The effect of first-line imatinib interim therapy on the outcome of allogeneic stem cell transplantation in adults with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia

Blood. 2005 May 1;105(9):3449-57. doi: 10.1182/blood-2004-09-3785. Epub 2005 Jan 18.

Abstract

Previously, we suggested that imatinib incorporation into conventional chemotherapy as an alternative (imatinib interim therapy) might be a useful strategy for bridging the time to allogeneic stem cell transplantation (SCT) for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Here, we provide an updated report on this strategy in 29 patients. At the time of enrollment, 23 patients (79.3%) achieved complete remission (CR). After the first imatinib cycle, the median breakpoint cluster region-Abelson oncogene locus (BCR-ABL)/ABL ratios decreased by 0.77 log in 25 (86.2%) responders, and their BCR-ABL/ABL ratios decreased further by 0.34 log after the second imatinib cycle, which included 7 molecular CR. One patient (4.3%) relapsed during the imatinib therapy. The remaining 3 patients were primarily refractory to both imatinib and chemotherapy. Twenty-five (86.2%) of the 29 patients received transplants in first CR. With a median follow-up duration of 25 months after SCT, the 3-year estimated probabilities of relapse, nonrelapse mortality, disease-free survival, and overall survival were 3.8%, 18.7%, 78.1%, and 78.1%, respectively. In comparison to our historical control data, first-line imatinib interim therapy appears to provide a good quality of CR and a survival advantage for patients with Ph(+) ALL. Further long-term follow-up is needed to validate the results of this study.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Algorithms
  • Benzamides
  • Fusion Proteins, bcr-abl / genetics
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis
  • Piperazines / administration & dosage*
  • Piperazines / pharmacology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Probability
  • Pyrimidines / administration & dosage*
  • Pyrimidines / pharmacology
  • RNA, Messenger / analysis
  • Recurrence
  • Remission Induction
  • Survival Analysis
  • Transplantation, Homologous
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • RNA, Messenger
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl