Alternating versus concurrent schedules of imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL).
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.
Wassmann
Barbara
B
Department of Hematology and Oncology, Johann Wolfgang Goethe University, Frankfurt, Germany.
Pfeifer
Heike
H
Goekbuget
Nicola
N
Beelen
Dietrich W
DW
Beck
Joachim
J
Stelljes
Matthias
M
Bornhäuser
Martin
M
Reichle
Albrecht
A
Perz
Jolanta
J
Haas
Rainer
R
Ganser
Arnold
A
Schmid
Mathias
M
Kanz
Lothar
L
Lenz
Georg
G
Kaufmann
Martin
M
Binckebanck
Anja
A
Brück
Patrick
P
Reutzel
Regina
R
Gschaidmeier
Harald
H
Schwartz
Stefan
S
Hoelzer
Dieter
D
Ottmann
Oliver G
OG
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
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016044:Fusion Proteins, bcr-abl