The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia

Bone Marrow Transplant. 2003 Nov;32(9):897-901. doi: 10.1038/sj.bmt.1704231.

Abstract

We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Host Disease / prevention & control
  • Graft vs Leukemia Effect / drug effects*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Leukemia, Myeloid, Chronic-Phase / mortality
  • Leukemia, Myeloid, Chronic-Phase / therapy
  • Male
  • Middle Aged
  • Peripheral Blood Stem Cell Transplantation / methods*
  • Peripheral Blood Stem Cell Transplantation / mortality
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Transplantation, Isogeneic
  • Treatment Outcome
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives*

Substances

  • Cyclophosphamide
  • Vidarabine
  • fludarabine