Mini-allografts' for haematological malignancies: an alternative to conventional myeloablative marrow transplantation.

Abstract

Considerable morbidity and mortality are consequences of the myeloablative chemoradiotherapy utilised in conventional allogeneic marrow transplantation. This has generally restricted such potentially curative treatment to patients <50-55 years with normal organ function. Recent studies suggest that purine-analogue based non-myeloablative regimens are sufficiently immunosuppressive to facilitate allogeneic donor cell engraftment. To review the outcome of HLA-compatible sibling allogeneic peripheral blood progenitor cell (PBPC) transplants using fludarabine-based conditioning in patients ineligible for a conventional transplant, with emphasis on engraftment, graft vs host disease (GVHD) and graft vs tumour effects. Eleven patients (nine > or = 47 years age) with advanced haematological malignancies received one of three different fludarabine-based chemotherapy followed by infusion of granulocyte colony-stimulating factor mobilised PBPC. Cyclosporin-methotrexate was used as GVHD prophylaxis. Two patients died early; minimal non-haematological toxicity apart from mucositis occurred in the other nine. Eight of the nine evaluable patients had evidence of durable donor cell engraftment in preference to recipient cells. Acute GVHD (> or = grade 2) occurred in seven of eight patients with donor engraftment who survived beyond two months. Four patients are alive in complete remission 8-28 months post-transplant; another is alive in probable remission at four months. Fludarabine-based non myeloablative chemotherapy facilitates rapid engraftment of allogeneic donor cells, which produce powerful GVHD and graft vs tumour effects. This approach has the potential to extend the applicability of allogeneic stem cell transplants to patients traditionally regarded as too old or sick for conventional marrow transplants.