Anti-thymocyte globulin (thymoglobulin), tacrolimus, and sirolimus as acute graft-versus-host disease prophylaxis for unrelated hematopoietic stem cell transplantation

Biol Blood Marrow Transplant. 2012 Nov;18(11):1734-44. doi: 10.1016/j.bbmt.2012.06.004. Epub 2012 Jun 16.

Abstract

Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days -3, -2, and -1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Antilymphocyte Serum / therapeutic use*
  • Chronic Disease
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality
  • Graft vs Host Disease / prevention & control*
  • HLA Antigens / immunology
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Hematopoietic Stem Cell Transplantation / mortality
  • Histocompatibility Testing
  • Humans
  • Male
  • Middle Aged
  • Myeloablative Agonists / therapeutic use*
  • Prospective Studies
  • Recurrence
  • Severity of Illness Index
  • Sirolimus / therapeutic use*
  • Survival Rate
  • Tacrolimus / therapeutic use*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous
  • Unrelated Donors

Substances

  • Antilymphocyte Serum
  • HLA Antigens
  • Myeloablative Agonists
  • Sirolimus
  • Tacrolimus