A prospective randomized trial comparing cyclosporine and short course methotrexate with cyclosporine and mycophenolate mofetil for GVHD prophylaxis in myeloablative allogeneic bone marrow transplantation.
Cyclosporine (CSP) and short course methotrexate (MTX) have been the gold standard for GVHD prophylaxis for decades. Problems associated with MTX include increased time to hematopoietic engraftment, mucositis, and other organ toxicities. The combination of CSP with mycophenolate mofetil (MMF) has been used successfully for the prevention of graft rejection and GVHD in nonmyeloablative transplantation. We performed a prospective randomized trial comparing CSP and MTX with CSP and MMF in myeloablative (busulfan based) allogeneic 6/6 matched sibling bone marrow transplantation (BMT). The group receiving MMF (n = 21) had significantly less severe mucositis than did the group receiving MTX (n = 19) (21 vs 65%, P = 0.008). Median time to neutrophil engraftment was more rapid in the MMF group (11 vs 18 days, P < 0.001). The incidence of acute GVHD, as well as 100 day survival, was similar for both groups. The reduced toxicity of the CSP and MMF arm resulted in premature study closure. We conclude that a GVHD prophylaxis regimen of CSP and MMF after a myeloablative allogeneic preparative regimen is associated with faster hematopoietic engraftment, decreased incidence of mucositis, similar incidence of aGVHD, and comparable survival as compared to CSP and MTX.
Bolwell
B
B
Department of Hematology and Medical Oncology, Department of Biostatistics and Epidemiology, Taussig Cancer Center, The Cleveland Clinic Foundation, Cleveland, OH 44195, USA. bolwelb@ccf.org
Sobecks
R
R
Pohlman
B
B
Andresen
S
S
Rybicki
L
L
Kuczkowski
E
E
Kalaycio
M
M
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000008:administration & dosage; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D015994:Incidence; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D011446:Prospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002066:Busulfan; D009173:Mycophenolic Acid; D008727:Methotrexate