Molecular remission of chronic myeloid leukaemia following a non-myeloablative allogeneic peripheral blood stem cell transplant: in vivo and in vitro evidence for a graft-versus-leukaemia effect

Br J Haematol. 1999 Nov;107(2):396-400. doi: 10.1046/j.1365-2141.1999.01706.x.

Abstract

Two patients with chronic myeloid leukaemia (CML) received a non-myeloablative preparative regimen of cyclophosphamide and fludarabine, followed by an unmanipulated, G-CSF-mobilized, peripheral blood stem cell transplant from an HLA-identical sibling. Chimaerism, evaluated in myeloid and T-lymphoid lineages by PCR of minisatellite variable regions, showed day 14 post-transplant haemopoietic recovery to be 90% autologous in both patients. On day 30 the bone marrow showed only 1/20 and 2/18 donor metaphases. By day 100 post transplant both had 100% donor myeloid and lymphoid lineages as assessed by karyotype and minisatellite chimaerism analysis. They subsequently became RT-PCR negative for BCR-ABL. Both survive 7 and 14 months post transplant in molecular remission of CML. In one, donor T cells, stimulated with pre-transplant CML cells, induced 30-50% inhibition of pre-transplant leukaemic CFU-GM, but did not inhibit CFU-GM in the day 60 marrow (46% Ph-negative recipient, 54% donor). These results show that a non-myeloablative allotransplant can induce molecular remissions of CML through a graft-versus-leukaemia effect.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Leukemia Effect / drug effects
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Male
  • Middle Aged
  • Remission Induction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vidarabine / administration & dosage
  • Vidarabine / analogs & derivatives

Substances

  • Granulocyte Colony-Stimulating Factor
  • Cyclophosphamide
  • Vidarabine
  • fludarabine