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Chemotherapy-phased imatinib pulses improve long-term outcome of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: Northern Italy Leukemia Group protocol 09/00.

Authors :
Bassan R
Rossi G
Pogliani EM
Di Bona E
Angelucci E
Cavattoni I
Lambertenghi-Deliliers G
Mannelli F
Levis A
Ciceri F
Mattei D
Borlenghi E
Terruzzi E
Borghero C
Romani C
Spinelli O
Tosi M
Oldani E
Intermesoli T
Rambaldi A
Source :
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2010 Aug 01; Vol. 28 (22), pp. 3644-52. Date of Electronic Publication: 2010 Jul 06.
Publication Year :
2010

Abstract

Purpose: Short imatinib pulses were added to chemotherapy to improve the long-term survival of adult patients with Philadelphia chromosome (Ph) -positive acute lymphoblastic leukemia (ALL), to optimize complete remission (CR) and stem-cell transplantation (SCT) rates.<br />Patients and Methods: Of 94 total patients (age range, 19 to 66 years), 35 represented the control cohort (ie, imatinib-negative [IM-negative] group), and 59 received imatinib 600 mg/d orally for 7 consecutive days (ie, imatinib-positive [IM-positive] group), starting from day 15 of chemotherapy course 1 and from 3 days before chemotherapy during courses 2 to 8. Patients in CR were eligible for allogeneic SCT or, alternatively, for high-dose therapy with autologous SCT followed by long-term maintenance with intermittent imatinib.<br />Results: CR and SCT rates were greater in the IM-positive group (CR: 92% v 80.5%; P = .08; allogeneic SCT: 63% v 39%; P = .041). At a median observation time of 5 years (range, 0.6 to 9.2 years), 22 patients in the IM-positive group versus five patients in the IM-negative group were alive in first CR (P = .037). Patients in the IM-positive group had significantly greater overall and disease-free survival probabilities (overall: 0.38 v 0.23; P = .009; disease free: 0.39 v 0.25; P = .044) and a lower incidence of relapse (P = .005). SCT-related mortality was 28% (ie, 15 of 54 patients), and postgraft survival probability was 0.46 overall.<br />Conclusion: This imatinib-based protocol improved long-term outcome of adult patients with Ph-positive ALL. With SCT, post-transplantation mortality and relapse remain the major hindrance to additional therapeutic improvement. Additional intensification of imatinib therapy should warrant a better molecular response and clinical outcome, both in patients selected for SCT and in those unable to undergo this procedure.

Details

Language :
English
ISSN :
1527-7755
Volume :
28
Issue :
22
Database :
MEDLINE
Journal :
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
Publication Type :
Academic Journal
Accession number :
20606084
Full Text :
https://doi.org/10.1200/JCO.2010.28.1287