Tacrolimus plus sirolimus with or without ATG as GVHD prophylaxis in HLA-mismatched unrelated donor allogeneic stem cell transplantation.
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.
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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MA
Kharfan-Dabaja
Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Sevilla, Spain.
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http://orcid.org/0000-0003-0375-7570
R
Parody
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|College of Pharmacy, University of South Florida, Tampa, FL, USA.
J
J
Perkins
Hospital Universitario de Salamanca, Salamanca, Spain.
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O
Lopez-Godino
Hospital Universitario de Salamanca, Salamanca, Spain.
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L
Lopez-Corral
Hospital Universitario de Salamanca, Salamanca, Spain.
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L
Vazquez
Hospital Universitario de Salamanca, Salamanca, Spain.
D
D
Caballero
Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Sevilla, Spain.
J
J
Falantes
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J
J
Shapiro
Hospital Universitario Vall d'Hebron, Barcelona, Spain.
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G
Ortí
Hospital Universitario Vall d'Hebron, Barcelona, Spain.
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P
Barba
Hospital Universitario Vall d'Hebron, Barcelona, Spain.
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D
Valcárcel
Hospital Santa Creu i Sant Pau, Barcelona, Spain.
A
A
Esquirol
Hospital Santa Creu i Sant Pau, Barcelona, Spain.
R
R
Martino
Hospital Clínico de Valenci, Valencia, Spain.
J L
JL
Piñana
Hospital Clínico de Valenci, Valencia, Spain.
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C
Solano
Center for Evidence-Based Medicine, University of South Florida College of Medicine, Tampa, FL, USA.
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A
Tsalatsanis
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
J
J
Pidala
Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
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C
Anasetti
Department of Hematology, Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS)/CSIC, Sevilla, Spain.
J A
JA
Perez-Simón
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002908:Chronic Disease; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000517:prevention & control*; D006680:HLA Antigens; D006801:Humans; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013601:T-Lymphocytes; D016559:Tacrolimus / Q000008:administration & dosage*; D061349:Unrelated Donors
D006680:HLA Antigens; D020123:Sirolimus; D016559:Tacrolimus