Antirelapse effect of pretransplant exposure to rabbit antithymocyte globulin

Blood Adv. 2019 May 14;3(9):1394-1405. doi: 10.1182/bloodadvances.2018030247.

Abstract

It remains unknown why rabbit antithymocyte globulin (ATG; Thymoglobulin) has not affected relapse after hematopoietic cell transplantation (HCT) in randomized studies. We hypothesized that high pre-HCT ATG area under the curve (AUC) would be associated with a low incidence of relapse, whereas high post-HCT AUC would be associated with a high incidence of relapse. We measured serum levels of ATG capable of binding to mononuclear cells (MNCs), lymphocytes, T cells, CD4 T cells, or CD33 cells. We estimated pre- and post-HCT AUCs in 152 adult recipients of myeloablative conditioning and blood stem cells. High pre-HCT AUCs of MNC- and CD33 cell-binding ATG were associated with a low incidence of relapse and high relapse-free survival (RFS). There was a trend toward an association of high post-HCT AUC of lymphocyte-binding ATG with a high incidence of relapse and low RFS. High pre-HCT AUCs were also associated with faster engraftment and had no impact on graft-versus-host disease (GVHD) or fatal infections. High post-HCT AUCs were associated with a low risk of GVHD, seemed associated with an increased risk of fatal infections, and had no impact on engraftment. In conclusion, pre-HCT AUC seems to have a positive, whereas post-HCT AUC seems to have a negative, impact on relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Antilymphocyte Serum / metabolism
  • Antilymphocyte Serum / therapeutic use*
  • Area Under Curve
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control*
  • Hematopoietic Stem Cell Transplantation / adverse effects*
  • Humans
  • Leukemia / mortality
  • Leukemia / therapy
  • Lymphocytes / cytology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • ROC Curve
  • Rabbits
  • Recurrence
  • Survival Rate
  • Transplantation Conditioning / methods
  • Young Adult

Substances

  • Antilymphocyte Serum
  • thymoglobulin