Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia

Kh, Lee; Jh, Lee; Sj, Choi; Seol, Miee; Ys, Lee; Wk, Kim; Js, Lee; Ej, Seo; Jang, Seongsoo; Cj, Park; Hs, Chi

doi:10.1038/sj.leu.2403886

Cited by 141 publications

(93 citation statements)

References 30 publications

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“…[11][12][13] Median time to neutrophil recovery of at least 1.10 9 /l was 21 days (range, 1-43) and median time to platelet recovery of at least 50.10 9 /l was 16 days (range, 1-65).…”

Section: Resultsmentioning

confidence: 99%

“…11 High CHR rates are also achieved in newly diagnosed Ph þ ALL using imatinib at 600 mg daily together with an intensive four drugs-based induction chemotherapy. 12,13 Here, we report the results of a multicenter pilot study designed to evaluate the clinical efficacy and the tolerance of high-dose imatinib associated with a nonintensive sequential vincristine and dexamethasone chemotherapy schedule (Dexamethasone, Imatinib and Vincristine, DIV regimen) in a series of 31 patients with LBC and relapsed or resistant Ph þ ALL.…”

Section: Introductionmentioning

confidence: 99%

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High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia

et al. 2006

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Imatinib combined with high-dose chemotherapy is now becoming the gold standard for treatment of Philadelphia chromosome-positive acute leukemias. However, in all studies imatinib dosage was tapered to 400-600 mg per day. We decided to initiate a clinical trial to evaluate an opposite strategy based on high-dose imatinib (800 mg per day) combined with a less intensive chemotherapeutic regimen (vincristine and dexamethasone), which we called the DIV induction regimen. Thirty-one patients (18 relapsing or refractory Ph þ acute lymphoblastic leukemias and 13 lymphoid blast crisis chronic myelogenous leukemias) were enrolled. Complete remission (CR) was obtained in 28 out of 30 assessable patients. The median bcr-abl/abl ratio after the induction course was 0.1%. Median time to neutrophil recovery was 21 days. Fungus infections were observed in six patients out of 31 and possibly related to dexamethasone. Neuropathy due to vincristine was noted in 14 cases. Nine out of 19 patients under 55 years received allogenic stem cell transplantation after a median time of 78 days post-CR. Patients older than 55 years experienced a 90% CR rate without additional toxicities, suggesting the DIV regimen may also be proposed as a front line therapy in older patients.

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“…[11][12][13] Median time to neutrophil recovery of at least 1.10 9 /l was 21 days (range, 1-43) and median time to platelet recovery of at least 50.10 9 /l was 16 days (range, 1-65).…”

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia

et al. 2006

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“…In addition, adjustments for potential confounders in the comparisons with the pre-imatinib cohort from a nationwide registry allow unbiased estimates to be made, at least in Japan. Given the evidence for a substantial impact of imatinib in Ph þ ALL patients, 7,[14][15][16] it is unrealistic to conduct a prospective study comparing treatments with or without imatinib. Hence, a retrospective cohort design could be suboptimal to address the key questions.…”

Section: Discussionmentioning

confidence: 99%

“…The treatment of Ph þ ALL has changed dramatically since the introduction of imatinib and 490% of patients have achieved CR, 7,14,15 and allows SCT to be performed in a substantial proportion of patients in major or complete molecular remission. 8,[16][17][18] Actually, in the imatinib cohort, 97 of 100 patients (97%) achieved CR and 60 (60%) could receive allo-HSCT in their first CR. Several studies reported improved OS rates compared with that in the pre-imatinib era by incorporation of imatinib-based therapy.…”

Section: Discussionmentioning

confidence: 99%

Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR–ABL-positive acute lymphoblastic leukemia

et al. 2010

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A high complete remission (CR) rate has been reported in newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph þ ALL) following imatinib-based therapy. However, the overall effect of imatinib on the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is undetermined. Between 2002 and 2005, 100 newly diagnosed adult patients with Ph þ ALL were registered to a phase II study of imatinib-combined chemotherapy (Japan Adult Leukemia Study Group Ph þ ALL202 study) and 97 patients achieved CR. We compared clinical outcomes of 51 patients who received allo-HSCT in their first CR (imatinib cohort) with those of 122 historical control patients in the pre-imatinib era (pre-imatinib cohort). The probability of overall survival at 3 years after allo-HSCT was 65% (95% confidence interval (CI), 49-78%) for the imatinib cohort and 44% (95% CI, 35-52%) for the pre-imatinib cohort. Multivariate analysis confirmed that this difference was statistically significant (adjusted hazard ratio, 0.44, P ¼ 0.005). Favorable outcomes of the imatinib cohort were also observed for disease-free survival (P ¼ 0.007) and relapse (P ¼ 0.002), but not for non-relapse mortality (P ¼ 0.265). Imatinib-based therapy is a potentially useful strategy for newly diagnosed patients with Ph þ ALL, not only providing them more chance to receive allo-HSCT, but also improving the outcome of allo-HSCT.

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“…Importantly, patients with Ph-positive ALL are now treated with imatinib-containing regimens in specific studies that appear to highly improve the outcome of these high-risk patients. [41][42][43] Otherwise, the choice between ASCT or chemotherapy is still open. One may consider that the use of ASCT significantly reduces the total duration of treatment.…”

Section: Discussionmentioning

confidence: 99%

Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials

et al. 2005

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To evaluate the results of autologous stem cell transplantation (ASCT) in a large population of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR), we performed an individual data-based overview of the last three trials from the LALA group. Overall, 349 patients with ALL prospectively randomized in the consecutive LALA-85, -87, and -94 trials to receive either ASCT or chemotherapy as post-CR treatment were analyzed. Eligibility criteria were 15-50-year-old patients without sibling donors in both LALA-85/87 trials and 15-55-year-old patients with high-risk ALL and no sibling donors in the LALA-94 trial. Intent-to-treat analysis, which compared 175 patients from the ASCT arm to 174 patients from the chemotherapy arm, showed that ASCT was associated with a lower cumulative incidence of relapse (66 vs 78% at 10 years; P ¼ 0.05), without significant gain in disease-free or overall survival. Despite a possible lack of statistical power, a nested case-control analysis performed in 85 patient pairs adjusted for time to transplant and prognostic covariates confirmed these intent-to-treat results in patients actually transplanted. Of interest, the reduced relapse risk after ASCT translated in better disease-free survival in the 300 rapid responders who reached CR after the first induction course.

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Clinical effect of imatinib added to intensive combination chemotherapy for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia

Cited by 141 publications

References 30 publications

High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia

High-dose imatinib mesylate combined with vincristine and dexamethasone (DIV regimen) as induction therapy in patients with resistant Philadelphia-positive acute lymphoblastic leukemia and lymphoid blast crisis of chronic myeloid leukemia

Pre-transplant imatinib-based therapy improves the outcome of allogeneic hematopoietic stem cell transplantation for BCR–ABL-positive acute lymphoblastic leukemia

Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials

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