Clinical Features, Treatment, and Outcome of Pediatric Steroid Refractory Acute Graft-Versus-Host Disease: A Multicenter Study

Anne B. Verbeek, Suze A. Jansen, Erik G.J. von Asmuth, Arjan C. Lankester, Dorine Bresters, Marc Bierings, Alexander B. Mohseny, Caroline A. Lindemans, Emilie P. Buddingh

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2 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)600.e1-600.e9
JournalTransplantation and Cellular Therapy
Issue number9
Publication statusPublished - Sept 2022


  • Allogeneic HSCT
  • Pediatric
  • Steroid refractory graft-versus-host disease
  • Humans
  • Hematopoietic Stem Cell Transplantation
  • Retrospective Studies
  • Child
  • Cohort Studies
  • Graft vs Host Disease
  • Steroids


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