title: 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.
authors.affiliation: Bone Marrow Transplant Service, Department of Clinical Haematology and Medical Oncology, Royal Melbourne Hospital, Melbourne, Australia. dritchie@malaghan.org.nz
authors.forename: David S
authors.initials: DS
authors.lastname: Ritchie
authors.forename: James
authors.initials: J
authors.lastname: Morton
authors.forename: Jeff
authors.initials: J
authors.lastname: Szer
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
authors.forename: Simon
authors.initials: S
authors.lastname: Durrant
authors.forename: Peter
authors.initials: P
authors.lastname: Shuttleworth
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Grigg
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology*; D020350:Graft vs Tumor Effect / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan