Intensive Postremission Chemotherapy in Adults with Acute Myeloid Leukemia

Mayer, Roland; Rb, Davis; Schiffer, CA; Dt, Berg; Bl, Powell; Schulman, Philip; Ga, Omura; Je, Moore; Or, McIntyre; Frei, Emil

doi:10.1056/nejm199410063311402

Cited by 1,305 publications

(881 citation statements)

References 43 publications

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“…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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“…The pivotal randomized trial reported by Meyer and the Cancer and Acute Leukemia Group B (CALGB) colleagues compared consolidation therapy with high-dose cytarabine 3 g/m 2 IV over 2-3 hr every 12 hr on Days 1, 3, and 5 for 4 courses, to lower cytarabine dose schedules. High-dose cytarabine consolidations were followed by 4 additional courses of 2 1 5 chemotherapy [71]. The latter addition has been omitted from the subsequent comparative trials, an important consideration since later studies using this regimen as the standard of care reported five-year survival rates of 20-30% rather than 40% [72].…”

Section: Younger Patients With Amlmentioning

confidence: 99%

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

2015

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“…Studies indicate that post-remission intensification therapy with high dose cytarabine (HIDAC) decreases the risk of relapse for patients with AML in first complete remission [1,2]. However, disease recurrence still remains the most common cause of failure after HIDAC.…”

Section: Introductionmentioning

confidence: 99%

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

et al. 2008

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The most important problem in the therapy of patients with acute myeloid leukemia (AML) is relapse after intensive therapy. We sought to determine if interleukin-2 (low-dose with intermittent boluses) administration could be feasibly administered after standard therapy to potentiate anti-tumor immunity in a fashion analogous to the post-allogeneic stem cell transplant ''graft-vs-leukemic'' effect. Adults with de novo AML received daunorubicin and cytosine arabinoside induction therapy. Patients achieving complete remission received high dose ara-C (HIDAC) for three courses followed by low dose rIL-2 (Amgen), administered by continuous infusion (450,000 U/m 2 /day) for 10 weeks with intermittent boluses (500,000/U/m 2 over 2 hr) given in weekly intervals starting on Week 4. Of the 32 enrolled patients, 27 achieved CR; 8/11 who received rIL-2 completed therapy. 6/11 are long term survivors (median follow-up, 139 months). rIL-2 was well tolerated and associated with a 5-fold increase in circulating NK-lymphocytes and a 3-fold increase in circulating T-cells. Mononuclear cells from patients receiving rIL-2 exhibited enhanced cytolytic activity in vitro against cryopreserved autologous leukemia cells. This study supports further investigation of immunotherapy in the post-intensive chemotherapy setting in the management of patients with AML. Am. J. Hematol. 83:771-777, 2008. V

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Intensive Postremission Chemotherapy in Adults with Acute Myeloid Leukemia

Cited by 1,305 publications

References 43 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

Acute myeloid leukemia—Major progress over four decades and glimpses into the future

Low dose interleukin‐2 following intensification therapy with high dose cytarabine for acute myelogenous leukemia in first complete remission

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