Haematologica (May 2024)

Anti-T-lymphocyte globulin exposure is associated with acute graft-versus-host disease and relapse in pediatric acute lymphoblastic leukemia patients undergoing hematopoietic stem cell transplantation: a multinational prospective study

  • Lisa V.E. Oostenbrink,
  • Erik G.J. von Asmuth,
  • Cornelia M. Jol-van der Zijde,
  • Anja M. Jansen-Hoogendijk,
  • Carly Vervat,
  • Robbert G.M. Bredius,
  • Maarten J.D. van Tol,
  • Marco W. Schilham,
  • Petr Sedlacek,
  • Marianne Ifversen,
  • Adriana Balduzzi,
  • Peter Bader,
  • Christina Peters,
  • Dirk Jan A.R. Moes,
  • Arjan C. Lankester

DOI
https://doi.org/10.3324/haematol.2023.284632
Journal volume & issue
Vol. 999, no. 1

Abstract

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Anti T-lymphocyte globulin (ATLG) is used in hematopoietic stem cell transplantation (HSCT) to prevent graft-versus-host disease (GvHD) and graft failure. To date, insight in ATLG pharmacokinetics and -dynamics (PK/PD) is limited, and population PK (POPPK) models are lacking. In this prospective study, we describe ATLG POPPK using NONMEM® and the impact of ATLG exposure on clinical outcome and immune reconstitution in a homogeneous cohort of pediatric acute lymphoblastic leukemia (ALL) patients transplanted with a matched unrelated donor and receiving uniform ATLG dosing. Based on 121 patients and 812 samples for POPPK analysis, a two-compartmental model with parallel linear and non-linear clearance and bodyweight as covariate, best described the ATLG concentrationtime data. The level of ATLG exposure (day active ATLG day 16 8.2%, p