Clinical Lymphoma Myeloma and Leukemia RSS feed: Articles in Press. Clinical Lymphoma, Myeloma & Leukemia is a peer-reviewed bimonthly journal that publishes original articles describing various aspects of clinical and translational research of lymphoma, myeloma and leukemia. Clinical Lymphoma, Myeloma& Leukemia is devoted to articles on detection, diagnosis, prevention, and treatment of lymphoma, myeloma, leukemia and related disorders including macroglobulinemia, amyloidosis, and plasma-cell dyscrasias. The main emphasis is on recent scientific developments in all areas related to lymphoma, myeloma and leukemia. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches. http://www.clinical-lymphoma-myeloma-leukemia.com//inpress?rss=yesElsevier Inc.en © 2012 Published by Elsevier Inc. Clinical Lymphoma Myeloma and Leukemia2152-26502012-05-14 © 2012 Published by Elsevier Inc. healthpermissions@elsevier.comhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000559/abstract?rss=yes Micro-Abstract: This phase II study assessed the efficacy and safety of lenalidomide in patients with relapsed/refractory acute myeloid leukemia (N = 18) and high-risk myelodysplastic syndrome (N = 9) with chromosome 5 abnormalities. The overall complete remission rate with or without platelet recovery was 7% (2/27). Activity of lenalidomide was limited to patients with noncomplex cytogenetics. Abstract: Background: Lenalidomide is effective in low-risk myelodysplastic syndromes (MDS) with deletion 5q. We conducted a phase II study to evaluate the safety and efficacy of lenalidomide in patients with relapsed/refractory acute myeloid leukemia (AML) and high-risk MDS with any chromosome 5 abnormality. Patients and Methods: Eighteen adults with AML and 9 with high-risk MDS were enrolled. Lenalidomide was given orally at doses 5 to 25 mg daily for 21 days of a 28-day cycle until disease progression or unacceptable adverse event. Results: Median age for all 27 patients was 64 years (range, 39-88 years) with a median of 2 previous therapies (range, 1-6 lines). Two patients (7%) with AML and 5q deletion and +8 cytogenetic abnormality in 2 separate clones achieved complete remission (CR) or CR without platelet recovery (CRp). Response durations were 4 and 6 months, respectively. No responses were seen in patients with chromosome 5 abnormality in a complex cytogenetic background. Twenty patients (74%) developed neutropenic fever or infection requiring hospitalization. Conclusions: Clinical activity of lenalidomide as single agent in AML and high-risk MDS with chromosome 5 abnormalities appears to be limited to patients with noncomplex cytogenetics. A Phase II Study of Lenalidomide Alone in Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes With Chromosome 5 Abnormalities - Corrected ProofYiming Chen, Hagop Kantarjian, Zeev Estrov, Stefan Faderl, Farhad Ravandi, Kristy Rey, Jorge Cortes, Gautam Borthakur10.1016/j.clml.2012.04.001Clinical Lymphoma Myeloma and Leukemia (2012)2012-05-14Clinical Lymphoma Myeloma and Leukemia2012-05-14ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000547/abstract?rss=yes Micro-Abstract: The mutational status and configuration of immunoglobulin heavy variable (IGHV) gene rearrangements was analyzed in 85 Serbian patients with chronic lymphocytic leukemia (CLL). We found that 55.3% of cases belonged to mutated and 44.7% to unmutated CLL, progressive disease predominating in the unmutated subset. IGHV gene use resembled that obtained for Mediterranean countries, except for underrepresentation of the IGHV4 subgroup in our cohort. Abstract: Background: Chronic lymphocytic leukemia (CLL) results from the clonal expansion of mature B lymphocytes and is characterized by extreme clinical heterogeneity. One of the most reliable prognostic markers in chronic lymphocytic leukemia (CLL) is the mutational status of immunoglobulin heavy variable (IGHV) genes, which defines 2 subsets, mutated CLL (M-CLL) and unmutated CLL (U-CLL), with different clinical courses. Biased IGHV gene use between M-CLL and U-CLL clones, as well as population differences in the IGHV gene repertoire have been reported. Patients and Methods: In this study, mutational status and configuration of IGHV-IGHD-IGHJ rearrangements in 85 Serbian patients were analyzed using reverse transcriptase–polymerase chain reaction (RT-PCR) and sequencing methodology. Results: We found that 55.3% of cases belonged to M-CLL and 44.7% belonged