Cyclosporine and mycophenolate mofetil prophylaxis with fludarabine and melphalan conditioning for unrelated donor transplantation: a prospective study of 22 patients with hematologic malignancies

• Published in: Bone marrow transplantation (Basingstoke) Vol. 33; no. 11; pp. 1123 - 1129
• Main Authors: RODRIGUEZ, R, PARKER, P, COHEN, S, SOMLO, G, ANGELOPOULOU, M, AL-KADHIMI, Z, FALK, P. M, SPIELBERGER, R, KOGUT, N, SAHEBI, F, SENITZER, D, SLOVAK, M, NADEMANEE, A, SCHRIBER, J, FORMAN, S. J, SMITH, D, O'DONNELL, M. R, STEIN, A, SNYDER, D. S, FUNG, H. C, KRISHNAN, A. Y, POPPLEWELL, L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-06-2004
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - toxicity; Biological and medical sciences; Blood cancer; Bone marrow; Bone marrow, stem cells transplantation. Graft versus host reaction; Cancer; Care and treatment; Chemotherapy; Conditioning; Cyclosporine - administration & dosage; Cyclosporins; Disease control; Disease prevention; Female; Fludarabine; Graft Survival; Graft versus host disease; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Health aspects; Hematologic Neoplasms - complications; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Hematopoietic stem cells; Humans; Leukemia; Male; Medical sciences; Melphalan; Melphalan - administration & dosage; Middle Aged; Mycophenolate mofetil; Mycophenolic acid; Mycophenolic Acid - administration & dosage; Mycophenolic Acid - analogs & derivatives; Myelofibrosis; Opportunistic Infections; Premedication - methods; Prophylaxis; Prospective Studies; Risk factors; Risk groups; Stem cell transplantation; Stem cells; Survival; Survival Analysis; Tissue Donors; Toxicity; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation Conditioning - methods; Transplants & implants; Treatment Outcome; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; United States; Antineoplastic agent; Stem cell; Hematopoietic cell; Homograft; reduced-intensity conditioning; Prevention; Melphalan; Graft; Adult; Ciclosporin; Human; Immunopathology; Purine nucleotide; Unrelated donor; Graft versus host reaction; Malignant hemopathy; Non myeloablative treatment; Alkylating agent; Fludarabine; Treatment; Antimetabolic; hematopoietic cell transplantation; Immunosuppressive agent; Mycophenolate mofetil; graft-versus-host disease
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704493

In an attempt to decrease toxicity in high-risk patients undergoing unrelated donor hematopoietic stem cell transplantation (URD HSCT), we tested a combination of cyclosporine (CSP) and mycophenolate mofetil (MMF) as graft-versus-host disease (GVHD) prophylaxis with the reduced-intensity conditioning regimen fludarabine/melphalan (Flu/Mel). A total of 22 adult patients with advanced myeloid (n=15) and lymphoid (n=7) malignancies were treated. All patients received Flu 25 mg/m2 for 5 days and Mel 140 mg/m2, with CSP 3 mg/kg daily and MMF 15 mg/kg three times a day. The median age was 49 years (range 18-66). Durable engraftment was seen in all but one patient with myelofibrosis. The 1-year nonrelapse mortality was 32%, 27% from GVHD. The cumulative incidence of acute GVHD grade 2-4 and 3-4 was 63 and 41%, respectively. With a median follow-up of 18 months, the disease-free survival (DFS) and overall survival (OS) are 55 and 59%, respectively. For patients with AML and MDS (n=14), the DFS and OS is 71%. For patients undergoing a second transplant (n=14), the DFS and OS is 57%. In conclusion, this regimen is associated with acceptable toxicity but high rates of GVHD in high-risk patients undergoing URD HSCT. Encouraging disease control for patients with advanced myeloid malignancies was observed.