of their increased asparagine synthetase activity. Afterward, other mechanisms associated with asparaginase resistance were reported. Not only leukemic cells but also patients themselves may play a role in causing asparaginase resistance, which has been associated with unfavorable outcome in children with ALL. This article will briefly review asparaginase therapy in children with ALL and comprehensively analyze recent reports on the potential mechanisms of asparaginase resistance.

  15. Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study

    PubMed Central

    Desjonquères, A; Chevallier, P; Thomas, X; Huguet, F; Leguay, T; Bernard, M; Bay, J-O; Tavernier, E; Charbonnier, A; Isnard, F; Hunault, M; Turlure, P; Renaud, M; Bastié, J-N; Himberlin, C; Lepretre, S; Lioure, B; Lhéritier, V; Asnafi, V; Beldjord, K; Lafage-Pochitaloff, M; Béné, M C; Ifrah, N; Dombret, H

    2016-01-01

    The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph− ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph− ALL younger adults (18–63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14–24%) and 13.3% (8–18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21–38%) and 25% (17–33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients. PMID:27935576

  16. Inhibiting Polo-like kinase 1 causes growth reduction and apoptosis in pediatric acute lymphoblastic leukemia cells.

    PubMed

    Hartsink-Segers, Stefanie A; Exalto, Carla; Allen, Matthew; Williamson, Daniel; Clifford, Steven C; Horstmann, Martin; Caron, Huib N; Pieters, Rob; Den Boer, Monique L

    2013-10-01

    This study investigated Polo-like kinase 1, a mitotic regulator often over-expressed in solid tumors and adult hematopoietic malignancies, as a potential new target in the treatment of pediatric acute lymphoblastic leukemia. Polo-like kinase 1 protein and Thr210 phosphorylation levels were higher in pediatric acute lymphoblastic leukemia (n=172) than in normal bone marrow mononuclear cells (n=10) (P<0.0001). High Polo-like kinase 1 protein phosphorylation, but not expression, was associated with a lower probability of event-free survival (P=0.042) and was a borderline significant prognostic factor (P=0.065) in a multivariate analysis including age and initial white blood cell count. Polo-like kinase 1 was necessary for leukemic cell survival, since short hairpin-mediated Polo-like kinase 1 knockdown in acute lymphoblastic leukemia cell lines inhibited cell proliferation by G2/M cell cycle arrest and induced apoptosis through caspase-3 and poly (ADP-ribose) polymerase cleavage. Primary patient cells with a high Polo-like kinase 1 protein expression were sensitive to the Polo-like kinase 1-specific inhibitor NMS-P937 in vitro, whereas cells with a low expression and normal bone marrow cells were resistant. This sensitivity was likely not caused by Polo-like kinase 1 mutations, since only one new mutation (Ser335Arg) was found by 454-sequencing of 38 pediatric acute lymphoblastic leukemia cases. This mutation did not affect Polo-like kinase 1 expression or NMS-P937 sensitivity. Together, these results indicate a pivotal role for Polo-like kinase 1 in pediatric acute lymphoblastic leukemia and show potential for Polo-like kinase 1-inhibiting drugs as an addition to current treatment strategies for cases expressing high Polo-like kinase 1 levels.

  17. Array comparative genomic hybridization and cytogenetic analysis in pediatric acute leukemias.

    PubMed

    Dawson, A J; Yanofsky, R; Vallente, R; Bal, S; Schroedter, I; Liang, L; Mai, S

    2011-10-01

    Most patients with acute lymphocytic leukemia (all) are reported to have acquired chromosomal abnormalities in their leukemic bone marrow cells. Many established chromosome rearrangements have been described, and their associations with specific clinical, biologic, and prognostic features are well defined. However, approximately 30% of pediatric and 50% of adult patients with all do not have cytogenetic abnormalities of clinical significance. Despite significant improvements in outcome for pediatric all, therapy fails in approximately 25% of patients, and these failures often occur unpredictably in patients with a favorable prognosis and "good" cytogenetics at diagnosis.It is well known that karyotype analysis in hematologic malignancies, although genome-wide, is limited because of altered cell kinetics (mitotic rate), a propensity of leukemic blasts to undergo apoptosis in culture, overgrowth by normal cells, and chromosomes of poor quality in the abnormal clone. Array comparative genomic hybridization (acgh-"microarray") has a greatly increased genomic resolution over classical cytogenetics. Cytogenetic microarray, which uses genomic dna, is a powerful tool in the analysis of unbalanced chromosome rearrangements, such as copy number gains and losses, and it is the method of choice when the mitotic index is low and the quality of metaphases is suboptimal. The copy number profile obtained by microarray is often called a "molecular karyotype."In the present study, microarray was applied to 9 retrospective cases of pediatric all either with initial high-risk features or with at least 1 relapse. The conventional karyotype was compared to the "molecular karyotype" to assess abnormalities as interpreted by classical cytogenetics. Not only were previously undetected chromosome losses and gains identified by microarray, but several karyotypes interpreted by classical cytogenetics were shown to be discordant with the microarray results. The complementary use of microarray

  18. Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia.

    PubMed

    den Hoed, M A H; Lopez-Lopez, E; te Winkel, M L; Tissing, W; de Rooij, J D E; Gutierrez-Camino, A; Garcia-Orad, A; den Boer, E; Pieters, R; Pluijm, S M F; de Jonge, R; van den Heuvel-Eibrink, M M

    2015-06-01

    Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia(ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treated with four high infusions MTX (HD-MTX: 5 g m(-2)) every other week according to the DCOG-ALL-10 protocol. Mucositis (National Cancer Institute grade ⩾ 3) was the most frequent occurring toxicity during the HD-MTX phase (20%) and occurred especially after the first MTX course. Mucositis was not associated with plasma MTX, plasma folate or plasma homocysteine levels. Patients with mucositis had higher erythrocyte folate levels at the start of protocol M than patients without mucositis (median 1.4 vs 1.2 μmol l(-1), P<0.008), this could reflect an increased MTX uptake in mucosal cells of patients with mucositis. From 17 single-nucleotide polymorphisms in the MTX pathway, only patients with the wild-type variant of rs7317112 SNP in the ABCC4 gene had more mucositis (AA (39%) vs AG/GG (15%), P=0.016). We found no evidence that erythrocyte folate levels mediate in the association between the rs7317112 and mucositis.

  19. Management of Invasive Fungal Infections in Pediatric Acute Leukemia and the Appropriate Time for Restarting Chemotherapy

    PubMed Central

    Tüfekçi, Özlem; Yılmaz Bengoa, Şebnem; Demir Yenigürbüz, Fatma; Şimşek, Erdem; Karapınar, Tuba Hilkay; İrken, Gülersu; Ören, Hale

    2015-01-01

    Objective: Rapid and effective treatment of invasive fungal infection (IFI) in patients with leukemia is important for survival. In this study, we aimed to describe variations regarding clinical features, treatment modalities, time of restarting chemotherapy, and outcome in children with IFI and acute leukemia (AL). Materials and Methods: The charts of all pediatric AL patients in our clinic between the years of 2001 and 2013 were retrospectively reviewed. All patients received prophylactic fluconazole during the chemotherapy period. Results: IFI was identified in 25 (14%) of 174 AL patients. Most of them were in the consolidation phase of chemotherapy and the patients had severe neutropenia. The median time between leukemia diagnosis and definition of IFI was 122 days. Twenty-four patients had pulmonary IFI. The most frequent finding on computed tomography was typical parenchymal nodules. The episodes were defined as proven in 4 (16%) patients, probable in 7 (28%) patients, and possible in 14 (56%) patients. The median time for discontinuation of chemotherapy was 27 days. IFI was treated successfully in all patients with voriconazole, amphotericin B, caspofungin, or posaconazole alone or in combination. Chemotherapy was restarted in 50% of the patients safely within 4 weeks and none of those patients experienced reactivation of IFI. All of them were given secondary prophylaxis. The median time for antifungal treatment and for secondary prophylaxis was 26 and 90 days, respectively. None of the patients died due to IFI. Conclusion: Our data show that rapid and effective antifungal therapy with rational treatment modalities may decrease the incidence of death and that restarting chemotherapy within several weeks may be safe in children with AL and IFI. PMID:25913290

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

    PubMed

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

    2015-12-01

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

  1. FLT3 is implicated in cytarabine transport by human equilibrative nucleoside transporter 1 in pediatric acute leukemia

    PubMed Central

    Català, Albert; Pastor-Anglada, Marçal; Caviedes-Cárdenas, Liska; Malatesta, Roberta; Rives, Susana; Vega-García, Nerea

    2016-01-01

    FLT3 abnormalities are negative prognostic markers in acute leukemia. Infant leukemias are a subgroup with frequent MLL (KMT2A) rearrangements, FLT3 overexpression and high sensitivity to cytarabine, but dismal prognosis. Cytarabine is transported into cells by Human Equilibrative Nucleoside Transporter-1 (hENT1, SLC29A1), but the mechanisms that regulate hENT1 in acute leukemia have been scarcely studied. We explored the expression and functional link between FLT3 and main cytarabine transporters in 50 pediatric patients diagnosed with acute lymphoblastic leukemia and MLL rearrangement (ALL-MLL+) and other subtypes of leukemia, and in leukemia cell lines. A significant positive correlation was found between FLT3 and hENT1 expression in patients. Cytarabine uptake into cells was mediated mainly by hENT1, hENT2 and hCNT1. hENT1-mediated uptake of cytarabine was transiently abolished by the FLT3 inhibitor PKC412, and this effect was associated with decreased hENT1 mRNA and protein levels. Noticeably, the cytotoxicity of cytarabine was lower when cells were first exposed to FLT3 inhibitors (PKC412 or AC220), probably due to decreased hENT1 activity, but we observed a higher cytotoxic effect if FLT3 inhibitors were administered after cytarabine. FLT3 regulates hENT1 activity and thereby affects cytarabine cytotoxicity. The sequence of administration of cytarabine and FLT3 inhibitors is important to maintain their efficacy. PMID:27391351

  2. Trisomy 8 in pediatric acute myeloid leukemia: A NOPHO-AML study.

    PubMed

    Laursen, Anne Cathrine Lund; Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas; Asdahl, Peter; Ha, Shau-Yin; Heldrup, Jesper; Jahnukainen, Kirsi; Jónsson, Ólafur G; Lausen, Birgitte; Palle, Josefine; Zeller, Bernward; Forestier, Erik; Hasle, Henrik

    2016-09-01

    Trisomy 8 (+8) is a common cytogenetic aberration in acute myeloid leukemia (AML); however, the impact of +8 in pediatric AML is largely unknown. We retrospectively investigated 609 patients from the NOPHO-AML database to determine the clinical and cytogenetic characteristics of +8 in pediatric AML and to investigate its prognostic impact. Complete cytogenetic data were available in 596 patients (98%) aged 0-18 years, diagnosed from 1993 to 2012, and treated according to the NOPHO-AML 1993 and 2004 protocols in the Nordic countries and Hong Kong. We identified 86 patients (14%) with +8. Trisomy 8 was combined with other cytogenetic aberrations in 68 patients (11%) (+8 other) and in 18 patients (3%), it was the sole abnormality (+8 alone). Trisomy 8 was associated with FAB M5 (36%) but otherwise clinically comparable with non-trisomy 8 patients. Trisomy 8 was favorable in patients of young age and with t(9;11). Trisomy 8 alone was associated with older age (median age 10.1 years), FAB M2 (33%), and FLT3-ITD mutations (58%). The 5-year event-free survival for patients with +8 alone was 50% and 5-year overall survival was 75%. In conclusion, +8 is one of the most common cytogenetic aberrations in pediatric AML. Trisomy 8 positive AML is a heterogeneous group and the majority of cases have additional cytogenetic aberrations. Patients with +8 alone differed from patients with +8 other and were associated with older age, FAB M2, and FLT3-ITD aberrations. There were no differences in survival despite the more frequent occurrence of FLT3-ITD in +8 alone. © 2016 Wiley Periodicals, Inc.

  3. TSER polymorphism is not associated with risk of pediatric acute lymphoblastic leukemia

    PubMed Central

    Qiao, Zhaohua; Lou, Dan; Ruan, Li

    2017-01-01

    Abstract Background: Accumulating studies have explored the effect of thymidylate synthase enhancer region (TSER) variation on risk of pediatric acute lymphoblastic leukemia (ALL) with controversial results. Therefore, this quantitative meta-analysis was performed to assess synthetically the association of TSER variation with susceptibility to develop pediatric ALL. Methods: The PubMed, ScienceDirect, Google Scholar, Wanfang Database, and China National Knowledge Infrastructure were systematically retrieved to obtain the published case-control studies about the relationship between TSER variation and pediatric ALL risk. The quality assessment of the included studies was preformed and relevant information was collected. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the strength of association. Results: This meta-analysis finally included 2681 children with ALL and 3854 matched controls from 11 investigations. The quantitative synthesis results found no significant association between TSER variation and susceptibility to pediatric ALL in overall comparisons under 5 genetic models (2R/3R vs 3R/3R: OR = 0.95, 95% CI = 0.84–1.07, P = 0.41; 2R/2R vs 3R/3R: OR = 0.99, 95% CI = 0.84–1.16, P = 0.90; 2R2R vs 3R/3R+2R/3R: OR = 1.05, 95% CI = 0.92–1.21, P = 0.45; 2R/3R+2R/2R vs 3R/3R: OR = 0.97, 95% CI = 0.87–1.09, P = 0.63; 2R vs 3R: OR = 1.03, 95% CI = 0.92–1.15, P = 0.61). Similarly, there was no significant association existed in the stratification analyses according to ethnicity, control source, and quality score. Conclusion: This meta-analysis shows that TSER variation is not related to the development risk of pediatric ALL. PMID:28207544

  4. Clinical Courses of Two Pediatric Patients with Acute Megakaryoblastic Leukemia Harboring the CBFA2T3-GLIS2 Fusion Gene

    PubMed Central

    Ishibashi, Mayu; Yokosuka, Tomoko; Yanagimachi, Masakatsu D.; Iwasaki, Fuminori; Tsujimoto, Shin-ichi; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Kajiwara, Ryosuke; Tanaka, Fumiko; Goto, Hiroaki; Yokota, Shumpei

    2016-01-01

    Acute megakaryoblastic leukemia (AMKL) in children without Down syndrome (DS) has an extremely poor outcome with 3-year survival of less than 40%, whereas AMKL in children with DS has an excellent survival rate. Recently, a novel recurrent translocation involving CBFA2T3 and GLIS2 was identified in about 30% of children with non-DS AMKL, and the fusion gene was reported as a strong poor prognostic factor in pediatric AMKL. We report the difficult clinical courses of pediatric patients with AMKL harboring the CBFA2T3-GLIS2 fusion gene. PMID:27094503

  5. The role of 18F-FDG PET/CT in pediatric lymph-node acute lymphoblastic leukemia involvement.

    PubMed

    Cistaro, Angelina; Saglio, Francesco; Asaftei, Sebastian; Fania, Piercarlo; Berger, Massimo; Fagioli, Franca

    2011-01-01

    In pediatric oncology, positron emission tomography/computed tomography (PET/CT) is emerging as an essential diagnostic tool in characterizing suspicious neoplastic lesions and staging malignant diseases. Most studies regarding the possible role of FDG-PET/CT in the management of acute lymphoblastic leukemia (ALL) patients are limited to adults. Here we report a pediatric patient with recurrent ALL, in which FDG-PET/CT was used both to define more precisely the cause of lymphadenopathy and to assess the effect of the second-line therapy.

  6. Improved outcome of pediatric patients with acute megakaryoblastic leukemia in the AML-BFM 04 trial.

    PubMed

    Schweitzer, Jana; Zimmermann, Martin; Rasche, Mareike; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Reinhardt, Dirk; Klusmann, Jan-Henning

    2015-08-01

    Despite recent advances in the treatment of children with acute megakaryoblastic leukemia (AMKL) using intensified treatment protocols, clear prognostic indicators, and treatment recommendations for this acute myeloid leukemia (AML) subgroup are yet to be defined. Here, we report the outcome of 97 pediatric patients with de novo AMKL (excluding Down syndrome [DS]) enrolled in the prospective multicenter studies AML-BFM 98 and AML-BFM 04 (1998-2014). AMKL occurred in 7.4 % of pediatric AML cases, at younger age (median 1.44 years) and with lower white blood cell count (mean 16.5 × 10(9)/L) as compared to other AML subgroups. With 60 ± 5 %, children with AMKL had a lower 5-year overall survival (5-year OS; vs. 68 ± 1 %, P log rank = 0.038). Yet, we achieved an improved 5-year OS in AML-BFM 04 compared to AML-BFM 98 (70 ± 6 % vs. 45 ± 8 %, P log rank = 0.041). Allogeneic hematopoietic stem cell transplantation in first remission did not provide a significant survival benefit (5-year OS 70 ± 11 % vs. 63 ± 6 %; P Mantel-Byar = 0.85). Cytogenetic data were available for n = 78 patients. AMKL patients with gain of chromosome 21 had a superior 5-year OS (80 ± 9 %, P log rank = 0.034), whereas translocation t(1;22)(p13;q13) was associated with an inferior 5-year event-free survival (38 ± 17 %, P log rank = 0.04). However, multivariate analysis showed that treatment response (bone marrow morphology on day 15 and 28) was the only independent prognostic marker (RR = 4.39; 95 % CI, 1.97-9.78). Interestingly, GATA1-mutations were detected in six patients (11 %) without previously known trisomy 21. Thus, AMKL (excluding DS) remains an AML subgroup with inferior outcome. Nevertheless, with intensive therapy regimens, a steep increase in the survival rates was achieved.

  7. Absolute Lymphocyte Count (ALC) after Induction Treatment Predicts Survival of Pediatric Patients with Acute Lymphoblastic Leukemia.

    PubMed

    Farkas, Tamas; Müller, Judit; Erdelyi, Daniel J; Csoka, Monika; Kovacs, Gabor T

    2017-01-30

    Absolute Lymphocyte Count (ALC) has been recently established as a prognostic factor of survival in pediatric Acute Lymphoblastic Leukemia (ALL). A retrospective analysis of 132 patients treated according the BFM - ALLIC 2002 protocol was performed in a single institution. A possible association between ALC values and Overall Survival (OS) or Event-Free Survival (EFS) was evaluated at multiple time points during induction chemotherapy. ALC higher than 350 cells/μL measured on the 33th day of induction was associated with better Overall- and Event-Free Survival in both Kaplan-Meier (OS 88.6% vs. 40%; p < 0.001 / EFS 81.6% vs. 30%; p < 0.001) and Cox regression (OS HR 8.77 (3.31-23.28); p < 0.001) and EFS HR 6.61 (2.79-15.63); p < 0.001) analyses. There was no association between survival and measured ALC values from earlier time points (day of diagnosis, days 8 and 15) of induction therapy. Patients with low ALC values tend to have higher risk (MR or HR groups) and a higher age at diagnosis (>10 years). With help of day 33 ALC values of 350 cells/μL cutoff it was possible to refine day 33 flow cytometry (FC) Minimal Residual Disease (MRD) results within the negative cohort: higher ALC values were significantly associated with better survival. ALC on day 33 (350 cells/μL) remained prognostic for OS and EFS in multivariate analysis after adjusting it for age, cytogenetics, immunophenotype and FC MRD of induction day 33. According to these findings ALC on day 33 of induction is a strong predictor of survival in pediatric ALL.

  8. Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.

    PubMed

    Parasole, Rosanna; Petruzziello, Fara; Menna, Giuseppe; Mangione, Argia; Cianciulli, Emilio; Buffardi, Salvatore; Marchese, Luciano; Nastro, Anna; Misuraca, Aldo; Poggi, Vincenzo

    2010-06-01

    Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.

  9. Impact of registration on clinical trials on infection risk in pediatric acute myeloid leukemia.

    PubMed

    Dix, David; Aplenc, Richard; Bowes, Lynette; Cellot, Sonia; Ethier, Marie-Chantal; Feusner, Jim; Gillmeister, Biljana; Johnston, Donna L; Lewis, Victor; Michon, Bruno; Mitchell, David; Portwine, Carol; Price, Victoria; Silva, Mariana; Stobart, Kent; Yanofsky, Rochelle; Zelcer, Shayna; Beyene, Joseph; Sung, Lillian

    2016-04-01

    Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.

  10. Heterogeneity in mechanisms of emergent resistance in pediatric T-cell acute lymphoblastic leukemia

    PubMed Central

    Sutton, Rosemary; Venn, Nicola C.; Bendak, Katerina; Anderson, Denise; Marshall, Glenn M.; Cole, Catherine H.

    2016-01-01

    Relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem and is thought to be associated with clonal selection during treatment. In this study we used an established pre-clinical model of induction therapy to increase our understanding of the effect of engraftment and chemotherapy on clonal selection and acquisition of drug resistance in vivo. Immune-deficient mice were engrafted with patient diagnostic specimens and exposed to a repeated combination therapy consisting of vincristine, dexamethasone, L-asparaginase and daunorubicin. Any re-emergence of disease following therapy was shown to be associated with resistance to dexamethasone, no resistance was observed to the other three drugs. Immunoglobulin/T-cell receptor gene rearrangements closely matched those in respective diagnosis and relapse patient specimens, highlighting that these clonal markers do not fully reflect the biological changes associated with drug resistance. Gene expression profiling revealed the significant underlying heterogeneity of dexamethasone-resistant xenografts. Alterations were observed in a large number of biological pathways, yet no dominant signature was common to all lines. These findings indicate that the biological changes associated with T-ALL relapse and resistance are stochastic and highly individual, and underline the importance of using sophisticated molecular techniques or single cell analyses in developing personalized approaches to therapy. PMID:27623214

  11. Heterogeneity in mechanisms of emergent resistance in pediatric T-cell acute lymphoblastic leukemia.

    PubMed

    Yadav, Babasaheb D; Samuels, Amy L; Wells, Julia E; Sutton, Rosemary; Venn, Nicola C; Bendak, Katerina; Anderson, Denise; Marshall, Glenn M; Cole, Catherine H; Beesley, Alex H; Kees, Ursula R; Lock, Richard B

    2016-09-13

    Relapse in pediatric T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem and is thought to be associated with clonal selection during treatment. In this study we used an established pre-clinical model of induction therapy to increase our understanding of the effect of engraftment and chemotherapy on clonal selection and acquisition of drug resistance in vivo. Immune-deficient mice were engrafted with patient diagnostic specimens and exposed to a repeated combination therapy consisting of vincristine, dexamethasone, L-asparaginase and daunorubicin. Any re-emergence of disease following therapy was shown to be associated with resistance to dexamethasone, no resistance was observed to the other three drugs. Immunoglobulin/T-cell receptor gene rearrangements closely matched those in respective diagnosis and relapse patient specimens, highlighting that these clonal markers do not fully reflect the biological changes associated with drug resistance. Gene expression profiling revealed the significant underlying heterogeneity of dexamethasone-resistant xenografts. Alterations were observed in a large number of biological pathways, yet no dominant signature was common to all lines. These findings indicate that the biological changes associated with T-ALL relapse and resistance are stochastic and highly individual, and underline the importance of using sophisticated molecular techniques or single cell analyses in developing personalized approaches to therapy.

  12. The mutational landscape in pediatric acute lymphoblastic leukemia deciphered by whole genome sequencing.

    PubMed

    Lindqvist, Carl Mårten; Nordlund, Jessica; Ekman, Diana; Johansson, Anna; Moghadam, Behrooz Torabi; Raine, Amanda; Övernäs, Elin; Dahlberg, Johan; Wahlberg, Per; Henriksson, Niklas; Abrahamsson, Jonas; Frost, Britt-Marie; Grandér, Dan; Heyman, Mats; Larsson, Rolf; Palle, Josefine; Söderhäll, Stefan; Forestier, Erik; Lönnerholm, Gudmar; Syvänen, Ann-Christine; Berglund, Eva C

    2015-01-01

    Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications.

  13. Treatment delay and the risk of relapse in pediatric acute lymphoblastic leukemia.

    PubMed

    Yeoh, Amelia; Collins, Anna; Fox, Kahlia; Shields, Sarah; Ritchie, Petra; Kirby, Maria; Revesz, Tamas

    2017-03-13

    Delays or interruptions in chemotherapy due to toxicity such as neutropenia or severe infections are common in the treatment of pediatric acute lymphoblastic leukemia (ALL). Based on the reports of worse outcomes in children with poorer compliance with therapy, there has been concern that toxicity-induced therapy interruptions could also compromise treatment outcome. In a retrospective study of treatment delays in our hospital between 2003 and 2013, the case notes of 141 patients were reviewed. The cumulative lengths of delays during the whole length of chemotherapy, during the intensive phase of treatment, and during maintenance treatment were analyzed. Within these categories, delays were split between less and more than the median value. The risk of relapse did not differ between patients with a longer or shorter delay during the total length of treatment or during the intensive phase. In addition, there was a trend when comparing patients above vs below the mean in length of treatment delays during maintenance, and there was a statistically significant difference in relapses when comparing patients in the lowest and highest quartiles of maintenance delays, with fewer relapses among those patients in the highest quartile for treatment delays.

  14. Banding cytogenetic analysis in pediatric patients with acute lymphoblastic leukemia (ALL) in a Brazilian population

    PubMed Central

    2013-01-01

    Background Cytogenetic studies in Brazilian population about childhood acute lymphoblastic leukemia (ALL), the most common childhood malignancy, are scarce. Moreover, Brazilian race is very heterogeneous and is made by the confluence of people of several different origins, from the original Native Brazilians, with the influx of Portuguese colonizers, Black African slaves, and recent European, Arab and Japanese immigration. The purpose of this prospective, multicentric study was to assess the sociodemographic, clinic and cytogenetic characteristics of the children treated for ALL in the Northeast region of Brazil. Results This study includes thirty patients between 4 months and 17 years old treated for ALL from January 1st, 2009 to November 30th, 2010. Cytogenetic analysis showed that in nineteen out of thirty patients (64%) presented some chromosome abnormalities, in which 53% corresponds to numerical abnormalities, 21% structural and numerical abnormalities, and 26% only structural changes. Moreover, seven patients presented complexes karyotype not yet described in the literature. Taken together these results show the importance of the cytogenetic analysis in ALL pediatric patients and illustrates that the studied population presented unexpected complexes karyotypes which were correlated to poor outcome. Conclusion The results demonstrate the importance of banding cytogenetics for ALL diagnosis despite the use of most modern techniques such as FISH and aCGH, and provide reliable insight into the ALL in Brazil. PMID:24025689

  15. The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment.

    PubMed

    Owens, Joyce L; Hanson, Sheila J; McArthur, Jennifer A; Mikhailov, Theresa A

    2013-10-31

    High survival rates for pediatric leukemia are very promising. With regard to treatment, children tend to be able to withstand a more aggressive treatment protocol than adults. The differences in both treatment modalities and outcomes between children and adults make extrapolation of adult studies to children inappropriate. The higher success is associated with a significant number of children experiencing nutrition-related adverse effects both in the short and long term after treatment. Specific treatment protocols have been shown to deplete nutrient levels, in particular antioxidants. The optimal nutrition prescription during, after and long-term following cancer treatment is unknown. This review article will provide an overview of the known physiologic processes of pediatric leukemia and how they contribute to the complexity of performing nutritional assessment in this population. It will also discuss known nutrition-related consequences, both short and long term in pediatric leukemia patients. Since specific antioxidants have been shown to be depleted as a consequence of therapy, the role of oxidative stress in the pediatric leukemia population will also be explored. More pediatric studies are needed to develop evidence based therapeutic interventions for nutritional complications of leukemia and its treatment.

  16. ETO2-GLIS2 Hijacks Transcriptional Complexes to Drive Cellular Identity and Self-Renewal in Pediatric Acute Megakaryoblastic Leukemia.

    PubMed

    Thirant, Cécile; Ignacimouttou, Cathy; Lopez, Cécile K; Diop, M'Boyba; Le Mouël, Lou; Thiollier, Clarisse; Siret, Aurélie; Dessen, Phillipe; Aid, Zakia; Rivière, Julie; Rameau, Philippe; Lefebvre, Céline; Khaled, Mehdi; Leverger, Guy; Ballerini, Paola; Petit, Arnaud; Raslova, Hana; Carmichael, Catherine L; Kile, Benjamin T; Soler, Eric; Crispino, John D; Wichmann, Christian; Pflumio, Françoise; Schwaller, Jürg; Vainchenker, William; Lobry, Camille; Droin, Nathalie; Bernard, Olivier A; Malinge, Sébastien; Mercher, Thomas

    2017-03-13

    Chimeric transcription factors are a hallmark of human leukemia, but the molecular mechanisms by which they block differentiation and promote aberrant self-renewal remain unclear. Here, we demonstrate that the ETO2-GLIS2 fusion oncoprotein, which is found in aggressive acute megakaryoblastic leukemia, confers megakaryocytic identity via the GLIS2 moiety while both ETO2 and GLIS2 domains are required to drive increased self-renewal properties. ETO2-GLIS2 directly binds DNA to control transcription of associated genes by upregulation of expression and interaction with the ETS-related ERG protein at enhancer elements. Importantly, specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia.

  17. Molecular Targeting of the Oncoprotein PLK1 in Pediatric Acute Myeloid Leukemia: RO3280, a Novel PLK1 Inhibitor, Induces Apoptosis in Leukemia Cells

    PubMed Central

    Wang, Na-Na; Li, Zhi-Heng; Zhao, He; Tao, Yan-Fang; Xu, Li-Xiao; Lu, Jun; Cao, Lan; Du, Xiao-Juan; Sun, Li-Chao; Zhao, Wen-Li; Xiao, Pei-Fang; Fang, Fang; Su, Guang-Hao; Li, Yan-Hong; Li, Gang; Li, Yi-Ping; Xu, Yun-Yun; Zhou, Hui-Ting; Wu, Yi; Jin, Mei-Fang; Liu, Lin; Ni, Jian; Wang, Jian; Hu, Shao-Yan; Zhu, Xue-Ming; Feng, Xing; Pan, Jian

    2015-01-01

    Polo-like kinase 1 (PLK1) is highly expressed in many cancers and therefore a biomarker of transformation and potential target for the development of cancer-specific small molecule drugs. RO3280 was recently identified as a novel PLK1 inhibitor; however its therapeutic effects in leukemia treatment are still unknown. We found that the PLK1 protein was highly expressed in leukemia cell lines as well as 73.3% (11/15) of pediatric acute myeloid leukemia (AML) samples. PLK1 mRNA expression was significantly higher in AML samples compared with control samples (82.95 ± 110.28 vs. 6.36 ± 6.35; p < 0.001). Kaplan-Meier survival analysis revealed that shorter survival time correlated with high tumor PLK1 expression (p = 0.002). The 50% inhibitory concentration (IC50) of RO3280 for acute leukemia cells was between 74 and 797 nM. The IC50 of RO3280 in primary acute lymphocytic leukemia (ALL) and AML cells was between 35.49 and 110.76 nM and 52.80 and 147.50 nM, respectively. RO3280 induced apoptosis and cell cycle disorder in leukemia cells. RO3280 treatment regulated several apoptosis-associated genes. The regulation of DCC, CDKN1A, BTK, and SOCS2 was verified by western blot. These results provide insights into the potential use of RO3280 for AML therapy; however, the underlying mechanisms remain to be determined. PMID:25574601

  18. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  19. Pediatric non-Down syndrome acute megakaryoblastic leukemia is characterized by distinct genomic subsets with varying outcomes.

    PubMed

    de Rooij, Jasmijn D E; Branstetter, Cristyn; Ma, Jing; Li, Yongjin; Walsh, Michael P; Cheng, Jinjun; Obulkasim, Askar; Dang, Jinjun; Easton, John; Verboon, Lonneke J; Mulder, Heather L; Zimmermann, Martin; Koss, Cary; Gupta, Pankaj; Edmonson, Michael; Rusch, Michael; Lim, Joshua Yew Suang; Reinhardt, Katarina; Pigazzi, Martina; Song, Guangchun; Yeoh, Allen Eng Juh; Shih, Lee-Yung; Liang, Der-Cherng; Halene, Stephanie; Krause, Diane S; Zhang, Jinghui; Downing, James R; Locatelli, Franco; Reinhardt, Dirk; van den Heuvel-Eibrink, Marry M; Zwaan, C Michel; Fornerod, Maarten; Gruber, Tanja A

    2017-03-01

    Acute megakaryoblastic leukemia (AMKL) is a subtype of acute myeloid leukemia (AML) in which cells morphologically resemble abnormal megakaryoblasts. While rare in adults, AMKL accounts for 4-15% of newly diagnosed childhood AML cases. AMKL in individuals without Down syndrome (non-DS-AMKL) is frequently associated with poor clinical outcomes. Previous efforts have identified chimeric oncogenes in a substantial number of non-DS-AMKL cases, including RBM15-MKL1, CBFA2T3-GLIS2, KMT2A gene rearrangements, and NUP98-KDM5A. However, the etiology of 30-40% of cases remains unknown. To better understand the genomic landscape of non-DS-AMKL, we performed RNA and exome sequencing on specimens from 99 patients (75 pediatric and 24 adult). We demonstrate that pediatric non-DS-AMKL is a heterogeneous malignancy that can be divided into seven subgroups with varying outcomes. These subgroups are characterized by chimeric oncogenes with cooperating mutations in epigenetic and kinase signaling genes. Overall, these data shed light on the etiology of AMKL and provide useful information for the tailoring of treatment.

  20. Use of Minimal Residual Disease Assessment to Redefine Induction Failure in Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    O'Connor, David; Moorman, Anthony V; Wade, Rachel; Hancock, Jeremy; Tan, Ronald M R; Bartram, Jack; Moppett, John; Schwab, Claire; Patrick, Katharine; Harrison, Christine J; Hough, Rachael; Goulden, Nick; Vora, Ajay; Samarasinghe, Sujith

    2017-02-20

    Purpose Our aim was to determine the role of end-of-induction (EOI) minimal residual disease (MRD) assessment in the identification and stratification of induction failure in patients with pediatric acute lymphoblastic leukemia (ALL) and to identify genetic abnormalities that drive disease in these patients. Patients and Methods Analysis included 3,113 patients who were treated in the Medical Research Council UKALL2003 multicenter randomized trial (NCT00222612) between 2003 and 2011. MRD was measured by using standardized real-time quantitative PCR. Median follow-up was 5 years 9 months. Results Fifty-nine patients (1.9%) had morphologic induction failure with 5-year event-free survival (EFS) of 50.7% (95% CI, 37.4 to 64.0) and 5-year overall survival of 57.7% (95% CI, 44.2 to 71.2). Of these, a small proportion of patients with M2 marrow (6 of 44) and a low EOI MRD level (< 0.01%) had 5-year EFS of 100%. Conversely, among patients with morphologic remission 2.3% (61 of 2,633) had high MRD (≥ 5%) and 5-year EFS of 47.0% (95% CI, 32.9 to 61.1), which was similar to those with morphologic induction failure. Redefining induction failure to include morphologic induction failure and/or MRD ≥ 5% identified 3.9% (120 of 3,133 patients) of the trial cohort with 5-year EFS of 48.0% (95% CI, 39.3 to 58.6). Induction failure (morphologic or MRD ≥ 5%) occurred most frequently in T-ALL (10.1%; 39 of 386 T-ALL cases) and B-other ALL, that is, lacking established chromosomal abnormalities (5.6%; 43 of 772 B-other cases). Genetic testing within the B-other group revealed the presence of PDGFRB gene fusions, particularly EBF1-PDGFRB, in almost one third of B-other ALL cases. Conclusion Integration of EOI MRD level with morphology identifies induction failure more precisely than morphology alone. Prevalence of EBF1-PDGFRB fusions in this group highlights the importance of genetic screening to identify abnormalities that may be targets for novel agents.

  1. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  2. Applying molecular epidemiology in pediatric leukemia.

    PubMed

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

  3. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there?

    PubMed

    Pui, Ching-Hon; Mullighan, Charles G; Evans, William E; Relling, Mary V

    2012-08-09

    Improved supportive care, more precise risk stratification, and personalized chemotherapy based on the characteristics of leukemic cells and hosts (eg, pharmacokinetics and pharmacogenetics) have pushed the cure rate of childhood acute lymphoblastic leukemia to near 90%. Further increase in cure rate can be expected from the discovery of additional recurrent molecular lesions, coupled with the development of novel targeted treatment through high-throughput genomics and innovative drug-screening systems. We discuss specific areas of research that promise to further refine current treatment and to improve the cure rate and quality of life of the patients.

  4. Asparaginase in acute lymphoblastic leukemia.

    PubMed

    Kawedia, Jitesh D; Rytting, Michael E

    2014-09-01

    Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug.

  5. An evaluation of diagnostic techniques utilized in the initial workup of pediatric patients with acute lymphocytic leukemia.

    PubMed

    Kuntz, D J; Leonard, J C; Nitschke, R M; Vanhoutte, J J; Wilson, D A; Basmadjian, G P

    1984-07-01

    The records of 32 pediatric patients with acute lymphocytic leukemia (ALL) were reviewed to evaluate the role of various diagnostic techniques used to assess the extent of extramedullary disease. Our findings indicate that adequate screening for hepatosplenomegaly is obtained by clinical assessment and for bone and renal involvement by bone scintigraphy including concomitant renal imaging. We recommend that radiographs be restricted to scintigraphically abnormal areas and/or sites of bone pain. Liver-spleen scintigraphy, gallium studies, intravenous pyelography, and ultrasound studies of the abdomen and pelvis should be utilized only to answer specific clinical questions. Evaluation in this manner reduces both radiation exposure and patient expense, while it adequately defines the extent of disease in these organs.

  6. What Is Acute Myeloid Leukemia?

    MedlinePlus

    ... Acute Myeloid Leukemia (AML) What Is Acute Myeloid Leukemia? Cancer starts when cells in a part of ... the body from doing their jobs. Types of leukemia Not all leukemias are the same. There are ...

  7. Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    2012-01-01

    Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at subnanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design. PMID:22662287

  8. Discovery of Novel Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    Liu, Jing; Yang, Chao; Simpson, Catherine; Deryckere, Deborah; Van Deusen, Amy; Miley, Michael J; Kireev, Dmitri; Norris-Drouin, Jacqueline; Sather, Susan; Hunter, Debra; Korboukh, Victoria K; Patel, Hari S; Janzen, William P; Machius, Mischa; Johnson, Gary L; Earp, H Shelton; Graham, Douglas K; Frye, Stephen V; Wang, Xiaodong

    2012-02-09

    Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design.

  9. Institutional experience with clofarabine and cytarabine in relapsed pediatric acute myeloid leukemia.

    PubMed

    Moreno, Lucas; Fernandez-Navarro, Jose Maria; Del Mar Andres, Maria; Bautista, Francisco; Tasso, Maria; Verdeguer, Amparo

    2012-01-01

    Cytarabine (1000 mg/m/d intravenous for 5 d) and clofarabine (40 mg/m/d intravenous for 5 d) were given every 28 days to 9 children with relapsed acute myeloid leukemia at our institution. Among 19 courses, there were 18 infectious episodes. Median hospitalization time was 13 days (7.7 to 30.5 d) per cycle. Hepatobiliary abnormalities included alanine aminotransferase/aspartate aminotransferase elevation and hyperbilirubinemia. Four patients achieved complete remission (one after an earlier allogeneic Haematopoietic Progenitor Cell Transplant). Four patients are alive disease free. In summary, a proportion of children responded and was able to receive allogeneic Haematopoietic Progenitor Cell Transplant. Side effects were tolerable, although hospitalization time was prolonged.

  10. Use of cytosar in pediatric acute myelocytic leukemia and leukemic meningitis.

    PubMed

    Sullivan, M P

    1982-01-01

    For children with acute myelocytic leukemia, 5-day courses of Cytosar in combination with cyclophosphamide (with or without vincristine sulfate and prednisone) has shown excellent, age related results in relapse patients. The regimen known as Mini-COAP has been incorporated into front-line studies. Cytosar given intrathecally in combination with methotrexate has produced superior results in treating meningeal disease in the African presentation of Burkitt disease. This "synchronizing" technique has been incorporated into a high Cytoxan-high methotrexate regimen with coordinated intrathecal therapy with good results. Triple (Cytosar, methotrexate, and hydrocortisone) intrathecal prophylaxis is now demonstrated to have equivalent effectiveness to conventional CNS prophylaxis employing radiotherapy 2400 R and 5 doses of intrathecal methotrexate.

  11. Effective VCR/DEX pulse maintenance therapy in the KYCCSG ALL-02 protocol for pediatric acute lymphoblastic leukemia.