to U-CLL, with progressive disease predominating in the unmutated subset. Most frequently expressed was the IGHV3 subgroup (55.7%), followed by IGHV1 (27.3%), IGHV4 (12.5%), IGHV5 (2.3%), IGHV2 (1.1%), and IGHV6 (1.1%). The distribution of IGHD subgroups was as follows: IGHD3, 39.1%; IGHD2, 21.8%; IGHD6, 12.6%; IGHD1, 10.3%; IGHD4, 8%; IGHD5, 6.9%; and IGHD7, 1.1%. The most frequent IGHJ gene was IGHJ4 (48.9%), followed by IGHJ6 (28.4%), IGHJ3 (11.4%), and IGHJ5 (11.4%). In 15.3% of cases, heavy complementarity-determining region 3 (VH CDR3) amino acid sequences could be assigned to previously defined stereotyped clusters. Conclusions: Our study showed a strong correlation between IGHV gene mutational status and clinical course of CLL. IGHV gene use was comparable to that obtained for Mediterranean countries, with the exception of the IGHV4 subgroup, which was underrepresented in our cohort. Mutational Status and Gene Repertoire of IGHV-IGHD-IGHJ Rearrangements in Serbian Patients With Chronic Lymphocytic Leukemia - Corrected ProofTeodora Karan-Djurasevic, Vuk Palibrk, Tatjana Kostic, Vesna Spasovski, Gordana Nikcevic, Sanja Srzentic, Milica Colovic, Natasa Colovic, Ana Vidovic, Darko Antic, Biljana Mihaljevic, Sonja Pavlovic, Natasa Tosic10.1016/j.clml.2012.03.005Clinical Lymphoma Myeloma and Leukemia (2012)2012-05-07Clinical Lymphoma Myeloma and Leukemia2012-05-07ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000468/abstract?rss=yes Micro-Abstract: Transformed mycosis fungoides (tMF) is an aggressive disease with a median survival of 12-24 months. In this retrospective analysis of 12 patients with tMF, treatment with pralatrexate resulted in an objective response of 25% per independent central review and 58% per investigator assessment. Pralatrexate was well tolerated, with no toxicity-related discontinuations, which makes this an additional option for tMF treatment. Abstract: Background: Transformed mycosis fungoides (tMF) is an aggressive disease, with poor prognosis and a median survival of 24 months. Patients And Methods: In the Pralatrexate in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma (PROPEL) study, 12 patients with tMF were treated with a median of 10 pralatrexate doses (starting dose of 30 mg/m2) administered weekly for 6 weeks in a 7-week cycle. The median number of prior systemic therapies was 3. Results: This retrospective analysis showed that the objective response rate in this subgroup was 25% (n = 3) per independent central review and 58% (n = 7) per investigator assessment, with this discrepancy likely attributed to challenges with photodocumentation of cutaneous lesions. The median duration of response and the median progression-free survival were 2.2 and 1.7 months, respectively, per central review, whereas median duration of response was 4.4 months, and median progression-free survival was 5.3 months per investigator assessment. Median survival was 13 months. Grade 1-3 mucositis was reported in 7 (58%) patients. Grade 4 adverse events were fatigue (n = 1) and thrombocytopenia (n = 1). Pralatrexate was well tolerated, with no toxicity-related discontinuations. Conclusions: Based on these results, pralatrexate may be a treatment option for patients with relapsed or refractory tMF. Pralatrexate Is an Effective Treatment for Relapsed or Refractory Transformed Mycosis Fungoides: A Subgroup Efficacy Analysis From the PROPEL Study - Corrected ProofFrancine Foss, Steven M. Horwitz, Bertrand Coiffier, Nancy Bartlett, Leslie Popplewell, Barbara Pro, Lauren C. Pinter-Brown, Andrei Shustov, Richard R. Furman, Corinne Haioun, Tony Koutsoukos, Owen A. O'Connor10.1016/j.clml.2012.01.010Clinical Lymphoma Myeloma and Leukemia (2012)2012-04-27Clinical Lymphoma Myeloma and Leukemia2012-04-27ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS215226501200050X/abstract?rss=yesClinical Binding Properties, Internalization Kinetics, and Clinicopathologic Activity of Brentuximab Vedotin: An Antibody-Drug Conjugate for CD30-Positive Lymphoid Neoplasms - Corrected ProofJonathan R. Fromm, Julie A. McEarchern, Dana Kennedy, Anju Thomas, Andrei R. Shustov, Ajay K. Gopal10.1016/j.clml.2012.01.012Clinical Lymphoma Myeloma and Leukemia (2012)2012-04-27Clinical Lymphoma Myeloma and Leukemia2012-04-27CASE REPORThttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000511/abstract?rss=yes Micro-Abstract: We evaluated the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). One hundred seven patients were enrolled. Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery (CRp) of 5%. The overall 4-week mortality rate was 9%. In conclusion, BIDFA is active and safe in heavily pretreated patients with myeloid malignancies. Abstract: Background: The purpose of this study was to evaluate the efficacy and safety of the combination of twice-daily fludarabine and cytarabine (BIDFA) in patients with refractory/relapsed acute myeloid leukemia (AML), high-risk myelodysplastic syndromes (MDS), and chronic myeloid leukemia in myeloid blast phase (CML-BP). Patients and Methods: One hundred seven patients with refractory/relapsed AML, intermediate and high-risk MDS, and CML-BP, with a performance status of 3 or less and normal organ function were treated. Patients received fludarabine 15 mg/m2 intravenously (IV) every 12 hours on days 1 to 5 and cytarabine 0.5 g/m2 IV over 2 hours every 12 hours on days 1 to 5. Gemtuzumab ozogamicin (GO) was administered at 3 mg/m2 IV on day 1 in the first 59 patients. Patients with CML-BP were allowed to receive concomitant tyrosine kinase inhibitors. Results: Overall, 27 (26%) patients responded with a complete remission (CR) rate of 21% and CR without platelet recovery of 5%. The overall 4-week mortality rate was 9%. The CR rates for patients with relapsed AML with first CR duration greater than or equal to 12 months, relapsed AML with first CR duration less than 12 months, and refractory/relapsed AML beyond first salvage were 56%, 26%, and 11%, respectively. With a median follow-up of 7 months, the 6-month event-free survival, overall survival, and complete remission CR duration rates were 18%, 35%, and 70%, respectively. Conclusion: BIDFA is active with an overall response rate of 26% in a heavily pretreated population. This combination is safe with a low 4-week mortality rate of 9%. Twice-Daily Fludarabine and Cytarabine Combination With or Without Gentuzumab Ozogamicin is Effective in Patients With Relapsed/Refractory Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, and Blast- Phase Chronic Myeloid Leukemia - Corrected ProofElias Jabbour, Guillermo Garcia-Manero, Jorge Cortes, Farhad Ravandi, William Plunkett, Varsha Gandhi, Stefan Faderl, Susan O'Brien, Gautam Borthakur, Tapan Kadia, Jan Burger, Marina Konopleva, Mark Brandt, Xuelin Huang, Hagop Kantarjian10.1016/j.clml.2012.03.003Clinical Lymphoma Myeloma and Leukemia (2012)2012-04-26Clinical Lymphoma Myeloma and Leukemia2012-04-26ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000493/abstract?rss=yes Micro-Abstract: To study the potential role of Delta-like-1 (DLK1) in myelodysplastic syndromes (MDS), we carried out a series of experiments and found that DLK1 mRNA levels are dysregulated in patients with MDS or acute myelogenous leukemia (AML), and its overexpression leads to dysfunction of 32D and 3T3 cells. We conclude that DLK1 dysfunction may contribute to abnormal hematopoiesis of MDS and may be 1 of the antioncogenes. Abstract: Delta-like-1 (DLK1) is frequently expressed at elevated levels in CD34+ cells from patients with MDS. To investigate its role in the pathogenesis of MDS, we tested bone marrow samples from a panel of patients with MDS, AML, or myeloproliferative neoplasms, with real-time polymerase chain reaction (PCR). We show here that DLK1 mRNA levels are higher in MDS patients and lower in AML patients than in healthy individuals. Myeloid progenitor 32D cells overexpressing DLK1 display increased apoptosis, reduced differentiation, and decreased cell number expansion, which is also accompanied by changes in cell cycle progression. Immortalized fibroblastic 3T3 cells can grow into tumors in nude mice but the size of tumors are smaller from those overexpressing DLK1. These observations suggest that DLK1 dysfunction may contribute to the ineffective hematopoiesis of MDS. The Effects of Increased Expression of DLK1 Gene on the Pathogenesis of Myelodysplastic Syndromes - Corrected ProofXiaotang Ma, Yue Zhang, Lin Yang, Zefeng Xu, Zhijian Xiao10.1016/j.clml.2012.03.002Clinical Lymphoma Myeloma and Leukemia (2012)2012-04-19Clinical Lymphoma Myeloma and Leukemia2012-04-19ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000043/abstract?rss=yes Micro-Abstract: In 83 patients with cytogenetically normal acute myeloid leukemia (CN-AML), those with NPM1 and wild-type FLT3 (FLT3-wt) mutation and their poor prognostic combination had distinctive flow cytometric