Anti-thymocyte globulin (thymoglobulin), tacrolimus, and sirolimus as acute graft-versus-host disease prophylaxis for unrelated hematopoietic stem cell transplantation.
Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days -3, -2, and -1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease.
Blood and Marrow Program, Department of Oncology, Wayne State University/Karmanos Cancer Center, Detroit, Michigan 48201, USA. alkadhiz@karmanos.org
Zaid
Z
Al-Kadhimi
Zartash
Z
Gul
Roberto
R
Rodriguez
Wei
W
Chen
Daryn
D
Smith
Alice
A
Mitchell
Muneer
M
Abidi
Lois
L
Ayash
Abhinav
A
Deol
Lawrence
L
Lum
Stephen
S
Forman
Voravit
V
Ratanatharathorn
Joseph
J
Uberti
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D012008:Recurrence; D012720:Severity of Illness Index; D020123:Sirolimus / Q000627:therapeutic use*; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
D000961:Antilymphocyte Serum; D006680:HLA Antigens; D019653:Myeloablative Agonists; D020123:Sirolimus; D016559:Tacrolimus