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
Affiliations
Lisa V.E. Oostenbrink
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Erik G.J. von Asmuth
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Cornelia M. Jol-van der Zijde
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Anja M. Jansen-Hoogendijk
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Carly Vervat
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Robbert G.M. Bredius
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Maarten J.D. van Tol
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Marco W. Schilham
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
Petr Sedlacek
Motol University Hospital, Prague, Czech Republic
Marianne Ifversen
Dept of children and adolescents medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen
Adriana Balduzzi
Pediatric Hematopoietic Stem Cell Transplant Unit, Fondazione IRCCS San Gerardo dei Tintori; School of Medicine and Surgery, Milano-Bicocca University, Monza
Peter Bader
University Hospital Frankfurt, Frankfurt am Main
Christina Peters
St. Anna Children's Hospital, Children’s Cancer Research Institute, Vienna
Dirk Jan A.R. Moes
Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden
Arjan C. Lankester
Willem-Alexander Children’s Hospital, Leiden University Medical Center, Leiden
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
