A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens.
Combination tacrolimus and sirolimus graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant in patients conditioned with a fractionated total body irradiation-based regimen has shown encouraging results. We studied this prophylaxis combination in 85 patients receiving a matched-sibling transplant conditioned with 3 different regimens:fludarabine-melphalan (n = 46); total body irradiation-etoposide (n = 28), and busulfan-cyclophosphamide (n = 11). The conditioning regimens were completed on day -4. Sirolimus and tacrolimus were started on day -3 to avoid overlap with conditioning therapy. All patients engrafted, with a median time to neutrophil engraftment of 15 days. The cumulative incidence of acute GVHD grades II to IV and III to IV was 43% and 19%, respectively, with no significant difference by conditioning regimen. The 2-year cumulative incidence of chronic GVHD was 46%. With a median follow-up of 26 months, disease-free survival was 58% and overall survival, 66%. The day-100 and 2-year nonrelapse mortality was 4.8% and 10.2%, respectively. The overall incidence of thrombotic microangiopathy was 19%, and it was significantly higher with busulfan/cyclophosphamide (55%, P = .005). Tacrolimus plus sirolimus is an effective combination for acute GVHD prophylaxis and is associated with very low nonrelapse mortality. Thrombotic microangiopathy is a significant complication with this regimen, particularly in patients receiving busulfan/cyclophosphamide.
Rodriguez
Roberto
R
Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
Nakamura
Ryotaro
R
Palmer
Joycelynne M
JM
Parker
Pablo
P
Shayani
Sepideh
S
Nademanee
Auyaporn
A
Snyder
David
D
Pullarkat
Vinod
V
Kogut
Neil
N
Rosenthal
Joseph
J
Smith
Eileen
E
Karanes
Chatchada
C
O'Donnell
Margaret
M
Krishnan
Amrita Y
AY
Senitzer
David
D
Forman
Stephen J
SJ
D000293:Adolescent; D000328:Adult; D002066:Busulfan / Q000008:administration & dosage; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D010865:Pilot Projects; D011829:Radiation Dosage; D035781:Siblings; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D057049:Thrombotic Microangiopathies / Q000139:chemically induced; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
D007166:Immunosuppressive Agents; D005047:Etoposide; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan; D020123:Sirolimus; D016559:Tacrolimus