Leukemia and Lymphoma (LEUKEMIA LYMPHOMA)

Publications in this journal

• Article: Viral infections and their management in patients with chronic lymphocytic leukemia. Melchardt T, Weiss L, Greil R, Egle A.

  Melchardt T, Weiss L, Greil R, Egle A
  Leukemia and Lymphoma 12/2012;
• Article: regulation of regulatory t cells

  chitta kasyapa taimur sher
  Leukemia and Lymphoma 01/2012;
• Article: Thrombopoietin Stimulates Myelodysplastic Syndrome Granulocyte-Macrophage and Erythroid Progenitor Proliferation

  Alessandra Ferrajoli, Moshe Talpaz, Razelle Kurzrock, David Harris, Quin Van, Elihu H. Estey, Zeev Estrov
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  ABSTRACT: Thrombopoietin (TPO) has been successfully used to stimulate megakaryocyte progenitor proliferation and platelet production both in vitro and in vivo. We and other investigators have found that TPO also stimulates normal marrow colony-forming unit granulocyte-macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) growth. In contrast to its effect on normal marrow precursors, TPO stimulates acute myelogenous leukemia (AML) progenitor proliferation in only 25% of the cases. Because the hematopoietic cells in Myelodysplastic syndrome (MDS) originate from both the normal and leukemic clones, we hypothesized that TPO may be a useful therapeutic agent for MDS. To test this hypothesis, we used fresh marrow samples taken from 14 MDS patients. We found that in the presence of fetal calf serum (FCS) and erythropoietin (EPO) TPO (5 to 40 ng/ml) MDS CFU-GM and BFU-E colony-forming cell proliferation were stimulated in a dose-dependent fashion by up to 103% and 93% respectively. This effect was similar to the stimulation obtained with optimal concentrations of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or interleukin-3 (IL-3). Furthermore, TPO increased the colony-stimulatory effects of G-CSF, GM-CSF, IL-3, and stem cell factor (SCF) on MDS marrow cells. However, depletion of either T lymphocytes or adherent cells abrogated the effect of TPO, suggesting that the effect is not a direct one but is mediated through interaction with cytokines produced by accessory cells. Taken together, our data suggest that the therapeutic role of TPO in the management of MDS warrants further investigation.
  Leukemia and Lymphoma 06/2009; 30(3-4):279-292.
• Article: The Hematopoietic Stem Cell Transplantation in Hodgkin's Disease: Questions and Controversies

  JoËL Fleury, Michel Legros, Herve Curé, Jacques Tortochaux, Paule Condat, Claude Dionet, Philippe Travade, Ernest Belembaogo, Françoise Tavernier, Fabrice Kwiatkowski, Philippe Chollet, Robert Plagne
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  ABSTRACT: Most patients with Hodgkin's disease (HD) are cured with chemotherapy and/or radiotherapy. However, half of those with advanced stage disease (IIIB, IV) do not respond adequately to treatment or relapse. Salvage therapy used in such cases gives from 10% to 50% complete remission but only 10% long term survival. The results of bone marrow transplantation reported in acute leukemia and non-Hodgkin's lymphoma encouraged some authors to develop this new therapeutic strategy in Hodgkin's disease. In the early 1980's promising results were achieved when refractory and relapsed patients were selected to receive myeloablative therapy followed by bone marrow transplantation. Today, high dose chemotherapy with hematopoietic stem cell transplantation (HSCT) is used more and more often in poor prognosis Hodgkin's disease.
  Leukemia and Lymphoma 06/2009; 15(5-6):419-432.
• Article: A Multivariate Study of Non Hodgkin's Lymphoma Involving Proliferation, Apoptosis, bcl-2 and the Microenvironment

  Vilasini Shetty, Suneel Mundle, Arceli Sanoy, Rupal Sanghvi, Jerome Loew, Bridget Marcus, John Showel, Stephanie Gregory, Azra Raza
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  ABSTRACT: The study was carried out on 22 patients with non-Hodgkin's lymphoma (NHL) who had received sequential infusions of two thymidine analogues iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). Cell cycle kinetic studies seemed to differentiate distinctly between low grade lymphoma (n = 8, LI = 2.6%) compared to that of intermediate grade (n = 9, LI = 13%. p = 0.0001) and high grade NHL (n = 5, LI = 16.3%. p = 0.0062). While the majority of 14 intermediate and high grade lymphomas had a high labeling index there were 3/14 patients with a LI of 5.5%, 5.5% and 4.1% respectively. A decrease in the rate of programmed cell death (PCD) or apoptosis due to the overexpression of bcl-2 has been implicated as the possible pathogenesis for follicular lymphoma. We determined the presence of bcl-2 protein immunohistochemically and apoptosis by in situ end labeling of DNA which detects cells in early stages of PCD not recognized morphologically. Nine NHL patients demonstrated PCD ranging from 1%-40%, while it was undetectable in 13/22 patients. Of these 13 cases, 6 showed the presence of bcl-2 expression. To understand the relationship of the microenvironment to the lymphoma cells, the presence of transforming growth factor beta (TGF-β) was determined immunohistochemically. TGF-β was present in all the cases where bcl-2 was present, except one. This study highlights some of the key biological features of NHL cells and their microenvironment.
  Leukemia and Lymphoma 06/2009; 18(3-4):273-279.
• Article: Cyclophosphamide, Ara-C and Topotecan (CAT) for Patients With Refractory or Relapsed Acute Leukemia

  Jorge Cortes, Elihu Estey, Miloslav Beran, Susan O'brien, Francis Giles, Charles Roller, Michael Keating, Hagop Kantarjian
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  ABSTRACT: Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodys-plastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergis-tic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100×109/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.
  Leukemia and Lymphoma 06/2009; 36(5-6):479-484.
• Article: Essential Thrombocythemia and Pregnancy

  Martin Griesshammer, Hermann Heimpel, Thomas C. Pearson
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  ABSTRACT: A review of the literature disclosed 106 pregnancies (preg.) in 57 women with essential thrombocythemia (ET). The success rate (baby alive) was 57% (60 live births/106 preg.), the rate of miscarriage 43% (46 miscarriages/106 preg.). The most frequent complication was spontaneous abortion during the first trimester in 36% (38 abortions/106 preg.). Other complications such as intrauterine death and stillbirth after the 28th week, which occured in 5% (7/106), premature delivery in 8% (8/106), pre-eclampsia in 4% (4/106), and fetal growth retardation in 4% (4/106) were rarer events. Placental infarction due to thrombosis seems to be the most consistent pathological event as far as the fetus is concerned. Maternal hemorrhage occured in 4% (3 minor and 1 major bleeding) and only 2 minor maternal thrombotic episodes have been observed. Interestingly, a decline in platelet count has been observed in 14 women and was associated with a successful preg. in 13/14 cases (93%). Aspirin (ASS) was the most frequently used drug in 47 of 93 recorded cases (51%). In 16 evaluable women treated with ASS the live birth rate was higher (12/16 preg., 75%) than for 21 untreated women (9/21 preg., 43%). In 5 cases interferon alpha (IFN) has been used successfully. In summary, 57% of women with ET had a live birth, maternal complications happened in 6%. Promising treatment modalities might be ASS and IFN. However, no definitive answer can be given on the ideal management for women with ET during pregnancy. A European register should be set up.
  Leukemia and Lymphoma 06/2009; 22(s1):57-63.
• Article: Characterization of CD34+ Human Hemopoietic Progenitor Cells from the Peripheral Blood: Enzyme-, Carbohydrate- and Immunocytochemistry, Morphometry, and Ultrastructure

  Juergen Thiele, Claudia Wickenhauser, Stephan E. Baldus, Thomas Kuemmel, Thomas K. Zirbes, Uta Drebber, Ruth Wirtz, Andreas Thiel, Martin-Leo Hansmann, Robert Fischer
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  ABSTRACT: Following an immunomagnetic isolation and enrichment procedure, CD34+ cells were harvested from the peripheral blood of about 50 healthy donors. A battery of cytochemical staining reactions, monoclonal and carbohydrate-specific antibodies, proliferation markers and lectins was applied on smears and sections from paraffin-embedded pellets. Additionally, a morphometric analysis and ultrastruc-tural investigation was carried out. More than 95% of the total yield of progenitor cells expressed CD34 and CD43 (MT1) and of these about 90% CD45 (LCA) and 25% CD45RA (MT2). The CD34VCD45RA population was thought to represent very primitive, probably not lineage-restricted stem cells. On the other hand, reactivity with ANAE, CD11c, CD15, CD20, Ret40f, KiMlP, and CD61 (ranging between 1 to 20%) was considered to indicate a transition into more differentiated elements of hemopoiesis. The failure to detect any staining with proliferation markers (Ki-67/MIBl, PCNA, KiS1) was in keeping with a quiescent status. Carbohydrate antigens revealed a pattern which underlines the fact that the CD34 and CD43 antigens belong to the family of heavily O-glycosylated sialomucins. Blood group antigens which are located at the peripheral regions of mucin-oligosaccharides (H type 2, Lewisx, Lewisa) could be demonstrated, but no t. A, B, Sialyl-Lewisx and Lewisy. Morphometric analysis revealed that CD34+ progenitors were larger than small lymphocytes. Electron microscopy showed a relatively primitive cytoplasmic organization and numerous tiny magnetic beads clustered at the plasma membrane.
  Leukemia and Lymphoma 06/2009; 16(5-6):483-492.
• Article: FAB and beyond.

  Barbara Bain
  Leukemia and Lymphoma 01/2008; 48(12):2282-3.
• Article: David Galton--reminiscences.

  Richard Peto, Eve Wiltshaw, S N Batliwalla
  Leukemia and Lymphoma 01/2008; 48(12):2293-4.
• Article: Viral infection or reactivation in patients during treatment with dasatinib: a call for screening?

  Harrys A Torres, Roy F Chemaly
  Leukemia and Lymphoma 01/2008; 48(12):2308-9.
• Article: Characterization of high-hyperdiploidy in childhood acute lymphoblastic leukemia with gain of a single chromosome 21.

  Angela Brown, Felix Niggli, Heinz Hengartner, Ueli Caflisch, Luisa Nobile, Thomas Kuhne, Regula Angst, Jean-Pierre Bourquin, David Betts
  Leukemia and Lymphoma 01/2008; 48(12):2457-60.
• Article: Complete molecular remission induced by concomitant cladribine--rituximab treatment in a case of multi-resistant hairy cell leukemia.

  Francesco Forconi, Francesca Toraldo, Elisa Sozzi, Teresa Amato, Donatella Raspadori, Francesco Lauria
  Leukemia and Lymphoma 01/2008; 48(12):2441-3.
• Article: Pregnancy in patients with chronic myeloid leukemia treated with imatinib.

  Mehmet Yilmaz, Osman Demirhan, Ercan Kuçukosmanoglu, Mustafa Pehlivan, Vahap Okan, Ozcan Balat, Sacide Pehlivan
  Leukemia and Lymphoma 01/2008; 48(12):2454-6.
• Article: Specific pattern of protein expression in acute myeloid leukemia harboring FLT3-ITD mutations.

  Sebastian Scholl, Christian Melle, Annett Bleul, Baerbel Spies-Weisshart, Christa Kunert, Klaus Höffken, Ferdinand von Eggeling
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  ABSTRACT: FLT3 activating mutations can be detected in about 35% of acute myeloid leukemia (AML). FLT3 internal tandem duplications (FLT3-ITD) represent the majority of FLT3 mutations (25 - 30%) while FLT3-TKD (tyrosine kinase domain) mutations can be found in about 7% of AML patients. In this study, we addressed the question whether especially primary AML cells carrying FLT3-ITD mutations show differences in terms of their protein expression pattern compared to FLT3 wild-type blasts. We investigated bone marrow samples that were isolated at diagnosis from 36 AML patients expressing either FLT3 wild-type (n = 16) or an activating FLT3 mutation (FLT3-ITD, n = 15; FLT3-TKD, n = 5). Proteomic analysis was performed by means of surface enhanced laser desorption/ionization-time of flight (SELDI-TOF) mass spectrometry which has shown its high efficiency in finding biomarkers in solid tumors. Here, we demonstrate that a large series of proteins is differently expressed in primary AML blasts harboring FLT3-ITD mutations. Furthermore, there are also significant differences of the protein expression profile between FLT3-ITD and FLT3-TKD mutations. Interestingly, further analysis of FLT3-ITD positive AML according to its response to the induction chemotherapy demonstrates putative prognostic markers for this subgroup of AML. We suggest that SELDI-TOF mass spectrometry represents a promising tool of proteomic analysis of AML that might help to establish new prognostic markers in AML.
  Leukemia and Lymphoma 01/2008; 48(12):2418-23.
• Article: Estimated number of cases, regional distribution and survival of patients diagnosed with acute myeloid leukemia between 1996 and 2000 in Rio Grande do Sul, Brazil.

  Marcelo Capra, Líbia Vilella, Waldir Veiga Pereira, Virgínia Maria Coser, Mário Sérgio Fernandes, Marco Antônio Schilling, Denise Almeida, Mauro Gross, Márcia Leite, Tânia Hellwig, Gilca Natchigal, Alice Zelmanowicz, Giorgio Paskulin, Jorge Neumann, Lúcia Silla
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  ABSTRACT: Rio Grande do Sul (RS), in South Brazil, with about 10 million inhabitants, is known for its agricultural activities and consequent increased human exposure to toxic agents. Patients with de novo acute myeloid leukemia (AML) were included based on information retrieved from all referral hospitals in RS between 1996 and 2000. A total of 532 patients were registered. Median age at diagnosis was 42 years. The estimated annual incidence was 1.11 cases/100,000 inhabitants/year. There was an estimated incidence of 0.5-1 case per 100,000 inhabitants up to the age of 45 years, and of 3.5 cases per 100,000 inhabitants aged 70 years and older, with no geographical clusters. The mean 5-year survival rate was 17% for all cases. There was an increased number of M3 cases, as already described for individuals of Latin-American and the mortality rate was similar to that described in the literature.
  Leukemia and Lymphoma 01/2008; 48(12):2381-6.
• Article: Prophylactic low-dose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma.

