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

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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.