    PubMed

    Okamoto, Yasuhiro; Koga, Yuki; Inagaki, Jiro; Ozono, Shuichi; Ueda, Koichiro; Shimoura, Maiko; Itonaga, Nobuyoshi; Shinkoda, Yuichi; Moritake, Hiroshi; Nomura, Yuko; Nakayama, Hideki; Hotta, Noriko; Hidaka, Yasufumi; Shimonodan, Hidemi; Suga, Naohiro; Tanabe, Takayuki; Nakashima, Kentaro; Fukano, Reiji; Kawano, Yoshifumi

    2016-02-01

    In a previous study of childhood acute lymphoblastic leukemia (ALL) by the Kyushu-Yamaguchi Children's Cancer Study Group, ALL-96, we achieved a 72.1 % 5-year event-free survival (EFS) and an 84.8 % 5-year overall survival (OS). In a subsequent study, ALL-02, we adopted a vincristine dexamethasone (VCR/DEX) pulse regimen as maintenance therapy in the context of the ALL-96 study using the same risk classification and treatment schedule. A total of 156 pediatric cases of ALL were treated with ALL-02. All of the patients were classified as standard-risk or high-risk. Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system (CNS) disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). The 7-year EFS and OS rates were 77.7 % (95 % CI 70.6-84.8 %) and 89.5 % (95 % CI 84.6-94.4 %), respectively. CNS 3 status [hazard ratio (HR) = 5.0, p = 0.009] and high white blood cell count at diagnosis (HR = 2.6, p = 0.047) were risk factors for poor EFS in multivariate analysis. Our strategies to categorize patients into two risk groups, and to treat with a VCR/DEX pulse were feasible and reasonably effective treatments for pediatric ALL.

  12. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  13. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  14. Treatment of Acute Promyelocytic (M3) Leukemia

    MedlinePlus

    ... Acute Myeloid Leukemia Treatment of Acute Promyelocytic (M3) Leukemia Early diagnosis and treatment of acute promyelocytic leukemia ( ... Comes Back After Treatment? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...

  15. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Long-term results in the treatment of acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

    PubMed

    Krischer, J P; Steuber, C P; Vietti, T J; Culbert, S J; Ragab, A H; Morgan, S K; Berry, D H; Hvizdala, E; Thomas, P J; Land, V J

    1989-01-01

    Complete remission (CR), 5-year remission duration (RD), and overall 5-year survival rates are 74%, 28% and 25%, respectively, for previously untreated children with acute nonlymphocytic leukemia diagnosed between 1977 and 1981, following induction therapy with vincristine, doxorubicin and prednisone (VAP), consolidation therapy with 6-thioguanine, cytosine arabinoside (TA) and cyclophosphamide/vincristine/cytosine arabinoside/prednisone (COAP), and maintenance therapy of alternating TA and COAP with or without VAP pulses. Approximately 20% are free of their disease for more than 5 years. High white blood cell counts (WBC) at diagnosis and M3 and M6 morphology were associated with lower CR rates, while M5 morphology was associated with higher CR rates. Patients with M1 morphology had shorter remission duration as compared to those with M4 or M5 morphology. Low WBC and age between 2 and 10 years at diagnosis were associated with longer remission durations and survival. Patients with M4 morphology also survived longer. The observed CR rates are comparable to other studies initiated at the same time as this study but survival is less than those reported more recently. Low WBC at diagnosis and M4/M5 morphology may identify relatively favorable prognostic groups.

  17. Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia

    PubMed Central

    Almamun, Md; Levinson, Benjamin T; van Swaay, Annette C; Johnson, Nathan T; McKay, Stephanie D; Arthur, Gerald L; Davis, J Wade; Taylor, Kristen H

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children under the age of 15. In addition to genetic aberrations, epigenetic modifications such as DNA methylation are altered in cancer and impact gene expression. To identify epigenetic alterations in ALL, genome-wide methylation profiles were generated using the methylated CpG island recovery assay followed by next-generation sequencing. More than 25,000 differentially methylated regions (DMR) were observed in ALL patients with ∼90% present within intronic or intergenic regions. To determine the regulatory potential of the DMR, whole-transcriptome analysis was performed and integrated with methylation data. Aberrant promoter methylation was associated with the altered expression of genes involved in transcriptional regulation, apoptosis, and proliferation. Novel enhancer-like sequences were identified within intronic and intergenic DMR. Aberrant methylation in these regions was associated with the altered expression of neighboring genes involved in cell cycle processes, lymphocyte activation and apoptosis. These genes include potential epi-driver genes, such as SYNE1, PTPRS, PAWR, HDAC9, RGCC, MCOLN2, LYN, TRAF3, FLT1, and MELK, which may provide a selective advantage to leukemic cells. In addition, the differential expression of epigenetic modifier genes, pseudogenes, and non-coding RNAs was also observed accentuating the role of erroneous epigenetic gene regulation in ALL. PMID:26308964

  18. Multi-agent chemotherapy overcomes glucocorticoid resistance conferred by a BIM deletion polymorphism in pediatric acute lymphoblastic leukemia.

    PubMed

    Soh, Sheila Xinxuan; Lim, Joshua Yew Suang; Huang, John W J; Jiang, Nan; Yeoh, Allen Eng Juh; Ong, S Tiong

    2014-01-01

    A broad range of anti-cancer agents, including glucocorticoids (GCs) and tyrosine kinase inhibitors (TKIs), kill cells by upregulating the pro-apoptotic BCL2 family member, BIM. A common germline deletion in the BIM gene was recently shown to favor the production of non-apoptotic BIM isoforms, and to predict inferior responses in TKI-treated chronic myeloid leukemia (CML) and EGFR-driven lung cancer patients. Given that both in vitro and in vivo GC resistance are predictive of adverse outcomes in acute lymphoblastic leukemia (ALL), we hypothesized that this polymorphism would mediate GC resistance, and serve as a biomarker of poor response in ALL. Accordingly, we used zinc finger nucleases to generate ALL cell lines with the BIM deletion, and confirmed the ability of the deletion to mediate GC resistance in vitro. In contrast to CML and lung cancer, the BIM deletion did not predict for poorer clinical outcome in a retrospective analysis of 411 pediatric ALL patients who were uniformly treated with GCs and chemotherapy. Underlying the lack of prognostic significance, we found that the chemotherapy agents used in our cohort (vincristine, L-asparaginase, and methotrexate) were each able to induce ALL cell death in a BIM-independent fashion, and resensitize BIM deletion-containing cells to GCs. Together, our work demonstrates how effective therapy can overcome intrinsic resistance in ALL patients, and suggests the potential of using combinations of drugs that work via divergent mechanisms of cell killing to surmount BIM deletion-mediated drug resistance in other cancers.

  19. Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts.

    PubMed

    Szymanska, Barbara; Wilczynska-Kalak, Urszula; Kang, Min H; Liem, Natalia L M; Carol, Hernan; Boehm, Ingrid; Groepper, Daniel; Reynolds, C Patrick; Stewart, Clinton F; Lock, Richard B

    2012-01-01

    Current regimens for induction therapy of pediatric acute lymphoblastic leukemia (ALL), or for re-induction post relapse, use a combination of vincristine (VCR), a glucocorticoid, and L-asparaginase (ASP) with or without an anthracycline. With cure rates now approximately 80%, robust pre-clinical models are necessary to prioritize active new drugs for clinical trials in relapsed/refractory patients, and the ability of these models to predict synergy/antagonism with established therapy is an essential attribute. In this study, we report optimization of an induction-type regimen by combining VCR, dexamethasone (DEX) and ASP (VXL) against ALL xenograft models established from patient biopsies in immune-deficient mice. We demonstrate that the VXL combination was synergistic in vitro against leukemia cell lines as well as in vivo against ALL xenografts. In vivo, VXL treatment caused delays in progression of individual xenografts ranging from 22 to >146 days. The median progression delay of xenografts derived from long-term surviving patients was 2-fold greater than that of xenografts derived from patients who died of their disease. Pharmacokinetic analysis revealed that systemic DEX exposure in mice increased 2-fold when administered in combination with VCR and ASP, consistent with clinical findings, which may contribute to the observed synergy between the 3 drugs. Finally, as proof-of-principle we tested the in vivo efficacy of combining VXL with either the Bcl-2/Bcl-xL/Bcl-w inhibitor, ABT-737, or arsenic trioxide to provide evidence of a robust in vivo platform to prioritize new drugs for clinical trials in children with relapsed/refractory ALL.

  20. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    PubMed Central

    2013-01-01

    Background Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic background, drug resistance and relapse in ALL is poorly understood. Results We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status. Conclusions Our results suggest an important biological role for DNA methylation in the differences between ALL subtypes and in their clinical outcome after treatment. PMID:24063430

  1. Second induction in pediatric patients with recurrent acute lymphoid leukemia using DFCI-ALL protocols.

    PubMed

    Dalle, Jean-Hugues; Moghrabi, Albert; Rousseau, Pierre; Leclerc, Jean-Marie; Barrette, Stephane; Bernstein, Mark L; Champagne, Josette; David, Michele; Demers, Jocelyn; Duval, Michel; Hume, Heather; Meyer, Patrick; Champagne, Martin A

    2005-02-01

    Between 15% and 30% of children with acute lymphoblastic leukemia (ALL) experience disease recurrence. With the possible exception of patients presenting with late isolated extramedullary relapse, induction of second complete remission (CR) is employed as a stepping stone to allogeneic hematopoietic stem cell transplantation (HSCT). The authors report their institutional experience in the management of children with recurrent ALL using the Dana Farber Cancer Institute (DFCI) ALL protocol in patients treated initially with that same protocol. Successful reinduction was followed by allogeneic HSCT when possible. Between April 1986 and May 2003, 34 patients with recurrent ALL, treated at initial diagnosis with DFCI-ALL protocol therapy, were given the same protocol as repeat induction chemotherapy. The median age was 4.6 years at diagnosis and 7.1 years at recurrence. Median duration of CR1 was 30.3 months. Second CR was obtained in 29 (85%) patients. Twenty went on to allogeneic HSCT; 10 of them currently remain in CR. Two additional patients treated with chemotherapy without HSCT are also in continuous CR2. Overall, 13 (38%) of the 34 patients are alive with a median follow-up of 105 months. There were no toxic deaths due to the reinduction therapy. One child died of cardiac failure after autologous HSCT. The treatment of children with recurrent ALL using the DFCI-ALL protocol induction regimen after initial use of the same protocol is associated with a high rate of second CR with no excess toxicity. However, the overall prognosis in these patients remains unsatisfactory and needs to be improved.

  2. Variations in mRNA and protein levels of Ikaros family members in pediatric T cell acute lymphoblastic leukemia

    PubMed Central

    Mitchell, Julie L.

    2016-01-01

    Background Pediatric T cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous disease in which the cells share phenotypic characteristics with normal human thymocytes. The Ikaros family of transcription factors includes five members that are required for normal T cell development and are implicated in leukemogenesis. The goal of this work was to correlate the pattern of expression of Ikaros family members with the phenotype of the T-ALL cells. Methods We obtained twenty-four samples from pediatric T-ALL patients and used multi-parameter flow cytometry to characterize each sample, comparing the phenotype of the leukemic cells with normal human thymocytes. Then, we defined the expression levels of each Ikaros family member to determine whether the mRNA levels or splicing or protein levels were similar to the normal patterns seen during human T cell development. Results Multi-parameter analysis of the phenotype of T-ALL cells revealed that each patient’s cells were unique and could not be readily correlated with stages of T cell development. Similarly, the pattern of Ikaros expression varied among patients. In most patients, Ikaros mRNA was the dominant family member expressed, but some patients’ cells contained mostly Helios, Aiolos, or Eos mRNA. Despite that most patients had elevated mRNA levels of Ikaros family members and unique patterns of mRNA splicing, most patients had significantly reduced protein levels of Ikaros and Aiolos. Conclusions Our analysis of the cell phenotype and Ikaros expression levels in T-ALL cells revealed the extent of heterogeneity among patients. While it is rarely possible to trace leukemic cells to their developmental origin, we found distinct patterns of Ikaros family mRNA levels in groups of patients. Further, mRNA and protein levels of Ikaros and Aiolos did not correlate, indicating that mRNA and protein levels are regulated via distinct mechanisms. PMID:27826566

  3. Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005–2011 – experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)

    PubMed Central

    Wachowiak, Jacek; Skalska-Sadowska, Jolanta; Wachowiak, Jacek; Zając-Spychała, Olga; Niewiadomska-Wojnałowicz, Izabela; Januszkiewicz-Lewandowska, Danuta; Balwierz, Walentyna; Pawińska-Wąsikowska, Katarzyna; Goździk, Jolanta; Chybicka, Alicja; Potocka, Kinga; Krawczuk-Rybak, Maryna; Muszyńska-Rosłan, Katarzyna; Adamkiewicz-Drożyńska, Elżbieta; Maciejka-Kapuścińska, Lucyna; Karolczyk, Grażyna; Kowalczyk, Jerzy; Wójcik, Beata; Badowska, Wanda; Urasiński, Tomasz; Ociepa, Tomasz; Matysiak, Michał; Sikorska-Fic, Barbara; Szczepański, Tomasz; Tomaszewska, Renata; Sobol, Grażyna; Wieczorek, Maria; Karpińska-Derda, Irena

    2014-01-01

    Aim of the study Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005–2011. Material and methods The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. Results Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. Conclusions The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy. PMID:24876821

  4. Drug-gene modeling in pediatric T-cell acute lymphoblastic leukemia highlights importance of 6-mercaptopurine for outcome.

    PubMed

    Beesley, Alex H; Firth, Martin J; Anderson, Denise; Samuels, Amy L; Ford, Jette; Kees, Ursula R

    2013-05-01

    Patients relapsing with T-cell acute lymphoblastic leukemia (T-ALL) face a dismal outcome. The aim of this study was to identify new markers of drug resistance and clinical response in T-ALL. We measured gene expression and drug sensitivity in 15 pediatric T-ALL cell lines to find signatures predictive of resistance to 10 agents used in therapy. These were used to generate a model for outcome prediction in patient cohorts using microarray data from diagnosis specimens. In three independent T-ALL cohorts, the 10-drug model was able to accurately identify patient outcome, indicating that the in vitro-derived drug-gene profiles were clinically relevant. Importantly, predictions of outcome within each cohort were linked to distinct drugs, suggesting that different mechanisms contribute to relapse. Sulfite oxidase (SUOX) expression and the drug-transporter ABCC1 (MRP1) were linked to thiopurine sensitivity, suggesting novel pathways for targeting resistance. This study advances our understanding of drug resistance in T-ALL and provides new markers for patient stratification. The results suggest potential benefit from the earlier use of 6-mercaptopurine in T-ALL therapy or the development of adjuvants that may sensitize blasts to this drug. The methodology developed in this study could be applied to other cancers to achieve patient stratification at the time of diagnosis.

  5. [Acute plasma cell leukemia].

    PubMed

    Monsalbe, V; Domíngues, C; Roa, I; Busel, D; González, S

    1989-01-01

    Plasma Cell Leukemia is a very rare form of plasmocytic dyscrasia, whose clinical and pathological characteristics warrant its recognition as a distinct subentity. We report the case of a 60 years old man who presented a rapidly fatal acute plasma cell leukemia, with multiple osteolytic lesions, hipercalcemia, renal and cardiac failure.

  6. Both mature KIR+ and immature KIR- NK cells control pediatric acute B-cell precursor leukemia in NOD.Cg-Prkdcscid IL2rgtmWjl/Sz mice.

    PubMed

    Kübler, Ayline; Woiterski, Jeanette; Witte, Kai-Erik; Bühring, Hans-Jörg; Hartwig, Udo F; Ebinger, Martin; Oevermann, Lena; Mezger, Markus; Herr, Wolfgang; Lang, Peter; Handgretinger, Rupert; Münz, Christian; André, Maya C

    2014-12-18

    Therapeutic natural killer (NK)-cell-mediated alloreactivity toward acute myeloid leukemia has largely been attributed to mismatches between killer immunoglobulin-like receptors (KIRs) on NK cells and their ligands, HLA class I molecules, on target cells. While adult acute B-cell precursor leukemia (BCP-ALL) appears to be resistant to NK-cell-mediated lysis, recent data indicate that pediatric BCP-ALL might yet be a target of NK cells. In this study, we demonstrate in a donor-patient-specific NOD.Cg-Prkdc(scid) IL2rg(tmWjl)/Sz (NSG) xenotransplantation model that NK cells mediate considerable alloreactivity toward pediatric BCP-ALL in vivo. Notably, both adoptively transferred mature KIR(+) NK cells and immature KIR(-) NK cells arising early posttransplantation in humanized NSG mice exerted substantial antileukemic activity. Low-dose and long-term treatment of humanized NSG mice with the DNA-demethylating agent 5-aza-cytidine distinctly enhanced the antitumor response, interestingly without inducing common inhibitory KIR expression but rather by promoting the differentiation of various NK-cell precursor subsets. Collectively, these data indicate that the future design of innovative therapy protocols should consider further exploitation of NK-cell-mediated immune responses for poor prognosis pediatric BCP-ALL patients.

  7. Vaccination to improve the persistence of CD19CAR gene-modified T cells in relapsed pediatric acute lymphoblastic leukemia.

    PubMed

    Rossig, C; Pule, M; Altvater, B; Saiagh, S; Wright, G; Ghorashian, S; Clifton-Hadley, L; Champion, K; Sattar, Z; Popova, B; Hackshaw, A; Smith, P; Roberts, T; Biagi, E; Dreno, B; Rousseau, R; Kailayangiri, S; Ahlmann, M; Hough, R; Kremens, B; Sauer, M G; Veys, P; Goulden, N; Cummins, M; Amrolia, P J

    2017-03-10

    Trials with second generation CD19 chimeric antigen receptors (CAR) T-cells report unprecedented responses but are associated with risk of cytokine release syndrome (CRS). Instead, we studied the use of donor Epstein-Barr virus-specific T-cells (EBV CTL) transduced with a first generation CD19CAR, relying on the endogenous T-cell receptor for proliferation. We conducted a multi-center phase I/II study of donor CD19CAR transduced EBV CTL in pediatric acute lymphoblastic leukaemia (ALL). Patients were eligible pre-emptively if they developed molecular relapse (>5 × 10(-4)) post first stem cell transplant (SCT), or prophylactically post second SCT. An initial cohort showed poor expansion/persistence. We therefore investigated EBV-directed vaccination to enhance expansion/persistence. Eleven patients were treated. No CRS, neurotoxicity or graft versus host disease (GVHD) was observed. At 1 month, 5 patients were in CR (4 continuing, 1 de novo), 1 PR, 3 had stable disease and 3 no response. At a median follow-up of 12 months, 10 of 11 have relapsed, 2 are alive with disease and 1 alive in CR 3 years. Although CD19CAR CTL expansion was poor, persistence was enhanced by vaccination. Median persistence was 0 (range: 0-28) days without vaccination compared to 56 (range: 0-221) days with vaccination (P=0.06). This study demonstrates the feasibility of multi-center studies of CAR T cell therapy and the potential for enhancing persistence with vaccination.Leukemia advance online publication, 10 March 2017; doi:10.1038/leu.2017.39.

  8. A Healthcare System Perspective on Implementing Genomic Medicine: Pediatric Acute Lymphoblastic Leukemia as a Paradigm

    PubMed Central

    Evans, William E.; Crews, Kristine R.; Pui, Ching-Hon

    2013-01-01

    The promise of genomic medicine has received great attention over the past decade, projecting how genomics will soon guide the prevention, diagnosis, and treatment of human diseases. However, this evolution has been slower than forecast, even where evidence is often strong (e.g., pharmacogenomics). Reasons include the requirement for institutional resources and the need for the will to push beyond barriers impeding health-care changes. Here, we illustrate how genomics has been deployed to advance the treatment of childhood leukemia. PMID:23462885

  9. Can Acute Myeloid Leukemia Be Prevented?

    MedlinePlus

    ... Causes, Risk Factors, and Prevention Can Acute Myeloid Leukemia Be Prevented? It’s not clear what causes most ... Myeloid Leukemia Be Prevented? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...

  10. Associations between genetic variants in folate and drug metabolizing pathways and relapse risk in pediatric acute lymphoid leukemia on CCG-1952

    PubMed Central

    Vujkovic, Marijana; Kershenbaum, Aaron; Wray, Lisa; McWilliams, Thomas; Cannon, Shannon; Devidas, Meenakshi; Stork, Linda; Aplenc, Richard

    2015-01-01

    Genetic variation in drug detoxification pathways may influence outcomes in pediatric acute lymphoblastic leukemia (ALL). We evaluated relapse risk and 24 variants in 17 genes in 714 patients in CCG-1961. Three TPMT and 1 MTR variant were associated with increased risks of relapse (rs4712327, OR 3.3, 95%CI 1.2–8.6; rs2842947, OR 2.7, 95%CI 1.1–6.8; rs2842935, OR 2.5, 95%CI 1.1–5.0; rs10925235, OR 4.9, 95%CI 1.1–25.1). One variant in SLC19A1 showed a protective effect (rs4819128, OR 0.5, 95%CI 0.3–0.9). Our study provides data that relapse risk in pediatric ALL is associated with germline variations in TPMT, MTR and SLC19A1. PMID:26605150

  11. NUP98/JARID1A is a novel recurrent abnormality in pediatric acute megakaryoblastic leukemia with a distinct HOX gene expression pattern.

    PubMed

    de Rooij, J D E; Hollink, I H I M; Arentsen-Peters, S T C J M; van Galen, J F; Berna Beverloo, H; Baruchel, A; Trka, J; Reinhardt, D; Sonneveld, E; Zimmermann, M; Alonzo, T A; Pieters, R; Meshinchi, S; van den Heuvel-Eibrink, M M; Zwaan, C Michel

    2013-12-01

    Cytogenetic abnormalities and early response to treatment are the main prognostic factors in acute myeloid leukemia (AML). Recently, NUP98/NSD1 (t(5; 11)(q35; p15)), a cytogenetically cryptic fusion, was described as recurrent event in AML, characterized by dismal prognosis and HOXA/B gene overexpression. Using split-signal fluorescence in situ hybridization, other NUP98-rearranged pediatric AML cases were identified, including several acute megakaryoblastic leukemia (AMKL) cases with a cytogenetically cryptic fusion of NUP98 to JARID1A (t(11;15)(p15;q35)). In this study we screened 105 pediatric AMKL cases to analyze the frequency of NUP98/JARID1A and other recurrent genetic abnormalities. NUP98/JARID1A was identified in 11/105 patients (10.5%). Other abnormalities consisted of RBM15/MKL1 (n=16), CBFA2T3/GLIS2 (n=13) and MLL-rearrangements (n=13). Comparing NUP98/JARID1A-positive patients with other pediatric AMKL patients, no significant differences in sex, age and white blood cell count were found. NUP98/JARID1A was not an independent prognostic factor for 5-year overall (probability of overall survival (pOS)) or event-free survival (probability of event-free survival (pEFS)), although the 5-year pOS for the entire AMKL cohort was poor (42 ± 6%). Cases with RBM15/MLK1 fared significantly better in terms of pOS and pEFS, although this was not independent from other risk factors in multivariate analysis. NUP98/JARID1A cases were characterized by HOXA/B gene overexpression, which is a potential druggable pathway. In conclusion, NUP98/JARID1A is a novel recurrent genetic abnormality in pediatric AMKL.

  12. The prognostic significance of early treatment response in pediatric relapsed acute myeloid leukemia: results of the international study Relapsed AML 2001/01

    PubMed Central

    Creutzig, Ursula; Zimmermann, Martin; Dworzak, Michael N.; Gibson, Brenda; Tamminga, Rienk; Abrahamsson, Jonas; Ha, Shau-Yin; Hasle, Henrik; Maschan, Alexey; Bertrand, Yves; Leverger, Guy; von Neuhoff, Christine; Razzouk, Bassem; Rizzari, Carmelo; Smisek, Petr; Smith, Owen P.; Stark, Batia; Reinhardt, Dirk; Kaspers, Gertjan L.

    2014-01-01

    The prognostic significance of early response to treatment has not been reported in relapsed pediatric acute myeloid leukemia. In order to identify an early and easily applicable prognostic factor allowing subsequent treatment modifications, we assessed leukemic blast counts in the bone marrow by morphology on days 15 and 28 after first reinduction in 338 patients of the international Relapsed-AML2001/01 trial. Both day 15 and day 28 status was classified as good (≤20% leukemic blasts) in 77% of patients. The correlation between day 15 and 28 blast percentages was significant, but not strong (Spearman correlation coefficient = 0.49, P<0.001). Survival probability decreased in a stepwise fashion along with rising blast counts at day 28. Patients with bone marrow blast counts at this time-point of ≤5%, 6–10%, 11–20% and >20% had 4-year probabilities of survival of 52%±3% versus 36%±10% versus 21%±9% versus 14%±4%, respectively, P<0.0001; this trend was not seen for day 15 results. Multivariate analysis showed that early treatment response at day 28 had the strongest prognostic significance, superseding even time to relapse (< or ≥12 months). In conclusion, an early response to treatment, measured on day 28, is a strong and independent prognostic factor potentially useful for treatment stratification in pediatric relapsed acute myeloid leukemia. This study was registered with ISRCTN code: 94206677. PMID:24763401

  13. Risk–Benefit Analysis of Pediatric-Inspired Versus Hyperfractionated Cyclophosphamide, Vincristine, Doxorubicin, and Dexamethasone Protocols for Acute Lymphoblastic Leukemia in Adolescents and Young Adults

    PubMed Central

    Guzauskas, Gregory F.; Villa, Kathleen F.; Vanhove, Geertrui F.; Fisher, Vicki L.

    2017-01-01

    Purpose: To estimate the risk–benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16–39 years) patients with Philadelphia-negative acute lymphoblastic leukemia. Methods: Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death. A Weibull distribution was fit to the progression-free survival curve of hyper-CVAD–treated AYA patients from a single-center study, and comparable patient data from a retrospective study of pediatric regimen–treated AYA patients were utilized to estimate a relative progression difference (hazard ratio = 0.51) and model survival differences. Health-state utilities were estimated based on treatment stage, with an assumption that the pediatric protocol had 0.10 disutility compared with hyper-CVAD before the maintenance phase of treatment. Total life-years and quality-adjusted life-years (QALYs) were compared between treatment protocols at 1, 5, and 10 years, with additional probabilistic sensitivity analyses. Results: Treatment with the pediatric-inspired protocol was associated with a 0.04 increase in life-years, but a 0.01 decrease in QALYs at 1 year. By years 5 and 10, the pediatric-inspired protocol resulted in 0.18 and 0.24 increase in life-years and 0.25 and 0.32 increase in QALYs, respectively, relative to hyper-CVAD. The lower quality of life associated with the induction and intensification phases of pediatric treatment was offset by more favorable progression-free survival and overall survival relative to hyper-CVAD. Conclusions: Our exploratory analysis suggests that, compared with hyper-CVAD, pediatric-inspired protocols may increase life-years throughout treatment stages and QALYs in the long term. PMID:27779442

  14. Protracted Administration of L-Asparaginase in Maintenance Phase Is the Risk Factor for Hyperglycemia in Older Patients with Pediatric Acute Lymphoblastic Leukemia.

    PubMed

    Yoshida, Hideki; Imamura, Toshihiko; Saito, Akiko M; Takahashi, Yoshihiro; Suenobu, So-ichi; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Kawasaki, Hirohide; Endo, Mikiya; Hori, Hiroki; Suzuki, Nobuhiro; Kosaka, Yoshiyuki; Kato, Koji; Yumura-Yagi, Keiko; Hara, Junichi; Oda, Megumi; Sato, Atsushi; Horibe, Keizo

    2015-01-01

    Although L-asparaginase related hyperglycemia is well known adverse event, it is not studied whether the profile of this adverse event is affected by intensification of L-asparaginase administration. Here, we analyzed the profile of L-asparaginase related hyperglycemia in a 1,176 patients with pediatric acute lymphoblastic leukemia treated according to the Japan Association of Childhood Leukemia Study ALL-02 protocol using protracted L-asparaginase administration in maintenance phase. We determined that a total of 75 L-asparaginase related hyperglycemia events occurred in 69 patients. Although 17 events (17/1176, 1.4%) developed in induction phase, which was lower incidence than those (10-15%) in previous reports, 45 events developed during the maintenance phase with protracted L-asparaginase administration. Multivariate analysis showed that older age at onset (≥ 10 years) was a sole independent risk factor for L-asparaginase-related hyperglycemia (P<0.01), especially in maintenance phase. Contrary to the previous reports, obesity was not associated with L-asparaginase-related hyperglycemia. These findings suggest that protracted administration of L-asparaginase is the risk factor for hyperglycemia when treating adolescent and young adult acute lymphoblastic leukemia patients.

  15. Prevalence and Predictors of Overweight and Obesity Among a Multiethnic Population of Pediatric Acute Lymphoblastic Leukemia Survivors: A Cross-Sectional Assessment.

    PubMed

    Brown, Austin L; Lupo, Philip J; Danysh, Heather E; Okcu, Mehmet F; Scheurer, Michael E; Kamdar, Kala Y

    2016-08-01

    As previous studies of obesity in survivors of pediatric acute lymphoblastic leukemia (ALL) have primarily been conducted among non-Hispanic white survivors or children treated on older protocols, our objective was to describe the prevalence and correlates of overweight status among an ethnically diverse population of pediatric ALL survivors, largely treated with more contemporary therapies. We evaluated the overweight/obesity status of pediatric ALL survivors (n=406) followed in the Texas Children's Cancer Center between 2004 and 2014. Survivors were classified as underweight, normal weight, overweight, or obese on the basis of their body mass index at their most current follow-up visit. Our results showed that Hispanic ethnicity (39% of the subjects) was associated with being overweight (adjusted odds ratio=1.88; 95% confidence interval, 1.13-3.14) or obese (adjusted odds ratio=2.84; 95% confidence interval, 1.59-5.06) at follow-up, even after adjusting for cranial radiotherapy (CRT) exposure. Body mass index z-score at diagnosis was also associated with overweight/obesity at follow-up. In addition, there was a statistically significant interaction between younger age at diagnosis and CRT, indicating that younger age at diagnosis was associated with obesity among patients who received CRT. These findings may help identify pediatric ALL patients that are at increased risk of being overweight or obese after treatment.

  16. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study

    PubMed Central

    Klusmann, Jan-Henning; Reinhardt, Dirk; Zimmermann, Martin; Kremens, Bernhard; Vormoor, Josef; Dworzak, Michael; Creutzig, Ursula; Klingebiel, Thomas

    2012-01-01

    the remainder of the pediatric high-risk acute myeloid leukemia patients the prognosis was not improved by allogeneic stem cell transplantation, which was, however, associated with a higher rate of late sequelae. PMID:21933851

  17. Acute Myeloid Leukemia (AML) (For Parents)

    MedlinePlus

    ... Your 1- to 2-Year-Old Acute Myeloid Leukemia (AML) KidsHealth > For Parents > Acute Myeloid Leukemia (AML) ... Treatment Coping en español Leucemia mieloide aguda About Leukemia Leukemia is a type of cancer that affects ...

  18. Twenty years of unrelated donor bone marrow transplantation for pediatric acute leukemia facilitated by the National Marrow Donor Program.

    PubMed

    MacMillan, Margaret L; Davies, Stella M; Nelson, Gene O; Chitphakdithai, Pintip; Confer, Dennis L; King, Roberta J; Kernan, Nancy A

    2008-09-01

    The National Marrow Donor Program (NMDP) has facilitated unrelated donor hematopoietic cell transplants for more than 20 years. In this time period, there have been many changes in clinical practice, including improvements in HLA typing and supportive care, and changes in the source of stem cells. Availability of banked unrelated donor cord blood (incorporated into the NMDP registry in 2000) as a source of stem cells has become an important option for children with leukemia, offering the advantages of immediate availability for children with high-risk disease, the need for a lesser degree of HLA match, and expanding access for those with infrequent HLA haplotypes. Overall survival (OS) in children with acute leukemia transplanted with unrelated donor bone marrow (BM) is markedly better in more recent years, largely attributable to less treatment-related mortality (TRM). Within this cohort, 2-year survival was markedly better for patients with acute lymphoblastic leukemia (ALL) in first complete response (CR1) (74%) versus second complete response (CR2) (62%) or more advanced disease (33%). Similar findings are observed with patients with AML, suggesting earlier referral to bone marrow transplant (BMT) is optimal for survival. Notably, this improvement over time was not observed in unmodified peripheral blood stem cell (PBSC) recipients, suggesting unmodified PBSC may not be the optimal stem cell source for children.

  19. Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling.

    PubMed

    Weston, Victoria J; Austen, Belinda; Wei, Wenbin; Marston, Eliot; Alvi, Azra; Lawson, Sarah; Darbyshire, Philip J; Griffiths, Mike; Hill, Frank; Mann, Jill R; Moss, Paul A H; Taylor, A Malcolm R; Stankovic, Tatjana

    2004-09-01

    To investigate possible causes of the variable response to treatment in pediatric B-precursor acute lymphoblastic leukemia (ALL) and to establish potential novel therapeutic targets, we used ionizing radiation (IR) exposure as a model of DNA damage formation to identify tumors with resistance to p53-dependent apoptosis. Twenty-one of 40 ALL tumors responded normally to IR, exhibiting accumulation of p53 and p21 proteins and cleavage of caspases 3, 7, and 9 and of PARP1. Nineteen tumors exhibited apoptotic resistance and lacked PARP1 and caspase cleavage; although 15 of these tumors had normal accumulation of p53 and p21 proteins, examples exhibited abnormal expression of TRAF5, TRAF6, and cIAP1 after IR, suggesting increased NF-kappaB prosurvival signaling as the mechanism of apoptotic resistance. The presence of a hyperactive PARP1 mutation in one tumor was consistent with such increased NF-kappaB activity. PARP1 inhibition restored p53-dependent apoptosis after IR in these leukemias by reducing NF-kappaB DNA binding and transcriptional activity. In the remaining 4 ALL tumors, apoptotic resistance was associated with a TP53 mutation or with defective activation of p53. We conclude that increased NF-kappaB prosurvival signaling is a frequent mechanism by which B-precursor ALL tumors develop apoptotic resistance to IR and that PARP1 inhibition may improve the DNA damage response of these leukemias.

  20. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  1. Blood Spotlight on iAMP21 acute lymphoblastic leukemia (ALL), a high-risk pediatric disease.

    PubMed

    Harrison, Christine J

    2015-02-26

    Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia. Breakage-fusion-bridge cycles followed by chromothripsis and other complex structural rearrangements of chromosome 21 underlie the mechanism giving rise to iAMP21. Patients with iAMP21 are older (median age 9 years), with a low white cell count. They have a high relapse rate when treated as standard risk. Recent studies have shown improved outcome on intensive therapy. Molecular targets for therapy are being sought.

  2. GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

    PubMed

    Mosaad, Youssef M; Elashery, Rasha; Darwish, Ahmad; Sharaf Eldein, Omar A; Barakat, Tarek; Marouf, Samy; Abou El-Khier, Noha T; Youssef, Laila F; Fawzy, Iman M

    2017-03-01

    To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

  3. IKZF1 deletion is an independent predictor of outcome in pediatric acute lymphoblastic leukemia treated according to the ALL-BFM 2000 protocol.

    PubMed

    Dörge, Petra; Meissner, Barbara; Zimmermann, Martin; Möricke, Anja; Schrauder, André; Bouquin, Jean-Pierre; Schewe, Denis; Harbott, Jochen; Teigler-Schlegel, Andrea; Ratei, Richard; Ludwig, Wolf-Dieter; Koehler, Rolf; Bartram, Claus R; Schrappe, Martin; Stanulla, Martin; Cario, Gunnar

    2013-03-01

    IKZF1 gene deletions have been associated with a poor outcome in pediatric precursor B-cell acute lymphoblastic leukemia. To assess the prognostic relevance of IKZF1 deletions for patients treated on Berlin-Frankfurt-Münster Study Group trial ALL-BFM 2000, we screened 694 diagnostic acute lymphoblastic leukemia samples by Multiplex Ligation-dependent Probe Amplification. Patients whose leukemic cells bore IKZF1 deletions had a lower 5-year event-free survival (0.69±0.05 vs. 0.85±0.01; P<0.0001) compared to those without, mainly due to a higher cumulative incidence of relapses (0.21±0.04 vs. 0.10±0.01; P=0.001). Although IKZF1 deletions were significantly associated with the P2RY8-CRLF2 rearrangement, their prognostic value was found to be independent from this association. Thus, IKZF1 deletion is an independent predictor of treatment outcome and a strong candidate marker for integration in future treatment stratification strategies on ALL-BFM protocols. Clinicaltrials.gov identifier: NCT00430118.

  4. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2017-02-20

    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); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  5. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  6. The Role of Histone Protein Modifications and Mutations in Histone Modifiers in Pediatric B-Cell Progenitor Acute Lymphoblastic Leukemia

    PubMed Central

    Janczar, Szymon; Janczar, Karolina; Pastorczak, Agata; Harb, Hani; Paige, Adam J. W.; Zalewska-Szewczyk, Beata; Danilewicz, Marian; Mlynarski, Wojciech

    2017-01-01

    While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable. In B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) there is a relative paucity of reports on the role of histone protein modifications (acetylation, methylation, phosphorylation) as compared to acute myeloid leukemia, T-cell ALL, or other hematologic cancers, and in this setting chromatin modifications are relatively less well studied and reviewed than DNA methylation. In this paper, we discuss the biomarker associations and evidence for a driver role of dysregulated global and loci-specific histone marks, as well as mutations in epigenetic modifiers in BCP-ALL. Examples of chromatin modifiers recurrently mutated/disrupted in BCP-ALL and associated with disease outcomes include MLL1, CREBBP, NSD2, and SETD2. Altered histone marks and histone modifiers and readers may play a particular role in disease chemoresistance and relapse. We also suggest that epigenetic regulation of B-cell differentiation may have parallel roles in leukemogenesis. PMID:28054944

  7. IL-7 Receptor Mutations and Steroid Resistance in Pediatric T cell Acute Lymphoblastic Leukemia: A Genome Sequencing Study

    PubMed Central

    Stubbs, Andrew P.; Vroegindeweij, Eric M.; Smits, Willem K.; van Marion, Ronald; Dinjens, Winand N. M.; Horstmann, Martin; Kuiper, Roland P.; Zaman, Guido J. R.; van der Spek, Peter J.; Pieters, Rob; Meijerink, Jules P. P.

    2016-01-01

    Background Pediatric acute lymphoblastic leukemia (ALL) is the most common childhood cancer and the leading cause of cancer-related mortality in children. T cell ALL (T-ALL) represents about 15% of pediatric ALL cases and is considered a high-risk disease. T-ALL is often associated with resistance to treatment, including steroids, which are currently the cornerstone for treating ALL; moreover, initial steroid response strongly predicts survival and cure. However, the cellular mechanisms underlying steroid resistance in T-ALL patients are poorly understood. In this study, we combined various genomic datasets in order to identify candidate genetic mechanisms underlying steroid resistance in children undergoing T-ALL treatment. Methods and Findings We performed whole genome sequencing on paired pre-treatment (diagnostic) and post-treatment (remission) samples from 13 patients, and targeted exome sequencing of pre-treatment samples from 69 additional T-ALL patients. We then integrated mutation data with copy number data for 151 mutated genes, and this integrated dataset was tested for associations of mutations with clinical outcomes and in vitro drug response. Our analysis revealed that mutations in JAK1 and KRAS, two genes encoding components of the interleukin 7 receptor (IL7R) signaling pathway, were associated with steroid resistance and poor outcome. We then sequenced JAK1, KRAS, and other genes in this pathway, including IL7R, JAK3, NF1, NRAS, and AKT, in these 69 T-ALL patients and a further 77 T-ALL patients. We identified mutations in 32% (47/146) of patients, the majority of whom had a specific T-ALL subtype (early thymic progenitor ALL or TLX). Based on the outcomes of these patients and their prednisolone responsiveness measured in vitro, we then confirmed that these mutations were associated with both steroid resistance and poor outcome. To explore how these mutations in IL7R signaling pathway genes cause steroid resistance and subsequent poor outcome, we

  8. [Successful treatment of a persistent rhino-cerebral mucormycosis in a pediatric patient with a debut of acute lymphoblastic leukemia].

    PubMed

    Cofré, Fernanda; Villarroel, Milena; Castellón, Loreto; Santolaya, María E

    2015-08-01

    The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.

  9. Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia

    PubMed Central

    Salina, Thais Ditolvo da Costa; Ferreira, Yvelise Antunes; Alves, Eliana Brasil; Ferreira, Cristina Motta; De Paula, Erich Vinícius; Mira, Marcelo Távora; Passos, Leny da Mota

    2016-01-01

    Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols. PMID:27526794

  10. Acute Appendicitis in Patients with Acute Leukemia

    PubMed Central

    Kim, Ki Up; Kim, Jin Kyeung; Won, Jong Ho; Hong, Dae Sik; Park, Hee Sook; Park, Kyeung Kyu

    1993-01-01

    The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids. Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia. PMID:8268146

  11. Toxicity profile of repeated doses of PEG-asparaginase incorporated into a pediatric-type regimen for adult acute lymphoblastic leukemia.

