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:10.3324/haematol.2023.284632

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^*

^*Corresponding author for this work

Department of Paediatrics and Adolescent Medicine

Abstract

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.

Original language	English
Journal	Haematologica
Volume	109
Issue number	9
Pages (from-to)	2854-2863
Number of pages	10
ISSN	0390-6078
DOIs	https://doi.org/10.3324/haematol.2023.284632
Publication status	Published - 1 Sept 2024

Keywords

Adolescent
Antilymphocyte Serum/administration & dosage
Child
Child, Preschool
Female
Graft vs Host Disease/etiology
Hematopoietic Stem Cell Transplantation/adverse effects
Humans
Infant
Male
Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy
Prospective Studies
Recurrence
Treatment Outcome

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Oostenbrink, L. V. E., Von Asmuth, E. G. J., Jol-van der Zijde, C. M., Jansen-Hoogendijk, A. M., Vervat, C., Bredius, R. G. M., Van Tol, M. J. D., Schilham, M. W., Sedlacek, P., Ifversen, M., Balduzzi, A., Bader, P., Peters, C., Moes, D. J. A. R., & Lankester, A. C. (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. Haematologica, 109(9), 2854-2863. https://doi.org/10.3324/haematol.2023.284632

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. / Oostenbrink, Lisa V E; Von Asmuth, Erik G J; Jol-van der Zijde, Cornelia M et al.
In: Haematologica, Vol. 109, No. 9, 01.09.2024, p. 2854-2863.

Research output: Contribution to journal › Journal article › Research › peer-review

Oostenbrink, LVE, Von Asmuth, EGJ, Jol-van der Zijde, CM, Jansen-Hoogendijk, AM, Vervat, C, Bredius, RGM, Van Tol, MJD, Schilham, MW, Sedlacek, P, Ifversen, M, Balduzzi, A, Bader, P, Peters, C, Moes, DJAR & Lankester, AC 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', Haematologica, vol. 109, no. 9, pp. 2854-2863. https://doi.org/10.3324/haematol.2023.284632

Oostenbrink LVE, Von Asmuth EGJ, Jol-van der Zijde CM, Jansen-Hoogendijk AM, Vervat C, Bredius RGM et al. 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. Haematologica. 2024 Sept 1;109(9):2854-2863. Epub 2024 May 9. doi: 10.3324/haematol.2023.284632

Oostenbrink, Lisa V E ; Von Asmuth, Erik G J ; Jol-van der Zijde, Cornelia M et al. / 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. In: Haematologica. 2024 ; Vol. 109, No. 9. pp. 2854-2863.

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abstract = "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{\textregistered} 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.",

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AU - Jansen-Hoogendijk, Anja M

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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

Abstract

Keywords

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