Rapid achievement of complete donor chimerism and low regimen-related toxicity after reduced conditioning with fludarabine, carmustine, melphalan and allogeneic transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 26; no. 3; pp. 243 - 250
• Main Authors: WÄSCH, R, REISSER, S, HAHN, J, BERTZ, H, ENGELHARDT, M, KUNZMANN, R, VEELKEN, H, HOLLER, E, FINKE, J
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.08.2000
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Blood; Bone marrow; Bone marrow transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Carmustine - administration & dosage; Carmustine - adverse effects; Chimerism; Conditioning; Cyclosporin A; Cyclosporine - therapeutic use; Female; Fludarabine; Follow-Up Studies; Graft vs Host Disease - etiology; Graft vs Host Disease - immunology; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Immunosuppressive Agents - therapeutic use; Leukapheresis; Male; Medical sciences; Melphalan; Melphalan - administration & dosage; Melphalan - adverse effects; Methotrexate; Methotrexate - therapeutic use; Middle Aged; Morbidity; Neoplasms - drug therapy; Neoplasms - immunology; Neoplasms - therapy; Peripheral blood; Prophylaxis; Prospective Studies; Remission; Stem cell transplantation; Stem cells; Survival Analysis; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Chimera; Transplantation Conditioning - methods; Transplantation Tolerance - drug effects; Transplantation Tolerance - immunology; Vidarabine - administration & dosage; Vidarabine - adverse effects; Vidarabine - analogs & derivatives; Antineoplastic agent; Human; Immunopathology; Toxicity; Carmustine; Stem cell; Treatment efficiency; Multicenter study; Hematopoietic cell; Homograft; Graft versus host reaction; Prevention; Chemotherapy; Fludarabine; Donor; Low; Phase II trial; Phase I trial; Ciclosporin; Chimerism; Methotrexate
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1702512

Between August 1998 and July 1999, 21 patients received a novel protocol of reduced conditioning with fludarabine, carmustine and melphalan (FBM) followed by matched-related allogeneic peripheral blood stem cell transplantation (PBSCT) in a prospective multi-center phase I/II study. Cyclosporin A and 'mini-methotrexate' were used for GVHD prophylaxis. Patients were included because of age, advanced disease, previous transplantation or co-morbidity. Hematopoietic engraftment after allogeneic transplantation was rapid with a median white blood count (WBC) >1 x 10(9)/l on day +11 (range 10-17) and a median platelet count >20 x 10(9)/l on day +13 (range 9-36). Donor chimerism was complete in 16/21 (76%) patients at all time points during follow-up and mixed at least on one occasion in 5/21 (24%) patients. The conditioning regimen was well tolerated with low toxicity even in previously transplanted patients. Thirteen patients (62%) developed acute GVHD grades II-IV. Nineteen out of 21 patients achieved complete (CR, n = 15) or partial remission (PR, n = 4) with a median patient follow-up of 354+ days (range 258-577) for patients alive. The reduced intensity protocol FBM is feasible with rapid engraftment, early achievement of complete donor chimerism, low toxicity, especially in heavily pretreated patients, and good response rates in advanced disease patients.