    PubMed

    Aldoss, Ibrahim; Douer, Dan; Behrendt, Carolyn E; Chaudhary, Preeti; Mohrbacher, Ann; Vrona, Janice; Pullarkat, Vinod

    2016-04-01

    Despite having been long regarded as too toxic for adult patients, pediatric-like regimens containing L-asparaginase have resulted in improved outcomes for adults with acute lymphoblastic leukemia (ALL). To characterize the spectrum of toxicity of repeated doses of polyethylene glycolated-asparaginase (PEG-asp) in adults, we reviewed all doses (2000 IU/m(2) ) administered as part of a pediatric-inspired regimen in adult ALL at our center. Subjects aged 18-60 yr with ALL (n = 152, 69.1% male) contributed 522 dose cycles to the study. Hepatotoxicity was the most common adverse event: grades 3-4 transaminitis and hyperbilirubinemia occurred in 53.9% and 23.7% of subjects, respectively. Hepatotoxicity was reversible; no cases of fulminate hepatic failure were observed. Other toxicities affecting at least 5% of subjects were grades 3-4 triglyceridemia in 50.9%, hypofibrinogenemia (<100 mg/dL) in 47.9%, clinical pancreatitis in 12.6%, venous thromboembolism in 11.2%, allergic reaction in 7.2%, and any grade bleeding in 5.3%. PEG-asp was always discontinued after grades 3-4 pancreatitis or allergic reaction. Otherwise, toxicities did not preclude administration of additional cycles of the drug. Our results suggest that repeated PEG-asp dosing is safe in adults aged 18-60 yr, even after occurrence of a drug-related toxicity.

  12. Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group.

    PubMed

    Hayakawa, F; Sakura, T; Yujiri, T; Kondo, E; Fujimaki, K; Sasaki, O; Miyatake, J; Handa, H; Ueda, Y; Aoyama, Y; Takada, S; Tanaka, Y; Usui, N; Miyawaki, S; Suenobu, S; Horibe, K; Kiyoi, H; Ohnishi, K; Miyazaki, Y; Ohtake, S; Kobayashi, Y; Matsuo, K; Naoe, T

    2014-10-17

    The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR-ABL-negative ALL. Patients aged 15-24 years (n=139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58-75%) and 73% (95% CI 64-80%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, P<0.001). These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR-ABL-negative ALL.

  13. Antibiotic prophylaxis with teicoplanin on alternate days reduces rate of viridans sepsis and febrile neutropenia in pediatric patients with acute myeloid leukemia.

    PubMed

    Boztug, Heidrun; Mühlegger, Nora; Pötschger, Ulrike; Attarbaschi, Andishe; Peters, Christina; Mann, Georg; Dworzak, Michael

    2017-01-01

    Intensive chemotherapy directed against acute myeloid leukemia of childhood is followed by profound neutropenia and high risk for bacterial and fungal infections, including viridans group streptococci as a common cause for gram-positive septicemia. Few retrospective studies have shown the efficacy of various antibiotic prophylactic regimens in children. We retrospectively studied 50 pediatric patients treated on the AML-BFM 2004 protocol between 2005 and 2015 at St. Anna Children's Hospital and assessed the effect of antibiotic prophylaxis on the frequency of febrile neutropenia and bacterial sepsis. Fifty pediatric patients underwent 199 evaluable chemotherapy cycles. Viridans sepsis occurred after none of 98 cycles with prophylactic administration of teicoplanin/vancomycin in comparison to 12 cases of viridans sepsis among 79 cycles without systemic antibacterial prophylaxis (0 vs. 15 %, p < 0.0001). In addition, there were significantly fewer episodes of febrile neutropenia in the teicoplanin/vancomycin group (44 % vs. no prophylaxis 82 %, p < 0.0001). Severity of infection seemed to be worse when no antibiotic prophylaxis had been administered with a higher rate of intensive care unit treatment (0/98, 0 %, vs. 4/79, 5 %, p = 0.038). So far, no increase of vancomycin-resistant enterococcus isolates in surveillance cultures was noticed. Antibiotic prophylaxis with teicoplanin (or vancomycin) appears safe and feasible and resulted in eradication of viridans sepsis and decreased incidence of febrile neutropenia in pediatric AML patients. The possibility to administer teicoplanin on alternate days on an outpatient basis or at home could contribute to patient's quality of life and decrease health care costs.

  14. Biological, Functional and Genetic Characterization of Bone Marrow-Derived Mesenchymal Stromal Cells from Pediatric Patients Affected by Acute Lymphoblastic Leukemia

    PubMed Central

    Conforti, Antonella; Biagini, Simone; Del Bufalo, Francesca; Sirleto, Pietro; Angioni, Adriano; Starc, Nadia; Li Pira, Giuseppina; Moretta, Francesca; Proia, Alessandra; Contoli, Benedetta; Genovese, Silvia; Ciardi, Claudia; Avanzini, Maria Antonietta; Rosti, Vittorio; Lo-Coco, Francesco; Locatelli, Franco; Bernardo, Maria Ester

    2013-01-01

    Alterations in hematopoietic microenvironment of acute lymphoblastic leukemia patients have been claimed to occur, but little is known about the components of marrow stroma in these patients. In this study, we characterized mesenchymal stromal cells (MSCs) isolated from bone marrow (BM) of 45 pediatric patients with acute lymphoblastic leukemia (ALL-MSCs) at diagnosis (day+0) and during chemotherapy treatment (days: +15; +33; +78), the time points being chosen according to the schedule of BM aspirates required by the AIEOP-BFM ALL 2009 treatment protocol. Morphology, proliferative capacity, immunophenotype, differentiation potential, immunomodulatory properties and ability to support long-term hematopoiesis of ALL-MSCs were analysed and compared with those from 41 healthy donors (HD-MSCs). ALL-MSCs were also genetically characterized through array-CGH, conventional karyotyping and FISH analysis. Moreover, we compared ALL-MSCs generated at day+0 with those isolated during chemotherapy. Morphology, immunophenotype, differentiation potential and in vitro life-span did not differ between ALL-MSCs and HD-MSCs. ALL-MSCs showed significantly lower proliferative capacity (p<0.001) and ability to support in vitro hematopoiesis (p = 0.04) as compared with HD-MSCs, while they had similar capacity to inhibit in vitro mitogen-induced T-cell proliferation (p = N.S.). ALL-MSCs showed neither the typical translocations carried by the leukemic clone (when present), nor other genetic abnormalities acquired during ex vivo culture. Our findings indicate that ALL-MSCs display reduced ability to proliferate and to support long-term hematopoiesis in vitro. ALL-MSCs isolated at diagnosis do not differ from those obtained during treatment. PMID:24244271

  15. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Treatment of Children with APL (Acute Promyelocytic Leukemia)

    MedlinePlus

    ... Childhood Leukemia Treatment of Children With Acute Promyelocytic Leukemia (APL) Treatment of acute promyelocytic leukemia (APL), the ... With Chronic Myelogenous Leukemia (CML) More In Childhood Leukemia About Childhood Leukemia Causes, Risk Factors, and Prevention ...

  17. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. What Are the Key Statistics about Acute Myeloid Leukemia?

    MedlinePlus

    ... What Are the Key Statistics About Acute Myeloid Leukemia? The American Cancer Society’s estimates for leukemia in ... Leukemia Research and Treatment? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...

  19. Pharmacogenetics of childhood acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, Elixabet; Gutierrez-Camino, Angela; Bilbao-Aldaiturriaga, Nerea; Pombar-Gomez, Maria; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2014-07-01

    Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients for which therapy fails while some patients experience severe toxicity. In the last few years, several pharmacogenetic studies have been performed to search for markers of outcome and toxicity in pediatric ALL. However, to date, TPMT is the only pharmacogenetic marker in ALL with clinical guidelines for drug dosing. In this article, we will provide an overview of the most important findings carried out in pharmacogenetics for pediatric ALL, such as the interest drawn by methotrexate transporters in the context of methotrexate treatment. Even if most of the studies are centered on coding genes, we will also point to new approaches focusing on noncoding regions and epigenetic variation that could be interesting for consideration in the near future.

  20. Acute Myeloid Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  1. Poor outcome in a pediatric patient with acute myeloid leukemia associated with a variant t(8;21) and trisomy 6.

    PubMed

    Kelly, Michael J; Meloni-Ehrig, Aurelia M; Manley, Peter E; Altura, Rachel A

    2009-02-01

    RUNX1T1/RUNX1 (formerly ETO/AML1) is a molecular marker that is usually associated with a favorable outcome in both pediatric and adult patients with acute myeloid leukemia (AML). We describe a 10-year-old girl with AML associated with an RUNX1T1/RUNX1 fusion. The patient's karyotype at the time of diagnosis was 46,X,-X,t(4;21;8)(q25;q22;q22),+6. She had an early relapse while being treated on a standard protocol and had significant difficulty in attaining a second remission. She subsequently underwent a matched related donor bone marrow transplant, but a second bone marrow relapse with extensive extramedullary disease followed on day +199. Cytogenetic analysis at second relapse showed evidence of clonal evolution in the form of a highly complex karyotype with numeric and structural abnormalities in addition to the t(4;21;8) and trisomy 6 detected in the diagnostic sample. Trisomy 6 is an uncommon cytogenetic abnormality in myeloid diseases. As a sole abnormality, it has been associated mainly with myelodysplastic syndrome and AML. The presence of this novel variant of t(8;21)(q22;q22) associated with trisomy 6 may have abrogated the usual favorable prognosis associated with RUNX1T1/RUNX1 in AML.

  2. Plasma homocysteine, methionine and S-adenosylhomocysteine levels following high-dose methotrexate treatment in pediatric patients with acute lymphoblastic leukemia or Burkitt lymphoma: association with hepatotoxicity.

    PubMed

    Kubota, Masaru; Nakata, Rieko; Adachi, Souichi; Watanabe, Ken-Ichiro; Heike, Toshio; Takeshita, Yasufumi; Shima, Midori

    2014-07-01

    This study aimed to investigate: (i) changes of plasma homocysteine, methionine and S-adenosylhomocysteine levels following high-dose methotrexate (HD-MTX) treatment and (ii) the correlation of these sulfur-containing amino acids with MTX-induced hepatotoxicity. Fifteen pediatric patients with acute lymphoblastic leukemia and one patient with Burkitt lymphoma, with a total of 26 treatment courses of HD-MTX, were enrolled. Homocysteine levels increased at 24 h after HD-MTX treatment, and showed marginal decreases at 48 and 72 h. Methionine levels showed a biphasic pattern, i.e. an initial decrease at 24 h followed by increases at 48 and 72 h. S-adenosylhomocysteine exhibited a marginal decrease at 24 h. Changes of homocysteine exhibited significant correlation only with a maximum increase of alanine aminotransferase or total bilirubin from baseline. This study has demonstrated, for the first time, simultaneous changes of plasma homocysteine, methionine and S-adenosylhomocysteine following HD-MTX. The potential of homocysteine as a marker of hepatotoxicity is also presented.

  3. Potentially life-threatening coagulopathy associated with simultaneous reduction in coagulation and fibrinolytic function in pediatric acute leukemia after hematopoietic stem-cell transplantation.

    PubMed

    Ishihara, Takashi; Nogami, Keiji; Matsumoto, Tomoko; Nomura, Akitaka; Takeshita, Yasufumi; Ochi, Satoshi; Shima, Midori

    2017-03-16

    The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma. In the SOS case, the ratios of T-EP and P-Peak to normal were simultaneously decreased at four weeks post-HSCT (Pre; ~1.1/1.1-1.4, Week+4; 0.14/0.0084, respectively). Similarly, in the TMA patient, both ratios were decreased at 3 weeks and recovered after 8 weeks (Pre; 1.2/~0.95, Week+3; 0.59/0.22, Week+8; 1.2/0.64-0.85). In the other patients, when SOS/TMA was not evident, the T/P-GA data remained within normal limits. These findings suggest that the simultaneous reduction of coagulation and fibrinolytic function in patients developing SOS/TMA can lead to a life-threatening coagulopathy. Further research is warranted to clarify global hemostatic function after HSCT to establish optimal supportive therapy for these critical clinical disorders of hemostasis.

  4. Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes

    PubMed Central

    Lindqvist, C. Mårten; Lundmark, Anders; Nordlund, Jessica; Freyhult, Eva; Ekman, Diana; Almlöf, Jonas Carlsson; Raine, Amanda; Övernäs, Elin; Abrahamsson, Jonas; Frost, Britt-Marie; Grandér, Dan; Heyman, Mats; Palle, Josefine; Forestier, Erik; Lönnerholm, Gudmar

    2016-01-01

    To characterize the mutational patterns of acute lymphoblastic leukemia (ALL) we performed deep next generation sequencing of 872 cancer genes in 172 diagnostic and 24 relapse samples from 172 pediatric ALL patients. We found an overall greater mutational burden and more driver mutations in T-cell ALL (T-ALL) patients compared to B-cell precursor ALL (BCP-ALL) patients. In addition, the majority of the mutations in T-ALL had occurred in the original leukemic clone, while most of the mutations in BCP-ALL were subclonal. BCP-ALL patients carrying any of the recurrent translocations ETV6-RUNX1, BCR-ABL or TCF3-PBX1 harbored few mutations in driver genes compared to other BCP-ALL patients. Specifically in BCP-ALL, we identified ATRX as a novel putative driver gene and uncovered an association between somatic mutations in the Notch signaling pathway at ALL diagnosis and increased risk of relapse. Furthermore, we identified EP300, ARID1A and SH2B3 as relapse-associated genes. The genes highlighted in our study were frequently involved in epigenetic regulation, associated with germline susceptibility to ALL, and present in minor subclones at diagnosis that became dominant at relapse. We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency. PMID:27590521

  5. Effect of the Polymorphism of Folylpolyglutamate Synthetase on Treatment of High-Dose Methotrexate in Pediatric Patients with Acute Lymphocytic Leukemia

    PubMed Central

    Huang, Zhen; Tong, Hong-Fei; Li, Yuan; Qian, Jiang-Chao; Wang, Ju-Xiang; Wang, Zhe; Ruan, Ji-Chen

    2016-01-01

    Background The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. Material/Methods 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment. Overall survival was analyzed by Kaplan-Meier method. Results No differences were observed between patients and controls regarding the distribution frequency of genotype and alleles of rs1544105. Patients carrying AA genotype had a significantly higher plasma concentration of MTX after 24 h than those carrying GG or GA (P<0.05) and no differences were found after 44 h. Kaplan-Meier survival analysis showed a longer median survival time in patients with AA than other genotypes with significant difference in overall survival. Conclusions Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX. PMID:27987364

  6. Newly Diagnosed Acute Promyelocytic Leukemia

    PubMed Central

    Avvisati, Giuseppe

    2011-01-01

    Acute promyelocytic leukemia (APL) represents a medical emergency with a high rate of early mortality. As a consequence, as soon as the diagnosis is suspected based upon cytologic criteria, it is necessary to start all- trans retinoic acid (ATRA) treatment without delay. For patients with newly diagnosed APL, induction therapy with ATRA plus anthracycline based chemotherapy is recommended. At present the combination of arsenic trioxide plus ATRA should be considered for patients who are not candidates for anthracycline-based therapy. For pediatric and adult patients with APL aged < 60 years who achieve a CR with induction, I recommend 3 intensive courses of consolidation chemotherapy associated to ATRA, targeted on the basis of the risk group at diagnosis. In patients treated with a very intensive consolidation chemotherapy maintenance treatment can be omitted. However If a maintenance treatment has to be adopted I suggest the use of intermittent ATRA for 15 days every 3 months for a period of 2 years, rather than ATRA associated to chemotherapy. Moreover, taking into account the medical literature, a reduced dosage of ATRA ( 25 mg/m2) in pediatric patients and a consolidation chemotherapy of reduced intensity in elderly patients is recommended. Furthermore, in order to maximize survival, careful attention should be reserved to the coagulopathy and to the appearance of the differentiation syndrome. Finally, PCR for the PML/RARA fusion gene on a bone marrow specimen every three months for two years, and then every six months for additional three years are needed during the follow-up. PMID:22220261

  7. The contributions of the European Medicines Agency and its pediatric committee to the fight against childhood leukemia

    PubMed Central

    Rose, Klaus; Walson, Philip D

    2015-01-01

    Background Although the diagnosis of childhood leukemia is no longer a death sentence, too many patients still die, more with acute myeloid leukemia than with acute lymphoblastic leukemia. The European Union pediatric legislation was introduced to improve pharmaceutical treatment of children, but some question whether the European Medicines Agency (EMA) approach is helping children with leukemia. Some have even suggested that the decisions of EMA pediatric committee (PDCO) are counterproductive. This study was designed to investigate the impact of PDCO-issued pediatric investigation plans (PIPs) for leukemia drugs. Methods All PIPs listed under “oncology” were downloaded from the EMA website. Non-leukemia decisions including misclassifications, waivers (no PIP), and solid tumors were discarded. The leukemia decisions were analyzed, compared to pediatric leukemia trials in the database http://www.clinicaltrials.gov, and discussed in the light of current literature. Results The PDCO leukemia decisions demand clinical trials in pediatric leukemia for all new adult drugs without prioritization. However, because leukemia in children is different and much rarer than in adults, these decisions have resulted in proposed studies that are scientifically and ethically questionable. They are also unnecessary, since once promising new compounds are approved for adults, more appropriate, prioritized pediatric leukemia trials are initiated worldwide without PDCO involvement. Conclusion EMA/PDCO leukemia PIPs do little to advance the treatment of childhood leukemia. The unintended negative effects of the flawed EMA/PDCO’s standardized requesting of non-prioritized testing of every new adult leukemia drug in children with relapsed or refractory disease expose these children to questionable trials, and could undermine public trust in pediatric clinical research. Institutions, investigators, and ethics committees/institutional review boards need to be skeptical of trials

  8. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  9. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  10. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-18

    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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    ClinicalTrials.gov

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. E2A-PBX1 exhibited a promising prognosis in pediatric acute lymphoblastic leukemia treated with the CCLG-ALL2008 protocol

    PubMed Central

    Hu, Yixin; He, Hailong; Lu, Jun; Wang, Yi; Xiao, Peifang; Li, Jianqin; Li, Jie; Sun, Yina; Lv, Hui; Fan, Junjie; Yao, Yanhua; Chai, Yihuan; Hu, Shaoyan

    2016-01-01

    Objective The objective of this study was to observe the prognosis of pediatric patients with E2A-PBX1-positive acute lymphoblastic leukemia (ALL) from the treatment with the CCLG-ALL2008 protocol. Design and methods Three hundred and forty-nine Chinese pediatric patients with pre-B-cell ALL were enrolled in this study from December 2008 to September 2013. Of these, 20 patients with E2A-PBX1 expression and 223 without the gene expression were stratified into two cohorts. Clinical and biological characteristics and 5-year event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS) were analyzed and compared between these two groups. Results The E2A-PBX1 fusion transcript was detected in 20 of 349 (5.7%) patients. Compared with the gene-negative subgroup, patients with E2A-PBX1 were younger in age but did not show significant differences in white blood cell (WBC) count or gender distribution at primary diagnosis. Moreover, there were more inferior karyotypes detected in the E2A-PBX1 subgroup (P=0.035). With the CCLG-ALL2008 treatment protocol, patients with E2A-PBX1 showed a favorable treatment response with lower minimal residual disease (MRD) levels (<10−4) at time point 1 (TP1, P=0.039) but no superior steroid response or histological remission. We also observed a promising survival outcome, with a 5-year EFS reaching 95.0%±4.9% versus 66.3%±3.9% in the gene-negative group (P=0.039). However, we did not find significant differences in RFS (P=0.061) and OS (P=0.113). Conclusion Our data provided clinical observation of Chinese pediatric patients. Patients with E2A-PBX1-positive ALL benefited well from the CCLG-ALL2008 protocol, a risk-based intensified treatment trial, with lower levels of MRD and longer RFS duration though they had no favorable characteristics at primary diagnosis. PMID:27920559

  14. How Is Acute Myeloid Leukemia Diagnosed?

    MedlinePlus

    ... Detection, Diagnosis, and Types How Is Acute Myeloid Leukemia Diagnosed? Certain signs and symptoms might suggest that ... of samples used to test for acute myeloid leukemia If signs and symptoms and/or the results ...

  15. PROGRESS IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

    2014-01-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

  16. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-02-13

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  17. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  19. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) Print A A A What's in this article? ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  20. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) A A A What's in this article? About ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  1. [Transformation of myelodysplastic syndrome to acute lymphoblastic leukemia: 2 new cases].

    PubMed

    Guillén, M; Madero, L; Parra, L; Hernández, C; Herrero, B; Carceller, F; Lassaletta, A; Sevilla, J

    2013-06-01

    Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells, with a variable risk of transformation to acute myeloid leukemia. Progression into acute lymphoblastic leukemia (ALL) is an extremely rare event, with very few cases published in children. In this report, we describe two cases of myelodysplastic syndromes that progressed to ALL. Moreover, we review previously reported cases of MDS transformation to acute lymphoblastic leukemia in the pediatric population whose prognosis seems to be similar to that for adults.

  2. Acute myeloid leukemia

    MedlinePlus

    ... types of leukemia, including AML: Blood disorders, including polycythemia vera , essential thrombocythemia , and myelodysplasia Certain chemicals (for ... More Anemia Bone marrow transplant Chemotherapy Immunodeficiency disorders Polycythemia vera Patient Instructions Bone marrow transplant - discharge Review ...

  3. A health-care system perspective on implementing genomic medicine: pediatric acute lymphoblastic leukemia as a paradigm.

    PubMed

    Evans, W E; Crews, K R; Pui, C-H

    2013-08-01

    The promise of genomic medicine has received great attention over the past decade, projecting how genomics will soon guide the prevention, diagnosis, and treatment of human diseases. However, this evolution has been slower than forecast, even where evidence is often strong (e.g., pharmacogenomics). Reasons include the requirement for institutional resources and the need for the will to push beyond barriers impeding health-care changes. Here, we illustrate how genomics has been deployed to advance the treatment of childhood leukemia.

  4. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-08

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  5. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2016-11-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  6. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-03-14

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  7. Acute lymphocytic leukemia (ALL)

    MedlinePlus

    ... made. Life-threatening symptoms can occur as normal blood counts drop. Causes Most of the time, no clear cause can be found for ALL. The following factors may play a role in the development of all types of leukemia: Certain chromosome problems Exposure to radiation, ...

  8. Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation for relapsed/refractory pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia without posttransplant tyrosine kinase inhibitor therapy.

    PubMed

    Sano, Hideki; Mochizuki, Kazuhiro; Akaihata, Mitsuko; Kobayashi, Shogo; Ohto, Hitoshi; Kikuta, Atsushi

    2017-03-01

    Intensive chemotherapy with tyrosine kinase inhibitor (TKI) improves the prognosis of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-ALL). However, the prognosis of cases of relapsed or refractory Ph-ALL remains poor. Here, we aimed to assess the efficacy of T-cell-rich HLA-haploidentical hematopoietic stem cell transplantation (TCR-haplo-HSCT) in eight patients with relapsed or refractory pediatric Ph-ALL. Transplant-related mortality was observed in two patients. All patients discontinued TKI after receiving TCR-haplo-HSCT. The 3-year probability of overall survival and event-free survival was 75.0 and 62.5%, respectively. These results indicate the efficacy of TCR-haplo-HSCT for relapsed/refractory pediatric Ph-ALL.

  10. Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. How Is Acute Lymphocytic Leukemia Diagnosed?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Diagnosed? Certain signs and symptoms can suggest that ... described below. Tests used to diagnose and classify ALL If your doctor thinks you have leukemia, he ...

  12. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  13. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  14. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-30

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-04-05

    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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-03-22

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Cellular Diagnosis, Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    ClinicalTrials.gov

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  18. Integrative computational in-depth analysis of dysregulated miRNA-mRNA interactions in drug-resistant pediatric acute lymphoblastic leukemia cells: an attempt to obtain new potential gene-miRNA pathways involved in response to treatment.

    PubMed

    Mesrian Tanha, Hamzeh; Mojtabavi Naeini, Marjan; Rahgozar, Soheila; Moafi, Alireza; Honardoost, Mohammad Amin

    2016-06-01

    Acute lymphoblastic leukemia (ALL) is the major neoplasia type among children. Despite the tremendous success of current treatment strategies, drug resistance still remains a major cause of chemotherapy failure and relapse in pediatric patients. Overwhelming evidence illustrates that microRNAs (miRNAs) act as post-transcriptional regulators of drug-resistance-related genes. The current study was aimed at how dysregulated miRNA-mRNA-signaling pathway interaction networks mediate resistance to four commonly used chemotherapy agents in pediatric ALL, including asparaginase, daunorubicin, prednisolone, and vincristine. Using public expression microarray datasets, a holistic in silico approach was utilized to investigate candidate drug resistance miRNA-mRNA-signaling pathway interaction networks in pediatric ALL. Our systems biology approach nominated significant drug resistance and cross-resistance miRNAs, mRNAs, and cell signaling pathways based on anti-correlative relationship between miRNA and mRNA expression pattern. To sum up, our systemic analysis disclosed either a new potential role of miRNAs, or a possible mechanism of cellular drug resistance, in chemotherapy resistance of pediatric ALL. The current study may shed light on predicting drug response and overcoming drug resistance in childhood ALL for subsequent generations of chemotherapies.

  19. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  20. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-31

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  1. The MLL recombinome of acute leukemias in 2013

    PubMed Central

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    2013-01-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (∼90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements. PMID:23628958

  2. The MLL recombinome of acute leukemias in 2013.

    PubMed

    Meyer, C; Hofmann, J; Burmeister, T; Gröger, D; Park, T S; Emerenciano, M; Pombo de Oliveira, M; Renneville, A; Villarese, P; Macintyre, E; Cavé, H; Clappier, E; Mass-Malo, K; Zuna, J; Trka, J; De Braekeleer, E; De Braekeleer, M; Oh, S H; Tsaur, G; Fechina, L; van der Velden, V H J; van Dongen, J J M; Delabesse, E; Binato, R; Silva, M L M; Kustanovich, A; Aleinikova, O; Harris, M H; Lund-Aho, T; Juvonen, V; Heidenreich, O; Vormoor, J; Choi, W W L; Jarosova, M; Kolenova, A; Bueno, C; Menendez, P; Wehner, S; Eckert, C; Talmant, P; Tondeur, S; Lippert, E; Launay, E; Henry, C; Ballerini, P; Lapillone, H; Callanan, M B; Cayuela, J M; Herbaux, C; Cazzaniga, G; Kakadiya, P M; Bohlander, S; Ahlmann, M; Choi, J R; Gameiro, P; Lee, D S; Krauter, J; Cornillet-Lefebvre, P; Te Kronnie, G; Schäfer, B W; Kubetzko, S; Alonso, C N; zur Stadt, U; Sutton, R; Venn, N C; Izraeli, S; Trakhtenbrot, L; Madsen, H O; Archer, P; Hancock, J; Cerveira, N; Teixeira, M R; Lo Nigro, L; Möricke, A; Stanulla, M; Schrappe, M; Sedék, L; Szczepański, T; Zwaan, C M; Coenen, E A; van den Heuvel-Eibrink, M M; Strehl, S; Dworzak, M; Panzer-Grümayer, R; Dingermann, T; Klingebiel, T; Marschalek, R

    2013-11-01

    Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.

  3. Mutational profiling of acute lymphoblastic leukemia with testicular relapse.

    PubMed

    Ding, Ling-Wen; Sun, Qiao-Yang; Mayakonda, Anand; Tan, Kar-Tong; Chien, Wenwen; Lin, De-Chen; Jiang, Yan-Yi; Xu, Liang; Garg, Manoj; Lao, Zhen-Tang; Lill, Michael; Yang, Henry; Yeoh, Allen Eng Juh; Koeffler, H Phillip

    2017-03-02

    Relapsed acute lymphoblastic leukemia (ALL) is the leading cause of deaths of childhood cancer. Although relapse usually happens in the bone marrow, extramedullary relapse occasionally occurs including either the central nervous system or testis (<1-2%). We selected two pediatric ALL patients who experienced testicular relapse and interrogated their leukemic cells with exome sequencing. The sequencing results and clonality analyses suggest that relapse of patient D483 directly evolved from the leukemic clone at diagnosis which survived chemotherapy. In contrast, relapse leukemia cells (both bone marrow and testis) of patient D727 were likely derived from a common ancestral clone, and testicular relapse likely arose independently from the bone marrow relapsed leukemia. Our findings decipher the mutational spectra and shed light on the clonal evolution of two cases of pediatric ALL with testicular relapse. Presence of CREBBP/NT5C2 mutations suggests that a personalized therapeutic approach should be applied to these two patients.

  4. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  5. Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-05

    Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Multilineage Dysplasia; Myeloid Sarcoma; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

  6. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  7. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  8. Epidemiology of acute lymphoblastic leukemia

    SciTech Connect

    Pendergrass, T.W.

    1985-06-01

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury.

  9. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. [Treatment of acute leukemias].

    PubMed

    Gross, R; Gerecke, D

    1982-11-12

    The effective treatment of acute (myeloblastic and lymphoblastic) leukaemias depends on the induction of remissions as well as on the maintenance of these remissions. Whereas the use of anthracyclines and of cytosine arabinoside in different combinations notably increased the rate of induction of remissions, their maintenance was less successful until now. We present a scheme using, beside MTX and 6-MP, modified COAP regimes periodically every 3 months. The follow-up of 26 patients treated in this way is encouraging since nearly one third remained in full haematological remission after 3 years of observation.

  11. Genetics Home Reference: acute promyelocytic leukemia

    MedlinePlus

    ... acute myeloid leukemia, a cancer of the blood-forming tissue ( bone marrow ). In normal bone marrow, hematopoietic ... 7186-203. Review. Citation on PubMed de Thé H, Chen Z. Acute promyelocytic leukaemia: novel insights into ...

  12. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Leukemia (AML) About Acute Myeloid Leukemia (AML) What’s New in Acute Myeloid Leukemia Research and Treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  13. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-03-27

    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); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  14. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia

    PubMed Central

    Ramsey, Laura B.; Janke, Laura J.; Payton, Monique A.; Cai, Xiangjun; Paugh, Steven W.; Karol, Seth E.; Kamdem, Landry Kamdem; Cheng, Cheng; Williams, Richard T.; Jeha, Sima; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.

    2015-01-01

    Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia. PMID:26252865

  15. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    PubMed

    Ramsey, Laura B; Janke, Laura J; Payton, Monique A; Cai, Xiangjun; Paugh, Steven W; Karol, Seth E; Kamdem Kamdem, Landry; Cheng, Cheng; Williams, Richard T; Jeha, Sima; Pui, Ching-Hon; Evans, William E; Relling, Mary V

    2015-01-01

    Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples) or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM) were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model) we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002). Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  16. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2017-01-31

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  18. Final results of a single institution experience with a pediatric-based regimen, the augmented Berlin-Frankfurt-Münster, in adolescents and young adults with acute lymphoblastic leukemia, and comparison to the hyper-CVAD regimen.

    PubMed

    Rytting, Michael E; Jabbour, Elias J; Jorgensen, Jeffrey L; Ravandi, Farhad; Franklin, Anna R; Kadia, Tapan M; Pemmaraju, Naveen; Daver, Naval G; Ferrajoli, Alessandra; Garcia-Manero, Guillermo; Konopleva, Marina Y; Borthakur, Gautam; Garris, Rebecca; Wang, Sa; Pierce, Sherry; Schroeder, Kurt; Kornblau, Steven M; Thomas, Deborah A; Cortes, Jorge E; O'Brien, Susan M; Kantarjian, Hagop M

    2016-08-01

    Several studies reported improved outcomes of adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated with pediatric-based ALL regimens. This prompted the prospective investigation of a pediatric Augmented Berlin-Frankfurt-Münster (ABFM) regimen, and its comparison with hyper-fractionated cyclophosphamide, vincristine, Adriamycin, and dexamethasone (hyper-CVAD) in AYA patients. One hundred and six AYA patients (median age 22 years) with Philadelphia chromosome- (Ph) negative ALL received ABFM from October 2006 through March 2014. Their outcome was compared to 102 AYA patients (median age 27 years), treated with hyper-CVAD at our institution. The complete remission (CR) rate was 93% with ABFM and 98% with hyper-CVAD. The 5-year complete remission duration (CRD) were 53 and 55%, respectively (P = 0.98). The 5-year overall survival (OS) rates were 60 and 60%, respectively. The MRD status on Day 29 and Day 84 of therapy was predictive of long-term outcomes on both ABFM and hyper-CVAD. Severe regimen toxicities with ABFM included hepatotoxicity in 41%, pancreatitis in 11%, osteonecrosis in 9%, and thrombosis in 19%. Myelosuppression-associated complications were most significant with hyper-CVAD. In summary, ABFM and hyper-CVAD resulted in similar efficacy outcomes, but were associated with different toxicity profiles, asparaginase-related with ABFM and myelosuppression-related with hyper-CVAD. Am. J. Hematol. 91:819-823, 2016. © 2016 Wiley Periodicals, Inc.

  19. Impact of Conditioning Regimen on Outcomes for Children with Acute Myeloid Leukemia Undergoing Transplantation in First Complete Remission. An Analysis on Behalf of the Pediatric Disease Working Party of the European Group for Blood and Marrow Transplantation.

    PubMed

    Lucchini, Giovanna; Labopin, Myriam; Beohou, Eric; Dalissier, Arnauld; Dalle, Jean Hughes; Cornish, Jacqueline; Zecca, Marco; Samarasinghe, Sujith; Gibson, Brenda; Locatelli, Franco; Bertrand, Yves; Abdel-Rahman, Fawzi; Socie, Gerald; Sundin, Mikael; Lankester, Arjan; Sedlacek, Peter; Hamladji, Rose Marie; Heilmann, Carsten; Afanasyev, Boris; Hough, Rachel; Peters, Cristina; Bader, Peter; Veys, Paul

    2017-03-01

    Hematopoietic stem cell transplantation (HSCT) represents the cornerstone of treatment in pediatric high-risk and relapsed acute myeloid leukemia (AML). The aim of the present study was to compare outcomes of pediatric patients with AML undergoing HSCT using 3 different conditioning regimens: total body irradiation (TBI) and cyclophosphamide (Cy); busulfan (Bu) and Cy; or Bu, Cy, and melphalan (Mel). In this retrospective study, registry data for patients > 2 and <18 years age undergoing matched allogeneic HSCT for AML in first complete remission (CR1) in 204 European Group for Blood and Marrow Transplantation centers between 2000 and 2010 were analyzed. Data were available for 631 patients; 458 patients received stem cells from a matched sibling donor and 173 from a matched unrelated donor. For 440 patients, bone marrow was used as stem cell source, and 191 patients received peripheral blood stem cells. One hundred nine patients received TBICy, 389 received BuCy, and 133 received BuCyMel as their preparatory regimen. Median follow-up was 55 months. Patients receiving BuCyMel showed a lower incidence of relapse at 5 years (14.7% versus 31.5% in BuCy versus 30% in TBICy, P < .01) and higher overall survival (OS) (76.6% versus 64% versus 64.5%, P = .04) and leukemia-free survival (LFS) (74.5% versus 58% versus 61.9%, P < .01), with a comparable nonrelapse mortality (NRM) (10.8% versus 10.5% versus 8.1%, P = .79). Acute graft-versus-host disease (GVHD) grades III and IV but not chronic GVHD, was higher in patients receiving BuCyMel. Older age at HSCT had an adverse impact on NRM and the use of peripheral blood as stem cell source was associated with increased chronic GVHD and NRM as well as lower LFS and OS. Among pediatric patients receiving HSCT for AML in CR1, the use of BuCyMel conditioning proved superior to TBICy and BuCy in reducing relapse and improving LFS.

  20. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  1. How Is Acute Lymphocytic Leukemia Classified?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Classified? Most types of cancers are assigned numbered ... ALL are now named as follows: B-cell ALL Early pre-B ALL (also called pro-B ...

  2. General Information about Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  3. Treatment Options for Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  4. Stages of Adult Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Adult acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... to radiation may increase the risk of developing ALL. Anything that increases your risk of getting a ...

  5. Acute myeloid leukemia presenting as galactorrhea

    PubMed Central

    Nambiar, K. Rakul; Devi, R. Nandini

    2016-01-01

    Acute myeloid leukemia (AML) presents with symptoms related to pancytopenia (weakness, infections, bleeding diathesis) and organ infiltration with leukemic cells. Galactorrhea is an uncommon manifestation of AML. We report a case of AML presenting with galactorrhea. PMID:27695173

  6. T-cell responses against CD19+ pediatric acute lymphoblastic leukemia mediated by bispecific T-cell engager (BiTE) are regulated contrarily by PD-L1 and CD80/CD86 on leukemic blasts

    PubMed Central

    Feucht, Judith; Kayser, Simone; Gorodezki, David; Hamieh, Mohamad; Döring, Michaela; Blaeschke, Franziska; Schlegel, Patrick; Bösmüller, Hans; Quintanilla-Fend, Leticia; Ebinger, Martin; Lang, Peter; Handgretinger, Rupert; Feuchtinger, Tobias

    2016-01-01

    T-cell immunotherapies are promising options in relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We investigated the effect of co-signaling molecules on T-cell attack against leukemia mediated by CD19/CD3-bispecific T-cell engager. Primary CD19+ ALL blasts (n≥10) and physiologic CD19+CD10+ bone marrow precursors were screened for 20 co-signaling molecules. PD-L1, PD-1, LAG-3, CD40, CD86, CD27, CD70 and HVEM revealed different stimulatory and inhibitory profiles of pediatric ALL compared to physiologic cells, with PD-L1 and CD86 as most prominent inhibitory and stimulatory markers. PD-L1 was increased in relapsed ALL patients (n=11) and in ALLs refractory to Blinatumomab (n=5). Exhaustion markers (PD-1, TIM-3) were significantly higher on patients' T cells compared to physiologic controls. T-cell proliferation and effector function was target-cell dependent and correlated to expression of co-signaling molecules. Blockade of inhibitory PD-1-PD-L and CTLA-4-CD80/86 pathways enhanced T-cell function whereas blockade of co-stimulatory CD28-CD80/86 interaction significantly reduced T-cell function. Combination of Blinatumomab and anti-PD-1 antibody was feasible and induced an anti-leukemic in vivo response in a 12-year-old patient with refractory ALL. In conclusion, ALL cells actively regulate T-cell function by expression of co-signaling molecules and modify efficacy of therapeutic T-cell attack against ALL. Inhibitory interactions of leukemia-induced checkpoint molecules can guide future T-cell therapies. PMID:27708227

  7. Acute Myeloid Leukemia, Version 2.2013

    PubMed Central

    O'Donnell, Margaret R.; Tallman, Martin S.; Abboud, Camille N.; Altman, Jessica K.; Appelbaum, Frederick R.; Arber, Daniel A.; Attar, Eyal; Borate, Uma; Coutre, Steven E.; Damon, Lloyd E.; Lancet, Jeffrey; Maness, Lori J.; Marcucci, Guido; Martin, Michael G.; Millenson, Michael M.; Moore, Joseph O.; Ravandi, Farhad; Shami, Paul J.; Smith, B. Douglas; Stone, Richard M.; Strickland, Stephen A.; Wang, Eunice S.; Gregory, Kristina M.; Naganuma, Maoko

    2014-01-01

    These NCCN Guidelines Insights summarize several key updates to the NCCN Guidelines for Acute Myeloid Leukemia and discuss the clinical evidence that support the recommendations. The updates described in this article focus on the acute promyelocytic leukemia (APL) section, featuring recommendations for additional induction/consolidation regimens in patients with low- or intermediate-risk APL, and providing guidance on maintenance strategies for APL. PMID:24029121

  8. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-02-07

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program.

    PubMed

    Halton, Jacqueline; Gaboury, Isabelle; Grant, Ronald; Alos, Nathalie; Cummings, Elizabeth A; Matzinger, Maryann; Shenouda, Nazih; Lentle, Brian; Abish, Sharon; Atkinson, Stephanie; Cairney, Elizabeth; Dix, David; Israels, Sara; Stephure, David; Wilson, Beverly; Hay, John; Moher, David; Rauch, Frank; Siminoski, Kerry; Ward, Leanne M

    2009-07-01

    Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to BMD and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age, 5.3 yr; 108 boys) with ALL (precursor B cell: N = 167; T cell: N = 19) who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco-lumbar spine radiograph, bone age (also used for metacarpal morphometry), and BMD. Vertebral morphometry was carried out by the Genant semiquantitative method. Twenty-nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bimodal, with most occurring in the midthoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared with those without (mean +/- SD, -2.1 +/- 1.5 versus -1.1 +/- 1.2; p < 0.001). LS BMD Z-score, second metacarpal percent cortical area Z-score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z-score, the odds for fracture increased by 80% (95% CI: 10-193%); the presence of back pain had an OR of 4.7 (95% CI: 1.5-14.5). These results show that vertebral compression is an under-recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined.

  10. Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-29

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  11. S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2017-02-23

    Acute Leukemias of Ambiguous Lineage; B-cell Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma

  12. 5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-06-03

    Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  13. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  14. Acute Appendicitis Secondary to Acute Promyelocytic Leukemia

    PubMed Central

    Rodriguez, Eduardo A.; Lopez, Marvin A.; Valluri, Kartik; Wang, Danlu; Fischer, Andrew; Perdomo, Tatiana

    2015-01-01

    Patient: Female, 43 Final Diagnosis: Myeloid sarcoma appendicitis Symptoms: Abdominal pain • chills • fever Medication: — Clinical Procedure: Laparoscopic appendectomy, bone marrow biopsy Specialty: Gastroenterology and Hepatology Objective: Rare disease Background: The gastrointestinal tract is a rare site for extramedullary involvement in acute promyelocytic leukemia (APL). Case Report: A 43-year-old female with no past medical history presented complaining of mild abdominal pain, fever, and chills for the past day. On examination, she was tachycardic and febrile, with mild tenderness of her right lower quadrant and without signs of peritoneal irritation. Laboratory examination revealed pancytopenia and DIC, with a fibrinogen level of 290 mg/dL. CT of the abdomen showed a thickened and hyperemic appendix without perforation or abscess, compatible with acute appendicitis. The patient was given IV broad-spectrum antibiotics and was transfused with packed red blood cells and platelets. She underwent uncomplicated laparoscopic appendectomy and bone marrow biopsy, which revealed neo-plastic cells of 90% of the total bone marrow cellularity. Flow cytometry indicated presence of 92.4% of immature myeloid cells with t (15: 17) and q (22: 12) mutations, and FISH analysis for PML-RARA demonstrated a long-form fusion transcript, positive for APL. Appendix pathology described leukemic infiltration with co-expression of myeloperoxidase and CD68, consistent with myeloid sarcoma of the appendix. The patient completed a course of daunorubicin, cytarabine, and all trans-retinoic acid. Repeat bone marrow biopsy demonstrated complete remission. She will follow up with her primary care physician and hematologist/oncologist. Conclusions: Myeloid sarcoma of the appendix in the setting of APL is very rare and it might play a role in the development of acute appendicitis. Urgent management, including bone marrow biopsy for definitive diagnosis and urgent surgical intervention

  15. Acute kidney injury after pediatric cardiac surgery

    PubMed Central

    Singh, Sarvesh Pal

    2016-01-01

    Acute kidney injury is a common complication after pediatric cardiac surgery. The definition, staging, risk factors, biomarkers and management of acute kidney injury in children is detailed in the following review article. PMID:27052074

  16. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-05

    Acute Myeloid 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); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  17. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-12-03

    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); Recurrent Adult Acute Myeloid Leukemia

  18. Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-03-09

    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); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  19. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-24

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-01

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  6. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  7. S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-02-13

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  9. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated 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; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-11-30

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  11. Advanced Vertebral Fracture among Newly Diagnosed Children with Acute Lymphoblastic Leukemia: Results of the Canadian STeroid-associated Osteoporosis in the Pediatric Population (STOPP) Research Program

    PubMed Central

    Halton, J.; Gaboury, I.; Grant, R.; Alos, N.; Cummings, E. A.; Matzinger, M.; Shenouda, N.; Lentle, B.; Abish, S.; Atkinson, S.; Cairney, E.; Dix, D.; Israels, S.; Stephure, D.; Wilson, B.; Hay, J.; Moher, D.; Rauch, F.; Siminoski, K.; Ward, L.M.

    2013-01-01

    Vertebral compression is a serious complication of childhood acute lymphoblastic leukemia (ALL). The prevalence and pattern of vertebral fractures, as well as their relationship to bone mineral density (BMD) and other clinical indices, have not been systematically studied. We evaluated spine health in 186 newly diagnosed children (median age 5.3 years, 108 boys) with ALL (precursor B cell: N=167; T-cell: N=19), who were enrolled in a national bone health research program. Patients were assessed within 30 days of diagnosis by lateral thoraco-lumbar spine radiograph, bone age (also used for metacarpal morphometry) and BMD. Vertebral morphometry was carried out by the Genant semi-quantitative method. Twenty-nine patients (16%) had a total of 75 grade 1 or higher prevalent vertebral compression fractures (53 thoracic, 71%; 22 lumbar). Grade 1 fractures as the worst grade were present in 14 children (48%), 9 patients (31%) had grade 2 fractures, and 6 children (21%) had grade 3 fractures. The distribution of spine fracture was bi-modal, with most occurring in the mid-thoracic and thoraco-lumbar regions. Children with grade 1 or higher vertebral compression had reduced lumbar spine (LS) areal BMD Z-scores compared to those without (mean±SD, −2.1±1.5 vs. −1.1±1.2; P < 0.001). LS BMD Z-score, second metacarpal percent cortical area Z-score, and back pain were associated with increased odds for fracture. For every 1 SD reduction in LS BMD Z-score, the odds for fracture increased by 80% (95% CI 10% to 193%); the presence of back pain had an odds ratio of 4.7 (95% CI, 1.5 to 14.5). These results show that vertebral compression is an under-recognized complication of newly diagnosed ALL. Whether the fractures will resolve through bone growth during or after leukemia chemotherapy remains to be determined. PMID:19210218

  12. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    ClinicalTrials.gov

    2017-01-17

    Acute Undifferentiated 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); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Childhood acute leukemia and intestinal parasitosis.

    PubMed

    Rivera-Luna, R; Cárdenas-Cardos, R; Martínez-Guerra, G; Ayón, A; Leal, C; Rivera-Ortegón, F

    1989-11-01

    Infectious complications are the leading cause of mortality in children with acute leukemia. Despite the fact that intestinal parasitosis is a rather frequent finding and a health problem in underdeveloped countries, in our experience the incidence of helminthic and protozoan infections among children with leukemia is uncommon. We analyzed 54 consecutive patients with leukemia in a period of 5 years, and only seven (12.9%) had intestinal parasites, four of whom died because of the infection or complication by the parasites. One hundred children without any malignancy were the control group, 26 (26%) of whom had intestinal parasitosis. When we compared the frequency of parasitosis in the control group with the children with leukemia and parasitosis, we found a statistical difference (p less than 0.05). We speculate that parasitic infections may reduce the risk of childhood leukemia.

  14. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  15. Insulin-like growth factor-binding protein-2 levels in pediatric patients with growth hormone deficiency, eating disorders and acute lymphoblastic leukemia.

    PubMed

    Barrios, V; Buño, M; Pozo, J; Muñoz, M T; Argente, J

    2000-01-01

    Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) is altered in different diseases and might be used as an indication of its severity. The aims of our study were to investigate: (1) the developmental pattern of the serum IGFBP-2 concentration at birth and during childhood and adolescence; (2) whether the serum IGFBP-2 level could be a marker for the diagnosis and evolution of diseases where the growth hormone (GH)-IGF axis is altered, and (3) whether this binding protein shows a relationship with IGF-I, its free fraction, IGFBP-1 and -3. We report reference values for 55 normal full-term newborns and 221 normal children who were divided into 5 groups according to their Tanner stage. Serum levels were higher in newborns when compared with Tanner stages I-V (p < 0.001, ANOVA), with no further changes throughout development. Furthermore, we studied IGFBP-2 levels in 24 children with congenital GH deficiency (GHD), 26 with acute lymphoblastic leukemia (ALL), 75 obese children, and 60 girls with anorexia nervosa (AN) at diagnosis and during a follow-up period. IGFBP-2 at diagnosis was increased in GHD, ALL and AN, and decreased in obesity (p < 0.05, ANOVA). During the follow-up, IGFBP-2 concentrations tended to normalize. IGFBP-2 correlated positively with IGFBP-1 and negatively with IGF-I and IGFBP-3 in normal subjects and at diagnosis of the pathologies studied. Although IGFBP-2 functions are not well understood, these results suggest a possible role for this protein in diseases where the GH-IGF axis is altered.

  16. The Expression and Prognostic Impact of CD95 Death Receptor and CD20, CD34 and CD44 Differentiation Markers in Pediatric Acute Lymphoblastic Leukemia

    PubMed Central

    M. Kamazani, Fatemeh; Bahoush-Mehdiabadi, Gholamreza; Aghaeipour, Mahnaz; Vaeli, Shahram; Amirghofran, Zahra

    2014-01-01

    Objective: This study investigated the expression and prognostic significance of the CD95 death receptor and CD20, a B cell-lineage associated marker, along with CD34 and CD44 non-lineage associated molecules in Iranian children with acute lymphoblastic leukemia (ALL). Methods: We performed immunophenotyping for expressions of the molecules in blood samples from children diagnosed with ALL by using a panel of monoclonal antibodies for flow cytometry analysis. The expression of markers was evaluated in relation to clinical and paraclinical features as well as response to treatment in the patients. Findings : CD95 showed a higher expression in T-ALL compared to B-ALL (P<0.001). Analysis of the clinical and laboratory findings at diagnosis in the group of B-ALL patients revealed an association between CD95 expression with lower white blood cell (WBC) numbers and bone marrow blasts (P<0.05). We detected a positive correlation between the expressions of CD95 and CD44 (r=0.445, P<0.01) in B-ALL patients. There was an association between CD20 expression and several poor prognostic factors that included increased extramedullary involvement (EMI) and decreased platelet numbers (P<0.008). The mean expression of CD34 in B-ALL was higher than T-ALL (P=0.004). At follow-up, complete remission duration (CRD) and survival duration did not significantly differ between patients who were positive or negative for each marker. Conclusion: Association of the studied molecules with several prognostic factors implies the significance of CD95 molecule as favorable and CD20 as unfavorable prognostic markers for childhood ALL. PMID:25755857

  17. The costs and cost-effectiveness of allogeneic peripheral blood stem cell transplantation versus bone marrow transplantation in pediatric patients with acute leukemia.

    PubMed

    Lin, Yu-Feng; Lairson, David R; Chan, Wenyaw; Du, Xianglin L; Leung, Kathryn S; Kennedy-Nasser, Alana A; Martinez, Caridad A; Gottschalk, Stephen M; Bollard, Catherine M; Heslop, Helen E; Brenner, Malcolm K; Krance, Robert A

    2010-09-01

    In a retrospective study, we evaluated the cost and cost-effectiveness of allogeneic peripheral blood stem cell transplantation (PBSCT) (n = 30) compared with bone marrow transplantation (BMT) (n = 110) in children with acute leukemia after 1 year of follow-up. Treatment success was defined as disease-free survival at 1 year posttransplantation. For patients at standard risk for disease, the treatment success rate was 57.1% for PBSCT recipients and 80.3% for BMT recipients (P = not significant [NS]). The average total cost per treatment success at 1 year in the standard-risk disease group was $512,294 for PBSCT recipients and $352,885 for BMT recipients (P = NS). For patients with high-risk disease, the treatment success rate was 18.8% for PBSCT recipients and 23.5% for BMT recipients (P = NS). The cumulative average cost was $457,078 in BMT recipients and $377,316 in PBSCT recipients (P = NS). Point estimates of the incremental cost-effectiveness ratio (ICER) indicate that in patients with standard-risk disease, allogeneic BMT had lower costs and greater effectiveness than PBSCT (ICER, -$687,108; 95% confidence interval [CI], $2.4 million to dominated). For patients with high-risk disease, BMT was more effective and more costly, and it had an ICER of $1.69 million (95% CI, $29.7 million to dominated) per additional treatment success. The comparative economic evaluation provides support for BMT in standard-risk patients, but much uncertainty precludes a clear advantage of either treatment option in patients with high-risk disease. More studies using larger and randomized controlled trials are needed to confirm the long-term cost-effectiveness of each procedure.

  18. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  19. Lack of association of the CEP72 rs924607 TT genotype with vincristine-related peripheral neuropathy during the early phase of pediatric acute lymphoblastic leukemia treatment in a Spanish population.

    PubMed

    Gutierrez-Camino, Angela; Martin-Guerrero, Idoia; Lopez-Lopez, Elixabet; Echebarria-Barona, Aizpea; Zabalza, Iñaki; Ruiz, Irune; Guerra-Merino, Isabel; Garcia-Orad, Africa

    2016-02-01

    Vincristine is a component of acute lymphoblastic leukemia (ALL) treatment with the potential to induce peripheral neuropathy. Recently, the CEP72 rs924607 TT genotype was found to be associated with vincristine-induced toxicity during the continuation phase in pediatric ALL patients treated on the Total XIIIB and COG AALL0433 protocols at St Jude Children's Research Hospital and Children's Oncology Group. This finding could provide a base for safer dosing of vincristine. Nevertheless, there are variations in vincristine regimens among ALL treatment protocols and phases in different populations. Therefore, the aim of this study was to determine whether the CEP72 rs924607 TT genotype is a useful marker of vincristine neuropathy during induction therapy among Spanish children with B-ALL treated on the LAL-SHOP protocols. No association was found between neurotoxicity during the induction phase and the rs924607 TT genotype. This lack of association could be because of population differences and/or differences in neurotoxicity etiology between induction and continuation phases of treatment.

  20. Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. PHF6 mutations in T-cell acute lymphoblastic leukemia.

    PubMed

    Van Vlierberghe, Pieter; Palomero, Teresa; Khiabanian, Hossein; Van der Meulen, Joni; Castillo, Mireia; Van Roy, Nadine; De Moerloose, Barbara; Philippé, Jan; González-García, Sara; Toribio, María L; Taghon, Tom; Zuurbier, Linda; Cauwelier, Barbara; Harrison, Christine J; Schwab, Claire; Pisecker, Markus; Strehl, Sabine; Langerak, Anton W; Gecz, Jozef; Sonneveld, Edwin; Pieters, Rob; Paietta, Elisabeth; Rowe, Jacob M; Wiernik, Peter H; Benoit, Yves; Soulier, Jean; Poppe, Bruce; Yao, Xiaopan; Cordon-Cardo, Carlos; Meijerink, Jules; Rabadan, Raul; Speleman, Frank; Ferrando, Adolfo

    2010-04-01

    Tumor suppressor genes on the X chromosome may skew the gender distribution of specific types of cancer. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with an increased incidence in males. In this study, we report the identification of inactivating mutations and deletions in the X-linked plant homeodomain finger 6 (PHF6) gene in 16% of pediatric and 38% of adult primary T-ALL samples. Notably, PHF6 mutations are almost exclusively found in T-ALL samples from male subjects. Mutational loss of PHF6 is importantly associated with leukemias driven by aberrant expression of the homeobox transcription factor oncogenes TLX1 and TLX3. Overall, these results identify PHF6 as a new X-linked tumor suppressor in T-ALL and point to a strong genetic interaction between PHF6 loss and aberrant expression of TLX transcription factors in the pathogenesis of this disease.

  2. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-03-27

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  3. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-12-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  4. An Initial Reintegration Treatment of Children with Acute Lymphoblastic Leukemia (ALL).

    ERIC Educational Resources Information Center

    Lurie, Michelle; Kaufman, Nadeen

    2001-01-01

    Evaluated the cognitive, psychological, and social adjustment of pediatric acute lymphoblastic leukemia (ALL) patients and assessed how their needs could best be met through reintegration programs focusing on learning/ educational needs. Findings from three case studies highlight the need for ALL patients to be provided with comprehensive programs…

  5. AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-19

    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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Idarubicin, Cytarabine, and Pravastatin Sodium in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-03-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia

  7. Guidelines for the management of bacterial and fungal infections during chemotherapy for pediatric acute leukemia or solid tumors: what is available in 2010?

    PubMed Central

    Castagnola, Elio; Caviglia, Ilaria; Haupt, Riccardo

    2011-01-01

    Febrile episodes and infections represent important complications during antineoplastic chemotherapy for pediatric neoplastic diseases. In the last years many international association published guidelines for the management of these complications in adults, but no document of this type was prepared for children. One of the major causes of this situation is probably the very low number of pediatric clinical trials with adequate power and design. The paper summarizes guidelines provided for the management of infectious complications in adults with cancer by different international and will comment on how much they may be translated in the management of pediatric patients. PMID:21647280

  8. Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-03-27

    Acute Biphenotypic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  9. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    ClinicalTrials.gov

    2016-07-18

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  10. CPX-351 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-04-25

    Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  11. Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project | Office of Cancer Genomics

    Cancer.gov

    TARGET researchers sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with activated kinase signaling, including Ph-like ALL, to establish the incidence of tyrosine kinase mutations in this cohort. The study confirmed previously identified somatic mutations in JAK and FLT3, but did not find novel alterations in any additional tyrosine kinases or downstream genes. The mechanism of kinase signaling activation in this high-risk subgroup of pediatric ALL remains largely unknown.

  12. Acute myelogenous leukemia (AML) -- children

    MedlinePlus

    ... LE, Heslop HE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice . 6th ed. Philadelphia, PA: ... Updated by: Adam S. Levy, MD, Division of Pediatric Hematology/Oncology, The Children's Hospital at Montefiore, Bronx, NY. ...

  13. Acute myelocytic leukemia after exposure to asbestos

    SciTech Connect

    Kishimoto, T.; Ono, T.; Okada, K.

    1988-08-15

    While the carcinogenicity of asbestos has been established in malignant mesotheliomas and lung cancers, and has recently been suspected in several other types of cancer, asbestos has not been implicated in the pathogenesis of acute leukemias. This article includes two cases of acute myelocytic leukemia in individuals with a long history of exposure to asbestos. Significant numbers of asbestos bodies were detected in specimens of their lungs and bone marrow. In addition, the kind of asbestos in both organs was crocidolite, which is implicated in carcinogenesis. No asbestos bodies were detected in the bone marrow specimens from a control group consisting of ten patients with lung cancer with similar occupational histories. The role of asbestos exposure in the development of leukemia requires further study.

  14. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    ClinicalTrials.gov

    2016-11-17

    Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

  15. CPI-613, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-12-23

    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); Recurrent Adult Acute Myeloid Leukemia

  16. Lenalidomide and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-03-28

    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); Recurrent Adult Acute Myeloid Leukemia

  17. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    ClinicalTrials.gov

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; 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); Recurrent Adult Acute Myeloid Leukemia

  18. Vaccine Therapy and Basiliximab in Treating Patients With Acute Myeloid Leukemia in Complete Remission

    ClinicalTrials.gov

    2017-01-03

    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)

  19. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis.

    PubMed

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R

    2015-08-15

    Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodies were conspicuous on biopsy and may serve as a morphologic clue to lymphocytic differentiation while molecular and immunophenotypic studies are pending. The patient was successfully treated with local radiation therapy and oral ponatinib.

  20. Pediatric Priapism: A Rare First Manifestation of Leukemia

    PubMed Central

    Hazra, Shankar Prasad; Gogoi, Debojit; Sharma, Pramod Kumar; Pal, Dilip Kumar; Chakraborty, Sudip C

    2013-01-01

    Priapism is a rare disease. It is an emergency condition with a poor prognosis, and the risk of impotence is 50% despite appropriate management. Though about 20% cases of all priapism are related to hematological disorders, the incidence of priapism in adult leukemic patients is only about 1-5 percent. The incidence in pediatric leukemia patient is even rarer. Here we present a case of priapism in a 14-year-old apparently healthy boy who found to have chronic myeloid leukemia on subsequent investigations. PMID:24381835

  1. Cytarabine With or Without SCH 900776 in Treating Adult Patients With Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  2. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Malignant Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  3. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Ixazomib (MLN9708) in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-20

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  5. Arsenic Trioxide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-04

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  6. Vorinostat and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2011-11-03

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  7. 47,XYY karyotype in acute myeloid leukemia.

    PubMed

    Palanduz, S; Aktan, M; Ozturk, S; Tutkan, G; Cefle, K; Pekcelen, Y

    1998-10-01

    A case of acute myelomonocytic leukemia (AMMoL; M4) with a 47,XYY karyotype is reported. This chromosome aneuploidy was found in both bone marrow cells and mitogen-stimulated lymphocytes. The contribution of XYY chromosomal constitution in the pathogenesis of AMMoL is controversial.

  8. Important milestones in acute leukemia in 2013.

    PubMed

    Rowe, Jacob M

    2013-09-01

    This year marked the occurrence of several important milestones in the treatment of acute leukemias. First, the standard 7 + 3 protocol for acute myeloid leukemia (AML) was developed 40 years ago, and with some adaptations, has stood the test of time. Second, the 1 millionth hematopoietic cell transplant was recorded this year. Stem cell transplant, the first reported by Dr E. Donnall Thomas in 1957, had been considered a rare procedure until about a decade ago. Today, it has become a proven and often life-saving therapy for patients with acute leukemia. Advances in the treatment of patients with AML continue to take place, many of which relate to an increased understanding of the clinical heterogeneity of known subtypes. Forty years ago, the regimen that has come to be known as 7+3 for acute myeloid leukemia (AML) was born [1,2]. Cytosine arabinoside, or arabinosylcytosine as it was then called, was given as a continuous intravenous infusion of 100 mg/m(2) for 7 days, and the anthracycline, daunorubicin, was administered at 45 mg/m(2) intravenously for 3 days. Sixteen patients were originally treated on this protocol, and 5 of 8 previously untreated and 2 of 8 previously treated patients achieved a complete response (CR). This regimen has withstood the test of time. Attempts to add or substitute other agents have not yielded superior results. The only major contemporary change is that a higher dose of daunorubicin is safe and has become the standard of care [3].

  9. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  10. A Case of T-cell Acute Lymphoblastic Leukemia Relapsed As Myeloid Acute Leukemia.

    PubMed

    Paganin, Maddalena; Buldini, Barbara; Germano, Giuseppe; Seganfreddo, Elena; Meglio, Annamaria di; Magrin, Elisa; Grillo, Francesca; Pigazzi, Martina; Rizzari, Carmelo; Cazzaniga, Giovanni; Khiabanian, Hossein; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A; Basso, Giuseppe

    2016-09-01

    A 4-year-old male with the diagnosis of T-cell acute lymphoblastic leukemia (T-ALL) relapsed after 19 months with an acute myeloid leukemia (AML). Immunoglobulin and T-cell receptor gene rearrangements analyses reveal that both leukemias were rearranged with a clonal relationship between them. Comparative genomic hybridization (Array-CGH) and whole-exome sequencing analyses of both samples suggest that this leukemia may have originated from a common T/myeloid progenitor. The presence of homozygous deletion of p16/INK4A, p14/ARF, p15/INK4B, and heterozygous deletion of WT1 locus remained stable in the leukemia throughout phenotypic switch, revealing that this AML can be genetically associated to T-ALL.

  11. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation

    PubMed Central

    Kunz, Joachim B.; Rausch, Tobias; Bandapalli, Obul R.; Eilers, Juliane; Pechanska, Paulina; Schuessele, Stephanie; Assenov, Yassen; Stütz, Adrian M.; Kirschner-Schwabe, Renate; Hof, Jana; Eckert, Cornelia; von Stackelberg, Arend; Schrappe, Martin; Stanulla, Martin; Koehler, Rolf; Avigad, Smadar; Elitzur, Sarah; Handgretinger, Rupert; Benes, Vladimir; Weischenfeldt, Joachim; Korbel, Jan O.; Muckenthaler, Martina U.; Kulozik, Andreas E.

    2015-01-01

    Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and is frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of T-cell acute lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. Compared to primary T-cell acute lymphoblastic leukemia, in relapse the number of single nucleotide variants and small insertions and deletions approximately doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, ‘type 1’ relapse derives from the primary leukemia whereas ‘type 2’ relapse originates from a common pre-leukemic ancestor. Relapse-specific changes included activation of the nucleotidase NT5C2 resulting in resistance to chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1 and SMARCA4. While mutations present in primary leukemia and in relapse were enriched for known drivers of leukemia, relapse-specific changes revealed an association with general cancer-promoting mechanisms. This study thus identifies mechanisms that drive progression of pediatric T-cell acute lymphoblastic leukemia to relapse and may explain the characteristic treatment resistance of this condition. PMID:26294725

  12. Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.

    PubMed

    Kunz, Joachim B; Rausch, Tobias; Bandapalli, Obul R; Eilers, Juliane; Pechanska, Paulina; Schuessele, Stephanie; Assenov, Yassen; Stütz, Adrian M; Kirschner-Schwabe, Renate; Hof, Jana; Eckert, Cornelia; von Stackelberg, Arend; Schrappe, Martin; Stanulla, Martin; Koehler, Rolf; Avigad, Smadar; Elitzur, Sarah; Handgretinger, Rupert; Benes, Vladimir; Weischenfeldt, Joachim; Korbel, Jan O; Muckenthaler, Martina U; Kulozik, Andreas E

    2015-11-01

    Relapsed precursor T-cell acute lymphoblastic leukemia is characterized by resistance against chemotherapy and is frequently fatal. We aimed at understanding the molecular mechanisms resulting in relapse of T-cell acute lymphoblastic leukemia and analyzed 13 patients at first diagnosis, remission and relapse by whole exome sequencing, targeted ultra-deep sequencing, multiplex ligation dependent probe amplification and DNA methylation array. Compared to primary T-cell acute lymphoblastic leukemia, in relapse the number of single nucleotide variants and small insertions and deletions approximately doubled from 11.5 to 26. Targeted ultra-deep sequencing sensitively detected subclones that were selected for in relapse. The mutational pattern defined two types of relapses. While both are characterized by selection of subclones and acquisition of novel mutations, 'type 1' relapse derives from the primary leukemia whereas 'type 2' relapse originates from a common pre-leukemic ancestor. Relapse-specific changes included activation of the nucleotidase NT5C2 resulting in resistance to chemotherapy and mutations of epigenetic modulators, exemplified by SUZ12, WHSC1 and SMARCA4. While mutations present in primary leukemia and in relapse were enriched for known drivers of leukemia, relapse-specific changes revealed an association with general cancer-promoting mechanisms. This study thus identifies mechanisms that drive progression of pediatric T-cell acute lymphoblastic leukemia to relapse and may explain the characteristic treatment resistance of this condition.

  13. MS-275 and GM-CSF in Treating Patients With Myelodysplastic Syndrome and/or Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-09-20

    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 Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. [Oncogenes and the origin of leukemia. Acute avian leukemia viruses].

    PubMed

    Graf, T

    1988-03-01

    Oncogenes have been intimately associated with the genesis of human neoplasms. A particularly useful system to study the mechanism of tumorigenesis is a small group of avian retroviruses that carry two oncogenes. These viruses causes acute leukemias and can transform hematopoietic cells in vitro. The mechanisms by which viral oncogenes affect the growth control and differentiation of their target cells is now understood in fair detail for two of these virus strains. In the avian erythroblastosis virus AEV, the v-erbB oncogene deregulates the growth control of erythroid precursors, while verbA blocks their terminal differentiation into erythrocytes. Based on the findings that v-erbB oncogene corresponds to a mutated growth factor receptor gene and that v-erbA corresponds to a mutated hormone receptor gene, models have been developed that explain the function of these two oncogenes on a molecular basis. The myelomonocytic leukemia virus MH2 acts by a completely different mechanism. In this case, the v-myc oncogene stimulates the proliferation of macrophage-like cells, while the v-mil gene stimulates them to produce their own growth factor, thus leading to autocrine growth. It will be interesting to determine whether the type of mechanisms of oncogene cooperativity elucidated for acute leukemia viruses are also operative during leukemogenesis in humans.

  15. Treatment of Adolescent and Young Adults with Acute Lymphoblastic Leukemia

    PubMed Central

    Ribera, Josep-Maria; Ribera, Jordi; Genescà, Eulàlia

    2014-01-01

    The primary objective of this review was to update and discuss the current concepts and the results of the treatment of acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA). After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALL in the AYA population, the main retrospective comparative studies stating the superiority of pediatric over adult-based protocols were reviewed. The most important prospective studies in young adults using pediatric inspired or pediatric unmodified protocols were also reviewed emphasizing their feasibility at least up to the age of 40 yr and their promising results, with event-free survival rates of 60–65% or greater. Results of trials from pediatric groups have shown that the unfavourable prognosis of adolescents is no more adequate. The majority of the older adolescents with ALL can be cured with risk-adjusted and minimal residual disease-guided intensive chemotherapy, without stem cell transplantation. However, some specific subgroups, which are more frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like), deserve particular attention. In summary, the advances in treatment of ALL in adolescents have been translated to young adults, and that explains the significant improvement in survival of these patients in recent years. PMID:25045460

  16. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  17. Factors associated with improved outcomes after second allogeneic hematopoietic cell transplantation for relapsed pediatric leukemia.

    PubMed

    Menon, Neethu N; Jenkins, Lydia M; Cui, Haiyan; Jenkins, Craig; Anwer, Faiz; Yeager, Andrew M; Katsanis, Emmanuel

    2016-03-01

    A second allogeneic (allo) hematopoietic cell transplant (HCT) is an important therapeutic consideration for patients relapsing after their first. We conducted a retrospective review of 41 pediatric patients with leukemia that underwent a second allo-HCT at our institution. Overall, 53.7 and 43.9 % of patients were alive and disease-free at 1 and 5 years, respectively, after the second allo-HCT. The factors affecting outcome by both univariate and multivariate analysis were interval between transplants and the use of a myeloablative conditioning (MAC) regimen prior to second transplant. Outcomes were inferior in patients who received their second transplant <6 months from their first HCT when compared to patients in whom the interval between HCTs was 6-12 or more than 12 months. Interval between HCTs was also significant when each type of leukemia (acute lymphoblastic leukemia (ALL) n = 21, acute myelogenous leukemia (AML) n = 11, and chronic myelogenous leukemia (CML) n = 7) was analyzed separately. In univariate analysis, use of the same donor and use of a matched sibling donor resulted in significant improved outcome. There was not a significant association between disease-free survival (DFS) and age, remission status, use of total body irradiation (TBI) before second HCT, or type of leukemia. Second allogeneic HCT can be a curative therapeutic option for leukemia patients relapsing after their first transplant. As more targeted therapies have become available, patients that relapse after first HCT are more likely to achieve remission. Therefore, it is anticipated that there will be more candidates for second HCT with improved performance and remission status, ultimately leading to a better outcome with the second HCT.

  18. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia

    PubMed Central

    te Winkel, Mariël L.; Pieters, Rob; Wind, Ernst-Jan D.; Bessems, J.H.J.M. (Gert); van den Heuvel-Eibrink, Marry M.

    2014-01-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking. PMID:24598854

  19. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    PubMed

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

  20. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-13

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  1. [Presence of B cell clones in acute myelomonocytic leukemia].

    PubMed

    Novoa, Viviana; Nuñez, Neri; Cervellini, Mirta; Starosta, Aida; Carballo, Orlando G

    2010-01-01

    The coexistence of acute myeloid leukemia and chronic lymphocytic leukemia in the same patient is rare. The majority of the cases correspond to patients that developed acute leukemia during the evolutionary course of a chronic lymphatic leukemia following treatment with chemotherapy drugs. We report a case of acute myelomonocytic leukemia concurrent with untreated B-cell chronic lymphocytic leukemia in which the use of flow cytometry analysis with a large panel of monoclonal antibodies, allowed the demonstration of different pathological populations and determine immunophenotyping patterns. Published cases of simultaneous chronic lymphocytic leukemia and acute leukemia are reviewed. The use of multiparametric flow cytometry to differentiate the populations demonstrates the utility of this technology in the diagnosis of these hematological malignancies.

  2. Targeting MTHFD2 in acute myeloid leukemia

    PubMed Central

    Pikman, Yana; Puissant, Alexandre; Alexe, Gabriela; Furman, Andrew; Chen, Liying M.; Frumm, Stacey M.; Ross, Linda; Fenouille, Nina; Bassil, Christopher F.; Lewis, Caroline A.; Ramos, Azucena; Gould, Joshua; Stone, Richard M.; DeAngelo, Daniel J.; Galinsky, Ilene; Clish, Clary B.; Kung, Andrew L.; Hemann, Michael T.; Vander Heiden, Matthew G.; Banerji, Versha

    2016-01-01

    Drugs targeting metabolism have formed the backbone of therapy for some cancers. We sought to identify new such targets in acute myeloid leukemia (AML). The one-carbon folate pathway, specifically methylenetetrahydrofolate dehydrogenase-cyclohydrolase 2 (MTHFD2), emerged as a top candidate in our analyses. MTHFD2 is the most differentially expressed metabolic enzyme in cancer versus normal cells. Knockdown of MTHFD2 in AML cells decreased growth, induced differentiation, and impaired colony formation in primary AML blasts. In human xenograft and MLL-AF9 mouse leukemia models, MTHFD2 suppression decreased leukemia burden and prolonged survival. Based upon primary patient AML data and functional genomic screening, we determined that FLT3-ITD is a biomarker of response to MTHFD2 suppression. Mechanistically, MYC regulates the expression of MTHFD2, and MTHFD2 knockdown suppresses the TCA cycle. This study supports the therapeutic targeting of MTHFD2 in AML. PMID:27325891

  3. Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-10-19

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Untreated Adult Acute Myeloid Leukemia

  4. Lithium Carbonate and Tretinoin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-10-19

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  5. Comparing Three Different Combination Chemotherapy Regimens in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-02

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  6. Azacitidine and Gemtuzumab Ozogamicin in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Acute lymphoid leukemia following polycythemia vera.

    PubMed

    Camós, M; Cervantes, F; Montoto, S; Hernández-Boluda, J C; Villamor, N; Montserrat, E

    1999-01-01

    The tendency to evolve into acute leukemia is a well-known characteristic of polycythemia vera (PV), which is shared with the remaining chronic myeloproliferative disorders and increases after the administration of cytotoxic agents. Acute transformation is usually of myeloid phenotype, whereas acute lymphoid leukemia (ALL) following PV is seldom observed. A 63-year-old woman is described who developed ALL at 6 years from the initial diagnosis of PV, for which she had received radioactive phosphorus and hydroxyurea. The ALL was of B-cell type, corresponding to the L-3 subtype of the FAB classification. Despite the administration of combination chemotherapy the patient died shortly after the diagnosis of acute leukemia. The present case adds to seven previously described patients with the above association, all of whom had received cytotoxic therapy for PV. Median interval from PV to ALL diagnosis was 10 years, and there was a predominance of the B-cell phenotype. The prognosis was poor since all but one of the patients had a short survival after ALL diagnosis. The possible etiological and pathogenetic link between PV and the subsequent ALL is discussed.

  8. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2017-03-22

    Adult Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Therapy-Related Myelodysplastic Syndrome

  9. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    ClinicalTrials.gov

    2017-03-20

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  10. Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-27

    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); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; de Novo Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  11. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  12. Global Characteristics of Childhood Acute Promyelocytic Leukemia

    PubMed Central

    Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

    2014-01-01

    Acute promyelocytic leukemia (APL) comprises approximately 5–10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent—de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed. PMID:25445717

  13. Genomic profiling of pediatric acute myeloid leukemia reveals a changing mutational landscape from disease diagnosis to relapse | Office of Cancer Genomics

    Cancer.gov

    The genomic and clinical information used to develop and implement therapeutic approaches for AML originated primarily from adult patients and has been generalized to patients with pediatric AML. However, age-specific molecular alterations are becoming more evident and may signify the need to age-stratify treatment regimens. The NCI/COG TARGET-AML initiative employed whole exome capture sequencing (WXS) to interrogate the genomic landscape of matched trios representing specimens collected upon diagnosis, remission, and relapse from 20 cases of de novo childhood AML.

  14. Expression of CD133 in acute leukemia.

    PubMed

    Tolba, Fetnat M; Foda, Mona E; Kamal, Howyda M; Elshabrawy, Deena A

    2013-06-01

    There have been conflicting results regarding a correlation between CD133 expression and disease outcome. To assess CD133 expression in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and to evaluate its correlation with the different clinical and laboratory data as well as its relation to disease outcome, the present study included 60 newly diagnosed acute leukemic patients; 30 ALL patients with a male to female ratio of 1.5:1 and their ages ranged from 9 months to 48 years, and 30 AML patients with a male to female ratio of 1:1 and their ages ranged from 17 to 66 years. Flow cytometric assessment of CD133 expression was performed on blast cells. In ALL, no correlations were elicited between CD133 expression and some monoclonal antibodies, but in AML group, there was a significant positive correlation between CD133 and HLA-DR, CD3, CD7 and TDT, CD13 and CD34. In ALL group, patients with negative CD133 expression achieved complete remission more than patients with positive CD133 expression. In AML group, there was no statistically significant association found between positive CD133 expression and treatment outcome. The Kaplan-Meier curve illustrated a high significant negative correlation between CD133 expression and the overall survival of the AML patients. CD133 expression is an independent prognostic factor in acute leukemia, especially ALL patients and its expression could characterize a group of acute leukemic patients with higher resistance to standard chemotherapy and relapse. CD133 expression was highly associated with poor prognosis in acute leukemic patients.

  15. Midostaurin and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia and FLT3 Mutation

    ClinicalTrials.gov

    2016-10-10

    Acute Myeloid Leukemia With FLT3/ITD Mutation; Acute Myeloid Leukemia With Gene Mutations; FLT3 Tyrosine Kinase Domain Point Mutation; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.

    PubMed

    Sinnett, Daniel; Labuda, Damian; Krajinovic, Maja

    2006-01-01

    Pediatric cancers affect approximately 1 in every 500 children before the age of 15. Little is known about the etiology of this heterogeneous group of diseases despite the fact they constitute the major cause of death by disease among this population. Because of its relatively high prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variation plays a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to common polymorphisms. The biochemical and genetic mechanisms contributing to cancer susceptibility are numerous and can be grouped into broad categories: (1) cellular growth and differentiation, (2) DNA replication and repair, (3) metabolism of carcinogens (4) apoptosis, (5) oxidative stress response and (6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted case-control studies. We showed that leukemogenesis in children may be associated with DNA variants in some of these genes and that the combination of genotypes seems to be more predictive of risk than either of them independently. We also observed that, at least at some loci, the parental genetics might be important in predicting the risk of cancer in this pediatric model of a complex disease. Taken together, these results indicate that the investigation of a single enzyme and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.

  17. Ipilimumab and Decitabine in Treating Patients With Relapsed or Refractory Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-06

    Chimerism; Hematopoietic Cell Transplantation Recipient; Myelodysplastic Syndrome With Excess Blasts-1; Myelodysplastic Syndrome With Excess Blasts-2; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  18. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  19. Immune reconstitution complicated by CMV retinitis in a pediatric patient who underwent haploidentical CD34+-selected hematopoietic stem cell transplant for acute lymphoblastic leukemia.

    PubMed

    Cesaro, Simone; Boaro, Maria Paola; Pillon, Marta; Calore, Elisabetta; Cermakova, Ivete; Perruccio, Katia; Mengoli, Carlo; Messina, Chiara

    2008-09-01

    We describe two episodes of CMV retinitis in a pediatric patient who underwent a CD34+ selected graft from his haploidentical father. Both recipient and donor were cytomegalovirus (CMV) seropositive. Both episodes occurred late post-grafting during a phase of complete immunological recovery with sufficient numbers of circulating CMV-specific clones. Antiviral treatment with foscarnet and ganciclovir was successful but prolonged treatment was required to prevent relapses. We hypothesize that this complication was more related to an immune reconstitution process than to an immune-deficient state post-grafting. We conclude that CMV retinitis is a late complication of HSCT that can occur despite satisfactory immune reconstitution. Usually, it is responsive to antiviral therapy. Dilated fundoscopic examination is essential both for examining patients with reduced visual acuity and for screening asymptomatic patients.

  20. Vorinostat and Azacitidine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-31

    Acute Erythroid Leukemia; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Myelodysplastic Syndrome With Ring Sideroblasts; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia; Refractory Anemia With Excess Blasts in Transformation

  1. Acute Myeloid Leukemia: Advancements in Diagnosis and Treatment

    PubMed Central

    Yu, Meng-Ge; Zheng, Hu-Yong

    2017-01-01

    Objective: Leukemia is the most common pediatric malignancy and a major cause of morbidity and mortality in children. Among all subtypes, a lack of consensus exists regarding the diagnosis and treatment of acute myeloid leukemia (AML). Patient survival rates have remained modest for the past three decades in AML. Recently, targeted therapy has emerged as a promising treatment. Data Sources: We searched the PubMed database for recently published research papers on diagnostic development, target therapy, and other novel therapies of AML. Clinical trial information was obtained from ClinicalTrials.gov. For the major purpose of this review that is to outline the latest therapeutic development of AML, we only listed the ongoing clinical trials for reference. However, the published results of complete clinical trials were also mentioned. Study Selection: This article reviewed the latest developments related to the diagnosis and treatment of AML. In the first portion, we provided some novel insights on the molecular basis of AML, as well as provided an update on the classification of AML. In the second portion, we summarized the results of research on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/Fms-like tyrosine kinase 3 (FLT3) inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. We will also highlight ongoing research and clinical trials in pediatric AML. Results: We described clonal evolution and how it changes our view on leukemogenesis, treatment responses, and disease relapse. Pediatric-specific genomic mapping was discussed with a novel diagnostic method highlighted. In the later portion of this review, we summarized the researches on potential molecular therapeutic agents including monoclonal antibodies, tyrosine kinase/FLT3 inhibitors, epigenetic/demethylating agents, and cellular therapeutic agents. Conclusion: Gene sequencing techniques should set the basis for next-generation diagnostic

  2. Decitabine, Donor Natural Killer Cells, and Aldesleukin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-12-02

    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); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  3. Combination Chemotherapy and Dasatinib in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-04

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell Neoplasm

    ClinicalTrials.gov

    2017-03-13

    Adult Acute Myeloid Leukemia in Remission; Donor; Early Relapse of Acute Myeloid Leukemia; Late Relapse of Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm

  5. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  6. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  7. Diagnosis of Large Granular Lymphocytic Leukemia in a Patient Previously Treated for Acute Myeloblastic Leukemia

    PubMed Central

    Bozdag, Sinem Civriz; Namdaroglu, Sinem; Kayikci, Omur; Kaygusuz, Gülsah; Demiriz, Itir; Cinarsoy, Murat; Tekgunduz, Emre; Altuntas, Fevzi

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia. PMID:24416499

  8. Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-04-03

    B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Philadelphia Chromosome Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  9. Decitabine, Vorinostat, and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-19

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  10. Invasive Fungal Infections in Acute Leukemia

    PubMed Central

    Bhatt, Vijaya R.; Viola, George M.; Ferrajoli, Alessandra

    2011-01-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed. PMID:23556092

  11. Invasive fungal infections in acute leukemia.

    PubMed

    Bhatt, Vijaya R; Viola, George M; Ferrajoli, Alessandra

    2011-08-01

    Invasive fungal infection (IFI) is among the leading causes for morbidity, mortality, and economic burden for patients with acute leukemia. In the past few decades, the incidence of IFI has increased dramatically. The certainty of diagnosis of IFI is based on host factors, clinical evidence, and microbiological examination. Advancement in molecular diagnostic modalities (e.g. non-culture-based serum biomarkers such as β-glucan or galactomannan assays) and high-resolution radiological imaging has improved our diagnostic approach. The early use of these diagnostic tests assists in the early initiation of preemptive therapy. Nonetheless, the complexity of IFI in patients with leukemia and the limitations of these diagnostic tools still mandate astute clinical acumen. Its management has been further complicated by the increasing frequency of infection by non-Aspergillus molds (e.g. zygomycosis) and the emergence of drug-resistant fungal pathogens. In addition, even though the antifungal armamentarium has expanded rapidly in the past few decades, the associated mortality remains high. The decision to initiate antifungal treatment and the choice of anti-fungal therapy requires careful consideration of several factors (e.g. risk stratification, local fungal epidemiologic patterns, concomitant comorbidities, drug-drug interactions, prior history of antifungal use, overall cost, and the pharmacologic profile of the antifungal agents). In order to optimize our diagnostic and therapeutic management of IFI in patients with acute leukemia, further basic research and clinical trials are desperately needed.

