High rabbit-antihuman thymocyte globulin levels are associated with low likelihood of graft-vs-host disease and high likelihood of posttransplant lymphoproliferative disorder

Biol Blood Marrow Transplant. 2010 Jul;16(7):915-26. doi: 10.1016/j.bbmt.2010.02.027. Epub 2010 Mar 11.

Abstract

Rabbit-antithymocyte globulin (ATG) given with conditioning has the potential to decrease the likelihood of graft-versus-host disease (GVHD) or graft failure and to increase the likelihood of relapse or infections. After a given ATG dose, serum ATG levels are variable. Here we determined ATG levels on days 7 and 28 in 153 patients whose conditioning included 4.5 mg/kg ATG (thymoglobulin). Median follow-up was 547 days (range: 14-1519, minimum for patients who have not died, relapsed, developed second malignancy, or had graft failure, 365). Both high day 7 levels and high day 28 levels were associated with low likelihoods of grade II-IV acute GVHD and chronic GVHD needing systemic immunosuppressive therapy, and a high likelihood of posttransplant lymphoproliferative disorder (PTLD). Patients with day 7 ATG levels above 0.803 mg/L had 0.52-fold risk of developing chronic GVHD needing systemic therapy (P = 0.012) and patients with day 7 ATG levels above 1.436 mg/L had 5.84-fold risk of developing PTLD (P = 0.001) compared to patients with lower ATG levels. There was no association of ATG levels with relapse, death, or non-PTLD infections. Association with graft failure could not be evaluated due to only 4 graft failures in the cohort. In conclusion, patients with slow clearance of ATG have a low risk of GVHD, but a high risk of PTLD. The clearance of this relatively low dose of ATG does not impact the likelihood of relapse, death, or non-PTLD infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Antilymphocyte Serum / administration & dosage
  • Antilymphocyte Serum / blood*
  • Antilymphocyte Serum / immunology
  • Female
  • Follow-Up Studies
  • Graft vs Host Disease / blood*
  • Graft vs Host Disease / immunology
  • Histocompatibility Testing
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lymphoproliferative Disorders / blood
  • Lymphoproliferative Disorders / drug therapy
  • Lymphoproliferative Disorders / immunology*
  • Male
  • Middle Aged
  • Rabbits
  • Stem Cell Transplantation / adverse effects*
  • Survival Analysis
  • Tissue and Organ Harvesting / methods*
  • Treatment Outcome
  • Young Adult

Substances

  • Antilymphocyte Serum
  • Immunosuppressive Agents