• Roberto Rodriguez, Ryotaro Nakamura, Joycelynne M Palmer, Pablo Parker, Sepideh Shayani, Auyaporn Nademanee, David Snyder, Vinod Pullarkat, Neil Kogut, Joseph Rosenthal, Eileen Smith, Chatchada Karanes, Margaret O'Donnell, Amrita Y Krishnan, David Senitzer, and Stephen J Forman.
• Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010, USA.
• Blood. 2010 Feb 4; 115 (5): 1098-105.

AbstractCombination 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.

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