  12. Generation of Pediatric Leukemia Xenograft Models in NSG-B2m Mice: Comparison with NOD/SCID Mice.

    PubMed

    Gopalakrishnapillai, Anilkumar; Kolb, E Anders; Dhanan, Priyanka; Bojja, Aruna Sri; Mason, Robert W; Corao, Diana; Barwe, Sonali P

    2016-01-01

    Generation of orthotopic xenograft mouse models of leukemia is important to understand the mechanisms of leukemogenesis, cancer progression, its cross talk with the bone marrow microenvironment, and for preclinical evaluation of drugs. In these models, following intravenous injection, leukemic cells home to the bone marrow and proliferate there before infiltrating other organs, such as spleen, liver, and the central nervous system. Moreover, such models have been shown to accurately recapitulate the human disease and correlate with patient response to therapy and prognosis. Thus, various immune-deficient mice strains have been used with or without recipient preconditioning to increase engraftment efficiency. Mice homozygous for the severe combined immune deficiency (SCID) mutation and with non-obese diabetic background (NOD/SCID) have been used in the majority of leukemia xenograft studies. Later, NOD/SCID mice deficient for interleukin 2 receptor gamma chain (IL2Rγ) gene called NSG mice became the model of choice for leukemia xenografts. However, engraftment of leukemia cells without irradiation preconditioning still remained a challenge. In this study, we used NSG mice with null alleles for major histocompatibility complex class I beta2-microglobulin (β2m) called NSG-B2m. This is a first report describing the 100% engraftment efficiency of pediatric leukemia cell lines and primary samples in NSG-B2m mice in the absence of host preconditioning by sublethal irradiation. We also show direct comparison of the engraftment efficiency and growth rate of pediatric acute leukemia cells in NSG-B2m and NOD/SCID mice, which showed 80-90% engraftment efficiency. Secondary and tertiary xenografts in NSG-B2m mice generated by injection of cells isolated from the spleens of leukemia-bearing mice also behaved similar to the primary patient sample. We have successfully engrafted 25 acute lymphoblastic leukemia (ALL) and 5 acute myeloid leukemia (AML) patient samples with

  13. WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-09-12

    Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-09

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  15. Pediatric donor cell leukemia after allogeneic hematopoietic stem cell transplantation in AML patient from related donor.

    PubMed

    Bobadilla-Morales, Lucina; Pimentel-Gutiérrez, Helia J; Gallegos-Castorena, Sergio; Paniagua-Padilla, Jenny A; Ortega-de-la-Torre, Citlalli; Sánchez-Zubieta, Fernando; Silva-Cruz, Rocio; Corona-Rivera, Jorge R; Zepeda-Moreno, Abraham; González-Ramella, Oscar; Corona-Rivera, Alfredo

    2015-01-01

    Here we present a male patient with acute myeloid leukemia (AML) initially diagnosed as M5 and with karyotype 46,XY. After induction therapy, he underwent a HLA-matched allogeneic hematopoietic stem cell transplantation, and six years later he relapsed as AML M1 with an abnormal karyotype //47,XX,+10[2]/47,XX,+11[3]/48,XX,+10,+11[2]/46,XX[13]. Based on this, we tested the possibility of donor cell origin by FISH and molecular STR analysis. We found no evidence of Y chromosome presence by FISH and STR analysis consistent with the success of the allogeneic hematopoietic stem cell transplantation from the female donor. FISH studies confirmed trisomies and no evidence of MLL translocation either p53 or ATM deletion. Additionally 28 fusion common leukemia transcripts were evaluated by multiplex reverse transcriptase-polymerase chain reaction assay and were not rearranged. STR analysis showed a complete donor chimerism. Thus, donor cell leukemia (DCL) was concluded, being essential the use of cytological and molecular approaches. Pediatric DCL is uncommon, our patient seems to be the sixth case and additionally it presented a late donor cell leukemia appearance. Different extrinsic and intrinsic mechanisms have been considered to explain this uncommon finding as well as the implications to the patient.

  16. Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group.

    PubMed

    Duffner, Patricia K; Armstrong, Floyd Daniel; Chen, Lu; Helton, Kathleen J; Brecher, Martin L; Bell, Beverly; Chauvenet, Allen R

    2014-01-01

    Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with "standard-risk" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed ≥2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.

  17. Outcomes in patients with mixed phenotype acute leukemia in Morocco.

    PubMed

    Bachir, Fatima; Zerrouk, Jihane; Howard, Scott C; Graoui, Omar; Lahjouji, Ali; Hessissen, Leila; Bennani, Sanae; Quessar, Assmae; El Aouad, Rajae

    2014-08-01

    Mixed phenotype acute leukemia (MPAL) includes biphenotypic and bilineal types of leukemia, which constitute rare subtypes that require individualized therapy. Outcomes in Moroccan patients with MPAL are unknown. Among 1264 patients with acute leukemia, 20 were classified as having MPAL, including 17 with biphenotypic acute leukemia (1.3%) and 3 with bilineal leukemia (0.2%). There were 8 adults and 12 children. In 12 cases (60%), leukemic blasts expressed myeloid and T-lymphoid antigens, and, in 5 cases (25%), leukemic blasts expressed B lymphoid antigens plus myeloid antigens. Patients were initially treated on protocols for acute myeloid leukemia (n=4), acute lymphoblastic leukemia (ALL, n=14), or with palliative care (n=2). The probability of survival at 2 years in MPAL cases was 52%± 14%. Six of the 12 patients younger than 15 years remain alive versus 1 of 8 adult patients. Patients treated with ALL-directed therapy had significantly higher overall survival than those treated with acute myeloid leukemia-directed therapy (P=0.003). There was no association between the phenotypic characteristics and the clinical outcome (P=0.83). In conclusion, MPAL represents 1.5% of acute leukemia in Morocco. The prognosis is poor, but initial treatment with therapy directed toward ALL, improved supportive care, and the prevention of abandonment of therapy may improve outcomes in this subgroup of patients.

  18. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    MedlinePlus

    ... one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In ... 1 link) PubMed Sources for This Page Döhner H. Implication of the molecular characterization of acute myeloid ...

  19. Vancomycin-resistant Enterococcus bacteremia in a child with acute myeloid leukemia: successful treatment with daptomycin.

    PubMed

    Büyükcam, Ayşe; Karadağ Öncel, Eda; Özsürekçi, Yasemin; Cengiz, Ali B; Kuşkonmaz, Barış; Sancak, Banu

    2016-12-01

    Multiple-drug-resistant enterococcal infections canbe a serious problem in pediatric patients particularly concomitance with severe underlying diseases and lead to significant morbidity and mortality. The treatment options in children are limited compared with adults. We report a 3-year old-boy with acute myeloid leukemia (AML)-M7 and vancomycin-resistant enterococcus bacteremia successfully treated with daptomycin. Daptomycin may be an alternative therapy for VRE infections in children; more studies are needed for extended usage.

  20. Early Discharge and Outpatients Care in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia Previously Treated With Intensive Chemotherapy

    ClinicalTrials.gov

    2015-02-05

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  1. Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-02-27

    Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

  2. Molecular diagnosis of acute myeloid leukemia.

    PubMed

    Watt, Christopher D; Bagg, Adam

    2010-11-01

    The diagnosis and classification of acute myeloid leukemia is multifaceted, requiring the integration of a variety of laboratory findings, with genetic approaches now firmly established as a central component. Molecular genetic technologies continue to evolve and provide additional tiers of both clarity and complexity. Many have rapidly moved into clinical laboratories; others remain as relevant discovery tools, while some are poised to take their place in diagnostic testing menus. Here, we attempt to synthesize the role of various testing modalities and exciting nascent fundamental discoveries, with a view as to how these might be integrated into the contemporary and future evaluation of this group of aggressive hematologic malignancies.

  3. Acute Myeloid Leukemia: A Concise Review

    PubMed Central

    Saultz, Jennifer N.; Garzon, Ramiro

    2016-01-01

    Acute myeloid leukemia (AML) is a heterogeneous clonal disorder characterized by immature myeloid cell proliferation and bone marrow failure. Cytogenetics and mutation testing remain a critical prognostic tool for post induction treatment. Despite rapid advances in the field including new drug targets and increased understanding of the biology, AML treatment remains unchanged for the past three decades with the majority of patients eventually relapsing and dying of the disease. Allogenic transplant remains the best chance for cure for patients with intermediate or high risk disease. In this review, we discuss the landmark genetic studies that have improved outcome prediction and novel therapies. PMID:26959069

  4. Acute nonlymphocytic leukemia: the first 48 hours.

    PubMed

    Ringenberg, Q S; Doll, D C

    1990-08-01

    The initial care of patients with acute nonlymphocytic leukemia can be lifesaving. Such patients are most often treated at tertiary care centers where resident physicians, working under the supervision of a subspecialist, are responsible for the diagnosis and initial treatment. During the first 48 hours, the house officer must recognize and understand the management of perilous complications such as hyperleukocytosis, hemorrhage, and infection. Specific lifesaving measures will grant the patient and his physicians sufficient time to reach a decision regarding the initiation of curative induction chemotherapy.

  5. Blood group change in acute myeloid leukemia

    PubMed Central

    Nambiar, Rakul K.; Prakash, N. P.; Vijayalakshmi, K.

    2017-01-01

    Blood group antigens are either sugars or proteins found attached to the red blood cell membrane. ABO blood group antigens are the most clinically important antigens because they are the most immunogenic. As red blood cell antigens are inherited traits, they are usually not altered throughout the life of an individual. There have been occasional case reports of ABO blood group antigen change in malignant conditions. We report two such cases of ABO antigen alteration associated with acute myeloid leukemia. These patients had suppression of their blood group antigens during their leukemic phase, and the antigens were reexpressed when the patients attained remission. PMID:28127141

  6. Acute promyelocytic leukemia, arsenic, and PML bodies

    PubMed Central

    Le Bras, Morgane; Lallemand-Breitenbach, Valérie

    2012-01-01

    Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation. PMID:22778276

  7. Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-10-24

    B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B Lymphoblastic Lymphoma; Recurrent T Lymphoblastic Leukemia/Lymphoma; Refractory B Lymphoblastic Lymphoma; Refractory T Lymphoblastic Lymphoma; T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

  8. Cutaneous presentation preceding acute monocytic leukemia

    PubMed Central

    Jin, Xianhua; Li, Fuqiu; Li, Xue; Zhu, Wenjing; Mou, Yan; Huang, Yang; Zhao, Huanyu; Gao, Wei; Xia, Jianxin

    2017-01-01

    Abstract Rationale: Cutaneous presentation preceding acute myeloid leukemia (AML) is rare, and the prognosis is poor. Patient concerns: We report 4 cases of AML cutis, where skin infiltration precedes any blood or bone marrow evidence of leukemia. We also reviewed 13 cases reported in English and Chinese literature. The 4 cases all presented typical cutaneous lesions without any systemic evidence of leukemia. Histopathological examination found that dense monomorphous cell infiltration involved the dermis. Some cells surrounded blood vessels and skin appendages in a concentric manner or showed single-row arrangement in the collagen fiber bundles. Uninvolved papillary dermis was found to separate normal epidermis from dermal infiltration. Minor cells had a large kidney-shaped or oval nucleus with nucleoli and slightly eosinophilic cytoplasm. Immunohistochemical analysis was positive for CD4, CD56, while CD123 was negative in all cases. Diagnoses: AML-M5. Interventions: 2 patients received chemotherapy ,but others rejected treatment. Outcomes: Most patients died within 1 year after the onset of skin lesions. Lessons: These findings suggest that skin infiltration of AML may precede any systemic evidence, and typical cutaneous lesions in elderly individuals may be indicative for AML. PMID:28272239

  9. Decitabine and Valproic Acid in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Previously Treated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-09-27

    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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms.

    PubMed

    Hernández, Antonio F; Menéndez, Pablo

    2016-03-29

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events.

  11. Linking Pesticide Exposure with Pediatric Leukemia: Potential Underlying Mechanisms

    PubMed Central

    Hernández, Antonio F.; Menéndez, Pablo

    2016-01-01

    Leukemia is the most common cancer in children, representing 30% of all childhood cancers. The disease arises from recurrent genetic insults that block differentiation of hematopoietic stem and/or progenitor cells (HSPCs) and drives uncontrolled proliferation and survival of the differentiation-blocked clone. Pediatric leukemia is phenotypically and genetically heterogeneous with an obscure etiology. The interaction between genetic factors and environmental agents represents a potential etiological driver. Although information is limited, the principal toxic mechanisms of potential leukemogenic agents (e.g., etoposide, benzene metabolites, bioflavonoids and some pesticides) include topoisomerase II inhibition and/or excessive generation of free radicals, which may induce DNA single- and double-strand breaks (DNA-DSBs) in early HSPCs. Chromosomal rearrangements (duplications, deletions and translocations) may occur if these lesions are not properly repaired. The initiating hit usually occurs in utero and commonly leads to the expression of oncogenic fusion proteins. Subsequent cooperating hits define the disease latency and occur after birth and may be of a genetic, epigenetic or immune nature (i.e., delayed infection-mediated immune deregulation). Here, we review the available experimental and epidemiological evidence linking pesticide exposure to infant and childhood leukemia and provide a mechanistic basis to support the association, focusing on early initiating molecular events. PMID:27043530

  12. Adolescents and young adults with acute lymphoblastic leukemia.

    PubMed

    Stock, Wendy

    2010-01-01

    During the last decade, increasing attention has been paid to a unique group of patients with acute lymphoblastic leukemia (ALL) who lie at the crossroad of therapeutic care by pediatric and adult hematologists/oncologists. ALL is a disease that affects infants, children, adolescents, and adult patients. With current therapies, the vast majority of children with ALL are now long-term survivors; unfortunately, the same good results have not yet been obtained for adults with ALL. This review will describe current controversies surrounding the treatment of adolescents and young adults with ALL--a group who finds themselves in the transition from "pediatric" to "adult" treatment approaches. The review focuses on recent insights into disease biology, prognostic factors, and treatment outcomes that have led to a series of prospective clinical trials specifically designed for adolescents and younger adults (AYAs) with ALL. These trials have been designed to provide important new clinical, psychosocial, and biological insights, and to further improve the survival of this challenging and unique group of patients.

  13. Chromosome abnormalities in acute lymphoblastic leukemia

    SciTech Connect

    Rowley, J.D.

    1980-01-01

    Less information is available on the cytogenetic abnormalities in marrow cells of patients with acute lymphoblastic leukemia (ALL) than on abnormalities in acute nonlymphocytic leukemia (ANLL); nonetheless, some patterns of karyotypic change in ALL are evident. Even with banding, about 50% of patients appear to have a normal karyotype. The modal chromosome number tends to be higher in ALL than in ANLL. Every patient with B-cell ALL has had an abnormality of one chromosome No. 14 that involved the translocation of material to the end of the long arm. Among seven reported cases, the translocation was from 8q in three patients and 11q in one. Cells with a haploid or near-haploid (24 to 35) chromosome number have been reported in five patients with ALL and in four patients in a lymphoid blast crisis of chronic myelogeneous leukemia. The karyotype in the four ALL patients whose cells were analyzed with banding was remarkably consistent. All patients had the haploid number, usually with both sex chromosomes, plus an additional No. 10, 18, and 21. Evolution of the karyotype, which occurs in the leukemic cells of about 50% of patients, involves cells of patients who had an initially normal or an initially abnormal karyotype. The evidence regarding a correlation between the presence of an abnormal clone prior to treatment and response to treatment is contradictory at present. Some chromosome abnormalities, such as the presence of a Philadelphia (Ph/sup 1/) chromosome, a 14q+chromosome, or a haploid clone, are associated with a relatively short survival.

  14. Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-08

    Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  15. Sorafenib Tosylate and Chemotherapy in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-14

    Acute Myeloid Leukemia (Megakaryoblastic) With t(1;22)(p13;q13); RBM15-MKL1; Acute Myeloid Leukemia With a Variant RARA Translocation; Acute Myeloid Leukemia With Inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; Acute Myeloid Leukemia With t(6;9)(p23;q34); DEK-NUP214; Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Acute Myeloid Leukemia With Variant MLL Translocations; Untreated Adult Acute Myeloid Leukemia

  16. Cyclosporine, Pravastatin Sodium, Etoposide, and Mitoxantrone Hydrochloride in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2012-06-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  17. Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-12-22

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  18. Challenges of Clinical Trial Design for Targeted Agents Against Pediatric Leukemias

    PubMed Central

    Mussai, Francis Jay; Yap, Christina; Mitchell, Christopher; Kearns, Pamela

    2015-01-01

    The past 40 years have seen significant improvements in both event-free and overall survival for children with acute lymphoblastic and acute myeloid leukemia (ALL and AML, respectively). Serial national and international clinical trials have optimized the use of conventional chemotherapeutic drugs and, along with improvements in supportive care that have enabled the delivery of more intensive regimens, have been responsible for the major improvements in patient outcome seen over the past few decades. However, the benefits of dose intensification have likely now been maximized, and over the same period, the identification of new cytotoxic drugs has been limited. Therefore, challenges remain if survival is to be improved further. In pediatric ALL, 5-year-survival rates of over 85% have been achieved with risk-stratified therapy, but a notable minority of patients will still not be cured. In pediatric AML, different challenges remain. A slower improvement in overall survival has taken place in this patient population. Despite the obvious morphological heterogeneity of AML blasts, biological stratification is comparatively limited, and translation into risk-stratified therapeutic approaches has only best characterized by the use of retinoic acid for t(15;17)-positive AML. Even where prognostic markers have been identified, limited therapeutic options or multi-drug resistance of AML blasts has limited the impact on patient benefit. For both, the acute morbidities of current treatment remain significant and may be life-threatening alone. In addition, the Childhood Cancer Survivor Study (CCSS) highlighted many leukemia survivors develop one or more chronic medical conditions attributable to treatment (1, 2). As the biology of leukemogenesis has become better understood, key molecules and intracellular pathways have been identified that offer the possibility of targeting directly the leukemia cells while sparing normal cells. Consequently, there is now a drive to develop

  19. Vorinostat and Decitabine in Treating Patients With Advanced Solid Tumors or Relapsed or Refractory Non-Hodgkin's Lymphoma, Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-08-26

    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; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; 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 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; Secondary Acute Myeloid Leukemia; Splenic Marginal Zone Lymphoma; 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 Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic 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 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 Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic 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

  20. Novel gene targets detected by genomic profiling in a consecutive series of 126 adults with acute lymphoblastic leukemia.

    PubMed

    Safavi, Setareh; Hansson, Markus; Karlsson, Karin; Biloglav, Andrea; Johansson, Bertil; Paulsson, Kajsa

    2015-01-01

    In contrast to acute lymphoblastic leukemia in children, adult cases of this disease are associated with a very poor prognosis. In order to ascertain whether the frequencies and patterns of submicroscopic changes, identifiable with single nucleotide polymorphism array analysis, differ between childhood and adult acute lymphoblastic leukemia, we performed single nucleotide polymorphism array analyses of 126 adult cases, the largest series to date, including 18 paired diagnostic and relapse samples. Apart from identifying characteristic microdeletions of the CDKN2A, EBF1, ETV6, IKZF1, PAX5 and RB1 genes, the present study uncovered novel, focal deletions of the BCAT1, BTLA, NR3C1, PIK3AP1 and SERP2 genes in 2-6% of the adult cases. IKZF1 deletions were associated with B-cell precursor acute lymphoblastic leukemia (P=0.036), BCR-ABL1-positive acute lymphoblastic leukemia (P<0.001), and higher white blood cell counts (P=0.005). In addition, recurrent deletions of RASSF3 and TOX were seen in relapse samples. Comparing paired diagnostic/relapse samples revealed identical changes at diagnosis and relapse in 27%, clonal evolution in 22%, and relapses evolving from ancestral clones in 50%, akin to what has previously been reported in pediatric acute lymphoblastic leukemia and indicating that the mechanisms of relapse may be similar in adult and childhood cases. These findings provide novel insights into the leukemogenesis of adult acute lymphoblastic leukemia, showing similarities to childhood disease in the pattern of deletions and the clonal relationship between diagnostic and relapse samples, but with the adult cases harboring additional aberrations that have not been described in pediatric acute lymphoblastic leukemia.

  1. Nuclear imaging in the pediatric acute scrotum

    SciTech Connect

    Valvo, J.R.; Caldamone, A.A.; O'Mara, R.; Rabinowitz, R.

    1982-09-01

    The acute scrotum in the pediatric patient frequently presents a diagnostic dilemma for even the most experienced clinician. In an effort to improve testicular salvage in equivocal cases, immediate surgical intervention has been recommended, despite a large number of unnecessary explorations. Evaluating the sodium pertechnetate /sup 99m/Tc radioisotopic scan in 46 boys, we found this study to be a rapid, reliable, sensitive, and noninvasive test that allows the selection of those patients who require immediate surgical intervention.

  2. New Strategies in Acute Myelogenous Leukemia: Leukemogenesis and Personalized Medicine

    PubMed Central

    Gojo, Ivana; Karp, Judith E.

    2014-01-01

    Recent advances in molecular technology have unraveled the complexity of leukemogenesis and provided the opportunity to design more personalized and pathophysiology-targeted therapeutic strategies. Despite the use of intensive chemotherapy, relapse remains the most common cause for therapeutic failure in acute myelogenous leukemia (AML). The interactions between leukemia stem cells (LSC) and marrow microenvironment appear to be critical in promoting therapeutic resistance through progressive acquisition of genetic and epigenetic changes within leukemia cells and immune evasion, resulting in leukemia cell survival. With advances in genomic sequencing efforts, epigenetic and phenotypic characterization, personalized therapeutic strategies aimed at critical leukemia survival mechanisms may be feasible in the near future. Here, we review select novel approaches to therapy of AML such as targeting LSC, altering leukemia/marrow microenvironment interactions, inhibiting DNA repair or cell cycle checkpoints, and augmenting immune-based anti-leukemia activity. PMID:25324141

  3. Study of Posterior Reversible Encephalopathy Syndrome in Children With Acute Lymphoblastic Leukemia After Induction Chemotherapy.

    PubMed

    Tang, Ji-Hong; Tian, Jian-Mei; Sheng, Mao; Hu, Shao-Yan; Li, Yan; Zhang, Li-Ya; Gu, Qing; Wang, Qi

    2016-03-01

    Increasing occurrence of posterior reversible encephalopathy syndrome has been reported in children with acute lymphoblastic leukemia. However, the etiology of posterior reversible encephalopathy syndrome is not clear. To study the possible pathogenetic mechanisms and treatment of this complication, we reported 11 cases of pediatric acute lymphoblastic leukemia who developed posterior reversible encephalopathy syndrome after induction chemotherapy. After appropriate treatment, the clinical symptoms of posterior reversible encephalopathy syndrome in most cases disappeared even though induction chemotherapy continued. During the 1-year follow-up, no recurrence of posterior reversible encephalopathy syndrome was observed. Although the clinical and imaging features of posterior reversible encephalopathy syndrome may be diverse, posterior reversible encephalopathy syndrome should be recognized as a possible important complication of acute lymphoblastic leukemia when neurologic symptoms appear. In line with previous reports, our study also indicated that posterior reversible encephalopathy syndrome was reversible when diagnosed and treated at an early stage. Thus, the occurrence of posterior reversible encephalopathy syndrome should be considered and investigated to optimize the early induction scheme of acute lymphoblastic leukemia treatment.

  4. Histiocytic differentiation in acute monocytic leukemia.

    PubMed

    Ru, Yong-xin; Dong, Shu-xu; Zhao, Shi-xuan; Liang, Hao-yue; Wang, Hui-jun; Hu, Xiao; Mi, Ying-chang; Wang, Jian-xiang

    2016-01-01

    Myeloid histocytes of dendritic cells (DCs), Langerhans cells (LCs), and macrophages in varied tissues, as leukemic blasts in acute monoblastic and monocytic leukemia (AML-M5a and M5b), are derived from monocyte progenitors in bone marrow. Based on DC induction from hematopoietic stem cells, myeloid progenitors, and monocytes, and occasional expressions of histocyte-related antigens (HRAs) in M5, we presume some M5 cases share histiocytic phenotypes originally. To clarify the conception, 93 M5 cases were tested with antibodies for HRAs, CD1a, CD163, S100, fascin, and langerin by immunostaining, and their morphologic characteristics were studied by light and transmission electron microscopy. The study revealed that 23 M5 cases were positive for two or more kinds of HRAs and shared a serial of histocytic immunophenotype and morphologic features, which were closely associated with M5b subtype and expression of CD14 in M5.

  5. Precision medicine for acute myeloid leukemia.

    PubMed

    Lai, Catherine; Karp, Judith E; Hourigan, Christopher S

    2016-01-01

    The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints.

  6. Precision Medicine for Acute Myeloid Leukemia

    PubMed Central

    Lai, Catherine; Karp, Judith E.; Hourigan, Christopher S.

    2016-01-01

    The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints. PMID:26514194

  7. Acute lymphoblastic leukemia and developmental biology

    PubMed Central

    Campos-Sanchez, Elena; Toboso-Navasa, Amparo; Romero-Camarero, Isabel; Barajas-Diego, Marcos

    2011-01-01

    The latest scientific findings in the field of cancer research are redefining our understanding of the molecular and cellular basis of the disease, moving the emphasis toward the study of the mechanisms underlying the alteration of the normal processes of cellular differentiation. The concepts best exemplifying this new vision are those of cancer stem cells and tumoral reprogramming. The study of the biology of acute lymphoblastic leukemias (ALLs) has provided seminal experimental evidence supporting these new points of view. Furthermore, in the case of B cells, it has been shown that all the stages of their normal development show a tremendous degree of plasticity, allowing them to be reprogrammed to other cellular types, either normal or leukemic. Here we revise the most recent discoveries in the fields of B-cell developmental plasticity and B-ALL research and discuss their interrelationships and their implications for our understanding of the biology of the disease. PMID:22031225

  8. Pneumomediastinum after acute lymphoblastic leukemia and chemotherapy?

    PubMed Central

    Cruz-Portelles, Alain

    2014-01-01

    Pneumomediastinum, pneumorachis and subcutaneous emphysema are frequently benign and most commonly result from air escaping from the upper respiratory tract, intrathoracic airways, or gastrointestinal tract. Gas can also be generated by certain infections or reach the mediastinal space from outside air after trauma or surgery. In the article presented by Showkat et al a 14-year-old male patient with acute lymphoblastic leukemia (ALL) under chemotherapy developed pneumomediastinum, pneumorachis and subcutaneous emphysema. In the author’s opinion, these complications were caused by ALL or chemotherapy that progressed to severe respiratory failure until the patient finally died in the intensive care unit. I would like to underline some important points, which have been raised following a paper published in the October issue of World Journal of Clinical Cases. PMID:24868520

  9. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-04-03

    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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Translocation t(8;14)(q24;q11) with concurrent PTEN alterations and deletions of STIL/TAL1 and CDKN2A/B in a pediatric case of acute T-lymphoblastic leukemia: A genetic profile associated with adverse prognosis.

    PubMed

    Skalska-Sadowska, Jolanta; Dawidowska, Małgorzata; Szarzyńska-Zawadzka, Bronisława; Jarmuż-Szymczak, Małgorzata; Czerwińska-Rybak, Joanna; Machowska, Ludomiła; Derwich, Katarzyna

    2017-04-01

    We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations. This case documents an unfavorable prognostic potential of a co-occurrence of this set of molecular genetic events and addresses risk stratification in T-ALL.

  11. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-03-13

    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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Pseudomonas Aeruginosa Endocarditis in Acute Myeloid Leukemia: A Rare Complication

    PubMed Central

    J, Barshay; A, Nemets; A, Ducach; G, Lugassy

    2008-01-01

    Infectious endocarditis is a rarely encountered complication among leukemia patient during induction therapy. We describe a young patient who developed prolonged high fever after aggressive chemotherapy for Acute Myeloid Leukemia. Pseudomonas Aeruginosa endocarditis was found to be the etiology for the febrile state. Our purpose is to emphasize the need for an early diagnosis of this rare, albeit treatable complication. PMID:23675106

  13. Acute erythroid leukemia with multilineage dysplasia in a cat.

    PubMed

    Shirani, Dariush; Nassiri, Seyed Mahdi; Aldavood, Seyed Javid; Seddigh, Hamideh Salari; Fathi, Ezzatollah

    2011-04-01

    Dysplastic features of erythroid and megakaryocytic lineages were observed in a cat with acute erythroid leukemia. We demonstrated that flow cytometry analysis of the expression of glycophorin A and CD71 by neoplastic cells can be helpful in the diagnosis of this type of feline leukemia.

  14. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    ClinicalTrials.gov

    2017-04-05

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  15. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePlus

    ... and Prevention What Are the Risk Factors for Acute Lymphocytic Leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  16. Genetics Home Reference: familial acute myeloid leukemia with mutated CEBPA

    MedlinePlus

    ... terminal C/EBPalpha mutation. Genes Chromosomes Cancer. 2010 Mar;49(3):237-41. doi: 10.1002/gcc. ... EBPalpha), in acute myeloid leukemia. Nat Genet. 2001 Mar;27(3):263-70. Citation on PubMed Renneville ...

  17. Endometrial and acute myeloid leukemia cancer genomes characterized

    Cancer.gov

    Two studies from The Cancer Genome Atlas (TCGA) program reveal details about the genomic landscapes of acute myeloid leukemia (AML) and endometrial cancer. Both provide new insights into the molecular underpinnings of these cancers.

  18. Serum metabonomics of acute leukemia using nuclear magnetic resonance spectroscopy

    PubMed Central

    Musharraf, Syed Ghulam; Siddiqui, Amna Jabbar; Shamsi, Tahir; Choudhary, M. Iqbal; Rahman, Atta-ur

    2016-01-01

    Acute leukemia is a critical neoplasm of white blood cells. In order to differentiate between the metabolic alterations associated with two subtypes of acute leukemia, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), we investigated the serum of ALL and AML patients and compared with two controls (healthy and aplastic anemia) using 1H NMR (nuclear magnetic resonance) spectroscopy. Thirty-seven putative metabolites were identified using Carr-Purcell-Meiboom-Gill (CPMG) sequence. The use of PLS-DA and OPLS-DA models gave results with 84.38% and 90.63% classification rate, respectively. The metabolites responsible for classification are mainly lipids, lactate and glucose. Compared with controls, ALL and AML patients showed serum metabonomic differences involving aberrant metabolism pathways including glycolysis, TCA cycle, lipoprotein changes, choline and fatty acid metabolisms. PMID:27480133

  19. Clofarabine, Cytarabine, and Filgrastim Followed by Infusion of Non-HLA Matched Ex Vivo Expanded Cord Blood Progenitors in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-08-13

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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 Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. [Problems in maintenance therapy in acute myeloid leukemias in adults].

    PubMed

    Gürtler, R; Raderecht, C

    1975-01-01

    Problems of maintaining therapy for acute myelocytic leukemias in adults are discussed. The analysis of the maintaining therapy in 22 patients affected with an acute myelocytic leukemia and living for more than 6 months revealed that the interval therapy with a high dosage of cytostatic combinations in the sense of the COAP scheme is preferable compared with the daily administration of 6-mercaptopurin, in addition methotrexate twice a week. Reasons for this are discussed.

  1. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  2. [Acute myeloid leukemia originating from the same leukemia clone after the complete remission of acute lymphoid leukemia].

    PubMed

    Matsuda, Isao; Nakamaki, Tsuyoshi; Amaya, Hiroshi; Kiyosaki, Masanobu; Kawakami, Keiichiro; Yamada, Kazunari; Yokoyama, Akihiro; Hino, Ken-ichiro; Tomoyasu, Shigeru

    2003-09-01

    A 22-year-old female was diagnosed as having acute lymphoid leukemia (ALL) in February 1995, from the findings of peroxidase negative, CD10+, CD19+, TdT+ and rearrangement of IgH and TCR beta. AdVP (doxorubicin, vincristine and prednisolone) therapy achieved a complete remission (CR). Bone marrow transplantation had to be abandoned because of the lack of an HLA-identical donor. Intensification therapy was thus carried out repeatedly. In June 1998, myeloblast with Auer rods, peroxidase positive, CD13+, CD33+ and HLA-DR+, appeared. The patient was diagnosed as having lineage switch acute myeloid leukemia (AML) from ALL. Though A-DMP (cytosine arabinoside, daunorubicin, 6-mercaptopurine) therapy was resistant, AdVP therapy led to a CR. The patient died of cardiotoxicity from anthracyclines in February 1999. From the results of the Ramasamy method using the clonal rearrangements of the Ig heavy chain gene locus, the origin of the pathological cells of ALL and AML was indicated to be the same leukemia clone.

  3. Acute promyelocytic leukemia: new issues on pathogenesis and treatment response.

    PubMed

    Vitoux, Dominique; Nasr, Rihab; de The, Hugues

    2007-01-01

    Pathogenesis of acute promyelocytic leukemia appears to be one of the best understood among human malignancies. The ability of retinoic acid (RA) and arsenic trioxide to directly target the oncogenic promyelocytic leukemia-retinoic receptor A (PML-RARA) fusion protein also made this disease the first model for oncogene-targeted therapies. A set of recent data has significantly increased the complexity of our view of acute promyelocytic leukemia pathogenesis, as well as of therapeutic response. This review summarizes and discusses these findings, which yield novels questions and models.

  4. The evolution of clinical trials for infant acute lymphoblastic leukemia

    PubMed Central

    Kotecha, R S; Gottardo, N G; Kees, U R; Cole, C H

    2014-01-01

    Acute lymphoblastic leukemia (ALL) in infants has a significantly inferior outcome in comparison with older children. Despite initial improvements in survival of infants with ALL since establishment of the first pediatric cooperative group ALL trials, the poor outcome has plateaued in recent years. Historically, infants were treated on risk-adapted childhood ALL protocols. These studies were pivotal in identifying the need for infant-specific protocols, delineating prognostic categories and the requirement for a more unified approach between study groups to overcome limitations in accrual because of low incidence. This subsequently led to the development of collaborative infant-specific studies. Landmark outcomes have included the elimination of cranial radiotherapy following the discovery of intrathecal and high-dose systemic therapy as a superior and effective treatment strategy for central nervous system disease prophylaxis, with improved neurodevelopmental outcome. Universal prospective identification of independent adverse prognostic factors, including presence of a mixed lineage leukemia rearrangement and young age, has established the basis for risk stratification within current trials. The infant-specific trials have defined limits to which conventional chemotherapeutic agents can be intensified to optimize the balance between treatment efficacy and toxicity. Despite variations in therapeutic intensity, there has been no recent improvement in survival due to the equilibrium between relapse and toxicity. Ultimately, to improve the outcome for infants with ALL, key areas still to be addressed include identification and adaptation of novel prognostic markers and innovative therapies, establishing the role of hematopoietic stem cell transplantation in first complete remission, treatment strategies for relapsed/refractory disease and monitoring and timely intervention of late effects in survivors. This would be best achieved through a single unified

  5. Risk Factors for Acute Leukemia in Children: A Review

    PubMed Central

    Belson, Martin; Kingsley, Beverely; Holmes, Adrianne

    2007-01-01

    Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics. PMID:17366834

  6. How I treat hematologic emergencies in adults with acute leukemia.

    PubMed

    Zuckerman, Tsila; Ganzel, Chezi; Tallman, Martin S; Rowe, Jacob M

    2012-09-06

    Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. Whereas clinical trials form the backbone for the management of acute leukemia, emergent clinical situations, predictable or not, are common and do not readily lend themselves to clinical trial evaluation. Furthermore, practice guidelines are often lacking. Not only are prospective trials impractical because of the emergent nature of the issue at hand, but clinicians are often reluctant to randomize such patients. Extensive practical experience is crucial and, even if there is no consensus, management of such emergencies should be guided by an understanding of the underlying pathophysiologic mechanisms.

  7. [Our experiences in the treatment of acute leukemias].

    PubMed

    Jelić, S; Dragović, M; Vidaković, B; Plecas, V

    1976-01-01

    This paper deals with observations concerning treatment of acute leukemia in the Department of haematology of The Clinical hospital of Belgrade during the period from 1970 to 1975, and with results of the treatment itself. During the last five years, 27 patients with different types of acute leukemia were treated. The type of acute leukemia was determined using cytological criteria of Levy and Lortholary and cytochemical criteria as described by Hayhoe. One thrid of the patients died during the first days of hospitalisation, before any effect of cytostatic treatment could be evaluated. The cause of death in those patients was septic shock, intracranial haemorrhage or cardiovascular colapsus; initial signs of those complications of acute leukemia were allready present before diagnosis. Those data point to the fact that diagnosis of acute leukemia is often made too late, when irreversible ocmplications of the disease are allready established. Patients over sixty, often "fragile" to aggresive cytostatic therapy, may enter complete and relatively long lasting remission with induction therapy cosisting of 6-mercaptopurine and methotrexate only. Allthough the number of cases was rather limited, the authors had rather disappointing results with the 06-LA-66 protocole in adult lymphoblastic leukemia. The first with COAP treatment protocole seem encouraging. Adequate cytostatic therapy was in several cases impossible, duo to the lack of adequate substitution therapy; such inadequate cytostatic therapy resulted in partial remissions with a rather poor quality survival. A beeter cooperation is needed between hospital centers and institutions which provide matherial for the substitution theapy.

  8. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults.

    PubMed

    Testi, Anna Maria; D'Angiò, Mariella; Locatelli, Franco; Pession, Andrea; Lo Coco, Francesco

    2014-01-01

    The outcome of adults and children with Acute Promyelocytic Leukemia (APL) has dramatically changed since the introduction of all trans retinoic acid (ATRA) therapy. Based on the results of several multicenter trials, the current recommendations for the treatment of patients with APL include ATRA and anthracycline-based chemotherapy for the remission induction and consolidation, and ATRA combined with low-dose chemotherapy for maintenance. This has improved the prognosis of APL by increasing the complete remission (CR) rate, actually > 90%, decreasing the induction deaths and by reducing the relapse rate, leading to cure rates nowadays exceeding 80% considering both adults and children.1-9 More recently the combination of ATRA and arsenic trioxide (ATO) as induction and consolidation therapy has been shown to be at least not inferior and possibly superior to ATRA plus chemotherapy in adult patients with APL conventionally defined as non-high risk (Sanz score).10 Childhood APL has customarily been treated on adult protocols. Data from several trials have shown that the overall outcome in pediatric APL appears similar to that reported for the adult population; however, some clinical and therapeutic aspects differ in the two cohorts which require some important considerations and treatment adjustments.

