Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 52; no. 3; pp. 438 - 444
• Main Authors: Kharfan-Dabaja, M A, Parody, R, Perkins, J, Lopez-Godino, O, Lopez-Corral, L, Vazquez, L, Caballero, D, Falantes, J, Shapiro, J, Ortí, G, Barba, P, Valcárcel, D, Esquirol, A, Martino, R, Piñana, J L, Solano, C, Tsalatsanis, A, Pidala, J, Anasetti, C, Perez-Simón, J A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-03-2017; Nature Publishing Group
• Subjects: 692/308/2171; 692/700/565/251; Acute Disease; Adolescent; Adult; Aged; Allografts; Antilymphocyte serum; Bone marrow; Care and treatment; Cell Biology; Chronic Disease; Confidence intervals; Depletion; Diagnosis; Disease-Free Survival; Donors; Dosage and administration; Epstein-Barr virus; Female; Globulins; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft vs. host disease; Graft-versus-host reaction; Health risks; Hematology; Hematopoietic stem cell transplantation; Hematopoietic stem cells; Histocompatibility antigen HLA; HLA Antigens; Humans; Internal Medicine; Lymphocyte Depletion; Lymphocytes T; Male; Medicine; Medicine & Public Health; Middle Aged; original-article; Prophylaxis; Public Health; Rapamycin; Retrospective Studies; Sirolimus; Sirolimus - administration & dosage; Statistical analysis; Stem Cell Transplantation; Stem Cells; Survival Rate; T-Lymphocytes; Tacrolimus; Tacrolimus - administration & dosage; Thymocytes; Transplantation; Unrelated Donors
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2016.269

HLA-matched related or unrelated donors are not universally available. Consequently, patients can be offered hematopoietic stem cell transplantation (HSCT) from alternative donors, including mismatched unrelated donors (MMURD), known to cause a higher incidence of acute GVHD (aGVHD) and chronic GVHD.
In vivo
T-cell-depletion strategies, such as antithymocyte globulin (ATG) therapy, significantly decrease the risk of GVHD. We performed a multicenter, retrospective study comparing tacrolimus (TAC) and sirolimus (SIR) with or without ATG in 104 patients (TAC-SIR=45, TAC-SIR-ATG=59) who underwent MMURD HSCT. Use of ATG was associated with a lower incidence, albeit not statistically significant, of grades 2–4 aGVHD (46% vs 64%,
P
=0.09), no difference in grades 3–4 aGVHD (10% vs 15%,
P
=0.43), a trend for a lower incidence of moderate/severe chronic GVHD (16% vs 37%,
P
=0.09) and more frequent Epstein–Barr virus reactivation (54% vs 18%,
P
=0.0002). There were no statistically significant differences in 3-year overall survival (OS) (TAC-SIR-ATG=40% (95% confidence interval (CI)=24–56%) vs TAC-SIR=54% (95% CI=37–70%),
P
=0.43) or 3-year cumulative incidence of relapse/progression (TAC-SIR-ATG=40% (95% CI=28–58%) vs TAC-SIR=22% (95% CI=13–39%),
P
=0.92). An intermediate Center for International Blood & Marrow Transplant Research disease risk resulted in a significantly lower non-relapse mortality and better OS at 3 years. Our study suggests that addition of ATG to TAC-SIR in MMURD HSCT does not affect OS when compared with TAC-SIR alone.