Steroids Ineffective in Treating One-Third of Acute GVHD Pediatric Patients, Study Finds

A study investigating the clinical phenotype of acute graft-versus-host disease (GVHD) in children reveals that one-third of pediatric patients with the disease are not successfully treated with steroids as a primary GVHD therapy.

“Children with acute GHVD are usually treated with therapies studied predominantly in adults with assumptions as to the expected effectiveness in younger patients. As children have unique underlying diseases, comorbidities, and pharmacokinetics, the characteristics of acute GVHD in children and response to therapy may differ from adults and warrants specific investigation,” the authors said.

The study, published in Bone Marrow Transplant, investigated 370 pediatric University of Minnesota allogeneic hematopoietic cell transplantation (HCT) patients who developed grade I-IV acute GVHD between January 1990 and December 2016. The patients evaluated were treated systemically with prednisone 60 mg/m²/day day followed by an 8-week taper as initial therapy.

After day 28, the overall response occurred in 65% of patients. The researchers noted that initial GVHD grade did not predict day 28 response, but the Minnesota GVHD Risk Score predicted response with 68% standard risk patients achieving complete or partial response at day 28.

“This is the largest pediatric series examining the clinical phenotype of acute GVHD at diagnosis and response to uniform upfront steroid therapy. The strength of these data include weekly GVHD organ staging, structured protocol driven eligibility, and uniform upfront GVHD therapy, facilitating identification of patient and transplant factors associated with outcomes,” the authors said.

The researchers concluded that innovative GVHD trials need to be conducted to evaluate less toxic therapies for standard risk patients and novel approaches for patients with high risk GVHD.

“If established drug treatment regimens from studies in adults are to be repurposed for novel pediatric GVHD trials, careful dose escalation studies may need to be performed in children to establish the optimal dose and schedule of new GVHD agents,” they said. “As the clinical phenotype of acute GVHD in children is different than adults, pediatric specific GVHD trials may be warranted.”

Reference

Macmillan ML, Holtan SG, Rashidi A, et al. Pediatric acute GVHD: clinical phenotype and response to upfront steroids [published online January 2020]. Bone Marrow Transplant. doi:10.1038/s41409-019-0651-9.