  Ruben Niesvizky, Déborah Martínez-Baños, Jessica Jalbrzikowski, Paul Christos, Jessica Furst, Maria De Sancho, Tomer Mark, Roger Pearse, Madhu Mazumdar, Faiza Zafar, Karen Pekle, John Leonard, David Jayabalan, Morton Coleman
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  ABSTRACT: Multiple myeloma (MM) patients have a propensity for thromboembolic events (TE), and treatment with thalidomide/dexamethasone or lenalidomide/dexamethasone increases this risk. This report describes the use of low-dose aspirin (81 mg) as primary thromboprophylaxis in three series of MM patients receiving thalidomide or lenalidomide with other drugs. In the first regimen (clarithromycin, thalidomide, dexamethasone), initiation of low-dose aspirin negated the occurrence of any further TE. In a second study, prophylactic aspirin given with thalidomide/dexamethasone resulted in a rate of TE similar to that seen with dexamethasone alone (without aspirin). A third study (n = 72) evaluated thrombosis rates with aspirin and a lenalidomide-containing regimen (clarithromycin, lenalidomide, dexamethasone). Of nine occurrences of thromboembolism, five were associated with aspirin interruption or poor compliance. Low-dose aspirin appears to reduce the incidence of thrombosis with these regimens. Routine use of aspirin as antithrombotic prophylaxis in MM patients receiving immunomodulatory drugs with corticosteroids is warranted.
  Leukemia and Lymphoma 01/2008; 48(12):2330-7.
• Article: Biologic predictors in follicular lymphoma: importance of markers of immune response.

  Todd Kelley, Rose Beck, Ahmed Absi, Tao Jin, Brad Pohlman, Eric Hsi
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  ABSTRACT: We sought to identify biologic indicators of prognosis in a series of 94 follicular lymphoma (FL) patients, focusing on markers of the host immune response as well as of B-cell maturation. Immune response was assessed with immunostains for CD68 (for lymphoma-associated macrophages, LAMs) and FOXP3 (regulatory T-cells). Lymphoma cells were evaluated for expression of bcl-2, CD10, and MUM-1. Clinical data were obtained for FLIPI, presence of bulky disease, presence of B-symptoms, treatment, and overall survival (OS). For the 69 initially treated patients, extrafollicular CD68+ cells (ef-CD68) and follicular FOXP3+ cells (f-FOXP3) were associated with shorter OS, while receipt of rituximab was associated with longer OS. Multivariable analysis showed ef-CD68 was the only independent factor associated with shorter OS. In subset analysis, ef-CD68 remained statistically significant in rituximab-naïve but not rituximab-treated patients. We confirm the importance of LAMs and f-FOXP3 as predictors of OS in FL.
  Leukemia and Lymphoma 01/2008; 48(12):2403-11.
• Article: Paclitaxel and filgrastim for hematopoietic progenitor cell mobilization in patients with hematologic malignancies after failure of a prior mobilization regimen.

  Trevor McKibbin, Julianna Burzynski, Rebecca Greene, Jose Ochoa-Bayona, T W Tsai, Natalie Callander, Cesar Freytes
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  ABSTRACT: Paclitaxel and G-CSF have been evaluated for HPC mobilization in breast cancer and found to have tolerable toxicity with a predictable time to initiate leukapheresis. However, this approach has not been reported in patients with hematologic malignancies failing prior mobilization. We report a case-series of 26 adults given paclitaxel and G-CSF for HPC mobilization after failure of an initial mobilization. Patients received paclitaxel 250 mg/m(2) followed by G-CSF 10-16 mcg/kg/day. Compared to the initial regimen, paclitaxel mobilization produced greater CD34+ cell yields (median 1.53 x 10(6) CD34+ cells/kg vs. 0.79 x 10(6) CD34+ cells/kg, p = 0.004). Seventy-six percent of patients initiated leukapheresis on day 8, the remainder on day 9 or 10. Three patients developed febrile neutropenia resulting in one death prior to leukapheresis. Overall, 73% of patients proceeded with autologous HPC transplant. This case-series suggests paclitaxel may be an option for HPC mobilization in patients failing prior regimens.
  Leukemia and Lymphoma 01/2008; 48(12):2360-6.
• Article: FLT3 internal tandem duplication in low risk MDS: clinical and basic science relevance.

  Deborah Rund
  Leukemia and Lymphoma 01/2008; 48(12):2302-3.