TY - JOUR
T1 - Clinical Features, Treatment, and Outcome of Pediatric Steroid Refractory Acute Graft-Versus-Host Disease
T2 - A Multicenter Study
AU - Verbeek, Anne B.
AU - Jansen, Suze A.
AU - von Asmuth, Erik G.J.
AU - Lankester, Arjan C.
AU - Bresters, Dorine
AU - Bierings, Marc
AU - Mohseny, Alexander B.
AU - Lindemans, Caroline A.
AU - Buddingh, Emilie P.
N1 - Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.
PY - 2022/9
Y1 - 2022/9
N2 - Steroid-refractory acute graft-versus-host disease (SR-aGvHD) is a severe complication in pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to assess clinical course and outcomes of pediatric SR-aGvHD. We performed a retrospective nationwide multicenter cohort study in the Netherlands. All patients aged 0 to 18 years who underwent transplantation between 2010 and 2020 with SR-aGvHD were included. For each patient, weekly clinical aGvHD grade and stage, immunosuppressive treatment and clinical outcomes were collected. The primary study endpoint was the clinical course of SR-aGvHD over time. As a secondary outcome, factors influencing overall survival and SR-aGvHD remission were identified using a multistate Cox model. 20% of transplanted children developed grade II-IV aGvHD, of which 51% (n = 81) was SR-aGvHD. In these patients, second-line therapy was started at a median of 8 days after initial aGvHD-diagnosis. Forty-nine percent of SR-aGvHD patients received 3 or more lines of therapy. One year after start of second-line therapy, 34 patients (42%) were alive and in remission of aGvHD, 14 patients (17%) had persistent GvHD, and 33 patients (41%) had died. SR-aGvHD remission rate was lower in cord blood graft recipients than in bone marrow (BM) or peripheral blood stem cell (PBSC) recipients (hazard ratio [HR] = 0.51, 0.27-0.94, P =.031). Older age was associated with higher mortality (HR = 2.62, 1.04-6.60, P =.04, fourth quartile [aged 13.9-17.9] versus first quartile [aged 0.175-3.01]). In BM/PBSC recipients older age was also associated with lower remission rates (HR = 0.9, 0.83-0.96, P =.004). Underlying diagnosis, donor matching or choice of second-line therapy were not associated with outcome. Respiratory insufficiency caused by pulmonary GvHD was a prominent cause of death (26% of deceased). Our study demonstrates that SR-aGvHD confers a high mortality risk in pediatric HSCT. Older age and use of CB grafts are associated with an unfavorable outcome. Multicenter studies investigating novel treatment strategies to prevent pediatric SR-aGvHD and inclusion of children in ongoing trials, together with timely initiation of second-line interventions are pivotal to further reduce GvHD-related mortality.
AB - Steroid-refractory acute graft-versus-host disease (SR-aGvHD) is a severe complication in pediatric allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to assess clinical course and outcomes of pediatric SR-aGvHD. We performed a retrospective nationwide multicenter cohort study in the Netherlands. All patients aged 0 to 18 years who underwent transplantation between 2010 and 2020 with SR-aGvHD were included. For each patient, weekly clinical aGvHD grade and stage, immunosuppressive treatment and clinical outcomes were collected. The primary study endpoint was the clinical course of SR-aGvHD over time. As a secondary outcome, factors influencing overall survival and SR-aGvHD remission were identified using a multistate Cox model. 20% of transplanted children developed grade II-IV aGvHD, of which 51% (n = 81) was SR-aGvHD. In these patients, second-line therapy was started at a median of 8 days after initial aGvHD-diagnosis. Forty-nine percent of SR-aGvHD patients received 3 or more lines of therapy. One year after start of second-line therapy, 34 patients (42%) were alive and in remission of aGvHD, 14 patients (17%) had persistent GvHD, and 33 patients (41%) had died. SR-aGvHD remission rate was lower in cord blood graft recipients than in bone marrow (BM) or peripheral blood stem cell (PBSC) recipients (hazard ratio [HR] = 0.51, 0.27-0.94, P =.031). Older age was associated with higher mortality (HR = 2.62, 1.04-6.60, P =.04, fourth quartile [aged 13.9-17.9] versus first quartile [aged 0.175-3.01]). In BM/PBSC recipients older age was also associated with lower remission rates (HR = 0.9, 0.83-0.96, P =.004). Underlying diagnosis, donor matching or choice of second-line therapy were not associated with outcome. Respiratory insufficiency caused by pulmonary GvHD was a prominent cause of death (26% of deceased). Our study demonstrates that SR-aGvHD confers a high mortality risk in pediatric HSCT. Older age and use of CB grafts are associated with an unfavorable outcome. Multicenter studies investigating novel treatment strategies to prevent pediatric SR-aGvHD and inclusion of children in ongoing trials, together with timely initiation of second-line interventions are pivotal to further reduce GvHD-related mortality.
KW - Allogeneic HSCT
KW - Pediatric
KW - Steroid refractory graft-versus-host disease
KW - Humans
KW - Hematopoietic Stem Cell Transplantation
KW - Retrospective Studies
KW - Child
KW - Cohort Studies
KW - Graft vs Host Disease
KW - Steroids
UR - http://www.scopus.com/inward/record.url?scp=85135179940&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2022.06.008
DO - 10.1016/j.jtct.2022.06.008
M3 - Article
C2 - 35717003
AN - SCOPUS:85135179940
SN - 2666-6367
VL - 28
SP - 600.e1-600.e9
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 9
ER -