A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study.
- Creators
- Hunault-Berger, Mathilde
- Leguay, Thibaut
- Thomas, Xavier
- Legrand, Ollivier
- Huguet, Françoise
- Bonmati, Caroline
- Escoffre-Barbe, Martine
- Legros, Laurence
- Turlure, Pascal
- Chevallier, Patrice
- Larosa, Fabrice
- Garban, Frederic
- Reman, Oumedaly
- Rousselot, Philippe
- Dhédin, Nathalie
- Delannoy, André
- Lafage-Pochitaloff, Marina
- Béné, Marie Christine
- Ifrah, Norbert
- Dombret, Hervé
- Renseigné, Non
- Others:
- Service des maladies du sang ; Centre Hospitalier Universitaire d'Angers (CHU Angers) ; PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)
- Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL) ; Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL) ; Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
- Hôpital Edouard Herriot [CHU - HCL] ; Hospices Civils de Lyon (HCL)
- Laboratoire d'Hématologie [Purpan] ; CHU Toulouse [Toulouse]
- Service d'hématologie clinique ; Université de Rennes 1 (UR1) ; Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou
- Institut de Biologie Valrose (IBV) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS) ; COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)
- Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges] ; CHU Limoges
- Service d'hématologie ; Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
- TheREx ; Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG) ; Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Département de cancérologie et d'hématologie ; CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon
- Hôpital de Jolimont ; Haine-Saint-Paul and Cliniques Universitaires St Luc
- Institut Paoli-Calmettes ; Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)
- Service d'Immunologie [CHRU Nancy] ; Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
- Service d'hématologie clinique [Avicenne] ; Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
- Lymphocyte et cancer ; IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM)
Description
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.
Abstract
International audience
Additional details
- URL
- https://hal.archives-ouvertes.fr/hal-00821138
- URN
- urn:oai:HAL:hal-00821138v1
- Origin repository
- UNICA