Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

LVE. Oostenbrink, EGJ. Von Asmuth, CM. Jol-van der Zijde, AM. Jansen-Hoogendijk, C. Vervat, RGM. Bredius, MJD. Van Tol, MW. Schilham, P. Sedlacek, M. Ifversen, A. Balduzzi, P. Bader, C. Peters, DJAR. Moes, AC. Lankester

. 2024 ; 109 (9) : 2854-2863. [pub] 20240901

Language English Country Italy

Document type Journal Article, Multicenter Study

Persistent link   https://www.medvik.cz/link/bmc24019183

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 concentration-time data. The level of ATLG exposure (day active ATLG <1 AU/mL, median 16 days post-HSCT) was strongly associated with aGVHD grade II-IV, with a lower incidence in patients with prolonged active ATLG exposure (≤day 16 50% vs. >day 16 8.2%; P<0.001). When stratified for remission state, patients transplanted in complete remission (CR) 2 or 3 with prolonged ATLG exposure had a higher relapse risk, while this effect was not seen in CR1 patients (P=0.010). High level ATLG exposure was associated with delayed CD4 T-cell recovery at 4 and 8 weeks post-HSCT, but not at 12 weeks, and overall and relapse-free survival were not influenced by CD4 recovery at 12 weeks post-HSCT. This study underlines the importance of individualized ATLG exposure with the use of model-informed precision dosing in order to optimize the HSCT outcome in pediatric ALL.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24019183
003      
CZ-PrNML
005      
20241024111637.0
007      
ta
008      
241015s2024 it f 000 0|eng||
009      
AR
024    7_
$a 10.3324/haematol.2023.284632 $2 doi
035    __
$a (PubMed)38721739
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a it
100    1_
$a Oostenbrink, Lisa V E $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden. V.E.Oostenbrink@LUMC.nl
245    10
$a 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 / $c LVE. Oostenbrink, EGJ. Von Asmuth, CM. Jol-van der Zijde, AM. Jansen-Hoogendijk, C. Vervat, RGM. Bredius, MJD. Van Tol, MW. Schilham, P. Sedlacek, M. Ifversen, A. Balduzzi, P. Bader, C. Peters, DJAR. Moes, AC. Lankester
520    9_
$a 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 concentration-time data. The level of ATLG exposure (day active ATLG <1 AU/mL, median 16 days post-HSCT) was strongly associated with aGVHD grade II-IV, with a lower incidence in patients with prolonged active ATLG exposure (≤day 16 50% vs. >day 16 8.2%; P<0.001). When stratified for remission state, patients transplanted in complete remission (CR) 2 or 3 with prolonged ATLG exposure had a higher relapse risk, while this effect was not seen in CR1 patients (P=0.010). High level ATLG exposure was associated with delayed CD4 T-cell recovery at 4 and 8 weeks post-HSCT, but not at 12 weeks, and overall and relapse-free survival were not influenced by CD4 recovery at 12 weeks post-HSCT. This study underlines the importance of individualized ATLG exposure with the use of model-informed precision dosing in order to optimize the HSCT outcome in pediatric ALL.
650    _2
$a lidé $7 D006801
650    12
$a transplantace hematopoetických kmenových buněk $x škodlivé účinky $x metody $7 D018380
650    12
$a nemoc štěpu proti hostiteli $x etiologie $x prevence a kontrola $7 D006086
650    _2
$a dítě $7 D002648
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a předškolní dítě $7 D002675
650    12
$a antilymfocytární sérum $x aplikace a dávkování $7 D000961
650    _2
$a prospektivní studie $7 D011446
650    _2
$a mladiství $7 D000293
650    12
$a akutní lymfatická leukemie $x terapie $x mortalita $x diagnóza $7 D054198
650    _2
$a kojenec $7 D007223
650    _2
$a recidiva $7 D012008
650    _2
$a výsledek terapie $7 D016896
655    _2
$a časopisecké články $7 D016428
655    _2
$a multicentrická studie $7 D016448
700    1_
$a Von Asmuth, Erik G J $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Jol-van der Zijde, Cornelia M $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Jansen-Hoogendijk, Anja M $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Vervat, Carly $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Bredius, Robbert G M $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Van Tol, Maarten J D $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Schilham, Marco W $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden
700    1_
$a Sedlacek, Petr $u Motol University Hospital, Prague, Czech Republic
700    1_
$a Ifversen, Marianne $u Dept of children and adolescents medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen
700    1_
$a Balduzzi, Adriana $u Pediatric Hematopoietic Stem Cell Transplant Unit, Fondazione IRCCS San Gerardo dei Tintori; School of Medicine and Surgery, Milano-Bicocca University, Monza
700    1_
$a Bader, Peter $u University Hospital Frankfurt, Frankfurt am Main
700    1_
$a Peters, Christina $u St. Anna Children's Hospital, Children's Cancer Research Institute, Vienna
700    1_
$a Moes, Dirk Jan A R $u Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden
700    1_
$a Lankester, Arjan C $u Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden. A.Lankester@LUMC.nl
773    0_
$w MED00001963 $t Haematologica $x 1592-8721 $g Roč. 109, č. 9 (2024), s. 2854-2863
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38721739 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20241015 $b ABA008
991    __
$a 20241024111631 $b ABA008
999    __
$a ok $b bmc $g 2201802 $s 1231156
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 109 $c 9 $d 2854-2863 $e 20240901 $i 1592-8721 $m Haematologica $n Haematologica $x MED00001963
LZP    __
$a Pubmed-20241015

Find record

Citation metrics

Archiving options