  9. Acute Promyelocytic Leukemia (APL): Comparison Between Children and Adults

    PubMed Central

    Testi, Anna Maria; D’Angiò, Mariella; Locatelli, Franco; Pession, Andrea; Lo Coco, Francesco

    2014-01-01

    The outcome of adults and children with Acute Promyelocytic Leukemia (APL) has dramatically changed since the introduction of all trans retinoic acid (ATRA) therapy. Based on the results of several multicenter trials, the current recommendations for the treatment of patients with APL include ATRA and anthracycline-based chemotherapy for the remission induction and consolidation, and ATRA combined with low-dose chemotherapy for maintenance. This has improved the prognosis of APL by increasing the complete remission (CR) rate, actually > 90%, decreasing the induction deaths and by reducing the relapse rate, leading to cure rates nowadays exceeding 80% considering both adults and children.1–9 More recently the combination of ATRA and arsenic trioxide (ATO) as induction and consolidation therapy has been shown to be at least not inferior and possibly superior to ATRA plus chemotherapy in adult patients with APL conventionally defined as non-high risk (Sanz score).10 Childhood APL has customarily been treated on adult protocols. Data from several trials have shown that the overall outcome in pediatric APL appears similar to that reported for the adult population; however, some clinical and therapeutic aspects differ in the two cohorts which require some important considerations and treatment adjustments. PMID:24804005

  10. Decitabine as Maintenance Therapy After Standard Therapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-12-05

    Acute Myeloid Leukemia With Myelodysplasia-Related Changes; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Untreated Adult Acute Myeloid Leukemia

  11. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-04

    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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  12. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    ClinicalTrials.gov

    2017-03-13

    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); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  13. Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-09-16

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2017-01-25

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  15. GTI-2040 and High-Dose Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    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); Recurrent Adult Acute Myeloid Leukemia

  16. The PAX5 gene is frequently rearranged in BCR-ABL1-positive acute lymphoblastic leukemia but is not associated with outcome. A report on behalf of the GIMEMA Acute Leukemia Working Party

    PubMed Central

    Iacobucci, Ilaria; Lonetti, Annalisa; Paoloni, Francesca; Papayannidis, Cristina; Ferrari, Anna; Storlazzi, Clelia Tiziana; Vignetti, Marco; Cilloni, Daniela; Messa, Francesca; Guadagnuolo, Viviana; Paolini, Stefania; Elia, Loredana; Messina, Monica; Vitale, Antonella; Meloni, Giovanna; Soverini, Simona; Pane, Fabrizio; Baccarani, Michele; Foà, Robin; Martinelli, Giovanni

    2010-01-01

    Background Recently, in genome-wide analyses of DNA copy number abnormalities using single nucleotide polymorphism microarrays, genetic alterations targeting PAX5 were identified in over 30% of pediatric patients with acute lymphoblastic leukemia. So far the occurrence of PAX5 alterations and their clinical correlation have not been investigated in adults with BCR-ABL1-positive acute lymphoblastic leukemia. Design and Methods The aim of this study was to characterize the rearrangements on 9p involving PAX5 and their clinical significance in adults with BCR-ABL1-positive acute lymphoblastic leukemia. Eighty-nine adults with de novo BCR-ABL1-positive acute lymphoblastic leukemia were enrolled into institutional (n=15) or GIMEMA (Gruppo Italiano Malattie EMatologiche dell’Adulto) (n=74) clinical trials and, after obtaining informed consent, their genome was analyzed by single nucleotide polymorphism arrays (Affymetrix 250K NspI and SNP 6.0), genomic polymerase chain reaction analysis and re-sequencing. Results PAX5 genomic deletions were identified in 29 patients (33%) with the extent of deletions ranging from a complete loss of chromosome 9 to the loss of a subset of exons. In contrast to BCR-ABL1-negative acute lymphoblastic leukemia, no point mutations were found, suggesting that deletions are the main mechanism of inactivation of PAX5 in BCR-ABL1-positive acute lymphoblastic leukemia. The deletions were predicted to result in PAX5 haploinsufficiency or expression of PAX5 isoforms with impaired DNA-binding. Deletions of PAX5 were not significantly correlated with overall survival, disease-free survival or cumulative incidence of relapse, suggesting that PAX5 deletions are not associated with outcome. Conclusions PAX5 deletions are frequent in adult BCR-ABL1-positive acute lymphoblastic leukemia and are not associated with a poor outcome. PMID:20534699

  17. Elastase mediated fibrinolysis in acute promyelocytic leukemia.

    PubMed

    Oudijk, E J; Nieuwenhuis, H K; Bos, R; Fijnheer, R

    2000-06-01

    The bleeding syndrome of acute promyelocytic leukemia (APL) is complex and consists of disseminated intravascular coagulation (DIC) and hyperfibrinolysis. Elastase, derived from malignant promyelocytes, is believed to mediate the fibrinogeno- and fibrinolysis by aspecific proteolysis. In this study we measured the role of elastase in fifteen patients with APL by using an assay for elastase degraded fibrin(ogen) and the results were compared with those obtained in patients with sepsis induced DIC. High levels of elastase were observed in sepsis and APL. The levels of fibrinogen and fibrin degradation products were significantly higher in APL patients compared to patients with sepsis induced DIC. Nevertheless, the level of elastase degraded fibrin(ogen) was higher in the sepsis group (635.3 ng/ml, compared to 144.3 ng/ml in APL; p <0.0001). So, the enormous increase in fibrin and fibrinogen degradation products in APL cannot be explained by elastase activity. This study suggests a minor role for elastase mediated proteolysis in the hemorrhagic diathesis in APL patients.

  18. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    PubMed Central

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  19. [Prognostic factors in acute nonlymphoid leukemias].

    PubMed

    Capelli, D; Tedeschi, A; Montillo, M; Corvatta, L; Bartocci, C; Montroni, M; Leoni, P

    1996-10-01

    Our retrospective study was aimed at assessing parameters affecting the prognosis of acute non lymphoid leukemia (ANLL). Since 1988 to 1994 we observed 84 patients: 52 males, 32 females. For each patient we considered at diagnosis: age, fever, performance status, platelets, hemoglobin and white blood cell count, extramidollary disease, bone marrow blastosis, phenotype and cytogenetic abnormalities of blasts cells. All the parameters listed above were correlated with the time to achieve the complete remission (CR), CR duration and the overall survival. Statistical tests as t-student and chi square test were used. Statistical analysis of the parameters considered revealed that the only value affecting the achievement of a CR was the age. The prognostic significance of immunophenotyping in ANLL has been a controversial issue, with a number of conflicting reports. In our study only the terminal deoxynucleotidyl transferase was significantly associated with prognosis. Our study, as data reported in literature, confirms that the prognostic impact of the various parameters in ANLL is controversial. The study of prognostic factors and of the immunophenotype is important to identify the clinical and the biologic profile of the disease and to evaluate the optimal post-remission treatment.

  20. Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2017-01-05

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Myelodysplastic Syndrome; Childhood Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

  1. Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia

    PubMed Central

    Poglio, Sandrine; Lewandowski, Daniel; Calvo, Julien; Caye, Aurélie; Gros, Audrey; Laharanne, Elodie; Leblanc, Thierry; Landman-Parker, Judith; Baruchel, André; Soulier, Jean; Ballerini, Paola; Clappier, Emmanuelle; Pflumio, Françoise

    2016-01-01

    T cell acute lymphoblastic leukemia (T-ALL) develops through accumulation of multiple genomic alterations within T-cell progenitors resulting in clonal heterogeneity among leukemic cells. Human T-ALL xeno-transplantation in immunodeficient mice is a gold standard approach to study leukemia biology and we recently uncovered that the leukemia development is more or less rapid depending on T-ALL sample. The resulting human leukemia may arise through genetic selection and we previously showed that human T-ALL development in immune-deficient mice is significantly enhanced upon CD7+/CD34+ leukemic cell transplantations. Here we investigated the genetic characteristics of CD7+/CD34+ and CD7+/CD34− cells from newly diagnosed human T-ALL and correlated it to the speed of leukemia development. We observed that CD7+/CD34+ or CD7+/CD34− T-ALL cells that promote leukemia within a short-time period are genetically similar, as well as xenograft-derived leukemia resulting from both cell fractions. In the case of delayed T-ALL growth CD7+/CD34+ or CD7+/CD34− cells were either genetically diverse, the resulting xenograft leukemia arising from different but branched subclones present in the original sample, or similar, indicating decreased fitness to mouse micro-environment. Altogether, our work provides new information relating the speed of leukemia development in xenografts to the genetic diversity of T-ALL cell compartments. PMID:27191650

  2. The role of p38 mitogen-activated protein kinase in serum-induced leukemia inhibitory factor secretion by bone marrow stromal cells from pediatric myelodysplastic syndromes.

    PubMed

    da Costa, Simone V; Roela, Rosimeire A; Junqueira, Mara Souza; Arantes, Camila; Brentani, M Mitzi

    2010-04-01

    Stromal cells from pediatric myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) associated with MDS (MDS-AML) present high expression of leukemia inhibitor factor (LIF). We demonstrated using mitogen-activated protein kinase (MAPK) inhibitors that in stromal cells from pediatric MDS and MDS-AML, p38MAPK was critical in serum-induced secretion of LIF. The serum induction of phosphorylated p38MAPK form was observed only in stromal cells from healthy children, whereas in MDS and MDS-AML basal levels were maintained suggesting constitutive p38MAPK activation. Our study suggested the possible importance in pediatric MDS of p38MAPK signaling pathway which may be a future therapeutic target.

  3. Bacillus cereus bacteremia in an adult with acute leukemia.

    PubMed

    Funada, H; Uotani, C; Machi, T; Matsuda, T; Nonomura, A

    1988-03-01

    Bacillus cereus, which used to be considered non-pathogenic, was isolated from the blood of a patient with acute leukemia who was receiving intensive chemotherapy. Fatal bacteremia developed with a clinical syndrome of acute gastroenteritis, followed by both meningoencephalitis with subarachnoid hemorrhage and multiple liver abscesses probably caused by infective vasculitis. Surveillance stool cultures revealed colonization with the organism prior to the onset of diarrhea, and repetitive blood cultures were found to be positive. Thus, this case suggested some new important clinicopathologic features of true B. cereus bacteremia complicating acute leukemia.

  4. Pediatric chronic myeloid leukemia is a unique disease that requires a different approach

    PubMed Central

    Schultz, Kirk R.; Metzler, Markus; Millot, Frederic; Suttorp, Meinolf

    2016-01-01

    Chronic myelogenous leukemia (CML) in children is relatively rare. Because of a lack of robust clinical study evidence, management of CML in children is not standardized and often follows guidelines developed for adults. Children and young adults tend to have a more aggressive clinical presentation than older adults, and prognostic scores for adult CML do not apply to children. CML in children has been considered to have the same biology as in adults, but recent data indicate that some genetic differences exist in pediatric and adult CML. Because children with CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in children with CML may be distinct from those in adults and require careful monitoring. Aggressive strategies, such as eradication of CML stem cells with limited duration and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to avoid lifelong exposure to TKIs and their associated adverse effects. Blood and marrow transplantation in pediatric CML is currently indicated only for recurrent progressive disease, and the acute and long-term toxicities of this option should be carefully evaluated against the complications associated with lifelong use of TKIs. PMID:26511135

  5. Acute lymphoblastic leukemia in a pygmy hippopotamus (Hexaprotodon liberiensis).

    PubMed

    McCurdy, Paul; Sangster, Cheryl; Lindsay, Scott; Vogelnest, Larry

    2014-12-01

    A captive, 31-yr-old, intact male pygmy hippopotamus presented with nonspecific signs of weight loss, inappetence, diarrhea, and lethargy. After 5 wk of diagnostic investigation and symptomatic treatment, an acute leukemic process with concurrent polycystic kidney disease was suspected. The animal's condition continued to deteriorate prompting euthanasia. Necropsy, histopathologic, and immunohistochemical examination confirmed acute T-cell lymphoblastic leukemia and polycystic kidneys. Acute T-cell lymphoblastic leukemia has not previously been documented in this species; however, polycystic kidney disease has been reported. This case report adds to the increasing number of pygmy hippopotamuses diagnosed with polycystic kidney disease and describes acute T-cell lymphoblastic leukemia, a previously unreported disease of this species.

  6. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  7. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia

    PubMed Central

    Oshima, Koichi; Khiabanian, Hossein; da Silva-Almeida, Ana C.; Tzoneva, Gannie; Abate, Francesco; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Carpenter, Zachary; Penson, Alex; Perez-Garcia, Arianne; Eckert, Cornelia; Nicolas, Concepción; Balbin, Milagros; Sulis, Maria Luisa; Kato, Motohiro; Koh, Katsuyoshi; Paganin, Maddalena; Basso, Giuseppe; Gastier-Foster, Julie M.; Devidas, Meenakshi; Loh, Mignon L.; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A.

    2016-01-01

    Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID:27655895

  8. Pattern of subtypes of acute lymphoblastic leukemia in India.

    PubMed

    Kamat, D M; Gopal, R; Advani, S H; Nair, C N; Kumar, A; Saikia, T; Nadkarni, J J; Nadkarni, J S

    1985-01-01

    Leukemic cells from 124 acute lymphoblastic leukemia (ALL) and 31 chronic lymphatic leukemia (CLL) were examined for sheep erythrocyte receptor (E), surface immunoglobulin (SIg) and their reactivity with a panel of monoclonal antibodies recognizing specific surface antigens including pan-T, Common ALL and Ia antigens. In acute lymphatic leukemia, 33% of patients reveal T-cell receptor associated with higher age group, mediastinal mass and high WBC count. Common ALL was predominant between 2 and 9-yr age group. Among chronic lymphatic leukemia, 2 patients were found to be T-CLL while 29 revealed presence of SIg. Ia antigen was detected in 44.4% of ALL and 64% fo CLL patients. The pattern of surface marker observed in our series may be related to our life style, socio-economic and environmental factors.

  9. Leukomogenic factors downregulate heparanase expression in acute myeloid leukemia cells

    SciTech Connect

    Eshel, Rinat; Ben-Zaken, Olga; Vainas, Oded; Nadir, Yona; Minucci, Saverio; Polliack, Aaron; Naparstek, Ella; Vlodavsky, Israel; Katz, Ben-Zion; E-mail: bkatz@tasmc.healt.gov.il

    2005-10-07

    Heparanase is a heparan sulfate-degrading endoglycosidase expressed by mature monocytes and myeloid cells, but not by immature hematopoietic progenitors. Heparanase gene expression is upregulated during differentiation of immature myeloid cells. PML-RAR{alpha} and PLZF-RAR{alpha} fusion gene products associated with acute promyelocytic leukemia abrogate myeloid differentiation and heparanase expression. AML-Eto, a translocation product associated with AML FAB M2, also downregulates heparanase gene expression. The common mechanism that underlines the activity of these three fusion gene products involves the recruitment of histone deacetylase complexes to specific locations within the DNA. We found that retinoic acid that dissociates PML-RAR{alpha} from the DNA, and which is used to treat acute promyelocytic leukemia patients, restores heparanase expression to normal levels in an acute promyelocytic leukemia cell line. The retinoic acid effects were also observed in primary acute promyelocytic leukemia cells and in a retinoic acid-treated acute promyelocytic leukemia patient. Histone deacetylase inhibitor reverses the downregulation of heparanase expression induced by the AML-Eto fusion gene product in M2 type AML. In summary, we have characterized a link between leukomogenic factors and the downregulation of heparanase in myeloid leukemic cells.

  10. What's New in Adult Acute Lymphocytic Leukemia (ALL) in Adults Research?

    MedlinePlus

    ... in Adults About Acute Lymphocytic Leukemia (ALL) What’s New in Acute Lymphocytic Leukemia Research and Treatment? Researchers ... have the Philadelphia chromosome. Gene expression profiling This new lab technique is being studied to help identify ...

  11. Eosinophilia in a cat with acute leukemia.

    PubMed

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-09-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified.

  12. Eosinophilia in a cat with acute leukemia

    PubMed Central

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-01-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified. PMID:22379202

  13. Acute monoblastic leukemia in a FeLV-positive cat.

    PubMed

    Prihirunkit, Kreangsak; Narkkong, Nual Anong; Apibal, Suntaree

    2008-03-01

    A 1.6-year-old male domestic short hair cat was brought to the Veterinary Medical Teaching Hospital, Kasetsart University, with signs of severe anemia, depression, and general lymph node enlargement. Complete blood count revealed leukocytosis and massive undifferentiated blasts. Testing for antibodies specific to feline leukemia virus (FeLV) was positive, and FeLV nucleic acid was confirmed by nested polymerase chain reaction. Base on cytochemistry and ultrastructure, the cat was diagnosed with acute monoblastic leukemia.

  14. Successful cell-mediated cytokine-activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation.

    PubMed

    Gesundheit, Benjamin; Shapira, Michael Y; Resnick, Igor B; Amar, Avraham; Kristt, Don; Dray, Lilianne; Budowski, Einat; Or, Reuven

    2009-03-01

    Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell-mediated cytokine-activated immunotherapy in a high-risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft-versus-leukemia effect, presenting as a reversible episode of graft-versus-host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed.

  15. Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li; Caywood, Emi H

    2015-10-01

    Growing insight into prognosis of pediatric acute myeloid leukemia (AML) survival has led to improved outcome over time and could be further enhanced through investigation using a large number of patients. To characterize the extent of the association of pediatric AML survival with its identified prognostic factors, we analyzed the United States population-based Surveillance Epidemiology and End Results (SEER) large dataset of 3442 pediatric AML patients diagnosed and followed between 1973 and 2011 using a Cox proportional hazards model stratified by year of diagnosis. Patients diagnosed between 10 and 19 years of age were at a higher risk of death compared to those diagnosed before age 10 (adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.17-1.44). African Americans (1.27, 1.09-1.48) and Hispanics (1.15, 1.00-1.32) had an elevated risk of mortality than Caucasians. Compared to the subtype acute promyelocytic leukemia, AML with minimal differentiation (2.44, 1.78-3.35); acute erythroid leukemia (2.34, 1.60-3.40); AML without maturation (1.87, 1.35-2.59); and most other AML subtypes had a higher risk of mortality, whereas AML with inv(16) had a substantially lower risk. Age at diagnosis, race-ethnicity, AML subtype, county level poverty and geographic region appeared as significant prognostic factors of pediatric AML survival in the US. Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome.

  16. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  17. Association of energy intake and expenditure with obesity: A cross-sectional study of 150 pediatric patients following treatment for leukemia.

    PubMed

    Srivastava, Richa; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

    2017-03-13

    Increased obesity in leukemia survivors has been attributed to chemotherapy and radiation. Data on total energy intake (TEI) and total energy expenditure (TEE) are lacking in obese childhood leukemia patients after completion of therapy from India. We conducted a cross-sectional study in pediatric acute leukemia patients after completion of therapy wherein energy intake was assessed by 24-hour recall method. TEE was calculated using Harris-Benedict equation, by assessing the physical activity level using Physical Activity Questionnaire for children and basal metabolic rate by World Health Organization equation. Indian Academy of Pediatrics 2015 guidelines for BMI were used for defining overweight and obesity. Nutritional status was assessed in 150 leukemia patients after completion of therapy. Twenty-five percent of leukemia patients after completion of therapy were overweight and obese versus 11% of healthy controls (p = 0.042). The mean ratio of TEI/required energy intake (REI), TEE/required energy expenditure (REE), and (TEI:REI)/(TEE:REE) were significantly higher in overweight and obese group versus nonobese survivors (p < 0.001, p = 0.091, p < 0.001, respectively). Multivariate analysis showed higher income (HR-2.3, p = 0.04), increased TEI/REI (HR-4, p = 0.049) and higher (TEI:REI)/(TEE:REE) (HR-3.1, p = 0.039) to be significant factors predicting obesity. Obesity in leukemia patients after completion of therapy is associated with increased energy intake, causing imbalance between energy intake and TEE in these patients.

  18. Acute myelogenous leukemia and glycogen storage disease 1b.

    PubMed

    Pinsk, Maury; Burzynski, Jeffrey; Yhap, Margaret; Fraser, Robert B; Cummings, Brian; Ste-Marie, Micheline

    2002-12-01

    Glycogen storage disease 1b (GSD 1b) is caused by a deficiency of glucose-6-phosphate translocase and the intracellular accumulation of glycogen. The disease presents with failure to thrive, hepatomegaly, hypoglycemia, lactic acidosis, as well as neutropenia causing increased susceptibility to pyogenic infections. We present a case of a young woman with GSD 1b who developed acute myelogenous leukemia while on long-term granulocyte colony-stimulating factor therapy. The presence of two rare diseases in a single patient raises suspicion that GSD 1b and acute myelogenous leukemia are linked. Surveillance for acute myelogenous leukemia should become part of the long-term follow-up for GSD 1b.

  19. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2016-07-08

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  20. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia

    PubMed Central

    Knaus, Hanna A.; Kanakry, Christopher G.; Luznik, Leo; Gojo, Ivana

    2016-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body’s own immune system to fight leukemic cells. PMID:25981611

  1. Immunomodulatory Drugs: Immune Checkpoint Agents in Acute Leukemia.

    PubMed

    Knaus, Hanna A; Kanakry, Christopher G; Luznik, Leo; Gojo, Ivana

    2017-01-01

    Intrinsic immune responses to acute leukemia are inhibited by a variety of mechanisms, such as aberrant antigen expression by leukemia cells, secretion of immunosuppressive cytokines and expression of inhibitory enzymes in the tumor microenvironment, expansion of immunoregulatory cells, and activation of immune checkpoint pathways, all leading to T cell dysfunction and/or exhaustion. Leukemic cells, similar to other tumor cells, hijack these inhibitory pathways to evade immune recognition and destruction by cytotoxic T lymphocytes. Thus, blockade of immune checkpoints has emerged as a highly promising approach to augment innate anti-tumor immunity in order to treat malignancies. Most evidence for the clinical efficacy of this immunotherapeutic strategy has been seen in patients with metastatic melanoma, where anti-CTLA-4 and anti-PD-1 antibodies have recently revolutionized treatment of this lethal disease with otherwise limited treatment options. To meet the high demand for new treatment strategies in acute leukemia, clinical testing of these promising therapies is commencing. Herein, we review the biology of multiple inhibitory checkpoints (including CTLA-4, PD-1, TIM-3, LAG-3, BTLA, and CD200R) and their contribution to immune evasion by acute leukemias. In addition, we discuss the current state of preclinical and clinical studies of immune checkpoint inhibition in acute leukemia, which seek to harness the body's own immune system to fight leukemic cells.

  2. 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).

  3. Decitabine and Total-Body Irradiation Followed By Donor Bone Marrow Transplant and Cyclophosphamide in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-09

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  4. MTHFR polymorphisms in childhood acute lymphoblastic leukemia: influence on methotrexate therapy

    PubMed Central

    Umerez, Maitane; Gutierrez-Camino, Ángela; Muñoz-Maldonado, Carmen; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2017-01-01

    Methotrexate (MTX) is an important component in the therapy used to treat childhood acute lymphoblastic leukemia (ALL). Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme for MTX pharmacokinetics. Two single-nucleotide polymorphisms in MTHFR gene, C677T and A1298C, affecting MTHFR activity, have been widely studied as potential markers of MTX toxicity and/or outcome in pediatric ALL. In this review, we show that the majority of published reports do not find association or present opposite effect. Therefore, MTHFR C677T and A1298C polymorphisms do not seem to be good markers of MTX-related toxicity and/or outcome in pediatric ALL. The efforts should be focused on other genes, such as transporter genes or microRNA-related genes. PMID:28392709

  5. Clinical significance of previously cryptic copy number alterations and loss of heterozygosity in pediatric acute myeloid leukemia and myelodysplastic syndrome determined using combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray analyses.

    PubMed

    Koh, Kyung-Nam; Lee, Jin Ok; Seo, Eul Ju; Lee, Seong Wook; Suh, Jin Kyung; Im, Ho Joon; Seo, Jong Jin

    2014-07-01

    The combined array comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH+SNP microarray) platform can simultaneously detect copy number alterations (CNA) and copy-neutral loss of heterozygosity (LOH). Eighteen children with acute myeloid leukemia (AML) (n=15) or myelodysplastic syndrome (MDS) (n=3) were studied using CGH+SNP microarray to evaluate the clinical significance of submicroscopic chromosomal aberrations. CGH+SNP microarray revealed CNAs at 14 regions in 9 patients, while metaphase cytogenetic (MC) analysis detected CNAs in 11 regions in 8 patients. Using CGH+SNP microarray, LOHs>10 Mb involving terminal regions or the whole chromosome were detected in 3 of 18 patients (17%). CGH+SNP microarray revealed cryptic LOHs with or without CNAs in 3 of 5 patients with normal karyotypes. CGH+SNP microarray detected additional cryptic CNAs (n=2) and LOHs (n=5) in 6 of 13 patients with abnormal MC. In total, 9 patients demonstrated additional aberrations, including CNAs (n=3) and/or LOHs (n=8). Three of 15 patients with AML and terminal LOH>10 Mb demonstrated a significantly inferior relapse-free survival rate (P=0.041). This study demonstrates that CGH+SNP microarray can simultaneously detect previously cryptic CNAs and LOH, which may demonstrate prognostic implications.

  6. Backtracking RAS mutations in high hyperdiploid childhood acute lymphoblastic leukemia.

    PubMed

    Wiemels, Joseph L; Kang, Michelle; Chang, Jeffrey S; Zheng, Lily; Kouyoumji, Carina; Zhang, Luoping; Smith, Martyn T; Scelo, Ghislaine; Metayer, Catherine; Buffler, Patricia; Wiencke, John K

    2010-10-15

    High hyperdiploidy is the single largest subtype of childhood acute lymphoblastic leukemia (ALL) and is defined by the presence of 51-68 chromosomes in a karyotype. The 5 or more extra chromosomes characterizing this subtype are known to occur in a single mitotic event, prenatally. We screened for RAS mutations among 517 acute childhood leukemias (including 437 lymphocytic, of which 393 were B-cell subtypes) and found mutations in 30% of high hyperdiploids compared to only 10% of leukemias of other subtypes (P<0.0001). We assessed whether KRAS mutations occurred before birth using a PCR-restriction enzyme-mediated Taqman quantitative PCR reaction, and found no evidence for prenatal KRAS mutations in 14 patients tested. While RAS mutations were previously associated with prior chemical exposures in childhood and adult leukemias, in this study RAS-mutated cases were not significantly associated with parental smoking when compared to study controls. IGH rearrangements were backtracked in three RAS-positive patients (which were negative for KRAS mutation at birth) and found to be evident before birth, confirming a prenatal origin for the leukemia clone. We posit a natural history for hyperdiploid leukemia in which prenatal mitotic catastrophe is followed by a postnatal RAS mutation to produce the leukemic cell phenotype.

  7. 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.

  8. No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

    SciTech Connect

    Bender, A.P.; Robison, L.L.; Kashmiri, S.V.; McClain, K.L.; Woods, W.G.; Smithson, W.A.; Heyn, R.; Finlay, J.; Schuman, L.M.; Renier, C.

    1988-05-15

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.

  9. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

    PubMed Central

    2011-01-01

    Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR), and the standardized average annual incidence rates (SAAIR) per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level). Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3); acute lymphoblastic leukemia (ALL) was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million), followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million), and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million). The 1-4 years age group had the highest SAAIR for ALL (77.7 per million). For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million) and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million). The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8%) were classified as high

  10. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-02-07

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  11. Acute megakaryoblastic leukemia. Blast cell aggregates simulating metastatic tumor.

    PubMed

    Pui, C H; Rivera, G; Mirro, J; Stass, S; Peiper, S; Murphy, S B

    1985-11-01

    Acute megakaryoblastic leukemia is a rare leukemia that can present diagnostic problems. We describe two children who have this disease and had clumps of blast cells in their bone marrow, a finding usually attributed to metastatic tumor. The megakaryocytic origin of the cells was supported by their cytochemical staining pattern (positive alpha-naphthyl acetate esterase resistant to sodium fluoride inhibition and negative alpha-naphthyl butyrate esterase) and by the presence of factor VIII-related antigen. Ultrastructural studies of blast cells from one patient demonstrated platelet peroxidase. The mechanism of blast cell clump formation in these cases is unknown; nevertheless, awareness that this feature can occur in acute megakaryoblastic leukemia may avoid a misdiagnosis of metastatic solid tumor.

  12. Relapse of Biphenotypic Acute Leukemia as a Breast Mass

    PubMed Central

    2016-01-01

    In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia. PMID:28053635

  13. Acute lymphocytic leukemia recurring in the spinal epidural space.

    PubMed

    Higashida, Tetsuhiro; Kawasaki, Takashi; Sakata, Katsumi; Tanabe, Yutaka; Kanno, Hiroshi; Yamamoto, Isao

    2007-08-01

    A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL.

  14. Ultrastructural observations on a variant of acute promyelocytic leukemia.

    PubMed

    Djaldetti, M; Gardyn, J; Maran, R; Floru, S; Mittelman, M

    1993-03-01

    A patient with acute leukemia is presented in whom the leukemic cells, as seen by light microscopy were typical promyelocytes. The cells had normal or slightly invaginated nuclei with typical cytoplasmic granules and the diagnosis was confirmed by cytochemistry. The clinical course was rapid and the patient died of disseminated intravascular coagulation and urosepsis within a few days of diagnosis. However, electron microscopic examination showed cells with extremely convoluted and lobulated nuclei with nuclear pockets and cytoplasmic bridges as well as the complete absence of cytoplasmic granules in the majority of the cells. Furthermore, the urine lysozyme (muramidase) was elevated. These findings suggest that the leukemia in this patient may be classified as a hypogranular variant of acute promyelocytic leukemia (APL), with monocytoid ultrastructural appearances.

  15. Radiolabeled BC8 Antibody, Busulfan, Cyclophosphamide Followed by Donor Stem Cell Transplant in Treating Patients With Acute Myelogenous Leukemia in First Remission

    ClinicalTrials.gov

    2016-11-14

    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)

  16. Azacitidine in Combination With Mitoxantrone, Etoposide Phosphate, and Cytarabine in Treating Patients With Relapsed and Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-31

    Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  17. Antibodies: Immunoconjugates and autologous cellular therapy in acute lymphoblastic leukemia.

    PubMed

    Advani, Anjali

    2015-01-01

    Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies--blinatumomab, inotuzumab, and CAR T cells--are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years.

  18. Acute myeloid leukemia therapeutics: CARs in the driver's seat.

    PubMed

    Mardiros, Armen; Brown, Christine E; Budde, L Elizabeth; Wang, Xiuli; Forman, Stephen J

    2013-12-01

    Acute myeloid leukemia remains a difficult disease to cure and novel therapeutic approaches are needed. To this end, we developed CD123 chimeric antigen receptor (CAR) redirected T cells which exhibited potent antileukemic activity. We discuss what we learned during the development of CD123 CARs and future directions for this immunotherapy.

  19. Reasons for optimism in the therapy of acute leukemia.

    PubMed

    Rowe, Jacob M

    2015-01-01

    Distinct progress has been made in recent years in the therapy of acute leukemia. For acute myeloid leukemia (AML), this progress has been anchored in the increased understanding of genomic complexity. Multiple targets and the relationships among them pose new challenges along with new possibilities for the development of targeted therapies. A number of new drugs are in early clinical development for AML, one of which centers on the role of isocitrate dehydrogenase (IDH) in malignancy. Epigenetic modulation, intracellular pathways, and the microenvironment are all being explored for possible therapies to treat AML. Dramatic clinical progress has also been made in therapy of acute lymphoblastic leukemia (ALL) with the rapid approval of blinatumomab, a bispecific T-cell engager antibody. Yet caution must also be exercised-not every mutation is an epigenetic target and early publication of clinical data is often misleading. Until the survival outcome for adult patients with acute leukemia improves, further inquiry into the biology of the disease and progress in the development of new therapies are needed.

  20. Phase I Trial of AZD1775 and Belinostat in Treating Patients With Relapsed or Refractory Myeloid Malignancies or Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-03

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  1. Acute myeloid leukemia cells polarize macrophages towards a leukemia supporting state in a Growth factor independence 1 dependent manner

    PubMed Central

    Al-Matary, Yahya S.; Botezatu, Lacramioara; Opalka, Bertram; Hönes, Judith M.; Lams, Robert F.; Thivakaran, Aniththa; Schütte, Judith; Köster, Renata; Lennartz, Klaus; Schroeder, Thomas; Haas, Rainer; Dührsen, Ulrich; Khandanpour, Cyrus

    2016-01-01

    The growth of malignant cells is not only driven by cell-intrinsic factors, but also by the surrounding stroma. Monocytes/Macrophages play an important role in the onset and progression of solid cancers. However, little is known about their role in the development of acute myeloid leukemia, a malignant disease characterized by an aberrant development of the myeloid compartment of the hematopoietic system. It is also unclear which factors are responsible for changing the status of macrophage polarization, thus supporting the growth of malignant cells instead of inhibiting it. We report herein that acute myeloid leukemia leads to the invasion of acute myeloid leukemia-associated macrophages into the bone marrow and spleen of leukemic patients and mice. In different leukemic mouse models, these macrophages support the in vitro expansion of acute myeloid leukemia cell lines better than macrophages from non-leukemic mice. The grade of macrophage infiltration correlates in vivo with the survival of the mice. We found that the transcriptional repressor Growth factor independence 1 is crucial in the process of macrophage polarization, since its absence impedes macrophage polarization towards a leukemia supporting state and favors an anti-tumor state both in vitro and in vivo. These results not only suggest that acute myeloid leukemia-associated macrophages play an important role in the progression of acute myeloid leukemia, but also implicate Growth factor independence 1 as a pivotal factor in macrophage polarization. These data may provide new insights and opportunities for novel therapies for acute myeloid leukemia. PMID:27390361

  2. MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia

    PubMed Central

    Jones, Courtney L.; Gearheart, Christy M.; Fosmire, Susan; Delgado-Martin, Cristina; Evensen, Nikki A.; Bride, Karen; Waanders, Angela J.; Pais, Faye; Wang, Jinhua; Bhatla, Teena; Bitterman, Danielle S.; de Rijk, Simone R.; Bourgeois, Wallace; Dandekar, Smita; Park, Eugene; Burleson, Tamara M.; Madhusoodhan, Pillai Pallavi; Teachey, David T.; Raetz, Elizabeth A.; Hermiston, Michelle L.; Müschen, Markus; Loh, Mignon L.; Hunger, Stephen P.; Zhang, Jinghui; Garabedian, Michael J.; Porter, Christopher C.

    2015-01-01

    The outcome for pediatric acute lymphoblastic leukemia (ALL) patients who relapse is dismal. A hallmark of relapsed disease is acquired resistance to multiple chemotherapeutic agents, particularly glucocorticoids. In this study, we performed a genome-scale short hairpin RNA screen to identify mediators of prednisolone sensitivity in ALL cell lines. The incorporation of these data with an integrated analysis of relapse-specific genetic and epigenetic changes allowed us to identify the mitogen-activated protein kinase (MAPK) pathway as a mediator of prednisolone resistance in pediatric ALL. We show that knockdown of the specific MAPK pathway members MEK2 and MEK4 increased sensitivity to prednisolone through distinct mechanisms. MEK4 knockdown increased sensitivity specifically to prednisolone by increasing the levels of the glucocorticoid receptor. MEK2 knockdown increased sensitivity to all chemotherapy agents tested by increasing the levels of p53. Furthermore, we demonstrate that inhibition of MEK1/2 with trametinib increased sensitivity of ALL cells and primary samples to chemotherapy in vitro and in vivo. To confirm a role for MAPK signaling in patients with relapsed ALL, we measured the activation of the MEK1/2 target ERK in matched diagnosis-relapse primary samples and observed increased phosphorylated ERK levels at relapse. Furthermore, relapse samples have an enhanced response to MEK inhibition compared to matched diagnosis samples in xenograft models. Together, our data indicate that inhibition of the MAPK pathway increases chemosensitivity to glucocorticoids and possibly other agents and that the MAPK pathway is an attractive target for prevention and/or treatment of relapsed disease. PMID:26324703

  3. Best Practices in Adolescent and Young Adult Patients with Acute Lymphoblastic Leukemia: A Focus on Asparaginase.

    PubMed

    Boissel, Nicolas; Sender, Leonard S

    2015-09-01

    The inclusion of asparaginase in chemotherapy regimens to treat acute lymphoblastic leukemia (ALL) has had a positive impact on survival in pediatric patients. Historically, asparaginase has been excluded from most treatment protocols for adolescent and young adult (AYA) patients because of perceived toxicity in this population, and this is believed to have contributed to poorer outcomes in these patients. However, retrospective analyses over the past 12 years have shown that 2-, 5-, and 7-year overall survival of AYA patients is significantly improved with pediatric versus adult protocols. The addition of asparaginase to adult protocols yielded high rates of first remission and improved survival. However, long-term survival remains lower compared with what has been seen in pediatrics. The notion that asparaginase is poorly tolerated by AYA patients has been challenged in multiple studies. In some, but not all, studies, the incidences of hepatic and pancreatic toxicities were higher in AYA patients, whereas the rates of hypersensitivity reactions did not appear to differ with age. There is an increased risk of venous thromboembolic events, and management with anti-coagulation therapy is recommended. Overall, the risk of therapy-related mortality is low. Together, this suggests that high-intensity pediatric protocols offer an effective and tolerable approach to treating ALL in the AYA population.

  4. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-12-06

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  5. Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

    ClinicalTrials.gov

    2014-10-23

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; 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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  6. The acute lymphoblastic leukemia of Down Syndrome - Genetics and pathogenesis.

    PubMed

    Izraeli, Shai

    2016-03-01

    Children with Down Syndrome (DS) are at markedly increased risk for acute lymphoblastic leukemia (ALL). The ALL is of B cell precursor (BCP) phenotype. T-ALL is only rarely diagnosed as well as infant leukemia. Gene expression profiling and cytogenetics suggest that DS-ALL is an heterogeneous disease. More than half of the leukemias are characterized by aberrant expression of the thymic stromal lymphopoietin (TSLP) receptor CRLF2 caused by genomic rearrangements. These rearrangements are often associated with somatic activating mutations in the receptors or in the downstream components of the JAK-STAT pathway. The activation of JAK-STAT pathway suggests that targeted therapy with JAK or downstream inhibitors may be effective for children with DS-ALL. The basis of the increased risk of BCP-ALL and in particular of the CRLF2 aberrations is presently unknown. Neither is it known which genes on the trisomic chromosome 21 are involved.

  7. Multifaceted approach to the diagnosis and classification of acute leukemias.

    PubMed

    McKenna, R W

    2000-08-01

    Until recently, the diagnosis and classification of acute myeloid (AML) and acute lymphoblastic (ALL) leukemias was based almost exclusively on well-defined morphologic criteria and cytochemical stains. Although most cases can be diagnosed by these methods, there is only modest correlation between morphologic categories and treatment responsiveness and prognosis. The expansion of therapeutic options and improvement in remission induction and disease-free survival for both AML and ALL have stimulated emphasis on defining good and poor treatment response groups. This is most effectively accomplished by a multifaceted approach to diagnosis and classification using immunophenotyping, cytogenetics, and molecular analysis in addition to the traditional methods. Immunophenotyping is important in characterizing morphologically poorly differentiated acute leukemias and in defining prognostic categories of ALL. Cytogenetic and molecular studies provide important prognostic information and are becoming vitally important in determining the appropriate treatment protocol. With optimal application of these techniques in the diagnosis of acute leukemias, treatment strategies can be more specifically directed and new therapeutic approaches can be evaluated more effectively.

  8. Childhood Cancer: Leukemia (For Parents)

    MedlinePlus

    ... acute. Acute childhood leukemias are also divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) , depending on ... Bone Marrow Childhood Cancer Neutropenia Stem Cell Transplants Acute Lymphoblastic Leukemia (ALL) Chemotherapy Radiation Therapy Chronic Myelogenous Leukemia (CML) ...

