ATG prevents severe acute graft-versus-host disease in mismatched unrelated donor hematopoietic cell transplantation

Biol Blood Marrow Transplant. 2011 Aug;17(8):1237-44. doi: 10.1016/j.bbmt.2010.12.705. Epub 2011 Jan 6.

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.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antilymphocyte Serum / therapeutic use*
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Rabbits
  • Retrospective Studies
  • Survival Analysis
  • Transplantation Conditioning / adverse effects
  • Transplantation, Homologous / adverse effects
  • Unrelated Donors
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents