HLA-matched related hematopoietic cell transplantation for chronic-phase CML using a targeted busulfan and cyclophosphamide preparative regimen

Blood. 2003 Jul 1;102(1):31-5. doi: 10.1182/blood-2002-08-2619. Epub 2003 Feb 20.

Abstract

Allogeneic blood or marrow transplantation (BMT) is a curative therapy for chronic myeloid leukemia (CML). We have previously reported that the pharmacologic targeting of busulfan combined with cyclophosphamide (TBU/CY) can minimize regimen-related toxicity while preserving antileukemic effects. We report here on 131 consecutive chronic-phase CML patients treated with allogeneic related BMT using a TBU/CY preparative regimen, where the busulfan dose was targeted to achieve a steady-state plasma concentration of at least 900 ng/mL. The median age of the patients was 43 years (range, 14-66 years). Estimates of the probabilities of nonrelapse mortality, relapse, survival, and disease-free survival 3 years after transplantation were 14%, 8%, 86%, and 78%, respectively. Age had no statistically significant effect on survival. Although approximately 60% of the patients developed clinically extensive chronic graft-versus-host disease, the median Karnofsky score at last contact date among survivors was 95%. Of surviving patients, 11% were molecularly positive for the bcr-abl mRNA at last contact, with a median level of bcr-abl transcripts of 4.6 copies/microg RNA. These data suggest that TBU/CY is a very effective preparative regimen for CML in chronic phase, associated with an expected survival at 3 years of approximately 85%, with most patients being in molecular remission.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / toxicity
  • Busulfan / administration & dosage
  • Cohort Studies
  • Cyclophosphamide / administration & dosage
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Histocompatibility Testing
  • Histocompatibility*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Middle Aged
  • Retrospective Studies
  • Survival Analysis
  • Transplantation, Homologous / immunology
  • Treatment Outcome

Substances

  • Cyclophosphamide
  • Busulfan