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ABSTRACT: Background: Second generation tyrosine kinase inhibitors have been introduced recently as first-line treatment for chronic phase-chronic myelogenous leukemia. We aimed to evaluate the efficacy and safety of second generation tyrosine kinase inhibitors vs. imatinib as first-line treatment for these patients. Design and Methods: Systematic review and meta-analysis of randomized controlled trials comparing second generation tyrosine kinase inhibitors to imatinib as first-line treatment in chronic phase-chronic myelogenous leukemia patients. Outcomes assessed were: complete cytogenetic response and major molecular response at 12, 18 and 24 months; all-cause mortality and progression to accelerated phase/blastic crisis at 12, 18 and 24 months and chronic myelogenous leukemia related mortality and toxicity on last follow-up. Relative risks were estimated and pooled using a fixed effect model. Results: Our search yielded four trials including 2120 patients. At 12 months, treatment with second generation tyrosine kinase inhibitors significantly improved both complete cytogenetic response and major molecular response, [Relative risk 1.16, 95% CI 1.09 to 1.23 and relative risk 1.68, 95% CI, 1.48 to 1.91, respectively]. While major molecular response was improved at all-time points, complete cytogenetic response improved at 18 months but not at 24 months. Importantly, rate of progression to accelerated phase / blastic crisis was significantly lower with the newer tyrosine kinase inhibitors throughout all time points. Second generation tyrosine kinase inhibitors improved chronic myelogenous leukemia related mortality without a statistically significant difference in all-cause mortality at 12, 18 and 24 months. Conclusions: Second generation tyrosine kinase inhibitors can be added safely to the first-line treatment armamentarium of chronic phase-chronic myelogenous leukemia patients. Although an advantage is suggested by surrogate parameters, longer follow-up is necessary to see if this translates into superior overall survival.
Haematologica 08/2012; · 6.42 Impact Factor
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ABSTRACT: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.
To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.
We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.
Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).
Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival (HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates (RR 1.03; 95% CI 0.99 to 1.07), relapse rates (RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival (HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias (RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections (RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm (RR 1.33; 95% CI 1.00 to 1.56).
In summary, colony-stimulating factors should not be given routinely to acute myelogenous leukemia patients post-chemotherapy since they do not affect overall survival or infectious parameters including the rate of bacteremias and invasive fungal infections.
Cochrane database of systematic reviews (Online) 01/2012; 6:CD008238. · 5.72 Impact Factor
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ABSTRACT: Imatinib at a dose of 400 mg daily is considered frontline treatment in chronic phase chronic myeloid leukemia (CP-CML). We conducted a systematic review and meta-analysis of randomized controlled trials comparing frontline treatment with imatinib 400 mg daily versus higher doses (≥600 mg daily) in patients with CP-CML. The search yielded four trials, randomizing 1,673 patients. At 12 months, high dose compared with standard dose imatinib improved complete cytogenetic response (CCyR) (RR 1.17, 95% CI 1.08-1.26, four trials, I(2) = 33%) as well as major molecular response (MMolR) (RR 1.26, 95% CI 1.12-1.42, four trials, I(2) = 0%). There was no difference in all-cause mortality or disease progression at the end of follow up. Adverse events requiring discontinuation were more common in the high-dose arm (RR 1.98, 95% CI 1.20-3.26, three trials, I(2) = 0%), as were Grade III/IV neutropenia and thrombocytopenia: RR 1.56, 95% CI 1.15-2.12 and RR 1.86, 95% CI 1.28-2.70, respectively. There is currently insufficient evidence to support the routine use of higher doses of imatinib as frontline treatment for CP-CML. Extended follow up is needed to evaluate if the superior CCyR and MMolR with higher doses of imatinib will translate to long-term clinical benefit.
American Journal of Hematology 08/2011; 86(8):657-62. · 4.67 Impact Factor
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ABSTRACT: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer. Colony-stimulating factors (CSFs) are frequently administered during and after chemotherapy to reduce complications. However, their safety with regard to disease-related outcomes and survival in AML is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the impact of CSFs on patient outcomes, including survival.
To assess the safety/efficacy of CSFs with regard to disease-related outcomes and survival in patients with AML.
We conducted a comprehensive search strategy. We identified relevant randomized clinical trials by searching the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to July 2010), LILACS (up to December 2009), databases of ongoing trials and relevant conference proceedings.
Randomized controlled trials that compared the addition of CSFs during and following chemotherapy to chemotherapy alone in patients with AML. We excluded trials evaluating the role of CSFs administered for the purpose of stem cell collection and/or priming (e.g. before and/or only for the duration of chemotherapy).
Two review authors appraised the quality of trials and extracted data. For each trial, we expressed results as relative risk (RR) with 95% confidence intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard ratios (HRs).
The search yielded 19 trials including 5256 patients. The addition of CSFs to chemotherapy yielded no difference in all-cause mortality at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01; 95% CI 0.98 to 1.05, respectively) or in overall survival(HR 1.00; 95% 0.93 to 1.08). There was no difference in complete remission rates(RR 1.03; 95% CI 0.99 to 1.07), relapse rates(RR 0.97; 95% CI 0.89 to 1.05) and disease-free survival(HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of bacteremias(RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal infections(RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse events requiring discontinuation of CSFs as compared to the control arm(RR 1.33; 95% CI 1.00 to 1.56).
The addition of CSFs to chemotherapy does not adversely influence all-cause mortality, complete remission or relapse rates in patients with AML. Although the benefit of CSFs is limited to reduction of neutropenic and febrile days, they can be administered safely when necessary.
Cochrane database of systematic reviews (Online) 01/2011; · 5.72 Impact Factor
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ABSTRACT: The optimal postremission therapy in adults with acute lymphoblastic leukemia (ALL) is still a matter of debate. The objective of this study was to compare the various potential therapeutic options for patients who achieved first complete remission.
The authors conducted a systematic review and meta-analysis of randomized trials, including patients with standard-risk (SR) All and high-risk (HR) ALL who received first postremission therapy. Outcomes assessed were all-cause mortality (ACM), disease recurrence (relapse), and nonrelapse mortality (NRM). Relative risks (RRs) with 95% confidence intervals (CIs) were estimated and pooled.
Overall, there was a significant reduction in ACM in the allogenic stem cell transplantation (alloSCT) arm (RR, 0.88; 95% CI, 0.8-0.97) compared with autologous stem cell transplantation (ASCT) or chemotherapy. Subgroup analyses revealed a similar pattern among SR patients (RR, 0.8; 95% CI, 0.68-0.94) but a nonsignificant advantage for alloSCT among HR patients (RR, 0.88; 95% CI, 0.76-1.01). There was an increase in NRM (RR, 2.99; 95% CI, 1.37-6.53) and a decrease in the relapse rate in the alloSCT arm (RR, 0.52; 95% CI, 0.33-0.83). There was no difference in ACM or the relapse rate between the ASCT and chemotherapy arms.
Overall, alloSCT was superior to ASCT or chemotherapy for patients with ALL in first complete remission. The survival advantage was of greater statistical significance for patients with SR ALL than for patients with HR ALL.
Cancer 07/2010; 116(14):3447-57. · 4.77 Impact Factor
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ABSTRACT: Between 1983–1988, 72 patients with acute leukemia and 4 with aplastic anemia were treated in the Hematology Unit of The Chaim Sheba Medical Center. Ten patients with acute leukemia developed invasive pulmonary aspergillosis and 2 with aplastic anemia developed invasive aspergillosis of the nose and paranasal sinuses. These infections were diagnosed during a period of profound neutropenia while these patients were receiving broad spectrum antibiotics. The diagnosis of pulmonary aspergillosis was based on positive sputum cultures in 4 cases and on the appearance of typical clinical and radiologic features in six. In 2 culture-positive and in one culture-negative patient, the diagnosis was confirmed at autopsy. Thus, the diagnosis was definitive in 5 patients and probable in the remaining five patients. The 5 patients who achieved remission responded to antifungal treatment and recovered, while of the 5 who eventually died from the fungal infection, 4 did not achieve remission, and one died while in complete remission. In the 2 patients with aplastic anemia, aspergillosis was detected in cultures from necrotic nasal tissue. Both patients remained neutropenic, failed to respond to antifungal treatment and died within a short time after diagnosis. From this experience it appears that invasive aspergillosis in neutropenic patients is potentially curable if treated early by amphotericin B, provided that the neutrophil count recovers.
06/2009; 4(4):257-262.
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ABSTRACT: Acute infusion reactions are the most common documented adverse reactions reported with rituximab, with overt cytokine release syndrome, and hematological adverse events being much rarer. The clinical course of a patient with mantle cell lymphoma, who developed acute thrombocytopenia and leukopenia following rituximab administration, is described and the literature reviewed. Serum complement and the levels of three cytokines--TNF-alpha, IL-6, and IL-1, were measured 2 days after the infusion of rituximab by using ELISA assay. Drug-dependent antibodies against platelets were evaluated by two procedures as follows: an immunofluorescence test applying flow cytometry and Monoclonal Antibody Immobilization of Platelet Antigen (MAIPA). Serum levels of TNF-a were significantly increased compared with normal, whereas those of IL-6 and IL-1 were not increased significantly. Flow cytometry assay and the MAIPA assay failed to detect rituximab-dependent antibodies against platelets. Complement levels were decreased compared with normal. Literature search yielded 10 publications reporting on another 15 patients. The most common type of lymphoma was mantle cell lymphoma, six patients had bone marrow involvement, and 10 patients had splenomegaly. In 10 patients, acute cytopenia was preceded by cytokine release syndrome or infusion-related symptoms. Usually, thrombocytopenia was not associated with bleeding manifestations. Thrombocytopenia was the most commonly acute cytopenia reported. The postulated pathogenesis is associated with cytokine release syndrome and complement activation. Patients with potential risk factors like splenomegaly and bone marrow involvement, who develop clinical manifestations compatible with cytokine release syndrome, should be closely monitored for rituximab-associated cytopenia.
American Journal of Hematology 05/2009; 84(4):247-50. · 4.67 Impact Factor
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ABSTRACT: Rituximab, an anti CD20 monoclonal antibody, has now become a cornerstone in the treatment of many CD20 positive hematological malignancies and a variety of autoimmune disorders. In contrast to the acute allergic and cytokine associated reactions, late adverse events of rituximab are indeed uncommon but at the same time probably under-reported. In this review, we detail late adverse events reported since its use in hemato-oncological neoplasias and other disorders. These adverse events include the development of late-onset neutropenia, defects of immune reconstitution with associated immune compromise, infections, progressive multifocal leukoencephalopathy, reactivation of hepatitis, intestinal perforation and interstitial pneumonitis. Possible mechanisms involved in rituximab-associated complications and the pathogenesis of these adverse effects are reviewed and discussed. Evidence based graded recommendations for the management of these adverse effects are proposed.
Leukemia & lymphoma 05/2009; 50(7):1083-95. · 2.40 Impact Factor
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ABSTRACT: The survival of 137 consecutive chronic lymphocytic leukemia patients, diagnosed between 1960 and 1982 and followed up at the Hematology Clinic of the Chaim Sheba Center, was correlated with demographic, clinical and laboratory data. The median survival time of the whole group was 104 months. Older age, hepatomegaly, anemia, thrombocytopenia and increased percent of lymphocytes in the peripheral blood at diagnosis were all associated with shorter survival. On the other hand, splenomegaly or lymph node enlargement did not influence survival. When divided according to both Rai's and the International Workshop staging systems, the survival of our patients seemed to be better than that reported in most previously published series of similar patients. We assume that this is related to a conservative approach to the treatment of chronic lymphocytic leukemia patients in this center.
European Journal Of Haematology 04/2009; 38(2):123 - 130. · 2.61 Impact Factor
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Journal of Clinical Oncology 04/2009; · 18.37 Impact Factor
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ABSTRACT: Immunosuppressive therapy is the treatment for aplastic anemia patients ineligible for transplantation. The role of hematopoietic growth factors as adjunct to treatment in these patients is unclear. We conducted a systematic review and meta-analysis of randomized controlled trials comparing treatment with immunosuppressive therapy and hematopoietic growth factors to immunosuppressive therapy alone in patients with aplastic anemia. Two reviewers appraised the quality of trials and extracted data. For each trial, results were expressed as relative risks with 95% confidence intervals (CI) for dichotomous data. The addition of hematopoietic growth factors yielded no difference in overall mortality at 100 days, one year and five years [relative risks 1.33 (95% CI 0.56-3.18), relative risks 0.90 (95% CI 0.50-1.63) and relative risks 0.89 (95% CI 0.55-1.46), respectively]. There was no difference in overall hematologic response and in the occurrence of infections. HGF significantly decreased the risk for relapse, relative risks 0.45 (95% CI 0.30-0.68, 3 trials). Hematopoietic growth factors were not associated with higher occurrence of myelodysplastic syndrome and acute myeloid leukemia or paroxysmal nocturnal hemoglobinuria. The addition of hematopoietic growth factors does not affect mortality, response rate or infections occurrence. Therefore, it should not be recommended routinely as an adjunct to the immunosuppressive therapy for patients with aplastic anemia.
Haematologica 04/2009; 94(5):712-9. · 6.42 Impact Factor
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ABSTRACT: The role of intravenous immunoglobulins (IVIG) prophylaxis in hypogammaglobulinemic patients with lymphoproliferative disorders (LPD) and plasma cell dyscrasias (PCD) has not been established. We performed a systematic review and meta-analysis of randomized-controlled trials comparing prophylaxis with polyvalent IVIG versus control. The primary outcomes were all-cause mortality and major infections. Nine trials, assessing patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), were included. No survival benefit could be demonstrated, RR 1.36 (95% CI 0.58-3.19, two trials), but there was a significant decrease in the occurrence of major infections, RR 0.45 (95% CI 0.27-0.75, three trials) and a significant reduction in clinically documented infections, RR 0.49 (95% CI 0.39-0.61, three trials). Adverse events, usually not requiring discontinuation of IVIG, occurred significantly more with IVIG. On the basis of the available data, IVIG cannot be recommended routinely for patients with CLL or MM with hypogammaglobulinemia and/or recurrent infections and should be considered on individual basis.
Leukemia & lymphoma 04/2009; 50(5):764-72. · 2.40 Impact Factor
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ABSTRACT: Because the role of immunoglobulins (IVIG) prophylaxis in patients undergoing hematopoietic stem-cell transplantation (HSCT) has not been established in terms of survival and infection prevention, we conducted a meta-analysis evaluating these issues.
Systematic review and meta-analysis of randomized-controlled trials comparing prophylaxis with polyvalent IVIG or cytomegalovirus (CMV)-IVIG and control or another preparation or dose. PUBMED, Cochrane Library, LILACS, and conference proceedings were searched. Two reviewers appraised the quality of trials and extracted data. Relative risks (RRs) with 95% CIs were estimated and pooled.
Thirty trials including 4,223 patients undergoing bone marrow transplantation (BMT) were included. There was no difference in all-cause mortality when polyvalent IVIG or CMV-IVIG was compared to control (RR, 0.99; 95% CI, 0.88 to 1.12; and RR, 0.86; 95% CI, 0.63 to 1.16, respectively). There was no difference in clinically documented infections when polyvalent IVIG was compared with control (RR, 1.00; 95% CI, 0.90 to 1.10; five trials). CMV infections were not significantly reduced with either polyvalent IVIG or CMV-IVIG. Interstitial pneumonitis was reduced with polyvalent IVIG in older studies but not in the more recent ones, nor in studies assessing CMV-IVIG. Polyvalent IVIG increased the risk for veno-occlusive disease (RR, 2.73; (95% CI, 1.11 to 6.71). Graft-versus-host disease was not affected.
Because there is no advantage in terms of survival or infection prevention, IVIG does not have a role in HSCT.
Journal of Clinical Oncology 01/2009; 27(5):770-81. · 18.37 Impact Factor
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ABSTRACT: Patients undergoing hematopoietic stem cell transplantation (HSCT) and those with lymphoproliferative disorders (LPD) have a higher incidence of infections due to secondary hypogammaglobulinemia. One approach is the prophylactic administration of intravenous immunoglobulins (IVIG). Randomized controlled trials (RCTs) showed conflicting results in terms of type, schedule, dose and hematological patients benefiting from IVIG. We therefore performed a systematic review and meta-analysis to evaluate the role of IVIG in these patients.
To determine whether prophylaxis with IVIG reduces mortality or affects other outcomes in patients with hematological malignancies.
PubMed (January 1966 to December 2007), CENTRAL (The Cochrane Library, up to 2007, issue 1), LILACS and conference proceedings published between 2002-2007 were searched. The terms "immunoglobulins" or "gammaglobulins" or specific gammaglobulins and similar and the terms "hematologic neoplasms" or "hematologic malignancies" or "transplant" or "autotransplant" or "allotransplant" or "bone marrow transplant" or "peripheral stem cell transplant" and similar were selected. References of all included trials and reviews identified were scanned for additional trials.
