A phase II pilot study of tacrolimus/sirolimus GVHD prophylaxis for sibling donor hematopoietic stem cell transplantation using 3 conditioning regimens

• Published in: Blood 2010-02, Vol.115 (5), p.1098-1105
• Main Authors: Rodriguez, Roberto, Nakamura, Ryotaro, Palmer, Joycelynne M., Parker, Pablo, Shayani, Sepideh, Nademanee, Auyaporn, Snyder, David, Pullarkat, Vinod, Kogut, Neil, Rosenthal, Joseph, Smith, Eileen, Karanes, Chatchada, O'Donnell, Margaret, Krishnan, Amrita Y., Senitzer, David, Forman, Stephen J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Busulfan - administration & dosage; Child; Cyclophosphamide - administration & dosage; Etoposide - administration & dosage; Female; Graft vs Host Disease - prevention & control; Hematologic and hematopoietic diseases; Hematopoietic Stem Cell Transplantation - methods; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Male; Medical sciences; Melphalan - administration & dosage; Middle Aged; Pilot Projects; Radiation Dosage; Siblings; Sirolimus - adverse effects; Sirolimus - therapeutic use; Survival Analysis; Tacrolimus - adverse effects; Tacrolimus - therapeutic use; Thrombotic Microangiopathies - chemically induced; Tissue Donors; Transplantation; Transplantation Conditioning - methods; Vidarabine - administration & dosage; Vidarabine - analogs & derivatives; Young Adult
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2009-03-207563

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.