findings: CN-AML with a mutation of NPM1 (NPMI-Mt) were CD34−, CD14−, and CD2pos and CD4+; those with FLT3-internal tandem duplications (ITD) were CD56pos, those with NPM1-Mt and FLT3-wt were CD34− and CD56−; and those with poor prognostic combination NPM1-wt and FLT3-ITD were CD34pos and TdTpos. Abstract: Methods: We retrospectively correlated NPM1 and FLT3 mutation status with flow cytometric profile of leukemic blasts in 83 adult patients with cytogenetically normal acute myeloid leukemia (CN-AML). Results: Mutation of the NPM1 gene (NPM1.mt) was found in 39 (47%) of 83 patients, and internal tandem duplication (ITD) of the FLT3 gene (FLT3-ITD) was seen in 38 (46%) of 83 patients. Patients with CN-AML and with NPM1.mt were less likely to express CD34 (33% vs. 93%; 2P = .0001), CD2 (0% vs. 14%; 2P = .0187), and CD14 (6% vs. 22%, 2P = .0476), and were more likely to express CD4 (65.5% vs. 37%; 2P = .0367) and CD19 (49% vs. 27%; 2P = .0506). The patients with CN-AML and with FLT3-ITD were more likely to express CD56 (47% vs. 23%; 2P = .0393). Moreover, patients with favorable prognostic combination of NPM1.mt and wild-type (wt) FLT3 (n = 18) were less likely to express CD34 (33% vs. 74% all others; 2P = .0021) and CD56 (6% vs. 37% all others; 2P = .0072). The group with an unfavorable prognostic combination of NPM1-wt and FLT3-ITD (n = 17) were more likely to express CD34 (88% vs. 45% all others; 2P = .0011) and TdT (40% vs. 2% all others; 2P = .0054). Conclusions: In patients with CN-AML, characteristic flow cytometric profile is associated with NPM1 and FLT3 mutation status.Detection of CD34, TdT, CD56, CD2, CD4, and CD14 by Flow Cytometry Is Associated With NPM1 and FLT3 Mutation Status in Cytogenetically Normal Acute Myeloid Leukemia - Corrected ProofBakul I. Dalal, Soudeh Mansoor, Mita Manna, Steven Pi, Giovanna Di Sauro, Donna E. Hogge10.1016/j.clml.2012.01.003Clinical Lymphoma Myeloma and Leukemia (2012)2012-04-05Clinical Lymphoma Myeloma and Leukemia2012-04-05ORIGINAL STUDYhttp://www.clinical-lymphoma-myeloma-leukemia.com/article/PIIS2152265012000092/abstract?rss=yes Micro-Abstract: Elevation of the methylmalonic acid level is a sensitive marker of vitamin B12 deficiency. Our cross-sectional observational study of 33 patients with myeloproliferative disorders found that 9 patients, 27.27% had occult deficiency despite having normal to elevated serum vitamin B12 levels. Early detection of vitamin B12 deficiency by using the methylmalonic acid measurement may prevent significant neurologic and hematologic complications in patients with myeloproliferative disorders. Abstract: In patients with myeloproliferative disorders, normal to high serum vitamin B12 concentrations have often been reported. The primary objective of this study was to determine whether normal or elevated serum vitamin B12 levels in myeloproliferative disorders might actually mask the true underlying vitamin B12 deficiency in some patients. Thirty-three patients (12 men, 21 women; mean age, 70.55 years [range, 37-90 years]) with polycythemia vera (n = 13), essential thrombocythemia (n = 12), chronic myelogenous leukemia (n = 5), and idiopathic myelofibrosis (IMF) (n = 3) were accrued over a period of 1 year, from March 2009 to February 2010. From all of the subjects, serum vitamin B12 level, methylmalonic acid level, a basic complete blood cell count panel, and liver and renal function tests were obtained. Normal to elevated serum vitamin B12 levels were recorded in all the patients. However, elevated serum methylmalonic acid levels were found in 9 (27.27%) patients, with a prevalence of 2 patients with polycythemia vera, 23% in polycythemia vera, 4 patients with essential thrombocythemia, 33.3% in essential thrombocythemia, 1 patient with chronic myelogenous leukemia, 20% in chronic myelogenous leukemia, and 2 patients with idiopathic myelofibrosis, 66.7% in IMF. Our data suggest that 27.27% of the total enrolled patients had occult vitamin B12 deficiency despite normal to elevated vitamin B12 levels on regular serum vitamin B12 testing. Does an Elevated Serum Vitamin B12 Level Mask Actual Vitamin B12 Deficiency in Myeloproliferative Disorders? - Corrected ProofDron Gauchan, Nitin Joshi, Amandeep Singh Gill, Vishal Patel, Vincent A. DeBari, Gunwant Guron, Michael Maroules10.1016/j.clml.2012.01.008Clinical Lymphoma Myeloma and Leukemia (2012)2012-03-19Clinical Lymphoma Myeloma and Leukemia2012-03-19ORIGINAL STUDY