Sirolimus, tacrolimus, and low-dose methotrexate for graft-versus-host disease prophylaxis in mismatched related donor or unrelated donor transplantation.
We studied the feasibility and activity of adding sirolimus to tacrolimus and low-dose methotrexate as graft-versus-host disease (GVHD) prophylaxis in recipients of alternative donor transplants. Forty-one patients with hematologic malignancies were conditioned with cyclophosphamide and total body irradiation. Marrow stem cells were from an HLA-A, -B, and -DR compatible, unrelated donor (n = 26, 68%), from a 5 of 6 antigen-matched unrelated donor (n = 8, 20%), or from a 5 of 6 antigen-matched family member (n = 5, 12%). Therapeutic serum levels of sirolimus were attained in most patients. All evaluable patients engrafted. An absolute neutrophil count of 500/microL was achieved on day +18 (range, 11-32 days). Sustained platelet counts of more than 20 000/ microL were attained on day +29 (range, 14-98 days). Grades 0-I acute GVHD occurred in 75% of patients. Grades II, III, and IV acute GVHD occurred in 13%, 8%, and 5%, respectively (total grades II-IV GVHD, 26%). Median survival is 366 days (95% CI 185, not estimable) and actuarial survival at 1 year is 52%. Oral sirolimus is tolerable, adequate blood levels are achievable, and there is a low rate of acute GVHD compared with historical data in this high-risk population. This novel agent is worthy of further study in allogeneic transplantation.
Antin
Joseph H
JH
Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA. jantin@partners.org
Kim
Haesook T
HT
Cutler
Corey
C
Ho
Vincent T
VT
Lee
Stephanie J
SJ
Miklos
David B
DB
Hochberg
Ephraim P
EP
Wu
Catherine J
CJ
Alyea
Edwin P
EP
Soiffer
Robert J
RJ
D000328:Adult; D016026:Bone Marrow Transplantation; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000097:blood; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence; D020123:Sirolimus / Q000008:administration & dosage* / Q000097:blood; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage* / Q000097:blood; D014019:Tissue Donors
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate