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Clinical Trial
. 2011 Feb;96(2):245-52.
doi: 10.3324/haematol.2010.027862. Epub 2010 Oct 22.

A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Mathilde Hunault-Berger  1 , Thibaut Leguay, Xavier Thomas, Ollivier Legrand, Françoise Huguet, Caroline Bonmati, Martine Escoffre-Barbe, Laurence Legros, Pascal Turlure, Patrice Chevallier, Fabrice Larosa, Frederic Garban, Oumedaly Reman, Philippe Rousselot, Nathalie Dhédin, André Delannoy, Marina Lafage-Pochitaloff, Marie Christine Béné, Norbert Ifrah, Hervé Dombret; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
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Clinical Trial

A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

Mathilde Hunault-Berger et al. Haematologica. 2011 Feb.

Abstract

Background: The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia.

Design and methods: Sixty patients received either continuous-infusion doxorubicin (12 mg/m(2)/day) and continuous-infusion vincristine (0.4 mg/day) on days 1-4 or pegylated liposomal doxorubicin (40 mg/m(2)) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors.

Results: Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm.

Conclusions: With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities.

Trial registration: ClinicalTrials.gov NCT00600977.

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Figures

Figure 1.
Figure 1.
Treatment protocol.
Figure 2.
Figure 2.
Event-free survival according to randomization arm.
Figure 3.
Figure 3.
Overall survival according to randomization arm.
See this image and copyright information in PMC

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