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: Scott R Solomon, Melissa Sanacore, Xu Zhang, Stacey Brown, Kent Holland, Lawrence E Morris, Asad Bashey
• Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation (Biol Blood Marrow Transplant) Vol. 20 Issue 11 Pg. 1828-34 (Nov 2014) ISSN: 1523-6536 [Electronic] United States
• PMID: 25064745 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Calcineurin Inhibitors
• Immunosuppressive Agents
• Cyclophosphamide
• Sirolimus

Topics

• Adult
• Aged
• Calcineurin Inhibitors (administration & dosage)
• Cyclophosphamide (administration & dosage)
• Disease-Free Survival
• Female
• Graft vs Host Disease (prevention & control)
• Hematologic Neoplasms (therapy)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Immunosuppressive Agents (administration & dosage)
• Male
• Middle Aged
• Peripheral Blood Stem Cell Transplantation (adverse effects, methods)
• Prospective Studies
• Sirolimus (administration & dosage)
• Tissue Donors
• Transplantation Chimera
• Transplantation Conditioning (adverse effects, methods)