  9. Impact of age on the survival of pediatric leukemia: an analysis of 15083 children in the SEER database

    PubMed Central

    Wu, Peng; Kang, Meiyun; Zhang, Xuejie; Lu, Qin; Fang, Yongjun

    2016-01-01

    BACKGROUND & AIMS Age at diagnosis is a key factor for predicting the prognosis of pediatric leukemia especially regarding the survivorship assessment. In this study, we aimed to assess the impact of this prognostic factor such as age in children with pediatric leukemia. METHODS In this study, Surveillance, Epidemiology, and End Results Program-registered children with leukemia during 1988-2013 were analyzed. All patients were divided into five groups according to the age at the time of diagnosis (<1, 1-4, 5-9, 10-15, >15 years old). Kaplan-Meier and multivariable Cox regression models were used to evaluate leukemia survival outcomes and risk factors. RESULTS There was significant variability in pediatric leukemia survival by age at diagnosis including ALL, AML and CML subtypes. According to the survival curves in each group, survival rate were peaked among children diagnosed at 1–4 years and steadily declined among those diagnosed at older ages in children with ALL. Infants (<1 year) had the lowest survivorship in children with either ALL or AML. However, children (1-4 years) harbored the worst prognosis suffering from CML. A stratified analysis of the effect of age at diagnosis was validated as independent predictors for the prognosis of pediatric leukemia. CONCLUSIONS Age at diagnosis remained to be a crucial determinant of the survival variability of pediatric leukemia patients. PMID:27590519

  10. GATA2 Inhibition Sensitizes Acute Myeloid Leukemia Cells to Chemotherapy

    PubMed Central

    Cao, Yanan; Xuan, Binbin; Fan, Yingchao; Sheng, Huiming; Zhuang, Wenfang

    2017-01-01

    Drug resistance constitutes one of the main obstacles for clinical recovery of acute myeloid leukemia (AML) patients. Therefore, the treatment of AML requires new strategies, such as adding a third drug. To address whether GATA2 could act as a regulator of chemotherapy resistance in human leukemia cells, we observed KG1a cells and clinical patients’ AML cells with a classic drug (Cerubidine) and Gefitinib. After utilizing chemotherapy, the expression of GATA2 and its target genes (EVI, SCL and WT1) in surviving AML cells and KG1a cells were significantly enhanced to double and quadrupled compared to its original level respectively. Furthermore, with continuous chemotherapeutics, AML cells with GATA2 knockdown or treated with GATA2 inhibitor (K1747) almost eliminated with dramatically reduced expression of WT1, SCL, EVI, and significantly increased apoptotic population. Therefore, we propose that reducing GATA2 expression or inhibition of its transcription activity can relieve the drug resistance of acute myeloid leukemia cells and it would be helpful for eliminating the leukemia cells in patients. PMID:28114350

  11. Acute lymphoblastic leukemia in a child with Fanconi's anaemia.

    PubMed

    Mushtaq, Naureen; Wali, Rabia; Fadoo, Zehra; Saleem, Ali Faisal

    2012-07-01

    Fanconi anaemia (FA) is an autosomal recessive inherited disorder with progressive bone marrow failure, associated congenital malformation and solid and haematological malignancies. Acute myeloid leukemia is the commonest haematological malignancy followed by myelodysplastic syndrome in children with FA. FA transformed into acute lymphoblastic leukemia (ALL) is a rare phenomenon and one of the rarest haematological malignancies associated with this disorder. We are reporting a 13 years old girl with FA and positive chromosomal breakage. She required regular blood product transfusion. She was planned for haematopoietic stem cell transplantation (HSCT) but the sibling-matched donor was found to have chromosomal breaks as well. Later on, her peripheral smear showed blast cell. Bone marrow showed pre-B ALL. She was started on chemotherapy but died shortly due to complications of the treatment. For this rare condition conservative management is indeed essential, however, safe and appropriate chemotherapy regimen is needed.

  12. Primary hepatic aspergillosis following induction chemotherapy for acute leukemia.

    PubMed

    Chasan, R; Patel, G; Malone, A; Finn, M; Huprikar, S

    2013-10-01

    Invasive aspergillosis (IA) contributes significantly to the burden of infectious complications in heavily immunosuppressed patients with acute leukemia. The infection is typically acquired via inhalation into the respiratory tract, and the lungs are most commonly involved. However, disseminated disease may occur and reports of isolated extrapulmonary infection suggest the gastrointestinal tract is likely an additional portal of entry for this organism. We describe a case of primary hepatic aspergillosis in a patient with acute myelogenous leukemia. The patient did not respond to medical therapy with antifungals and ultimately required surgical exploration and drainage. IA should be considered in an immunosuppressed patient with hepatic abscesses and may require a combined surgical and medical approach to therapy.

  13. Acute lymphoblastic leukemia presenting with bilateral serous macular detachment.

    PubMed

    Vieira, Luisa; Silva, Nuno Aguiar; Medeiros, Marco Dutra; Flores, Rita; Maduro, Vitor

    2015-01-01

    Acute lymphoblastic leukemia is a malignant hematopoietic neoplasia, which is rare in adults. Although ocular fundus alterations may be commonly observed in the course of the disease, such alterations are rarely the presenting signs of the disease. Here we describe the case of a patient with painless and progressive loss of visual acuity (right eye, 2/10; left eye, 3/10) developing over two weeks, accompanied by fever and cervical lymphadenopathy. Fundus examination showed bilateral macular serous detachment, which was confirmed by optical coherence tomography. Fluorescein angiography revealed hyperfluorescent pinpoints in the posterior poles. The limits of the macular detachment were revealed in the late phase of the angiogram. The results of blood count analysis triggered a thorough, systematic patient examination. The diagnosis of acute lymphoblastic leukemia B (CD10+) was established, and intensive systemic chemotherapy was immediately initiated. One year after the diagnosis, the patient remains in complete remission without any ophthalmologic alterations.

  14. New decision support tool for acute lymphoblastic leukemia classification

    NASA Astrophysics Data System (ADS)

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  15. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL.

  16. Pleural effusions in patients with acute leukemia and myelodysplastic syndrome.

    PubMed

    Faiz, Saadia A; Bashoura, Lara; Lei, Xiudong; Sampat, Keeran R; Brown, Tiffany C; Eapen, George A; Morice, Rodolfo C; Ferrajoli, Alessandra; Jimenez, Carlos A

    2013-02-01

    Pleural effusions are rarely observed in patients with acute myelogenous leukemia (AML), acute lymphocytic leukemia (ALL) and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN). Therefore the underlying etiology of pleural effusions and the efficacy and safety of pleural procedures in this population has not been well studied. In a retrospective review of cases from 1997 to 2007, we identified 111 patients with acute leukemia or MDS/MPN who underwent pleural procedures. Clinical characteristics were reviewed, and survival outcomes were estimated by Kaplan-Meier methods. A total of 270 pleural procedures were performed in 111 patients (69 AML, 27 ALL, 15 MDS/MPN). The main indications for pleural procedures were possible infection (49%) and respiratory symptoms (48%), and concomitant clinical symptoms included fever (34%), dyspnea (74%), chest pain (24%) and cough (37%). Most patients had active disease (61%). The most frequent etiology of pleural effusions was infection (47%), followed by malignancy (36%). Severe thrombocytopenia (platelet count < 20 × 10(3)/µL) was present in 43% of the procedures, yet the procedural complication rate was only 1.9%. Multivariate analysis revealed that older age, AML, MDS/MPN and active disease status were associated with a shorter median overall survival. Infection and malignant involvement are the most common causes of pleural effusion in patients with acute leukemia or MDS. After optimizing platelet count and coagulopathy, thoracentesis may be performed safely and with high diagnostic yield in this population. Survival in these patients is determined by the response to treatment of the hematologic malignancy.

  17. Acute megakaryoblastic leukemia and loss of the RUNX1 gene.

    PubMed

    Berger, Roland; Busson, Maryvonne; Dastugue, Nicole; Radford-Weiss, Isabelle; Michaux, Lucienne; Hagemeijer, Anne; Quilichini, Benoît; Benattar, Laurence; Bernard, Olivier; Romana, Serge P

    2006-01-01

    Since the RUNX1 gene contributes to megakaryopoiesis and acquired trisomy 21 is the most frequent numerical chromosome anomaly in acute megakaryoblastic leukemia (AMLK), a systematic study of RUNX1 abnormalities was performed by fluorescence in situ hybridization in AMLK patients. Four abnormalities were detected among 15 patients. One copy of RUNX1 was completeley or partially lost in three patients and translocated onto Xq24 in the fourth. The possible consequences of RUNX1 haploinsufficiency are discussed.

  18. Beating the Clock in T-cell Acute Lymphoblastic Leukemia.

    PubMed

    Carroll, William L; Aifantis, Iannis; Raetz, Elizabeth

    2017-02-15

    CDK4/6 inhibition was synergistic with dexamethasone and everolimus but antagonistic with conventional chemotherapy in T-cell acute lymphoblastic leukemia (T-ALL) preclinical models. Cyclin-dependent kinase inhibition in combination with glucocorticoids and mTOR inhibition offers a unique therapeutic opportunity in T-ALL. Clin Cancer Res; 23(4); 873-5. ©2016 AACRSee related article by Pikman et al., p. 1012.

  19. Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia.

    PubMed

    Sorà, Federica; Chiusolo, Patrizia; Laurenti, Luca; Autore, Francesco; Giammarco, Sabrina; Sica, Simona

    2016-01-01

    Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission.

  20. Massive Pulmonary Embolism at the Onset of Acute Promyelocytic Leukemia

    PubMed Central

    Sorà, Federica; Chiusolo, Patrizia; Laurenti, Luca; Autore, Francesco; Giammarco, Sabrina; Sica, Simona

    2016-01-01

    Life-threatening bleeding is a major and early complication of acute promyelocytic leukemia (APL), but in the last years there is a growing evidence of thromboses in APL. We report the first case of a young woman with dyspnea as the first symptom of APL due to massive pulmonary embolism (PE) successfully treated with thrombolysis for PE and heparin. APL has been processed with a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) obtaining complete remission. PMID:27413520

  1. Wntless (GPR177) expression correlates with poor prognosis in B-cell precursor acute lymphoblastic leukemia via Wnt signaling.

    PubMed

    Chiou, Shyh-Shin; Wang, Li-Ting; Huang, Shih-Bo; Chai, Chee-Yin; Wang, Shen-Nien; Liao, Yu-Mei; Lin, Pei-Chin; Liu, Kwei-Yan; Hsu, Shih-Hsien

    2014-10-01

    B-cell precursor acute lymphoblastic leukemia (BCP ALL) is the most common childhood leukemia, with a cure rate of 80%. Nevertheless, disease relapse is the most important prognostic factor for the disease outcome. We aimed to elucidate the role of Wnt secretion-regulating protein, Wntless (Wls)/GPR177, on disease outcome in pediatric patients with BCP ALL, and assess its pathogenetic role in the regulation of the disease. Wls expression was characterized and correlated with Wnt pathway signaling in the bone marrow leukemia cells isolated from 44 pediatric patients with BCP ALL. The overexpression of Wls was detected in leukemia cells and was significantly correlated with the disease relapse and poor survival in the patients. The high expression of Wls also correlated with the Wnt expression and consequent downstream signaling activation, which was shown to provide essential proliferation, transformation and anti-apoptotic activity during leukemogenesis. These results indicated that Wls played an essential role in disease relapse and poor survival in patients with BCP ALL. Therefore, Wls may provide a potential future therapeutic target, particularly for patients who do not respond to existing therapies and suffer relapse.

  2. The Acute Pediatric Scrotum: Presentation, Differential Diagnosis and Management

    PubMed Central

    Vasdev, Nikhil; Chadwick, David; Thomas, David

    2012-01-01

    Both pediatric and adult urologists frequently evaluate pediatric patients with an acute scrotum. We present a detailed review on the acute pediatric scrotum highlighting the clinical presentation, differential diagnosis and management of this common clinical condition. It is important to highlight that a testicular torsion is the most important differential diagnosis and the main priority in each case is to diagnosis and treat a potential testicular torsion is of the essence. The aim of our extensive review is to update/review the appropriate evaluation and management of the acute scrotum and to guide the clinician in distinguishing testicular torsion from the other conditions that commonly mimic this surgical emergency. This review is useful for trainees in UK and Europe who plan to take the FRCS (Urol) examination. PMID:24917714

  3. [Local involvement of the optic nerve by acute lymphoblastic leukemia].

    PubMed

    Bernardczyk-Meller, Jadwiga; Stefańska, Katarzyna

    2005-01-01

    The leucemias quite commonly involve the eyes and adnexa. In some cases it causes visual complants. Both, the anterior chamber of the eye and the posterior portion of the globe may sites of acute or chronic leukemia and leucemic relapse. We report an unique case of a 14 years old leucemic patient who suffered visual loss and papilloedema, due to a unilateral local involvement within optic nerve, during second relapse of acute lymphocytic leuemia. In spite of typical treatment of main disease, the boy had died. The authors present typical ophthalmic features of the leucemia, too.

  4. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

  5. Progress and perspectives in pediatric acute respiratory distress syndrome.

    PubMed

    Rotta, Alexandre Tellechea; Piva, Jefferson Pedro; Andreolio, Cinara; de Carvalho, Werther Brunow; Garcia, Pedro Celiny Ramos

    2015-01-01

    Acute respiratory distress syndrome is a disease of acute onset characterized by hypoxemia and infiltrates on chest radiographs that affects both adults and children of all ages. It is an important cause of respiratory failure in pediatric intensive care units and is associated with significant morbidity and mortality. Nevertheless, until recently, the definitions and diagnostic criteria for acute respiratory distress syndrome have focused on the adult population. In this article, we review the evolution of the definition of acute respiratory distress syndrome over nearly five decades, with a special focus on the new pediatric definition. We also discuss recommendations for the implementation of mechanical ventilation strategies in the treatment of acute respiratory distress syndrome in children and the use of adjuvant therapies.

  6. Promoter DNA Methylation Pattern Identifies Prognostic Subgroups in Childhood T-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Borssén, Magnus; Palmqvist, Lars; Karrman, Kristina; Abrahamsson, Jonas; Behrendtz, Mikael; Heldrup, Jesper; Forestier, Erik; Roos, Göran; Degerman, Sofie

    2013-01-01

    Background Treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has improved, but there is a considerable fraction of patients experiencing a poor outcome. There is a need for better prognostic markers and aberrant DNA methylation is a candidate in other malignancies, but its potential prognostic significance in T-ALL is hitherto undecided. Design and Methods Genome wide promoter DNA methylation analysis was performed in pediatric T-ALL samples (n = 43) using arrays covering >27000 CpG sites. Clinical outcome was evaluated in relation to methylation status and compared with a contemporary T-ALL group not tested for methylation (n = 32). Results Based on CpG island methylator phenotype (CIMP), T-ALL samples were subgrouped as CIMP+ (high methylation) and CIMP− (low methylation). CIMP− T-ALL patients had significantly worse overall and event free survival (p = 0.02 and p = 0.001, respectively) compared to CIMP+ cases. CIMP status was an independent factor for survival in multivariate analysis including age, gender and white blood cell count. Analysis of differently methylated genes in the CIMP subgroups showed an overrepresentation of transcription factors, ligands and polycomb target genes. Conclusions We identified global promoter methylation profiling as being of relevance for subgrouping and prognostication of pediatric T-ALL. PMID:23762353

  7. Patterns and severity of vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia.

    PubMed

    Lavoie Smith, Ellen M; Li, Lang; Chiang, ChienWei; Thomas, Karin; Hutchinson, Raymond J; Wells, Elizabeth M; Ho, Richard H; Skiles, Jodi; Chakraborty, Arindom; Bridges, Celia M; Renbarger, Jamie

    2015-03-01

    Vincristine, a critical component of combination chemotherapy treatment for pediatric acute lymphoblastic leukemia (ALL), can lead to vincristine-induced peripheral neuropathy (VIPN). Longitudinal VIPN assessments were obtained over 12 months from newly diagnosed children with ALL (N = 128) aged 1-18 years who received vincristine at one of four academic children's hospitals. VIPN assessments were obtained using the Total Neuropathy Score-Pediatric Vincristine (TNS©-PV), National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE©), Balis© grading scale, and Pediatric Neuropathic Pain Scale©-Five (PNPS©-5). Of children who provided a full TNS©-PV score, 85/109 (78%) developed VIPN (TNS©-PV ≥4). Mean TNS©-PV, grading scale, and pain scores were low. CTCAE©-derived grades 3 and 4 sensory and motor VIPN occurred in 1.6%/0%, and 1.9%/0% of subjects, respectively. VIPN did not resolve in months 8-12 despite decreasing dose density. VIPN was worse in older children. Partition cluster analysis revealed 2-3 patient clusters; one cluster (n = 14) experienced severe VIPN. In this population, VIPN occurs more commonly than previous research suggests, persists throughout the first year of treatment, and can be severe.

  8. ETS-related gene is a novel prognostic factor in childhood acute lymphoblastic leukemia.

    PubMed

    Zhao, Hai-Zhao; Jia, Ming; Luo, Ze-Bin; Xu, Xiao-Jun; Li, Si-Si; Zhang, Jing-Ying; Guo, Xiao-Ping; Tang, Yong-Min

    2017-01-01

    The ETS-related gene (ERG) has been demonstrated to be associated with overall survival in cytogenetically normal acute myeloid leukemia and acute T cell-lymphoblastic leukemia (T-ALL) in adult patients. However, there are no data available regarding the impact of ERG expression on childhood ALL. In the present study, ERG expression levels were analyzed in bone marrow samples from 119 ALL pediatric patients. ALL patients demonstrated higher ERG expression compared with the controls (P<0.0001). In addition, low ERG expression identified a group of patients with higher white blood cell counts (P=0.011), higher percentages of T-ALL immunophenotype (P=0.027), and higher relapse rates (P=0.009). Survival analyses demonstrated that low ERG expression was associated with inferior relapse-free survival (RFS) in childhood ALL (P=0.036) and was an independent prognostic factor in multivariable analyses for RFS. In conclusion, low ERG expression is associated with poor outcomes and may be used to serve as a molecular prognostic marker to identify patients with a high risk of relapse in childhood ALL.

  9. Dasatinib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Did Not Respond to Imatinib Mesylate

    ClinicalTrials.gov

    2013-02-04

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Meningeal Chronic Myelogenous Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  10. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  11. Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

    ClinicalTrials.gov

    2013-08-06

    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(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  12. Acute myocardial infarction as a finding of acute promyelocytic leukemia-related coagulation disorder.

    PubMed

    Özkurt, Zübeyde N; Aypar, Eda; Sarifakiogullari, Serpil; Taçoy, Gülten; Özdag, Murat; Kahraman, Seda; Çengel, Atiye

    2015-12-01

    Acute promyelocytic leukemia (APL) has one of the most favorable prognoses among other leukemia subtypes. However, the major cause of mortality in APL is disseminated intravascular coagulation at the presentation. We present a case of acute myocardial infarction (MI) at the time of APL diagnosis before treatment. The patient suffered from chest pain, sweating and giddiness. He was hypoxic, hypotensive and bradycardic. ECG showed inferior MI. Unfractioned heparin infusion (850 U/h) was started and 5 min after the previous ECG showed total ST resolution. We suggest that in this case, MI was not related to atherosclerotic plaque rupture but related to DIC manifestation.

  13. Delirium in acute promyelocytic leukemia patients: two case reports

    PubMed Central

    2013-01-01

    Background Delirium is a frequently misdiagnosed and inadequately treated neuropsychiatric complication most commonly observed in terminally ill cancer patients. To our knowledge this is the first report describing delirium in two patients aged less than 60 years and enrolled in an intensive chemotherapeutic protocol for acute promyelocytic leukemia. Case presentation Two female Caucasian acute promyelocytic leukemia patients aged 46 and 56 years developed delirium during their induction treatment with all-trans retinoic acid and idarubicin. In both cases symptoms were initially attributed to all-trans retinoic acid that was therefore immediately suspended. In these two patients several situations may have contribute to the delirium: in patient 1 a previous psychiatric disorder, concomitant treatments with steroids and benzodiazepines, a severe infection and central nervous system bleeding while in patient 2 steroid treatment and isolation. In patient 1 delirium was treated with short-term low-doses of haloperidol while in patient 2 non-pharmacologic interventions had a beneficial role. When the diagnosis of delirium was clear, induction treatment was resumed and both patients completed their therapeutic program without any relapse of the psychiatric symptoms. Both patients are alive and in complete remission as far as their leukemia is concerned. Conclusions We suggest that patients with acute promyelocytic leukemia eligible to intensive chemotherapy should be carefully evaluated by a multisciplinary team including psychiatrists in order to early recognize symptoms of delirium and avoid inadequate treatments. In case of delirium, both pharmacologic and non-pharmacologic interventions may be considered. PMID:24237998

  14. Relapsed acute lymphoblastic leukemia with unusual multiple bone invasions: A case report

    PubMed Central

    HANGAI, MAYUMI; WATANABE, KENTARO; SHIOZAWA, RYOSUKE; HIWATARI, MITSUTERU; IDA, KOHMEI; TAKITA, JUNKO

    2014-01-01

    The present study describes a unique pediatric case with multiple bone invasions of acute lymphoblastic leukemia (ALL) during remission. An eight-year-old male with a history of ALL was admitted complaining of intermittent and migrating pain in the limb 2 years following complete remission. Magnetic resonance imaging and whole-body positron emission tomography with 18F-fluorodeoxyglucose revealed abnormal multifocal involvement in the bones and corresponding soft tissues. Repeated bone marrow (BM) aspiration indicated normal cellular marrow without leukemic cells, and marked leukemic cell infiltration in different sections of the ilium, respectively. These findings suggested isolated bone relapse, and it is probable that systematic BM relapse occurred as a consequence. PMID:24944655

  15. Novel molecular and cellular therapeutic targets in acute lymphoblastic leukemia and lymphoproliferative disease

    PubMed Central

    Seif, Alix E.; Reid, Gregor S. D.; Teachey, David T.; Grupp, Stephan A.

    2010-01-01

    While the outcome for pediatric patients with lymphoproliferative disorders (LPD) or lymphoid malignancies, such as acute lymphoblastic leukemia (ALL), has improved dramatically, patients often suffer from therapeutic sequelae. Additionally, despite intensified treatment, the prognosis remains dismal for patients with refractory or relapsed disease. Thus, novel biologically targeted treatment approaches are needed. These targets can be identified by understanding how a loss of lymphocyte homeostasis can result in LPD or ALL. Herein, we review potential molecular and cellular therapeutic strategies that (i) target key signaling networks (e.g., PI3K/AKT/mTOR, JAK/STAT, Notch1, and SRC kinase family-containing pathways) which regulate lymphocyte growth, survival, and function; (ii) block the interaction of ALL cells with stromal cells or lymphoid growth factors secreted by the bone marrow microenvironment; or (iii) stimulate innate and adaptive immune responses. PMID:18716718

  16. Activation of a promyelocytic leukemia-tumor protein 53 axis underlies acute promyelocytic leukemia cure.

    PubMed

    Ablain, Julien; Rice, Kim; Soilihi, Hassane; de Reynies, Aurélien; Minucci, Saverio; de Thé, Hugues

    2014-02-01

    Acute promyelocytic leukemia (APL) is driven by the promyelocytic leukemia (PML)-retinoic acid receptor-α (PML-RARA) fusion protein, which interferes with nuclear receptor signaling and PML nuclear body (NB) assembly. APL is the only malignancy definitively cured by targeted therapies: retinoic acid (RA) and/or arsenic trioxide, which both trigger PML-RARA degradation through nonoverlapping pathways. Yet, the cellular and molecular determinants of treatment efficacy remain disputed. We demonstrate that a functional Pml-transformation-related protein 53 (Trp53) axis is required to eradicate leukemia-initiating cells in a mouse model of APL. Upon RA-induced PML-RARA degradation, normal Pml elicits NB reformation and induces a Trp53 response exhibiting features of senescence but not apoptosis, ultimately abrogating APL-initiating activity. Apart from triggering PML-RARA degradation, arsenic trioxide also targets normal PML to enhance NB reformation, which may explain its clinical potency, alone or with RA. This Pml-Trp53 checkpoint initiated by therapy-triggered NB restoration is specific for PML-RARA-driven APL, but not the RA-resistant promyelocytic leukemia zinc finger (PLZF)-RARA variant. Yet, as NB biogenesis is druggable, it could be therapeutically exploited in non-APL malignancies.

  17. T-cell acute lymphoid leukemia resembling Burkitt leukemia cell morphology: A case report

    PubMed Central

    YUE, QINGFANG; LIU, XINYUE; CHEN, LEI; LIU, ZHONGPING; CHEN, WANXIN

    2015-01-01

    Biphenotypic acute leukemia (BAL) is an uncommon type of cancer, which accounts for <5% of all adult ALs. Based upon a previously described scoring system, the European Group for the Immunological Classification of Leukemias (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based upon the number and degree of specificity of several markers for myeloid or T/B-lymphoid blasts. The present study describes a case of T-cell acute lymphoblastic leukemia (T-ALL) with Burkitt-like cytology, which according to the French-American-British classification, corresponded to a diagnosis of Burkitt type L3 ALL. Flow cytometry analysis demonstrated that the blasts were positive for T-lymphoid markers, cytoplasmic cluster of differentiation (CD)3, CD7 and CD56, and myeloid markers, CD13, CD33 and CD15. At first, a diagnosis of BAL was suggested by the EGIL score, however, according to the 2008 World Health Organization criteria, a case of T-ALL with aberrant myeloid markers was established. The study also reviewed the literature and discussed the limitations of the EGIL scoring system in clinical decision making, to aid in the selection of an appropriate therapeutic regimen. PMID:25663889

  18. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia

    PubMed Central

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H.K.; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1 expression. Two distinct but highly similar subtypes of B cell precursor ALLs that differed by their pre–B cell receptor (pre-BCR) status were induced and displayed maturation arrest at the pro-B/large pre–B II stages of differentiation, similar to human E2A-PBX1 ALL. Somatic activation of E2A-PBX1 in B cell progenitors enhanced self-renewal and led to acquisition of multiple secondary genomic aberrations, including prominent spontaneous loss of Pax5. In preleukemic mice, conditional Pax5 deletion cooperated with E2A-PBX1 to expand progenitor B cell subpopulations, increasing penetrance and shortening leukemia latency. Recurrent secondary activating mutations were detected in key signaling pathways, most notably JAK/STAT, that leukemia cells require for proliferation. These data support conditional E2A-PBX1 mice as a model of human ALL and suggest targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies. PMID:26301816

  19. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment

    PubMed Central

    Mussai, Francis; De Santo, Carmela; Abu-Dayyeh, Issa; Booth, Sarah; Quek, Lynn; McEwen-Smith, Rosanna M.; Qureshi, Amrana; Dazzi, Francesco; Vyas, Paresh

    2013-01-01

    Acute myeloid leukemia (AML) is the most common acute leukemia in adults and the second most common frequent leukemia of childhood. Patients may present with lymphopenia or pancytopenia at diagnosis. We investigated the mechanisms by which AML causes pancytopenia and suppresses patients’ immune response. This study identified for the first time that AML blasts alter the immune microenvironment through enhanced arginine metabolism. Arginase II is expressed and released from AML blasts and is present at high concentrations in the plasma of patients with AML, resulting in suppression of T-cell proliferation. We extended these results by demonstrating an arginase-dependent ability of AML blasts to polarize surrounding monocytes into a suppressive M2-like phenotype in vitro and in engrafted nonobese diabetic–severe combined immunodeficiency mice. In addition, AML blasts can suppress the proliferation and differentiation of murine granulocyte-monocyte progenitors and human CD34+ progenitors. Finally, the study showed that the immunosuppressive activity of AML blasts can be modulated through small-molecule inhibitors of arginase and inducible nitric oxide synthase, suggesting a novel therapeutic target in AML. The results strongly support the hypothesis that AML creates an immunosuppressive microenvironment that contributes to the pancytopenia observed at diagnosis. PMID:23733335

  20. Synchronous occurrence of acute lymphoblastic leukemia and wilms tumor in two patients: underlying etiology and combined treatment plan.

    PubMed

    Yi, Joanna S; Kamihara, Junne; Kesselheim, Jennifer C; Davies, Kimberly; van Hoff, Jack; Silverman, Lewis B; Mullen, Elizabeth A

    2017-05-01

    Synchronous cancers are extraordinarily rare in pediatric patients and present a therapeutic challenge. Patient A presented with synchronous unilateral Wilms tumor (WT) and standard-risk (SR) B-precursor acute lymphoblastic leukemia (ALL). Genetic testing revealed bialleleic BRCA2/FANCD1 mutations. Patient B, after SR B-precursor ALL induction therapy, was noted on fever workup to have a renal mass; pathology demonstrated lesion indeterminate between WT and nephrogenic rest. Therapy was customized for each patient to treat both cancers. Both patients have ongoing remission from their cancers, without excessive toxicity. We report two regimens for treating synchronous WT and ALL and recommend screening such patients for cancer predisposition.

  1. Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

    PubMed

    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Hasani, Seyed-Shahab-Adin; Naderi, Majid; Sadeghi-Bojd, Simin; Taheri, Mohsen

    2017-03-04

    We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

  2. Leukemia

    MedlinePlus

    ... version of this page please turn Javascript on. Leukemia What Is Leukemia? Leukemia is a cancer of the blood cells. ... diagnosed with leukemia are over 50 years old. Leukemia Starts in Bone Marrow Click for more information ...

  3. Pediatric Acute Bacterial Sinusitis: Diagnostic and Treatment Dilemmas.

    PubMed

    Fang, Andrea; England, Jasmin; Gausche-Hill, Marianne

    2015-11-01

    Acute bacterial sinusitis (ABS) is a common complication of a simple upper respiratory infection. Acute bacterial sinusitis and an upper respiratory infection, however, have different management plans. This article will help clinicians establish when a diagnosis of ABS can be made based on the latest guidelines from the American Academy of Pediatrics. Also covered will be the pathophysiology of ABS, the role of diagnostic imaging, the recognition of complications of ABS, and treatment options.

  4. Challenges in Treating Older Patients with Acute Myeloid Leukemia

    PubMed Central

    Eleni, Lagadinou D.; Nicholas, Zoumbos C.; Alexandros, Spyridonidis

    2010-01-01

    Whereas in younger patients diagnosed with acute myeloid leukemia (AML) treatment is straightforward and the goal is cure, the optimal treatment decision for older adults remains highly controversial. Physicians need to determine whether palliation, “something” beyond palliation, intensive therapy, or an investigational therapy is the most appropriate treatment option. This requires understanding of the biology and risk profile of the AML, clinical judgment in evaluating the functional status of the patient, communication skills in understanding the patient's wishes and social background, and medical expertise in available therapies. The physician has to accurately inform the patient about (a) the unique biological considerations of his leukemia and his prognosis; (b) the risks and benefits of all available treatment options; (c) novel therapeutic approaches and how the patient can get access to these treatments. Last but not least, he has to recommend a treatment. This paper tries to discuss each of these issues. PMID:20628485

  5. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

    PubMed

    Vyas, Paresh; Appelbaum, Frederick R; Craddock, Charles

    2015-01-01

    Allogeneic stem cell transplantation is an increasingly important treatment option in the management of adult acute myeloid leukemia (AML). The major causes of treatment failure remain disease relapse and treatment toxicity. In this review, Dr Vyas presents an overview of important recent data defining molecular factors associated with treatment failure in AML. He also identifies the emerging importance of leukemia stem cell biology in determining both response to therapy and relapse risk in AML. Dr Appelbaum discusses advances in the design and delivery of both myeloablative and reduced-intensity conditioning regimens, highlighting novel strategies with the potential to improve outcome. Dr Craddock discusses the development of both novel conditioning regimens and post-transplantation strategies aimed at reducing the risk of disease relapse.

  6. Reprint of: Allogeneic hematopoietic cell transplantation for acute myeloid leukemia.

    PubMed

    Vyas, Paresh; Appelbaum, Frederick R; Craddock, Charles

    2015-02-01

    Allogeneic stem cell transplantation is an increasingly important treatment option in the management of adult acute myeloid leukemia (AML). The major causes of treatment failure remain disease relapse and treatment toxicity. In this review, Dr Vyas presents an overview of important recent data defining molecular factors associated with treatment failure in AML. He also identifies the emerging importance of leukemia stem cell biology in determining both response to therapy and relapse risk in AML. Dr Appelbaum discusses advances in the design and delivery of both myeloablative and reduced-intensity conditioning regimens, highlighting novel strategies with the potential to improve outcome. Dr Craddock discusses the development of both novel conditioning regimens and post-transplantation strategies aimed at reducing the risk of disease relapse.

  7. Simultaneous acute appendicitis and pseudomembranous colitis in a pediatric patient.

    PubMed

    Vidrine, Steven R; Cortina, Chandler; Black, Marissa; Vidrine, Steven B

    2012-01-01

    Acute appendicitis is a common cause for pediatric surgery, with an increasing incidence as this population ages. Pseudomembranous colitis (PMC) from Clostridum difficle is being seen more frequently in pediatric patients, especially after treatment with antibiotics and in those with Hirschsprung's disease. Only three prior cases of appendicitis associated with PMC have been described in the literature, and all of them occurred in adult patients. Here, we describe the first documented pediatric case: a 16-year-old female who developed acute appendicitis while concomitantly being treated for suspected pseudomembranous colitis. We concur with previous authors that there may be an association between these two pathologies; furthermore, this association may not always be clinically apparent and may be both under-diagnosed and under-reported.

  8. [Development of acute myeloid leukemia from donor cells after allogeneic peripheral blood stem cell transplantation in a female patient with acute monoblastic leukemia].

    PubMed

    2011-01-01

    Development of leukemia from donor cells is a rare complication of allogeneic blood stem cells (BSC). The paper describes a case of evolving acute myeloid leukemia of a graft in a patient with resistant acute monoblastic leukemia after related allogeneic peripheral BSC transplantation. The rarity of this complication, difficulties in providing evidence for the donor origin of a leukemic clone demonstrate a need for all-round careful dynamic assessment of the hematopoietic system after allogeneic transplantation, by applying the current cytogenetic (fluorescence in situ hybridization) and molecular (hypervariable genomic region amplification test using the polymerase chain reaction, hypervariable number of tandem repeats (VNTR), and short number of tandem repeats (STR)) techniques, which permits errors to be avoided in the assessment of a clinical situation and in the diagnosis of leukemia from donor cells. There is no developed policy for treatment of acute graft-versus-leukemia.

  9. Acute leukemia occurring after radiotherapy and chemotherapy with a nitrosourea, PCNU.

    PubMed

    Shepard, K V; Larson, R; Le Beau, M M; Leichman, L; Levin, B

    1988-06-01

    Secondary acute leukemias can occur in patients who have been treated with chemotherapy. Several reports have shown that treatment with nitrosoureas can result in secondary leukemia, but this is the first report implicating the investigational drug PCNU as a cause. This case is unique because of the cytogenetic findings, the short latency period between the chemotherapy and the diagnosis of leukemia, and the successful treatment of the leukemia with high-dose cytarabine (ara-C).

  10. Early rehabilitative treatment for pediatric acute disseminated encephalomyelitis: case report.

    PubMed

    Carlisi, E; Pavese, C; Mandrini, S; Carenzio, G; Dalla Toffola, E

    2015-06-01

    Although the diagnosis of and therapy for acute disseminated encephalomyelitis (ADEM) have been extensively investigated, the role of rehabilitation in modifying its functional outcome has received little attention in the literature so far. We report a case of pediatric ADEM who showed complete functional recovery following early rehabilitative treatment, started in the Intensive Care Unit.

  11. Clofarabine, Cytarabine, and Filgrastim in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia, Advanced Myelodysplastic Syndrome, and/or Advanced Myeloproliferative Neoplasm

    ClinicalTrials.gov

    2016-12-27

    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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Untreated Adult Acute Myeloid Leukemia; Myeloproliferative Neoplasm With 10% Blasts or Higher

  12. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia.

    PubMed

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-08-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [(68)Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche.

  13. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia

    PubMed Central

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-01-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [68Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029

  14. Application of simplified bioclean apparatuses for treatment of acute leukemia.

    PubMed

    Hasegawa, H; Horiuchi, A

    1983-01-01

    We used a portable horizontal laminar-air-flow clean bed and an open horizontal laminar-air-flow fan (clean wall unit) for treating patients with acute leukemia. The level of cleanliness as shown in the nonviable and viable particle counts was class 100 and class 1,000 at the head and foot, respectively, of the bed in the clean-bed rooms, while it was class 100 and class 10,000 respectively, in the clean-wall-unit rooms. The level of cleanliness in the open wards, on the other hand, was class 1,000,000. The incidence of infectious complications in the clean-bed rooms was 3.1/100 days when the granulocyte count was 1,000/mm3 or less, 3.9/100 days when the count was 500/mm3 or less and 6.1/100 days when it was 100/mm3 or less. In the clean-wall-unit rooms, these values were 3.1, 3.7 and 7.1, respectively, while in the open wards they were 4.6, 6.1 and 15.0. Thus, it was ascertained that, as the granulocyte count decreased, the incidence of infectious complications became significantly higher in the open wards than in the clean-bed rooms or the clean-wall-unit rooms. No complication of pneumonia was found in 37 patients with acute leukemia in the clean-bed rooms or in 40 in the clean-wall-unit rooms. Among 36 patients treated in the open wards, on the other hand, the complication of pneumonia was found in four. From the above results, it is believed that the use of clean-bed rooms or clean-wall-unit rooms is an extremely effective supplementary treatment method for preventing respiratory tract infection complications in patients with acute leukemia.

  15. Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; L3 Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma

  16. Ecthyma gangrenosum in a patient with acute leukemia.

    PubMed

    Kryeziu, Emrush; Kryeziu, K; Bajraktari, Gjani; Abazi, M; Zylfiu, B; Rudhani, I; Sadiku, Sh; Ukimeri, A; Brovina, A; Dreshaj, Sh; Telaku, S

    2010-01-01

    Ecthymagangrenosum (EG)is a rare condition with characteristic clinical appearance of red maculae that progresses to a central area of necrosis surrounded by an erythematous halo. The most frequently it is caused by Pseudomonas bacteriaemia in neutropenic patient. The authors presents a patient with acute myloblastic leukemia M4 type in whom in relapse EG caused by Pseudomonas aeruginosa was found. The patient was treated with antibiotics and surgical debridement. The author wants to point out on clinical significance this condition with high mortality rate.

  17. [Effect of Ikaros in B Cell Acute Lymphoblastic Leukemia].

    PubMed

    Zhang, Hai-Ying; Bai, Hai

    2015-08-01

    The Ikaros - a DNA-binding zinc finger protein, acting as a regulator of chromatin remodeling and gene transcription, is crucial for regulating the development and function of the immune system and acting as a master regulator of hematopoietic differentiation. Function-loss mutations of IKZF1, gene encoding Ikaros are frequent in B cell acute lymphoblastic leukemia (B-ALL) and are associated with a poor prognosis. This review briefly summarizes the available data regarding the structure and function of Ikaros, the role of Ikaros as a tumor suppressor in B-ALL, and its regulation mechanism.

  18. Myelodysplastic Syndromes and Acute Myeloid Leukemia in the Elderly.

    PubMed

    Klepin, Heidi D

    2016-02-01

    Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic diseases that frequently affect older adults. Treatment is challenging. Management of older adults with MDS and AML needs to be individualized, accounting for both the heterogeneity of disease biology and patient characteristics, which can influence life expectancy and treatment tolerance. Clinical trials accounting for the heterogeneity of tumor biology and physiologic changes of aging are needed to define optimal standards of care. This article highlights key evidence related to the management of older adults with MDS and AML and highlights future directions for research.

  19. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    PubMed

    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko

    2015-01-01

    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  20. Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia

    PubMed Central

    Maude, Shannon L.; Tasian, Sarah K.; Vincent, Tiffaney; Hall, Junior W.; Sheen, Cecilia; Roberts, Kathryn G.; Seif, Alix E.; Barrett, David M.; Chen, I-Ming; Collins, J. Racquel; Mullighan, Charles G.; Hunger, Stephen P.; Harvey, Richard C.; Willman, Cheryl L.; Fridman, Jordan S.; Loh, Mignon L.; Grupp, Stephan A.

    2012-01-01

    CRLF2 rearrangements, JAK1/2 point mutations, and JAK2 fusion genes have been identified in Philadelphia chromosome (Ph)–like acute lymphoblastic leukemia (ALL), a recently described subtype of pediatric high-risk B-precursor ALL (B-ALL) which exhibits a gene expression profile similar to Ph-positive ALL and has a poor prognosis. Hyperactive JAK/STAT and PI3K/mammalian target of rapamycin (mTOR) signaling is common in this high-risk subset. We, therefore, investigated the efficacy of the JAK inhibitor ruxolitinib and the mTOR inhibitor rapamycin in xenograft models of 8 pediatric B-ALL cases with and without CRLF2 and JAK genomic lesions. Ruxolitinib treatment yielded significantly lower peripheral blast counts compared with vehicle (P < .05) in 6 of 8 human leukemia xenografts and lower splenic blast counts (P < .05) in 8 of 8 samples. Enhanced responses to ruxolitinib were observed in samples harboring JAK-activating lesions and higher levels of STAT5 phosphorylation. Rapamycin controlled leukemia burden in all 8 B-ALL samples. Survival analysis of 2 representative B-ALL xenografts demonstrated prolonged survival with rapamycin treatment compared with vehicle (P < .01). These data demonstrate preclinical in vivo efficacy of ruxolitinib and rapamycin in this high-risk B-ALL subtype, for which novel treatments are urgently needed, and highlight the therapeutic potential of targeted kinase inhibition in Ph-like ALL. PMID:22955920

  1. Co-operative leukemogenesis in acute myeloid leukemia and acute promyelocytic leukemia reveals C/EBPα as a common target of TRIB1 and PML/RARA

    PubMed Central

    Keeshan, Karen; Vieugué, Pauline; Chaudhury, Shahzya; Rishi, Loveena; Gaillard, Coline; Liang, Lu; Garcia, Elaine; Nakamura, Takuro; Omidvar, Nader; Kogan, Scott C.

    2016-01-01

    The PML/RARA fusion protein occurs as a result of the t(15;17) translocation in the acute promyelocytic leukemia subtype of human acute myeloid leukemia. Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia, including acute promyelocytic leukemia. We previously demonstrated that gain of chromosome 8-containing MYC is of central importance in trisomy 8, but the role of the nearby TRIB1 gene has not been experimentally addressed in this context. We have now tested the hypothesis that both MYC and TRIB1 have functional roles underlying leukemogenesis of trisomy 8 by using retroviral vectors to express MYC and TRIB1 in wild-type bone marrow and in marrow that expressed a PML/RARA transgene. Interestingly, although MYC and TRIB1 readily co-operated in leukemogenesis for wild-type bone marrow, TRIB1 provided no selective advantage to cells expressing PML/RARA. We hypothesized that this lack of co-operation between PML/RARA and TRIB1 reflected a common pathway for their effect: both proteins targeting the myeloid transcription factor C/EBPα. In support of this idea, TRIB1 expression abrogated the all-trans retinoic acid response of acute promyelocytic leukemia cells in vitro and in vivo. Our data delineate the common and redundant inhibitory effects of TRIB1 and PML/RARA on C/EBPα providing a potential explanation for the lack of selection of TRIB1 in human acute promyelocytic leukemia, and highlighting the key role of C/EBPs in acute promyelocytic leukemia pathogenesis and therapeutic response. In addition, the co-operativity we observed between MYC and TRIB1 in the absence of PML/RARA show that, outside of acute promyelocytic leukemia, gain of both genes may drive selection for trisomy 8. PMID:27390356

  2. ACUTE HEPATITIS ASSOCIATED WITH MOUSE LEUKEMIA

    PubMed Central

    Nelson, John B.

    1953-01-01

    The hepatitis of Princeton weanlings was not prevented by the prior injection of terramycin nor was the virus inactivated by exposure to room temperature. Eperythrozoon coccoides was not demonstrable in blood films from Swiss and Princeton mice infected with the corresponding type of hepatitis virus. Combined infection with this virus and eperythrozoa, originally obtained by Dr. R. B. McGhee from mice in association with Plasmodium berghei, was attended by the appearance of numerous organisms in the blood. The development of eperythrozoa in dually infected Princeton mice had no effect on the outcome of the hepatitis. In Swiss mice, animals with high natural resistance to hepatitis virus, the pathogenicity of this agent was markedly enhanced by combined infection with eperythrozoa. Eperythrozoa were maintained throughout 18 successive passages in normal Princeton and Swiss weanlings with intact spleens. The combined infection of Princeton mice with eperythrozoa and the virus component of Gledhill, Dick, and Andrewes, which is nearly inactive when injected alone, resulted in acute hepatitis with fatal outcome. PMID:13109101

  3. Novel drugs for older patients with acute myeloid leukemia.

    PubMed

    Montalban-Bravo, G; Garcia-Manero, G

    2015-04-01

    Acute myeloid leukemia (AML) is the second most common form of leukemia and the most frequent cause of leukemia-related deaths in the United States. The incidence of AML increases with advancing age and the prognosis for patients with AML worsens substantially with increasing age. Many older patients are ineligible for intensive treatment and require other therapeutic approaches to optimize clinical outcome. To address this treatment gap, novel agents with varying mechanisms of action targeting different cellular processes are currently in development. Hypomethylating agents (azacitidine, decitabine, SGI-110), histone deacetylase inhibitors (vorinostat, pracinostat, panobinostat), FMS-like tyrosine kinase receptor-3 inhibitors (quizartinib, sorafenib, midostaurin, crenolanib), cytotoxic agents (clofarabine, sapacitabine, vosaroxin), cell cycle inhibitors (barasertib, volasertib, rigosertib) and monoclonal antibodies (gentuzumab ozogamicin, lintuzumab-Ac225) represent some of these promising new treatments. This review provides an overview of novel agents that have either completed or are currently in ongoing phase III trials in patients with previously untreated AML for whom intensive treatment is not an option. Other potential drugs in earlier stages of development will also be addressed in this review.

  4. Acute Myeloid Leukemia: Focus on Novel Therapeutic Strategies

    PubMed Central

    Lin, Tara L.; Levy, M. Yair

    2012-01-01

    Acute myeloid leukemia (AML) is a heterogeneous disease with variable clinical outcomes. Cytogenetic analysis reveals which patients may have favorable risk disease, but 5-year survival in this category is only approximately 60%, with intermediate and poor risk groups faring far worse. Advances in our understanding of the biology of leukemia pathogenesis and prognosis have not been matched with clinical improvements. Unsatisfactory outcomes persist for the majority of patients with AML, particularly the elderly. Novel agents and treatment approaches are needed in the induction, post-remission and relapsed settings. The additions of clofarabine for relapsed or refractory disease and the hypomethylating agents represent recent advances. Clinical trials of FLT3 inhibitors have yielded disappointing results to date, with ongoing collaborations attempting to identify the optimal role for these agents. Potential leukemia stem cell targeted therapies and treatments in the setting of minimal residual disease are also under investigation. In this review, we will discuss recent advances in AML treatment and novel therapeutic strategies. PMID:22654526

  5. NUP98-MLL fusion in human acute myeloblastic leukemia.

    PubMed

    Kaltenbach, Sophie; Soler, Gwendoline; Barin, Carole; Gervais, Carine; Bernard, Olivier A; Penard-Lacronique, Virginie; Romana, Serge P

    2010-09-30

    Posttranscriptional modifications of histones play important roles in the control of chromatin structure and transcription. H3K4 (histone H3 lysine 4) methylation by the SET domain of the trithorax-group protein MLL (mixed-lineage leukemia) is important for the control of homeobox (HOX) gene expression during development. MLL is tethered to the HOXA locus through interaction of its amino-terminus with menin. MLL fusion proteins associated with human leukemia contain the menin interaction peptide and frequently recruit H3K79 (histone H3 lysine 79) methylation activity. This allows sustained expression of HOXA genes important for cellular transformation. We have characterized a novel recurrent chromosomal aberration, inv(11)(p15q23), as an isolated chromosomal abnormality in 2 patients with acute myeloid leukemia. This aberration is predicted to result in the expression of an NUP98 (nucleoporin 98 kDa)-MLL fusion protein that is unable to interact with menin. As expected, low levels of HOXA gene expression were observed in the patients' samples. This fusion protein is predicted to participate in cellular transformation by activating MLL targets other than HOXA genes.

  6. Physiologically based toxicokinetic modeling of secondary acute myelolytic leukemia.

    PubMed

    Mukhopadhyay, Manas Kumar; Nath, Debjani

    2014-01-01

    Benzene, designated as environmental and occupational carcinogen and hematotoxin, has been associated with secondary leukemia. To develop a toxicokinetic model of AML, benzene can be used as leukemogenic agent. The aim of the present study was to optimize the dose, period and time of cumulative benzene exposure of Swiss Albino mice and to analyze survival rate; alteration in cell cycle regulation and other clinical manifestations in mice exposed to benzene vapour at a dose 300 ppm × 6 h/day × 5 days/week for 2 weeks, i.e., 9000(a)ppm cumulative dose. Analyzing physiological parameters like plasma enzyme profile, complete hematology (Hb %, RBC indices and WBC differentials), hematopoietic cells morphology, expression of cell cycle regulatory proteins, tissue histology and analysis of DNA fragmentation, optimum conditions were established. Down regulation of p53 and p21 and up regulation of CDK2, CDK4, CDK6, cyclin D1 and E in this exposed group were marked as the optimum conditions of cellular deregulation for the development of secondary AML. Elevated level of Plasma AST/ALT with corresponding changes in liver histology showing extended sinusoids within the hepatocytic cell cords in optimally exposed animals also confirmed the toxicokinetic relation of benzene with leukemia. It can be concluded from the above observations that the 9000(a)ppm exposed animals can serve as the induced laboratory model of secondary acute myeloid leukemia.

  7. The genomic landscape of core-binding factor acute myeloid leukemias.

    PubMed

    Faber, Zachary J; Chen, Xiang; Gedman, Amanda Larson; Boggs, Kristy; Cheng, Jinjun; Ma, Jing; Radtke, Ina; Chao, Jyh-Rong; Walsh, Michael P; Song, Guangchun; Andersson, Anna K; Dang, Jinjun; Dong, Li; Liu, Yu; Huether, Robert; Cai, Zhongling; Mulder, Heather; Wu, Gang; Edmonson, Michael; Rusch, Michael; Qu, Chunxu; Li, Yongjin; Vadodaria, Bhavin; Wang, Jianmin; Hedlund, Erin; Cao, Xueyuan; Yergeau, Donald; Nakitandwe, Joy; Pounds, Stanley B; Shurtleff, Sheila; Fulton, Robert S; Fulton, Lucinda L; Easton, John; Parganas, Evan; Pui, Ching-Hon; Rubnitz, Jeffrey E; Ding, Li; Mardis, Elaine R; Wilson, Richard K; Gruber, Tanja A; Mullighan, Charles G; Schlenk, Richard F; Paschka, Peter; Döhner, Konstanze; Döhner, Hartmut; Bullinger, Lars; Zhang, Jinghui; Klco, Jeffery M; Downing, James R

    2016-12-01

    Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.

  8. Relapse specific mutations in NT5C2 in childhood acute lymphoblastic leukemia

    PubMed Central

    Meyer, Julia A.; Wang, Jinhua; Hogan, Laura E.; Yang, Jun J.; Dandekar, Smita; Patel, Jay P.; Tang, Zuojian; Zumbo, Paul; Li, Sheng; Zavadil, Jiri; Levine, Ross L.; Cardozo, Timothy; Hunger, Stephen P.; Raetz, Elizabeth A.; Evans, William E.; Morrison, Debra J.; Mason, Christopher E.; Carroll, William L.

    2013-01-01

    Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis despite intensive retreatment, due to intrinsic drug resistance1-2. The biological pathways that mediate resistance are unknown. Here we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten pediatric B lymphoblastic leukemia patients using RNA-sequencing. Transcriptome sequencing identified 20 newly acquired novel non-synonymous mutations not present at initial diagnosis, of which two patients harbored relapse specific mutations in the same gene, NT5C2, a 5′-nucleotidase. Full exon sequencing of NT5C2 was completed in 61 additional relapse specimens, identifying five additional cases. Enzymatic analysis of mutant proteins revealed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analogue therapies. Clinically, all patients who harbored NT5C2 mutations relapsed early, or within 36 months of initial diagnosis (p=0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug resistant clones in ALL. PMID:23377183

  9. Relapse-specific mutations in NT5C2 in childhood acute lymphoblastic leukemia.

    PubMed

    Meyer, Julia A; Wang, Jinhua; Hogan, Laura E; Yang, Jun J; Dandekar, Smita; Patel, Jay P; Tang, Zuojian; Zumbo, Paul; Li, Sheng; Zavadil, Jiri; Levine, Ross L; Cardozo, Timothy; Hunger, Stephen P; Raetz, Elizabeth A; Evans, William E; Morrison, Debra J; Mason, Christopher E; Carroll, William L

    2013-03-01

    Relapsed childhood acute lymphoblastic leukemia (ALL) carries a poor prognosis, despite intensive retreatment, owing to intrinsic drug resistance. The biological pathways that mediate resistance are unknown. Here, we report the transcriptome profiles of matched diagnosis and relapse bone marrow specimens from ten individuals with pediatric B-lymphoblastic leukemia using RNA sequencing. Transcriptome sequencing identified 20 newly acquired, novel nonsynonymous mutations not present at initial diagnosis, with 2 individuals harboring relapse-specific mutations in the same gene, NT5C2, encoding a 5'-nucleotidase. Full-exon sequencing of NT5C2 was completed in 61 further relapse specimens, identifying additional mutations in 5 cases. Enzymatic analysis of mutant proteins showed that base substitutions conferred increased enzymatic activity and resistance to treatment with nucleoside analog therapies. Clinically, all individuals who harbored NT5C2 mutations relapsed early, within 36 months of initial diagnosis (P = 0.03). These results suggest that mutations in NT5C2 are associated with the outgrowth of drug-resistant clones in ALL.

  10. Hypoxia inducible factor-1α regulates a pro-invasive phenotype in acute monocytic leukemia

    PubMed Central

    Migliavacca, Jessica; Percio, Stefano; Valsecchi, Roberta; Ferrero, Elisabetta; Spinelli, Antonello; Ponzoni, Maurilio; Tresoldi, Cristina; Pattini, Linda

    2016-01-01

    Hypoxia inducible transcription factors (HIFs) are the main regulators of adaptive responses to hypoxia and are often activated in solid tumors, but their role in leukemia is less clear. In acute myeloid leukemia (AML), in particular, controversial new findings indicate that HIF-1α can act either as an oncogene or a tumor suppressor gene, and this may depend on the stage of leukemia development and/or the AML sub-type. In this study, we find that HIF-1α promotes leukemia progression in the acute monocytic leukemia sub-type of AML through activation of an invasive phenotype. By applying a list of validated HIF-1α-target genes to different AML sub-types, we identified a HIF-1α signature that typifies acute monocytic leukemia when compared with all other AML sub-types. We validated expression of this signature in cell lines and primary cells from AML patients. Interestingly, this signature is enriched for genes that control cell motility at different levels. As a consequence, inhibiting HIF-1α impaired leukemia cell migration, chemotaxis, invasion and transendothelial migration in vitro, and this resulted in impaired bone marrow homing and leukemia progression in vivo. Our data suggest that in acute monocytic leukemia an active HIF-1α-dependent pro-invasive pathway mediates the ability of leukemic cells to migrate and invade extramedullary sites and may be targeted to reduce leukemia dissemination. PMID:27447550

  11. Philadelphia chromosome-positive leukemia stem cells in acute lymphoblastic leukemia and tyrosine kinase inhibitor therapy.

    PubMed

    Thomas, Xavier

    2012-06-26

    Leukemia stem cells (LSCs), which constitute a minority of the tumor bulk, are functionally defined on the basis of their ability to transfer leukemia into an immunodeficient recipient animal. The presence of LSCs has been demonstrated in acute lymphoblastic leukemia (ALL), of which ALL with Philadelphia chromosome-positive (Ph(+)). The use of imatinib, a tyrosine kinase inhibitor (TKI), as part of front-line treatment and in combination with cytotoxic agents, has greatly improved the proportions of complete response and molecular remission and the overall outcome in adults with newly diagnosed Ph(+) ALL. New challenges have emerged with respect to induction of resistance to imatinib via Abelson tyrosine kinase mutations. An important recent addition to the arsenal against Ph(+) leukemias in general was the development of novel TKIs, such as nilotinib and dasatinib. However, in vitro experiments have suggested that TKIs have an antiproliferative but not an antiapoptotic or cytotoxic effect on the most primitive ALL stem cells. None of the TKIs in clinical use target the LSC. Second generation TKI dasatinib has been shown to have a more profound effect on the stem cell compartment but the drug was still unable to kill the most primitive LSCs. Allogeneic stem cell transplantation (SCT) remains the only curative treatment available for these patients. Several mechanisms were proposed to explain the resistance of LSCs to TKIs in addition to mutations. Hence, TKIs may be used as a bridge to SCT rather than monotherapy or combination with standard chemotherapy. Better understanding the biology of Ph(+) ALL will open new avenues for effective management. In this review, we highlight recent findings relating to the question of LSCs in Ph(+) ALL.

  12. The concurrent occurrence of Leishmania chagasi infection and childhood acute leukemia in Brazil

    PubMed Central

    de Vasconcelos, Gisele Moledo; Azevedo-Silva, Fernanda; dos Santos Thuler, Luiz Claudio; Pina, Eugênia Terra Granado; Souza, Celeste S.F.; Calabrese, Katia; Pombo-de-Oliveira, Maria S.

    2014-01-01

    Objective This study investigated the co-existence of Leishmania chagasi infection and childhood leukemia in patients naïve to treatment; this has serious clinical and epidemiological implications. Methods The seroprevalence of L. chagasi antibodies prior to any treatment was investigated in children with clinical features of acute leukemia. Serological tests were performed in 470 samples drawn from under 14-year-old children from different regions of Brazil with clinical suspicion of acute leukemia. Acute leukemia subtypes were characterized by immunophenotyping using flow cytometry. Morphological analyses of bone marrow aspirates were systematically performed to visualize blast cells and/or the formation of L. chagasi amastigotes. Data analysis used a standard univariate procedure and the Pearson's chi-square test. Results The plasma of 437 children (93%) displayed antibodies against L. chagasi by indirect immunofluorescence assay and enzyme-linked immunosorbent assay tests. Of the 437 patients diagnosed from 2002 to 2006, 254 had acute lymphoblastic leukemia, 92 had acute myeloid leukemia, and 91 did not have acute leukemia. The seroprevalence of L. chagasi antibodies according to the indirect immunofluorescence assay test (22.5%) was similar in children with or without acute leukemia (p-value = 0.76). The co-existence of visceral leishmanasis and acute leukemia was confirmed in 24 children. The overall survival of these children was poor with a high death rate during the first year of leukemia treatment. Conclusion In the differential diagnosis of childhood leukemia, visceral leishmanasis should be considered as a potential concurrent disease in regions where L. chagasi is endemic. PMID:25305169

  13. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  14. Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia.

    PubMed

    Stringaris, Kate; Sekine, Takuya; Khoder, Ahmad; Alsuliman, Abdullah; Razzaghi, Bonnie; Sargeant, Ruhena; Pavlu, Jiri; Brisley, Gill; de Lavallade, Hugues; Sarvaria, Anushruthi; Marin, David; Mielke, Stephan; Apperley, Jane F; Shpall, Elizabeth J; Barrett, A John; Rezvani, Katayoun

    2014-05-01

    The majority of patients with acute myeloid leukemia will relapse, and older patients often fail to achieve remission with induction chemotherapy. We explored the possibility that leukemic suppression of innate immunity might contribute to treatment failure. Natural killer cell phenotype and function was measured in 32 consecutive acute myeloid leukemia patients at presentation, including 12 achieving complete remission. Compared to 15 healthy age-matched controls, natural killer cells from acute myeloid leukemia patients were abnormal at presentation, with downregulation of the activating receptor NKp46 (P=0.007) and upregulation of the inhibitory receptor NKG2A (P=0.04). Natural killer cells from acute myeloid leukemia patients had impaired effector function against autologous blasts and K562 targets, with significantly reduced CD107a degranulation, TNF-α and IFN-γ production. Failure to achieve remission was associated with NKG2A overexpression and reduced TNF-α production. These phenotypic and functional abnormalities were partially restored in the 12 patients achieving remission. In vitro co-incubation of acute myeloid leukemia blasts with natural killer cells from healthy donors induced significant impairment in natural killer cell TNF-α and IFN-γ production (P=0.02 and P=0.01, respectively) against K562 targets and a trend to reduced CD107a degranulation (P=0.07). Under transwell conditions, the inhibitory effect of AML blasts on NK cytotoxicity and effector function was still present, and this inhibitory effect was primarily mediated by IL-10. These results suggest that acute myeloid leukemia blasts induce long-lasting changes in natural killer cells, impairing their effector function and reducing the competence of the innate immune system, favoring leukemia survival.

  15. Identification of ILK as a novel therapeutic target for acute and chronic myeloid leukemia.

    PubMed

    de la Puente, Pilar; Weisberg, Ellen; Muz, Barbara; Nonami, Atsushi; Luderer, Micah; Stone, Richard M; Melo, Junia V; Griffin, James D; Azab, Abdel Kareem

    2015-09-09

    Current treatment options as well as clinical efficacy are limited for chronic myelogenous leukemia (CML), Ph+ acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). In response to the pressing need for more efficacious treatment approaches and strategies to override drug resistance in advanced stage CML, Ph+ ALL, and AML, we investigated the effects of inhibition of ILK as a potentially novel and effective approach to treatment of these challenging malignancies. Using the small molecule ILK inhibitor, Cpd22, and ILK knockdown, we investigated the importance of ILK in the growth and viability of leukemia. Our results suggest that the ILK inhibition may be an effective treatment for CML, Ph+ ALL, and AML as a single therapy, with ILK expression levels positively correlating with the efficacy of ILK inhibition. The identification of ILK as a novel target for leukemia therapy warrants further investigation as a therapeutic approach that could be of potential clinical benefit in both acute and chronic myeloid leukemias.

  16. [Epidemiological characteristics of acute lymphoblastic leukemia in children from Tuzla Canton].

    PubMed

    Hadziselimović, Admira; Tahirović, Husref

    2011-01-01

    This study was undertaken to determine epidemiological characteristics of acute lymphoblastic leukemia (ALL) in children aged 0-14 years from Tuzla Canton, during a 13-year period (1995-2007). This retrospective study analyzed patient medical records from University Department of Pediatrics, Tuzla University Clinical Center, as well as documentation of other medical facilities providing additional diagnostic and therapeutic treatment to these patients. Records on the population of children during the study period were obtained from Federal Department of Statistics. ALL was diagnosed in 41 children, 27 (66.0%) male and 14 (34.1%) female. The mean incidence rate for both sexes was 3.3/100,000 (2.3-4.4). It was higher in boys (4.2/100,000) than in girls (2.3/100,000). The highest incidence rate was recorded in 2002 (7.6/100,000). Study results provided reliable insight into the epidemiological characteristics of ALL in children from Tuzla Canton and proved useful for planning a pediatric health care program in the area.

  17. Unique characteristics of adolescent and young adult acute lymphoblastic leukemia, breast cancer, and colon cancer.

    PubMed

    Tricoli, James V; Seibel, Nita L; Blair, Donald G; Albritton, Karen; Hayes-Lattin, Brandon

    2011-04-20

    Each year in the United States, nearly 70 000 individuals between the ages of 15 and 40 years are diagnosed with cancer. Although overall cancer survival rates among pediatric and older adult patients have increased in recent decades, there has been little improvement in survival of adolescent and young adult (AYA) cancer patients since 1975 when collected data became adequate to evaluate this issue. In 2006, the AYA Oncology Progress Review Group made recommendations for addressing the needs of this population that were later implemented by the LIVESTRONG Young Adult Alliance. One of their overriding questions was whether the cancers seen in AYA patients were biologically different than the same cancers in adult and/or pediatric patients. On June 9-10, 2009, the National Cancer Institute (NCI) and the Lance Armstrong Foundation (LAF) convened a workshop in Bethesda, MD, entitled "Unique Characteristics of AYA Cancers: Focus on Acute Lymphocytic Leukemia (ALL), Breast Cancer and Colon Cancer" that aimed to examine the current state of basic and translational research on these cancers and to discuss the next steps to improve their prognosis and treatment.

  18. A rare aggravation of severe mucositis post chemotherapy in a child with acute lymphoblastic leukemia.

    PubMed

    Inati, Adlette; Akouri, Grace; Abbas, Hussein A

    2013-01-01

    Oral mucositis is a debilitating manifestation in children undergoing chemotherapy and radiotherapy. Children with mucositis should be properly managed in order to prevent further exacerbation and adverse complications. We hereby present the first report of a severe chemotherapy-induced mucositis, plausibly aggravated by improper dental hygiene leading to shedding of the ventral part of the tongue in a child with pre-B acute lymphoblastic leukemia (ALL). The patient steadily and gradually recovered her oral maneuvers and ability to speak several months later. Her tongue underwent hypertrophy as a compensatory mechanism. We recommend that critical and regular assessment of the oral mucosa and proper dental care and oral hygiene be emphasized in all pediatric patients receiving chemotherapy. Families of affected children need to be educated about the benefits and modes of optimal oral hygiene for their children and the need to seek immediate care for mouth pain and or lesions. Optimal treatment for mucositis needs to be instituted without delay in this high risk pediatric population. Such a preventive and therapeutic approach may prevent associated life threatening oral and systemic complications, promote rapid and complete mucosal healing, alleviate pain and improve quality of life in children with cancer.

  19. L-asparaginase in the treatment of patients with acute lymphoblastic leukemia

    PubMed Central

    Egler, Rachel A.; Ahuja, Sanjay P.; Matloub, Yousif

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that predominantly occurs in children between 2 and 10 years of age. L-asparaginase is an integral component of treatment for patients with ALL and since its introduction into pediatric treatment protocols in the 1960s, survival rates in children have progressively risen to nearly 90%. Outcomes for adolescent and young adult (AYA) patients, aged 15-39 years and diagnosed with ALL, have historically been less favorable. However, recent reports suggest substantially increased survival in AYA patients treated on pediatric-inspired protocols that include a greater cumulative dose of asparaginase. All  currently available asparaginases share the same mechanism of action - the deamination and depletion of serum asparagine levels - yet each displays a markedly different pharmacokinetic profile. Pegylated asparaginase derived from the bacterium Escherichia coli is used as first-line therapy; however, up to 30% of patients develop a treatment-limiting hypersensitivity reaction. Patients who experience a hypersensitivity reaction to an E. coli-derived asparaginase can continue treatment with Erwinia chrysanthemi asparaginase. Erwinia asparaginase is immunologically distinct from E. coli-derived asparaginases and exhibits no cross-reactivity. Studies have shown that with adequate dosing, therapeutic levels of Erwinia asparaginase activity can be achieved, and patients switched to Erwinia asparaginase due to hypersensitivity can obtain outcomes similar to patients who do not experience a hypersensitivity reaction. Therapeutic drug monitoring may be required to ensure that therapeutic levels of asparaginase activity are maintained. PMID:27440950

  20. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.

  1. Exogenous IL-33 overcomes T cell tolerance in murine acute myeloid leukemia

    PubMed Central

    Qin, Lei; Dominguez, Donye; Chen, Siqi; Fan, Jie; Long, Alan; Zhang, Minghui; Fang, Deyu; Zhang, Yi; Kuzel, Timothy M.; Zhang, Bin

    2016-01-01

    Emerging studies suggest that dominant peripheral tolerance is a major mechanism of immune escape in disseminated leukemia. Using an established murine acute myeloid leukemia (AML) model, we here show that systemic administration of recombinant IL-33 dramatically inhibits the leukemia growth and prolongs the survival of leukemia-bearing mice in a CD8+ T cell dependent manner. Exogenous IL-33 treatment enhanced anti-leukemia activity by increasing the expansion and IFN-γ production of leukemia-reactive CD8+ T cells. Moreover, IL-33 promoted dendritic cell (DC) maturation and activation in favor of its cross presentation ability to evoke a vigorous anti-leukemia immune response. Finally, we found that the combination of PD-1 blockade with IL-33 further prolonged the survival, with half of the mice achieving complete regression. Our data establish a role of exogenous IL-33 in reversing T cell tolerance, and suggest its potential clinical implication into leukemia immunotherapy. PMID:27517629

  2. Recommending randomized trials for pediatric leukemia: observer and physician report of recommendations.

    PubMed

    Hazen, Rebecca; Greenley, Rachel Neff; Drotar, Dennis; Kodish, Eric

    2007-06-01

    Physicians' presentation of treatment options in a non-coercive manner is critical for informed consent for participation in randomized clinical trials (RCTs). This study examined discrepancies between observer and physician report of treatment recommendations for pediatric leukemia RCTs. This study also assessed relationships between recommendations and decisions to participate in RCTs. Participants were 104 parents of children with leukemia and the treating physicians. Measures included observations of informed consent conferences (ICCs), physician report of treatment recommendations, and parent report of trial participation. Observation revealed that physicians recommended RCTs in 38% of ICCs, while physicians reported recommending RCTs in 73% of ICCs. Treatment recommendations were unrelated to decisions to participate in RCTs. Results highlight the importance of enhancing parent-physician communication regarding RCT participation.

  3. Myeloperoxidase-positive acute megakaryoblastic leukemia in a dog.

    PubMed

    Ferreira, Helena M T; Smith, Sionagh H; Schwartz, Anita M; Milne, Elspeth M

    2011-12-01

    A 16-month-old female spayed Labrador Retriever was referred to the University of Edinburgh for exercise intolerance, inappetence, and severe anemia. A CBC showed severe nonregenerative anemia and moderate numbers of atypical cells with morphologic features most consistent with megakaryoblastic origin. Similar cells were identified in a bone marrow aspirate and accounted for 23% of all nucleated cells. Atypical promegakaryocytes and megakaryocytes were also noted. Myelodysplastic syndrome affecting the megakaryocytic lineage was suspected. Cytologic examination of a fine-needle aspirate of the spleen revealed rare megakaryoblasts similar to those in blood and bone marrow. At necropsy, the bone marrow consisted of atypical megakaryoblasts and megakaryocytes that were also infiltrating spleen, liver, lymph nodes, renal perihilar tissue, and visceral adipose tissue, consistent with acute megakaryoblastic leukemia. Immunohistochemical analysis of splenic sections confirmed megakaryoblastic origin (immunoreactive for CD61 and von Willebrand factor). Some leukemic cells were also immunoreactive for myeloperoxidase (MPO). This aberrant immunophenotype suggested both megakaryocytic and granulocytic/monocytic differentiation of the leukemic cells. To our knowledge, this is the first report of MPO-positive acute megakaryoblastic leukemia in a dog.

  4. Treatment of Acute Lymphoblastic Leukemia from Traditional Chinese Medicine

    PubMed Central

    Huang, Hung-Jin; Kuo, Chia-Chen; Chen, Calvin Yu-Chian

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX) is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR), an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs) inhibit the thymidylate synthase (TS). Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM) as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment. PMID:25136372

  5. Postremission therapy in acute promyelocytic leukemia: room for improvement?

    PubMed

    Lancet, Jeffrey E

    2014-11-20

    A 29-year-old white man presented to the hospital with a 3-week history of fatigue, generalized weakness, gingival swelling and bleeding, and headaches. Laboratory work revealed WBC 30.4 k/μL, hemoglobin 7.9 g/dL, and platelets 16 k/μL. The WBC differential showed 64% blasts and 24% promyelocytes. Coagulation studies revealed prothrombin time (PT) 13.5 seconds, internationalized normalized ratio (INR) 1.3, fibrinogen 199 mg/dL, D-dimer greater than 1.0 μg/mL, and fibrin split products greater than 40 μg/mL. A bone-marrow aspirate with biopsy was performed, yielding the diagnosis of acute promyelocytic leukemia (APL), with t(15;17)(q23;q21.1) in all metaphases. Induction therapy commenced with daunorubicin, cytarabine (Ara-C), and all-trans retinoic acid (ATRA), and complete remission was documented 5 weeks later. PML-RARA fusion transcripts were still detected by reverse transcription polymerase chain reaction. He is now referred to you for consideration of postremission therapy in the setting of high-risk acute promyelocytic leukemia in first remission.

  6. Lymphocyte aromatic hydrocarbon responsiveness in acute leukemia of childhood

    SciTech Connect

    Blumer, J.L.; Dunn, R.; Esterhay, M.D.; Yamashita, T.S.; Gross, S.

    1981-12-01

    Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were examined in mitogen-stimulated cultured lymphocytes from children with acute leukemia in remission, with nonleukemic malignancies, and with no family or personal history of malignant disease. Neither morphological differences nor differences in mitogen responsivelness were observed among the three sources of cells studied. Levels of constitutive and dibenzanthracene-induced AHH activity were found to be similar among the three groups by analysis of variance. However, when results were analyzed in terms of inducibility ratios, it was found that cells from leukemic children were significantly less inducible (p < 0.005) than cells from unaffected children or children with nonleukemic malignancies. The reason for this difference became apparent when statistical criteria were employed for the phenotypic separation of individuals who were highly aromatic hydrocarbon responsive and minimally responsive. A significantly larger proportion (p < 0.001) of leukemic children than unaffected children or children with nonleukemic malignancy were found to be minimally aromatic hydrocarbon responsive. Moreover, in patients with acute lymphoblastic leukemia relapsing while on therapy, longer durations of the first remission were correlated (r = 0.63, p < 0.05) with the highly inducible AHH phenotype.

  7. [Acute myeloid leukemia. Genetic diagnostics and molecular therapy].

    PubMed

    Schlenk, R F; Döhner, K; Döhner, H

    2013-02-01

    Acute myeloid leukemia (AML) is a genetically heterogeneous disease. The genetic diagnostics have become an essential component in the initial work-up for disease classification, prognostication and prediction. More and more promising molecular targeted therapeutics are becoming available. A prerequisite for individualized treatment strategies is a fast pretherapeutic molecular screening including the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 as well as mutations in the genes NPM1, FLT3 and CEBPA. Promising new therapeutic approaches include the combination of all- trans retinoic acid and arsentrioxid in acute promyelocytic leukemia, the combination of intensive chemotherapy with KIT inhibitors in core-binding factor AML and FLT3 inhibitors in AML with FLT3 mutation, as well as gemtuzumab ozogamicin therapy in patients with low and intermediate cytogenetic risk profiles. With the advent of the next generation sequencing technologies it is expected that new therapeutic targets will be identified. These insights will lead to a further individualization of AML therapy.

  8. An update of current treatments for adult acute myeloid leukemia

    PubMed Central

    Gardin, Claude

    2016-01-01

    Recent advances in acute myeloid leukemia (AML) biology and its genetic landscape should ultimately lead to more subset-specific AML therapies, ideally tailored to each patient's disease. Although a growing number of distinct AML subsets have been increasingly characterized, patient management has remained disappointingly uniform. If one excludes acute promyelocytic leukemia, current AML management still relies largely on intensive chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), at least in younger patients who can tolerate such intensive treatments. Nevertheless, progress has been made, notably in terms of standard drug dose intensification and safer allogeneic HSCT procedures, allowing a larger proportion of patients to achieve durable remission. In addition, improved identification of patients at relatively low risk of relapse should limit their undue exposure to the risks of HSCT in first remission. The role of new effective agents, such as purine analogs or gemtuzumab ozogamicin, is still under investigation, whereas promising new targeted agents are under clinical development. In contrast, minimal advances have been made for patients unable to tolerate intensive treatment, mostly representing older patients. The availability of hypomethylating agents likely represents an encouraging first step for this latter population, and it is hoped will allow for more efficient combinations with novel agents. PMID:26660429

  9. Successful treatment of pediatric histiocytic sarcoma using abbreviated high-risk leukemia chemotherapy.

    PubMed

    Heath, Jessica L; Burgett, Shelly E; Gaca, Ana M; Jaffe, Ronald; Wechsler, Daniel S

    2014-10-01

    Histiocytic sarcoma (HS) is a malignant tumor composed of proliferating cells of histiocytic origin. True HS is exceedingly rare, particularly in pediatric patients. These tumors are frequently aggressive, and outcome for patients with HS has traditionally been poor. There is currently no consensus on the optimal management of these tumors, with the literature consisting largely of case reports and small case series utilizing a wide variety of therapies. We describe a case of HS in an 8-year-old female who was successfully treated with an abbreviated leukemia chemotherapy regimen.

  10. Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-09-23

    Adult B Lymphoblastic Lymphoma; Childhood B Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Lymphoblastic Lymphoma; Down Syndrome; Stage I B Lymphoblastic Lymphoma; Stage II B Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  11. [Acute lymphoblastic leukemia with T + PH1 monocytosis: a case report].

    PubMed

    Braham Jmili, Nejia; Sendi, Halima; Khelif, Abderrahim

    2011-01-01

    Acute lymphoblastic leukemia Type T PH1 positive (with t (9.22)) are exceptional. These effects can occur immediately or in the evolution of chronic myeloid leukemia known. We report the case of a patient aged 31 years with acute lymphoblastic leukemia T PH1 + cyologiques with cytological atypia. The overall appearance of blood and marrow: the signs of dysplasia the presence of a monocytic contingent, with blood monocytes evoked a myeloid acute leukemia AL. But the immunophenotype was unequivocally in favor of T- acute lymphoblastic leukemia with one aspect of lymphoid blasts in morphology and myeloperoxidase negative. The karyotype showed the presence of Philadelphia chromosome in all mitoses with additional abnormalities (chromosomes 2, 11.16…).

  12. Cardioprotection and Safety of Dexrazoxane in Patients Treated for Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Advanced-Stage Lymphoblastic Non-Hodgkin Lymphoma: A Report of the Children’s Oncology Group Randomized Trial Pediatric Oncology Group 9404

    PubMed Central

    Devidas, Meenakshi; Chen, Lu; Franco, Vivian I.; Pullen, Jeanette; Borowitz, Michael J.; Hutchison, Robert E.; Ravindranath, Yaddanapudi; Armenian, Saro H.; Camitta, Bruce M.; Lipshultz, Steven E.

    2016-01-01

    Purpose To determine the oncologic efficacy, cardioprotective effectiveness, and safety of dexrazoxane added to chemotherapy that included a cumulative doxorubicin dose of 360 mg/m2 to treat children and adolescents with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic non-Hodgkin lymphoma (L-NHL). Patients and Methods Patients were treated on Pediatric Oncology Group Protocol POG 9404, which included random assignment to treatment with or without dexrazoxane given as a bolus infusion immediately before every dose of doxorubicin. Cardiac effects were assessed by echocardiographic measurements of left ventricular function and structure. Results Of 573 enrolled patients, 537 were eligible, evaluable, and randomly assigned to an arm with or without dexrazoxane. The 5-year event-free survival (with standard error) did not differ between groups: 76.7% (2.7%) for the dexrazoxane group versus 76.0% (2.7%) for the doxorubicin-only group (P = .9). The frequencies of severe grade 3 or 4 hematologic toxicity, infection, CNS events, and toxic deaths were similar in both groups (P ranged from .26 to .64). Of 11 second malignancies, eight occurred in patients who received dexrazoxane (P = .17). The mean left ventricular fractional shortening, wall thickness, and thickness-to-dimension ratio z scores measured 3 years after diagnosis were worse in the doxorubicin-alone group (n = 55 per group; P ≤ .01 for all comparisons). Mean fractional shortening z scores measured 3.5 to 6.4 years after diagnosis remained diminished and were lower in the 21 patients who received doxorubicin alone than in the 31 patients who received dexrazoxane (−2.03 v −0.24; P ≤ .001). Conclusion Dexrazoxane was cardioprotective and did not compromise antitumor efficacy, did not increase the frequencies of toxicities, and was not associated with a significant increase in second malignancies with this doxorubicin-containing chemotherapy regimen. We recommend dexrazoxane as a

  13. Construction of protein profile classification model and screening of proteomic signature of acute leukemia

    PubMed Central

    Xu, Yun; Zhuo, Jiacai; Duan, Yonggang; Shi, Benhang; Chen, Xuhong; Zhang, Xiaoli; Xiao, Liang; Lou, Jin; Huang, Ruihong; Zhang, Qiongli; Du, Xin; Li, Ming; Wang, Daping; Shi, Dunyun

    2014-01-01

    The French-American-British (FAB) and WHO classifications provide important guidelines for the diagnosis, treatment, and prognostic prediction of acute leukemia, but are incapable of accurately differentiating all subtypes, and not well correlated with the clinical outcomes. In this study, we performed the protein profiling of the bone marrow mononuclear cells from the patients with acute leukemia and the health volunteers (control) by surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI_TOF_MS). The patients with acute leukemia were analyzed as unitary by the profiling that were grouped into acute promyelocytic leukemia (APL), acute myeloid leukemia-granulocytic (AML-Gran), acute myeloid leukemia-monocytic (AML-Mon) acute lymphocytic leukemia (ALL), and control. Based on 109 proteomic signatures, the classification models of acute leukemia were constructed to screen the predictors by the improvement of the proteomic signatures and to detect their expression characteristics. According to the improvement and the expression characteristics of the predictors, the proteomic signatures (M3829, M1593, M2121, M2536, M1016) characterized successively each group (CON, APL, AML-Gra, AML-Mon, ALL) were screened as target molecules for identification. Meanwhile, the proteomic-based class of determinant samples could be made by the classification models. The credibility of the proteomic-based classification passed the evaluation of Biomarker Patterns Software 5.0 (BPS 5.0) scoring and validated application in clinical practice. The results suggested that the proteomic signatures characterized by different blasts were potential for developing new treatment and monitoring approaches of leukemia blasts. Moreover, the classification model was potential in serving as new diagnose approach of leukemia. PMID:25337199

  14. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2016-10-18

    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); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  15. ST-elevation myocardial infarction and myelodysplastic syndrome with acute myeloid leukemia transformation.

    PubMed

    Jao, Geoffrey T; Knovich, Mary Ann; Savage, Rodney W; Sane, David C

    2014-04-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach--balloon angioplasty with the provisional use of bare-metal stents--might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days.

  16. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system.

    PubMed

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M

    2017-02-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06-27.17; odds ratio=6.86, 95% confidence interval, 1.86-25.26, respectively). CCR7 expression in the upper fourth quartile correlated with central

  17. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    PubMed Central

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  18. Laboratory Treated T Cells in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia, Non-Hodgkin Lymphoma, or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-12-08

    CD19-Positive Neoplastic Cells Present; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma

  19. Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

    PubMed

    Hart, J S; George, S L; Frei, E; Bodey, G P; Nickerson, R C; Freireich, E J

    1977-04-01

    A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems

  20. Recurrent Arterial Thrombosis as a Presenting Feature of a Variant M3-Acute Promyelocytic Leukemia

    PubMed Central

    Chotai, Pranit N.; Kasangana, Kalenda; Chandra, Abhinav B.; Rao, Atul S.

    2016-01-01

    Acute limb ischemia (ALI) is a common vascular emergency. Hematologic malignancies are commonly associated with derangement of normal hemostasis and thrombo-hemorrhagic symptoms during the course of the disease are common. However, ALI as an initial presenting feature of acute leukemia is rare. Due to the rarity of this presentation, there is a scarcity of prospective randomized data to optimally guide the management of these patients. Current knowledge is mainly based on isolated cases. We report our experience managing a patient who presented with ALI and was found to have occult leukemia. A review of all cases with ALI as a presenting feature of acute leukemia is also presented. PMID:27386455