Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

Leukemia. 2012 Nov;26(11):2367-74. doi: 10.1038/leu.2012.164. Epub 2012 Jun 18.

Abstract

We conducted a systemic evaluation to describe the effect of minimal residual disease (MRD) kinetics on long-term allogeneic transplantation outcome by analyzing 95 adult transplants with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) who received first-line two courses of imatinib-based chemotherapy (median follow-up 5 years). MRD monitoring was centrally evaluated by real-time quantitative PCR (4.5 log sensitivity). After the first course of imatinib-based chemotherapy, 33 patients (34.7%) achieved at least major molecular response. On the basis of MRD kinetics by the end of two courses of imatinib-based chemotherapy, we stratified entire patients into four subgroups: early-stable molecular responders (EMRs, n=33), late molecular responders (LMRs, n=35), intermediate molecular responders (IMRs, n=9) and poor molecular responders (PMRs, n=18). Multivariate analysis showed that the most powerful factor affecting long-term transplantation outcome was MRD kinetics. Compared with EMRs, IMRs or PMRs had significantly higher risk of treatment failure in terms of relapse and disease-free survival (DFS). LMRs had a tendency toward a lower DFS. Quantitative monitoring of MRD kinetics during the first-line imatinib-based chemotherapy course is useful in identifying subgroups of Ph-positive ALL transplants at a high risk of relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Combined Modality Therapy
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Neoplasm, Residual*
  • Philadelphia Chromosome*
  • Piperazines / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / surgery*
  • Prognosis
  • Pyrimidines / therapeutic use*
  • Real-Time Polymerase Chain Reaction
  • Young Adult

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate