Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study

Castaigné, Sylvie; Chevret, Sylvie; Archimbaud, E; Fenaux, Pierre; Bron, Dominique; Tilly, Hervé; Revel, Thierry de; Simon, Marc A.; Dupriez, Brigitte; Renoux, M; Janvier, Maud; Micléa, Jean-Michel; Thomas, Xavier; Bastard, Christian; Preudhomme, Claude; Bauters, F; Degos, Laurent; Dombret, Hervé

doi:10.1182/blood-2003-10-3561

Cited by 81 publications

(66 citation statements)

References 31 publications

(20 reference statements)

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“…Treatment modalities have already been detailed. 5 After receiving a timed-sequential induction therapy, complete remitters without allogeneic stem cell transplantation indication and related donor were randomized between the TSC ALFA-9000 consolidation 6 or 4 courses of high-dose cytarabine, according to the Cancer and Leukemia Group B (CALGB) schedule. 7 All patients registered on the study were randomized at registration to receive recombinant human GM-CSF (Leucomax, Schering Plough) given at a dose of 5 lg/kg/ day intravenously over 6 hours, from Day 1 through the last day of chemotherapy of each course (except salvage) of chemotherapy or no GM-CSF.…”

Section: Patients and Treatmentsmentioning

confidence: 99%

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Thomas

Raffoux

Renneville

et al. 2010

Cancer

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BACKGROUND:Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase‐specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) may enhance complete remission (CR) rate and event‐free survival (EFS) in younger adults with acute myeloid leukemia (AML).METHODS:In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM‐CSF concurrently with all cycles of chemotherapy. The effects of GM‐CSF on survival were reported herein with a long‐term follow‐up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers.RESULTS:The EFS rate was better in the GM‐CSF group (43% vs 34%; P = .04). GM‐CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM‐CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3‐ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM‐CSF priming, the difference in terms of EFS was highly significant (5‐year EFS, 39% with GM‐CSF vs 8% without GM‐CSF; P = .007).CONCLUSIONS:Sensitization of leukemic cells and their progenitors by GM‐CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor‐prognosis FLT3‐ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. © 2010 American Cancer Society.

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Section: Patients and Treatmentsmentioning

confidence: 99%

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Thomas

Raffoux

Renneville

et al. 2010

Cancer

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“…15 After CR achievement, patients received a moderate consolidation course with mitoxantrone 12 mg/m 2 /day for 1 day and AraC 120 mg/m 2 /day for 5 days ((1 þ 5) course) followed by an intensive consolidation course with idarubicine 12 mg/m 2 /day for 3 days and AraC 2000 mg/m 2 /12-h as 3-h intravenous bolus infusion for 6 days (24 g/m 2 ) in 20 cases, and allogeneic SCT with a matched related donor in one case.…”

Section: Treatmentmentioning

confidence: 99%

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

et al. 2005

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Despite the favorable prognosis of patients with acute myeloid leukemia (AML) with t(8;21)(q22;q22) translocation, relapses still occur in about 30% of the cases but no initial factors can strongly predict the risk of relapse. Several recent studies suggest that monitoring minimal residual disease (MRD) may identify patients at risk of relapse. We prospectively monitored AML1-ETO rearrangement by real-time quantitative PCR (RQ-PCR) in 21 patients uniformly treated in our center. Blood (PB) and bone marrow (BM) samples were collected during and after therapy. At diagnosis, levels of AML1-ETO transcript showed large variations and there was a trend for a higher relapse rate in patients with high pretreatment expression levels (P ¼ 0.065). After induction therapy, absolute transcript levels (below 10 À3 , compared to Kasumi cell line), or a greater than 3 log decrease by comparison to diagnosis levels, were significant predictors of the absence of relapse (P ¼ 0.02 and P ¼ 0.02, respectively). MRD levels after consolidation therapy were also significant indicators of relapse (P ¼ 10 À5 ). Comparison of BM and PB samples showed similar sensitivity for detecting AML1-ETO transcript. In conclusion, RQ-PCR appears to be an early predictive factor of the relapse risk in AML with t(8;21). PB samples can be used adequately to evaluate the level of MRD by this technique.

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“…The potential utility of DI was also investigated in a randomized study aimed at comparison of DI and timed sequential induction to a ''3 1 7'' induction in adults with AML. Treatment-related mortality (TRM), either during the induction or the postremission phase, was not significantly higher for the more intensive arms; notwithstanding, event-free survival and OS were similar in the three randomization arms [28].…”

Section: Resultsmentioning

confidence: 91%

Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: Feasibility, toxicity, and therapeutic results

et al. 2010

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The strategy named double induction (DI) in acute myeloid leukemia (AML) consists of two courses of chemotherapy irrespective of the degree of cytoreduction in the bone marrow (BM) after the first course, unless severe complications prohibit its application. We describe treatment results from a series of 33 patients in whom DI was adopted only after demonstration of persistence of more than 10% blast cells at day 15 (D15) examination of BM. All patients received as induction idarubicin, cytarabine, and etoposide. As second induction, we administered the combination of fludarabine, intermediate dose cytarabine, and Granulocyte colony stimulating factor (G-CSF). The median blast count at D15 was 30 (15-90). Overall, 30 of 33 patients were judged as eligible to receive DI, reasons for exclusion being in all cases active infection in the context of severe pancytopenia. Nineteen patients (63%) had unfavorable karyotype and 11 (37%) normal karyotype; seven of these had Fms-like tyrosine kinase gene internal tandem duplication (FLT3/ITD) mutation. Overall, complete remission (CR) was achieved in 20/30 patients (67%), while eight patients (27%) were refractory and two died of infectious complications. All refractory patients had unfavorable cytogenetics. All patients achieving CR were programmed to receive allogeneic stem cell transplantation (allo-SCT), which was actually performed in 11 patients. Our study suggest that D15 driven DI represents a feasible and effective therapeutic strategy in young adult AML patients, improving therapeutic results and not compromising feasibility of allo-SCT. When compared with conventional DI, it offers the potential to avoid unnecessary toxicity in a consistent proportion of patients. Am. J. Hematol. 85:687-690, 2010. V

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Randomized comparison of double induction and timed-sequential induction to a "3 + 7" induction in adults with AML: long-term analysis of the Acute Leukemia French Association (ALFA) 9000 study

Cited by 81 publications

References 31 publications

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Prognostic value of real-time quantitative PCR (RQ-PCR) in AML with t(8;21)

Day 15 bone marrow driven double induction in young adult patients with acute myeloid leukemia: Feasibility, toxicity, and therapeutic results

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