Graft-versus-host disease, donor chimerism, and organ toxicity in stem cell transplantation after conditioning with fludarabine and melphalan

Abstract

Hematopoietic stem cell transplantation may be used to induce a graft-versus-tumor effect against a range of malignancies. Pretransplantation conditioning regimens vary considerably in their degree of myelosuppression and immunosuppression, which may result in marked differences in the rate of T-cell engraftment and, as a consequence, the onset and severity of graft-versus-host disease (GVHD). We have examined the development of T-cell chimerism and the onset of GVHD following fludarabine and melphalan conditioning in 39 patients undergoing stem cell allografts from matched-sibling donors. Cyclosporin and short-course methotrexate were used as GVHD prophylaxis. Fatal regimen-related toxicity occurred in 4 patients. Rapid T-cell engraftment was found in all but 1 of the patients assessed, with more than 90% donor T-cell chimerism at 1 month posttransplantation. Of the evaluable patients, 43% developed grade 2-4 acute GVHD and 87% developed chronic GVHD (70% extensive). Overall, the combination of fludarabine and melphalan is intensely immunosuppressive, leads to rapid T-cell engraftment and results in substantial toxicity and GVHD, particularly in heavily pretreated patients.