Lower Absolute Lymphocyte Count Before Conditioning Predicts High Relapse Risk in Patients After Haploidentical Peripheral Blood Stem Cell Transplantation With Low Dose Anti-Thymocyte Globulin/Post-Transplant Cyclophosphamide for GvHD Prophylaxis

Cell Transplant. 2022 Jan-Dec:31:9636897221079739. doi: 10.1177/09636897221079739.

Abstract

Standard anti-thymocyte globulin (ATG) weight-based dosing often resulted in highly variable ATG exposure, which had profound effects on relapse and survival, especially in recipients with relatively low absolute lymphocyte count (ALC) before conditioning. Data regarding rabbit ATG pharmacokinetics and pharmacodynamics in the setting of HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) is lacking. We conducted a retrospective study on 90 consecutive patients who underwent haplo-PBSCT with low dose rabbit ATG (5 mg/kg) plus low dose post-transplant cyclophosphamide (50 mg/kg) based regimen for graft-versus-host disease (GvHD) prophylaxis. We compared serum concentration of ATG and post-transplant results between patients with ALC<500/μl and ALC≥500/μl before conditioning. Patients with ALC<500/μl had higher ATG concentrations, delayed immune reconstitution, lower incidence of grade II-IV acute GvHD (0 vs. 19.42%, P = 0.043), higher risk of Epstein-Barr virus infection within 100 days post-transplant (47.78% vs. 22.22%, P = 0.020) and 1-year relapse rate (33.33% vs.11.59%, P = 0.041), and lower 1-year overall survival (OS) (52.38% vs.79.71%, P = 0.004), 1-year relapse free survival (RFS) (47.62% vs. 75.36% for RFS, P = 0.014), and 1-year GvHD free relapse-free survival (GRFS) (42.89% vs. 65.22%, P = 0.043). ALC<500/μl before conditioning was a significant poor risk factor for relapse, OS, RFS, and GRFS.

Keywords: absolute lymphocyte count; anti-thymocyte globulin; haploidentical; peripheral blood stem cell transplantation; relapse; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antilymphocyte Serum / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Epstein-Barr Virus Infections* / complications
  • Epstein-Barr Virus Infections* / drug therapy
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / methods
  • Herpesvirus 4, Human
  • Humans
  • Lymphocyte Count
  • Peripheral Blood Stem Cell Transplantation* / adverse effects
  • Rabbits
  • Recurrence
  • Retrospective Studies
  • Transplantation Conditioning

Substances

  • Antilymphocyte Serum
  • Cyclophosphamide