title: Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.
abstract: Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.
authors.affiliation: Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;
authors.forename: Nathalie
authors.initials: N
authors.lastname: Dhédin
authors.affiliation: Department of Hematology, University Institute of Cancer, Toulouse, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Huynh
authors.affiliation: Department of Hematology, University Hospital Henri Mondor, AP-HP, Créteil, France;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
authors.affiliation: Department of Hematology, University Hospital, Bordeaux, France;
authors.forename: Reza
authors.initials: R
authors.lastname: Tabrizi
authors.affiliation: Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;
authors.forename: Kheira
authors.initials: K
authors.lastname: Beldjord
authors.affiliation: Department of Hematology, University Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades, INSERM U1151, and Onco-Hematology Laboratory, Assistance Publique Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Paris, France;
authors.forename: Vahid
authors.initials: V
authors.lastname: Asnafi
authors.affiliation: Department of Hematology, Hospital Lyon Sud, Pierre Bénite, France;
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Department of Hematology, University Hospital, Nantes, France;
authors.forename: Patrice
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Department of Hematology, University Hospital Pitié-Salpêtrière, Assistance Publique Hôpitaux de Paris, Paris, France;
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Nguyen
authors.affiliation: Department of Hematology, University Hospital, Lille, France;
authors.forename: Valérie
authors.initials: V
authors.lastname: Coiteux
authors.affiliation: Department of Hematology, Institut Gustave Roussy, Villejuif, France;
authors.forename: Jean-Henri
authors.initials: JH
authors.lastname: Bourhis
authors.affiliation: Department of Hematology, University Hospital, Montpellier, France;
authors.forename: Yosr
authors.initials: Y
authors.lastname: Hichri
authors.affiliation: Department of Hematology, University Hospital, Rennes, France;
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre-Barbe
authors.affiliation: Department of Hematology, University Hospital, Caen, France;
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.affiliation: Department of Hematology, University Hospital, Yvoir, Belgium;
authors.forename: Carlos
authors.initials: C
authors.lastname: Graux
authors.affiliation: Division of Hematology, Department of Medical Specialties, University Hospital, Geneva, and Faculty of Medicine, University of Geneva Switzerland and Swiss Group for Clinical Cancer Research, Bern, Switzerland;
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.affiliation: Department of Hematology, Institut Paoli Calmettes, Marseille, France;
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Division of Hematology, University Hospital of Zurich, Zurich, Switzerland;
authors.forename: Urs
authors.initials: U
authors.lastname: Schanz
authors.affiliation: Group for Research on Adult Acute Lymphoblastic Leukemia, Coordination Office, Pierre Bénite, France;
authors.forename: Véronique
authors.initials: V
authors.lastname: Lhéritier
authors.affiliation: Department of Hematology, University Hospital, Grenoble, France; and.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Department of Hematology and University Paris Diderot, Institut Universitaire d'Hématologie, EA-3518, University Hospital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
authors.affiliation: Department of Hematology and INSERM U 892/CNRS 6299, University Hospital, Angers, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
mesh_terms: D000293:Adolescent; D000328:Adult; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018365:Neoplasm, Residual; D017063:Outcome Assessment, Health Care / Q000379:methods*; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000628:therapy*; D012074:Remission Induction; D033581:Stem Cell Transplantation / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult