title: Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
abstract: The best strategy for incorporating imatinib in front-line treatment of Ph+ acute lymphoblastic leukemia (ALL) has not been established. We enrolled 92 patients with newly diagnosed Ph+ ALL in a prospective, multicenter study to investigate sequentially 2 treatment schedules with imatinib administered concurrent to or alternating with a uniform induction and consolidation regimen. Coadministration of imatinib and induction cycle 2 (INDII) resulted in a complete remission (CR) rate of 95% and polymerase chain reaction (PCR) negativity for BCR-ABL in 52% of patients, compared with 19% in patients in the alternating treatment cohort (P = .01). Remarkably, patients with and without a CR after induction cycle 1 (INDI) had similar hematologic and molecular responses after concurrent imatinib and INDII. In the concurrent cohort, grades III and IV cytopenias and transient hepatotoxicity necessitated interruption of induction in 87% and 53% of patients, respectively; however, duration of induction was not prolonged when compared with patients receiving chemotherapy alone. No imatinib-related severe hematologic or nonhematologic toxicities were noted with the alternating schedule. In each cohort, 77% of patients underwent allogeneic stem cell transplantation (SCT) in first CR (CR1). Both schedules of imatinib have acceptable toxicity and facilitate SCT in CR1 in the majority of patients, but concurrent administration of imatinib and chemotherapy has greater antileukemic efficacy.
authors.affiliation: Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wassmann
authors.forename: Heike
authors.initials: H
authors.lastname: Pfeifer
authors.forename: Nicola
authors.initials: N
authors.lastname: Goekbuget
authors.forename: Dietrich W
authors.initials: DW
authors.lastname: Beelen
authors.forename: Joachim
authors.initials: J
authors.lastname: Beck
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelljes
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Albrecht
authors.initials: A
authors.lastname: Reichle
authors.forename: Jolanta
authors.initials: J
authors.lastname: Perz
authors.forename: Rainer
authors.initials: R
authors.lastname: Haas
authors.forename: Arnold
authors.initials: A
authors.lastname: Ganser
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmid
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Georg
authors.initials: G
authors.lastname: Lenz
authors.forename: Martin
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Anja
authors.initials: A
authors.lastname: Binckebanck
authors.forename: Patrick
authors.initials: P
authors.lastname: Brück
authors.forename: Regina
authors.initials: R
authors.lastname: Reutzel
authors.forename: Harald
authors.initials: H
authors.lastname: Gschaidmeier
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Dieter
authors.initials: D
authors.lastname: Hoelzer
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Ottmann
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001549:Benzamides; D001853:Bone Marrow / Q000473:pathology; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000172:deficiency / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D011336:Probability; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D012074:Remission Induction; D016019:Survival Analysis; D014158:Transcription, Genetic; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl