title: Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study.
abstract: The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT). Overall, complete remission (CR) and BCR-ABL real-time quantitative polymerase chain reaction (RQ-PCR) negativity rates were 96% and 29%, respectively. All of the 22 CR patients (100%) with a donor actually received allogeneic SCT in first CR. At 18 months, the estimated cumulative incidence of relapse, disease-free survival, and overall survival were 30%, 51%, and 65%, respectively. These 3 end points compared very favorably with results obtained in the pre-imatinib LALA-94 trial. This study confirms the value of the combined approach and encourages prospective trials to define the optimal chemotherapy that has to be combined with imatinib and to carefully reevaluate the place of allogeneic SCT in this new context.
authors.affiliation: Department of Hematology, Hôpital Saint-Louis, Paris, France, and Department of Hematology, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: Adrienne
authors.initials: A
authors.lastname: de Labarthe
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Françoise
authors.initials: F
authors.lastname: Huguet-Rigal
authors.forename: Eric
authors.initials: E
authors.lastname: Delabesse
authors.forename: Francis
authors.initials: F
authors.lastname: Witz
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maury
authors.forename: Delphine
authors.initials: D
authors.lastname: Réa
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Cayuela
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Vekemans
authors.forename: Oumedaly
authors.initials: O
authors.lastname: Reman
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Arnaud
authors.initials: A
authors.lastname: Pigneux
authors.forename: Martine
authors.initials: M
authors.lastname: Escoffre
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: MacIntyre
authors.forename: Véronique
authors.initials: V
authors.lastname: Lhéritier
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Vernant
authors.forename: Xavier
authors.initials: X
authors.lastname: Thomas
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Hervé
authors.initials: H
authors.lastname: Dombret
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001549:Benzamides; D003561:Cytarabine / Q000627:therapeutic use; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000627:therapeutic use; D018365:Neoplasm, Residual; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000008:administration & dosage*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000401:mortality; D011743:Pyrimidines / Q000008:administration & dosage*; D012074:Remission Induction; D016019:Survival Analysis; D014184:Transplantation, Homologous
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003561:Cytarabine; D000068877:Imatinib Mesylate; D008942:Mitoxantrone