Improved survival after LTx-associated acute GVHD with mAb therapy targeting IL2RAb and soluble TNFAb: Single-center experience and systematic review

Am J Transplant. 2018 Dec;18(12):3007-3020. doi: 10.1111/ajt.14923. Epub 2018 Jun 23.

Abstract

Acute graft-versus-host disease (GVHD) after liver transplant (LTx) is a rare complication with a high mortality rate. Recently, monoclonal antibody (mAb) treatment, specifically with anti-interleukin 2 receptor antibodies (IL2RAb) and anti-tumor necrosis factor-α antibodies (TNFAb), has gained increasing interest. However, evidence is mostly limited to case reports and the efficacy remains unclear. Here, we describe 5 patients with LTx-associated GVHD from our center and provide the results of our systematic literature review to evaluate the potential therapeutic benefit of IL2RAb/TNFAb treatment. Of the combined population of 155 patients (5 in our center and 150 through systematic search), 24 were given mAb (15.5%)-4 with TNFAb (2.6%) and 17 with IL2RAb (11%) ("mAb group")-and compared with patients who received other treatments (referred to as "no-mAb group"). Two-sided Fisher exact tests revealed a better survival when comparing treatment with mAb versus no-mAb (11/24 vs 27/131; P = .018), TNFAb versus no-mAb (3/4 vs 27/131; P = .034), and IL2RAb versus no-mAb (8/17 vs 27/131; P = .029). This systematic review suggests a beneficial effect of mAb treatment and a promising role for TNFAb and IL2RAb as a first-line strategy to treat LTx-associated acute GVHD.

Keywords: clinical research/practice; complication; graft-versus-host disease (GVHD); liver transplantation/hepatology.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Female
  • Follow-Up Studies
  • Graft Rejection / drug therapy
  • Graft Rejection / etiology
  • Graft Rejection / mortality*
  • Graft Survival
  • Graft vs Host Disease / drug therapy
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / mortality*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / antagonists & inhibitors*
  • Liver Transplantation / adverse effects
  • Liver Transplantation / mortality*
  • Male
  • Middle Aged
  • Postoperative Complications
  • Prognosis
  • Retrospective Studies
  • Risk Factors
  • Survival Rate
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Antibodies, Monoclonal
  • IL2RA protein, human
  • Interleukin-2 Receptor alpha Subunit
  • Tumor Necrosis Factor-alpha