All RCTs comparing prophylaxis of IVIG with placebo, no treatment or another immunoglobulin preparation, different administration schedules or doses for patients with hematological malignancies were included. One author screened all abstracts identified through the search strategy and two reviewers independently inspected each reference identified by the search and applied inclusion criteria.
For each trial, results were expressed as relative risks (RR) with 95% confidence intervals (CI) for dichotomous data and weighted mean differences for continuous data. We conducted meta-analysis, where enough similar trials were available, using the fixed- effects model, unless significant heterogeneity was present. We performed sensitivity analyses to assess the effect of individual methodological quality measures on effect estimates, including allocation generation, concealment and blinding.
Forty trials were included: thirty included HSCT patients and ten included patients LPD. When polyvalent immunoglobulins or hyperimmune cytomegalovirus (CMV)-IVIG was compared to control for HSCT, there was no difference in all-cause mortality. Polyvalent immunoglobulins significantly reduced the risk for interstitial pneumonitis but increased the risk for veno-occlusive disease and adverse events. In LPD, no benefit in terms of mortality IVIG could be demonstrated but there was a decrease in clinically and microbiologically documented infections.
In patients undergoing HSCT, routine prophylaxis with IVIG is not supported. Its use may be considered in LPD patients with hypogammaglobulinemia and recurrent infections, for reduction of clinically documented infections.
Cochrane database of systematic reviews (Online) 02/2008; · 5.72 Impact Factor
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ABSTRACT: To determine the safety and outcome following standard-dose ibritumomab tiuxetan followed by BEAM high-dose chemotherapy and autologous stem cell transplantation (ASCT) in patients with chemo-refractory aggressive non-Hodgkin's lymphoma.
The study included 23 patients, median age 55 years (range, 35-66) with chemo-refractory lymphoma, either primary refractory (n = 11) or in refractory relapse (n = 12). Rituximab 250 mg/m(2) followed by ibritumomab tiuxetan 0.4 mCi/kg were given on day -14 and high-dose BEAM chemotherapy started on day -6.
All patients engrafted. Twenty-one patients are evaluable for response; 11 achieved CR, 9 achieved PR, 5 of whom converted to CR with additional radiation therapy (overall CR rate 76%). With a median follow-up of 17 months (range, 4-27) 16 patients are alive and 12 are progression-free. The estimated 2-year overall and progression-free survival are 67% (95% CI, 46-87%) and 52% (95% CI, 31-72%), respectively. The day-100 rate of treatment-related mortality was 9% (95% CI, 2-33%) and the 2-year cumulative incidence of relapse was 31% (95% CI, 17-57%). Extensive prior therapy (>3 lines), high LDH and IPI score at ASCT, bulky disease, and progression during last chemotherapy were risk factors for reduced survival.
Ibritumomab tiuxetan-BEAM and ASCT is relatively safe and may improve outcome in patients with refractory lymphoma. Although excess nonrelapse mortality can not be ruled out, relapse rate was relatively low, resulting in improved outcome. Standard-risk patients with chemo-sensitive disease may also benefit from ibritumomab tiuxetan-BEAM and ASCT. This hypothesis merits further study in larger-scale prospective randomized studies.
Experimental Hematology 05/2007; 35(4):534-40. · 2.90 Impact Factor
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ABSTRACT: Summarizing our vision of hemato-oncology in the 21st century, we believe that with time, and with the expected progress in both medicine and biotechnology, the role of non-specific chemotherapy will decrease, while that of targeted therapies will increase. Unfortunately, for most tumors chemotherapy is still the cornerstone of treatment. We should therefore focus on finding more targeted agents, better tailoring of treatments, and identifying the risk factors for cancer development and the means of prevention of--what is likely to be--the number one killer of this century.
The Israel Medical Association journal: IMAJ 01/2007; 8(12):843-4. · 1.02 Impact Factor
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Annals of the New York Academy of Sciences 12/2006; 165(1):400 - 406. · 3.15 Impact Factor
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ABSTRACT: The last decade has witnessed very significant developments in the field of bone marrow transplantation (BMT), resulting in the improved safety and availability of this procedure. The expansion of international registries of voluntary, unrelated donors, the establishment of banks of fetal cord blood stem cells, as well as improved technology for transplantation of stem cells derived from partially matched family members, offer this treatment to patients hitherto not eligible for BMT. In addition to better donor availability, there has been a change in the concept regarding the role of BMT in the treatment of cancer: the understanding that the transplanted donor cells are capable of mounting an immunological assault against the host malignant cells. This goal can be achieved without fully destroying the patient's bone marrow stem cells and thus prepare the patient for transplantation with a reduced dose intensity of the myelotoxic drugs. Such nonmyeloablative conditioning increases the safety of the procedure. These developments have resulted in a vast expansion of the patient population eligible for BMT, including patients older than those who could have benefited from conventional allogeneic BMT with its associated high mortality in the older age groups, and those lacking fully matched family donors. This article surveys these developments and reviews the clinical indications for BMT in selected malignancies that are evidence-based. The role of BMT and its timing, in the light of new alternative solutions already in the market, is also discussed. Such critical evaluation is particularly warranted in view of the vastly higher rate of BMT per capita in Israel, as compared to other western countries, and given the late side effects inherent in the procedure.
Harefuah 03/2005; 144(2):102-6, 150.
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ABSTRACT: The Ph1 chromosome has rarely been reported in T-lineage acute lymphoblastic leukemia (T-ALL), and the clinical relevance of this translocation in T-ALL is currently unknown. In chronic myelogenous leukemia (CML) some data indicate derivation of T-cells from the leukemic clone and only a few cases of T-derived blastic crisis have been reported and quite often disputed. Particularly in cases identified initially in blastic crisis it may be difficult to distinguish those from Ph1-positive T-ALL. We herein report 2 patients who presented with a clinical picture of Ph1-positive T-ALL and who raised a differential diagnosis from T-cell blastic crisis of CML. We review the literature and suggest clinical and laboratory features that can help in the diagnosis. According to our literature review, 23 cases of Ph1-positive T-ALL and 44 cases of T-cell blastic crisis of CML, including ours, were reported. Some major differences between the two entities could help in establishing a diagnosis of Ph1-positive T-cell blastic crisis of CML vs. Ph1-positive T-ALL: Male sex and younger age was more predominant in T-ALL. While in most cases of CML blastic crisis there was a history of CML there was no such history in the T-ALL cases. Medullary involvement with lymphoblastic leukemia was present in all cases of T-ALL but only in about half of the cases of CML blastic crisis. None of the CML-blastic crisis cases tested by RT-PCR showed the minor breakpoint transcript, while 2 cases with T-ALL had the minor breakpoint transcript and 1 had both transcripts. Combined morphologic and FISH analysis can help to distinguish between the two entities and was applied in one of our cases. Although both entities carry a severe prognosis, differentiating between them might have clinical relevance, especially in the imatinib era.
Acta Haematologica 02/2005; 113(3):181-9. · 1.35 Impact Factor
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Pia Raanani, Isaac Ben-Bassat,
Shlomit Gan,
Luba Trakhtenbrot,
Ziva Mark,
Osnat Ashur-Fabian,
Svetlana Itskovich,
Frida Brok-Simoni,
Gideon Rechavi,
Ninette Amariglio,
Arnon Nagler
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ABSTRACT: The objective of this study was to evaluate the kinetics of molecular response in chronic myeloid leukemia (CML) patients treated with imatinib and to compare between the fluorescent in situ hybridization (FISH), multiplex and real-time quantitative RT-PCR (RQ-PCR) methods with this respect.
Molecular follow-up was carried out on 24 CML patients treated with imatinib. FISH analysis was performed according to the standard protocol. For RT-PCR the multiplex and RQ-PCR methods were used.
Sixty-three percent and 52% of the patients achieved complete remission according to FISH and multiplex RT-PCR analyses, respectively. Seventy-five percent of the patients achieved remission within the first year of treatment. In 83% of the cases the FISH and RT-PCR results were concordant. RQ-PCR analysis was carried out on 32 of the 41 samples negative by multiplex RT-PCR but only nine were negative. All samples with a BCR-ABL/ABL ratio below 2% were also negative by FISH. There was an excellent correlation between the RQ-PCR and the FISH tests.
Molecular remission according to FISH and multiplex RT-PCR can be achieved by imatinib within 1 yr of therapy. There is a good correlation between the FISH, multiplex and RQ-PCR results in terms of the kinetics of disappearance of the BCR-ABL transcript and the predictability of each method for the other. Although RQ-PCR is the most sensitive method for molecular follow-up, FISH and multiplex RT-PCR can be used as complementary tools, at least during the early period of treatment.
European Journal Of Haematology 11/2004; 73(4):243-50. · 2.61 Impact Factor
