title: A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens.
abstract: 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.
authors: Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
authors: Roberto
authors: R
authors: Rodriguez
authors: Ryotaro
authors: R
authors: Nakamura
authors: Joycelynne M
authors: JM
authors: Palmer
authors: Pablo
authors: P
authors: Parker
authors: Sepideh
authors: S
authors: Shayani
authors: Auyaporn
authors: A
authors: Nademanee
authors: David
authors: D
authors: Snyder
authors: Vinod
authors: V
authors: Pullarkat
authors: Neil
authors: N
authors: Kogut
authors: Joseph
authors: J
authors: Rosenthal
authors: Eileen
authors: E
authors: Smith
authors: Chatchada
authors: C
authors: Karanes
authors: Margaret
authors: M
authors: O'Donnell
authors: Amrita Y
authors: AY
authors: Krishnan
authors: David
authors: D
authors: Senitzer
authors: Stephen J
authors: SJ
authors: Forman
mesh_terms: 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
chemical_list: D007166:Immunosuppressive Agents; D005047:Etoposide; D003520:Cyclophosphamide; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine; D008558:Melphalan; D020123:Sirolimus; D016559:Tacrolimus