title: Calcineurin inhibitor--free graft-versus-host disease prophylaxis with post-transplantation cyclophosphamide and brief-course sirolimus following reduced-intensity peripheral blood stem cell transplantation.
abstract: Calcineurin inhibitors (CNIs) form the foundation of current graft-versus-host disease (GVHD) prophylaxis regimens. We hypothesized that a CNI-free regimen consisting of post-transplantation cyclophosphamide (PTCy) and brief-course sirolimus would reduce chronic GVHD and nonrelapse mortality (NRM) after reduced-intensity conditioning allogeneic peripheral blood stem cell transplantation (PBSCT). Twenty-six patients (median age, 61 years) underwent unmanipulated PBSCT from an 8/8 locus-matched donor (matched related donor, n = 17; natched unrelated donor, n = 9). GVHD prophylaxis consisted of PTCy and brief-course sirolimus. Donor engraftment occurred in all patients. The cumulative incidence (CI) of grade II-IV acute GVHD, grade III-IV acute GVHD, and chronic GVHD was 46%, 15%, and 31% respectively. One-year NRM was 4%. The median time to immunosuppression discontinuation was day +138. With a median follow-up of 20 months, the estimated 2-year overall survival was 71%, estimated disease-free survival was 64%, and estimated relapse incidence was 32%. In patients with a lymphoid malignancy (eg, chronic lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease), 2-year disease-free survival was 100%, and there were no relapses. Good immune reconstitution was evidenced by low cytomegalovirus reactivation rate of 21% (4 of 19 at-risk patients). GVHD prophylaxis with PTCy and sirolimus achieves consistent donor engraftment, low rates of chronic GVHD and NRM, and excellent outcomes in recipients of HLA-identical related and unrelated donor allogeneic PBSCT.
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia. Electronic address: ssolomon@bmtga.com.
authors: Scott R
authors: SR
authors: Solomon
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Melissa
authors: M
authors: Sanacore
authors: Department of Mathematics and Statistics, Georgia State University, Atlanta, Georgia.
authors: Xu
authors: X
authors: Zhang
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Stacey
authors: S
authors: Brown
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Kent
authors: K
authors: Holland
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Lawrence E
authors: LE
authors: Morris
authors: Blood and Marrow Transplant Program, Northside Hospital, Atlanta, Georgia.
authors: Asad
authors: A
authors: Bashey
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D011446:Prospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D014019:Tissue Donors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D020123:Sirolimus
keywords: Allogeneic; Graft-versus-host disease; Peripheral blood stem cell transplantation; Post-transplantation cyclophosphamide; Reduced-intensity conditioning; Sirolimus