title: Acute lymphoblastic leukemia relapsing after first-line pediatric-inspired therapy: a retrospective GRAALL study.
abstract: The outcome of adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL) relapsing after pediatric-inspired front-line therapy is ill known. Here 229 relapsing Ph- ALL younger adults (18-63 years) treated within the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/-2005 trials were considered. Salvage regimens consisted of potentially curative therapies in 194 cases, low-intensity therapies in 21, allogeneic stem cell transplant (allo-SCT) in 6 and best supportive care in 8. Overall, 77 patients received allo-SCT after relapse. The median follow-up was 3.1 years. A second complete remission (CR2) was achieved in 121 patients (53%). In multivariate analysis, only younger age <45 years (P=0.008) and CR1 duration ⩾18 months (P=0.009) predicted CR2. Overall survival (OS) at 2 and 5 years was 19.3% (14-24%) and 13.3% (8-18%), respectively. In CR2 patients, disease-free survival (DFS) at 2 and 5 years was 29.0% (21-38%) and 25% (17-33%). In multivariate analysis, CR1 duration ⩾18 months and allo-SCT after relapse were associated with longer DFS (P<0.009 and P=0.004, respectively) and longer OS (P=0.004 and P<0.0001, respectively). In conclusion, although younger adults relapsing after pediatric-inspired ALL therapies retain a poor outcome, some of them may be cured if CR1 duration ⩾18 months and if allo-SCT can be performed in CR2. New therapies are definitely needed for these patients.
authors.affiliation: Hematology Department, University Hospital, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Desjonquères
authors.affiliation: Hematology Department, University Hospital, Nantes, France.
authors.forename: P
authors.initials: P
authors.lastname: Chevallier
authors.affiliation: Hematology Department, University Hospital, Lyon, France.
authors.forename: X
authors.initials: X
authors.lastname: Thomas
authors.affiliation: Hematology Department, University Hospital, Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Huguet
authors.affiliation: Hematology Department, University Hospital, Bordeaux, France.
authors.forename: T
authors.initials: T
authors.lastname: Leguay
authors.affiliation: Hematology Department, University Hospital, Rennes, France.
authors.forename: M
authors.initials: M
authors.lastname: Bernard
authors.affiliation: Hematology Department, University Hospital, Clermont-Ferrand, France.
authors.forename: J-O
authors.initials: JO
authors.lastname: Bay
authors.affiliation: Hematology Department, University Hospital, Saint-Etienne, France.
authors.forename: E
authors.initials: E
authors.lastname: Tavernier
authors.affiliation: Hematology Department, Institut Paoli-Calmette, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Charbonnier
authors.affiliation: Hematology Department, Hopital St-Antoine, Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Isnard
authors.affiliation: Hematology Department, University Hospital & University, INSERM U892/CNRS6299, Angers, France.
authors.forename: M
authors.initials: M
authors.lastname: Hunault
authors.affiliation: Hematology Department, University Hospital, Limoges, France.
authors.forename: P
authors.initials: P
authors.lastname: Turlure
authors.affiliation: Hematology Department, University Hospital, Poitiers, France.
authors.forename: M
authors.initials: M
authors.lastname: Renaud
authors.affiliation: Hematology Department, University Hospital, Dijon, France.
authors.forename: J-N
authors.initials: JN
authors.lastname: Bastié
authors.affiliation: Hematology Department, University Hospital, Reims, France.
authors.forename: C
authors.initials: C
authors.lastname: Himberlin
authors.affiliation: Hematology Department, Centre Henri Becquerel, Rouen, France.
authors.forename: S
authors.initials: S
authors.lastname: Lepretre
authors.affiliation: Hematology Department, University Hospital, Strasbourg, France.
authors.forename: B
authors.initials: B
authors.lastname: Lioure
authors.affiliation: GRAALL, Lyon, France.
authors.forename: V
authors.initials: V
authors.lastname: Lhéritier
authors.affiliation: Université Paris Descartes Sorbonne Cité, Institut Necker-Enfants Malades (INEM), Institut National de Recherche Médicale (INSERM) U1151, and Laboratory of Onco-Hematology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Necker Enfants-Malades, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Asnafi
authors.affiliation: Department of Molecular Biology, University Hospital Saint Louis (AP-HP), Paris, France.
authors.forename: K
authors.initials: K
authors.lastname: Beldjord
authors.affiliation: Département de Génétique, Aix Marseille University, APHM, Hopital Timone, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Lafage-Pochitaloff
authors.affiliation: Hematology Biology, University Hospital, Nantes, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Béné
authors.affiliation: Hematology Department, University Hospital & University, INSERM U892/CNRS6299, Angers, France.
authors.forename: N
authors.initials: N
authors.lastname: Ifrah
authors.affiliation: Hematology Department, University Hospital Saint-Louis, AP-HP, University Paris Diderot, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010677:Philadelphia Chromosome; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000069283:Rituximab; D000068877:Imatinib Mesylate