Long-Term Analysis Highlights Survival Improvements for Grade 3 aGvHD

Significant strides have been made in the survival rates of pediatric patients with grade 3 steroid-refractory acute graft-versus-host disease (aGvHD), although patients with the most severe cases (grade 4) of disease still have no or fewer benefits when it comes to long-term outcomes, according to new study findings.

The study findings offer a better understanding of how advances in allogeneic hematopoietic stem cell transplantation (HSCT) have impacted the outcomes of patients with severe aGvHD, which is crucial for valuing the efficacy of novel therapies as well as for informing new HSCT patients of their aGvHD risks, the researchers explained.

The retrospective analysis examined trends in overall survival (OS), relapse incidence (RI), and transplant-related mortality (TRM) over nearly 3 decades, stratifying 90 pediatric patients from 3 time periods: 1989-1998, 1999-2007, and 2008-2017.

Over the years, 100-day OS increased significantly for patients with grade 3 aGvHD, rising from 64% between the first cohort to 100% in the latest. The sharp rise in survival was largely explained by a reduction in TRM, which dropped from 28% to 0%.

According to the researchers, there are various factors that can explain the marked increase in survival among these patients, including:

• Better patient and donor selection
• Better and more precise HLA typing for matched unrelate donors
• Improved prevention and treatment of infectious complications
• Improved supportive care practices
• Early intervention and new drugs

However, the same was not observed among patients with grade 4 aGvHD, who did see improvements in OS, albeit minor. Between the first and latest cohort, 100-day OS improved from 42% to 54%. Similarly, TRM dropped modestly from 57% to 45%. Additionally, the improvement in 100-day OS did not translate into improved long-term outcomes, with 1-year and 5-year OS remaining stable at approximately 20%.

Comparing 5-year OS between grade 3 and grade 4 aGvHD, the researchers observed a 5-year OS that was nearly 3.5 times higher among those with grade 3 aGvHD (59% vs 17%).

“The RI among these groups was quite low, according with the literature data. No factors were associated with reduced RI in both aGvHD III or IV groups,” noted the researchers, who explained that the RI did not differ between the 3 time periods for patients with grade 3 aGvHD. Among the patients with grade 4 aGvHD, there was no significant differences in day 100, 1-year, and 5-year RIs.

Throughout the years in the analysis, 52 patients died, with the main cause being relapse/progression of the underlying disease (33%) for patients with aGvHD and being aGvHD itself for patients with grade 4 aGvHD (68%).

The researchers also observed other trends, writing: “…It emerges that during the three decades of HSCT the indications and the type of transplantation have changed. In particular, in the first decade we observed how the main indication for HSCT was relapsed or high risk [acute lymphoblastic leukemia] (more than 60% of HSCTs), while for the following decades it was significantly reduced. Consequently, the number of patients undergoing HSCT procedure after [total body irradiation] decreased.”

Reference

Berger M, Pessolano R, Carraro F, Saglio F, Vassallo E, Fagioli F. Steroid-refractory acute graft-versus-host disease graded III-IV in pediatric patients. A mono-institutional experience with a long-term follow-up. Pediatr Transplant. Published online August 26, 2020. doi: 10.1111/petr.13806.