title: Randomized study of reduced-intensity chemotherapy combined with imatinib in adults with Ph-positive acute lymphoblastic leukemia.
abstract: In this study, we randomly compared high doses of the tyrosine kinase inhibitor imatinib combined with reduced-intensity chemotherapy (arm A) to standard imatinib/hyperCVAD (cyclophosphamide/vincristine/doxorubicin/dexamethasone) therapy (arm B) in 268 adults (median age, 47 years) with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The primary objective was the major molecular response (MMolR) rate after cycle 2, patients being then eligible for allogeneic stem cell transplantation (SCT) if they had a donor, or autologous SCT if in MMolR and no donor. With fewer induction deaths, the complete remission (CR) rate was higher in arm A than in arm B (98% vs 91%; P = .006), whereas the MMolR rate was similar in both arms (66% vs 64%). With a median follow-up of 4.8 years, 5-year event-free survival and overall survival (OS) rates were estimated at 37.1% and 45.6%, respectively, without difference between the arms. Allogeneic transplantation was associated with a significant benefit in relapse-free survival (hazard ratio [HR], 0.69; P = .036) and OS (HR, 0.64; P = .02), with initial white blood cell count being the only factor significantly interacting with this SCT effect. In patients achieving MMolR, outcome was similar after autologous and allogeneic transplantation. This study validates an induction regimen combining reduced-intensity chemotherapy and imatinib in Ph+ ALL adult patients and suggests that SCT in first CR is still a good option for Ph+ ALL adult patients. This trial was registered at www.clinicaltrials.gov as #NCT00327678.
authors: Division of Hematology, Department of Medical Specialties, University Hospital and University of Geneva, Geneva, Switzerland; Swiss Group for Clinical Cancer Research, Bern, Switzerland;
authors: Yves
authors: Y
authors: Chalandon
authors: Division of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France;
authors: Xavier
authors: X
authors: Thomas
authors: Division of Hematology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France;
authors: Sandrine
authors: S
authors: Hayette
authors: Division of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France;
authors: Jean-Michel
authors: JM
authors: Cayuela
authors: Division of Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
authors: Claire
authors: C
authors: Abbal
authors: Division of Hematology, Institut Universitaire de Cancérologie, Toulouse, France;
authors: Françoise
authors: F
authors: Huguet
authors: Division of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France;
authors: Emmanuel
authors: E
authors: Raffoux
authors: Division of Hematology, Hôpital Haut-Levêque, Pessac, France;
authors: Thibaut
authors: T
authors: Leguay
authors: Division of Hematology, Hôpital Mignot, Versailles, France;
authors: Philippe
authors: P
authors: Rousselot
authors: Division of Hematology, Centre Henri Becquerel, Rouen, France;
authors: Stéphane
authors: S
authors: Lepretre
authors: Division of Hematology, Hôpital Pontchailloux, Rennes, France;
authors: Martine
authors: M
authors: Escoffre-Barbe
authors: Division of Hematology, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, University Paris Est Créteil, Créteil, France;
authors: Sébastien
authors: S
authors: Maury
authors: Division of Hematology, Hôpital Claude Huriez, Lille, France;
authors: Céline
authors: C
authors: Berthon
authors: Division of Hematology, Institut de Cancérologie Lucien-Neuwirth, Saint-Priest-en-Jarez, France;
authors: Emmanuelle
authors: E
authors: Tavernier
authors: Swiss Group for Clinical Cancer Research, Bern, Switzerland; Division of Hematology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;
authors: Jean-François
authors: JF
authors: Lambert
authors: Division of Hematology, Hôpital de la Timone, Marseille, France;
authors: Marina
authors: M
authors: Lafage-Pochitaloff
authors: Group for Research on Adult Acute Lymphoblastic Leukemia, Lyon, France;
authors: Véronique
authors: V
authors: Lhéritier
authors: Division of Biostatistics, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France; and.
authors: Sylvie
authors: S
authors: Chevret
authors: Division of Hematology, Centre Hospitalier Universitaire d'Angers and INSERM U892/Centre National de la Recherche Scientifique 6299, Angers, France.
authors: Norbert
authors: N
authors: Ifrah
authors: Division of Hematology, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, University Paris Diderot, Paris, France;
authors: Hervé
authors: H
authors: Dombret
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D033581:Stem Cell Transplantation; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate