title: ATG prevents severe acute graft-versus-host disease in mismatched unrelated donor hematopoietic cell transplantation.
abstract: Severe acute graft-versus-host disease (aGVHD) remains a major source of morbidity and mortality following mismatched unrelated donor hematopoietic cell transplantation (HCT). Through a retrospective analysis, we investigated the efficacy of GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) 7.5 mg/kg (1 mg/kg given on day -3, then 3.25 mg/kg/day on days -2 and -1 before stem cell infusion) followed by standard tacrolimus plus methotrexate in a consecutive series of 45 HLA partially matched unrelated donor HCT recipients. The cumulative incidence of grade III-IV aGVHD was 11% by 100 days (95% confidence interval [CI] 5%-25%). Moderate to severe chronic GVHD (per NIH consensus criteria) was 19% (95% CI 10%-36%) at 1 year, and 28% (95% CI 16%-48%) at 2 years. With a median follow-up time for surviving patients of 12 months (range: 5-39 months), overall survival was 55% (95% CI 39%-71%) at 1 year, and 45% (95% CI 27%-63%) at 2 years. Nonrelapse mortality was 11% (95% CI 5%-25%) by 100 days post-HCT, 26% (95% CI 16%-44%) by 1 year, and 30% (95% CI 18%-50%) by 2 years. The cumulative incidence of primary disease relapse was 23% (95% CI 13%-41%) at 1 year, and 33% (95% CI 20%-56%) by 2 years after HCT. Cytomegalovirus (CMV) infection or reactivation varied according to recipient and donor CMV serostatus. Epstein-Barr Virus (EBV) reactivation occurred in 54% (95% CI 40%-71%) of patients. Preemptive rituximab therapy was administered for EBV reactivation, however, posttransplant lymphoproliferative disorder was diagnosed in 5 (11%) cases, and was fatal in 1. A regimen of ATG 7.5 mg/kg total ending on day -1 effectively decreased the occurrence of grade III-IV aGVHD and severe chronic GVHD.
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Florida 33612, USA. joseph.pidala@moffitt.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Marcie
authors.initials: M
authors.lastname: Tomblyn
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.forename: Teresa
authors.initials: T
authors.lastname: Field
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandez
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.forename: Fred
authors.initials: F
authors.lastname: Locke
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Jose Leonel
authors.initials: JL
authors.lastname: Ochoa
authors.forename: Janelle
authors.initials: J
authors.lastname: Perkins
authors.forename: Cheryl
authors.initials: C
authors.lastname: Tate
authors.forename: Jamie
authors.initials: J
authors.lastname: Shapiro
authors.forename: Michelle
authors.initials: M
authors.lastname: Conwell
authors.forename: Ryan
authors.initials: R
authors.lastname: Bookout
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D012189:Retrospective Studies; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000009:adverse effects; D014184:Transplantation, Homologous / Q000009:adverse effects; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents