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Clinical Features, Treatment, and Outcome of Pediatric Steroid Refractory Acute Graft-Versus-Host Disease: A
Anne B Verbeek1, Suze A Jansen2, Erik G J von Asmuth1
1Willem-Alexander Children's Hospital, Department of Pediatrics, Pediatric Stem Cell Transplantation program, Leiden University Medical Center, Leiden, The Netherlands.
Insights
Steroid-refractory acute graft-versus-host disease (SR-aGvHD) in children undergoing HSCT has a high mortality rate. Older age and cord blood grafts are linked to worse outcomes, necessitating new treatment strategies.
Area of Science:
- Pediatric Hematology
- Immunology
- Transplantation Science
Background:
- Steroid-refractory acute graft-versus-host disease (SR-aGvHD) is a critical complication following pediatric allogeneic hematopoietic stem cell transplantation (HSCT).
- Effective management strategies for SR-aGvHD remain a significant challenge in pediatric HSCT outcomes.
Purpose of the Study:
- To evaluate the clinical course and outcomes of pediatric patients diagnosed with SR-aGvHD.
- To identify factors influencing overall survival and SR-aGvHD remission rates in this vulnerable population.
Main Methods:
- A retrospective nationwide multicenter cohort study was conducted in the Netherlands, including pediatric HSCT recipients (0-18 years) with SR-aGvHD between 2010-2020.
- Data collected included weekly aGvHD grade/stage, treatments, and outcomes. Multistate Cox models were used to analyze factors affecting survival and remission.
Main Results:
- 51% of pediatric HSCT recipients who developed grade II-IV aGvHD had the steroid-refractory form (n=81).
- 42% achieved remission one year after second-line therapy, while 41% died. Cord blood graft recipients had lower remission rates (HR=0.51).
- Older age was associated with higher mortality (HR=2.62) and lower remission rates in bone marrow/peripheral blood stem cell recipients (HR=0.9). Pulmonary GvHD was a major cause of death (26%).
Conclusions:
- Pediatric SR-aGvHD presents a substantial mortality risk, with older age and cord blood grafts being adverse prognostic factors.
- Timely second-line therapy initiation and multicenter trials for novel treatments are crucial to improve outcomes and reduce GvHD-related mortality in pediatric HSCT.
Abstract:
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.
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