Impact of acute GvHD severity on survival and disease relapse in pediatric patients undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia: an analysis based on the EBMT-PDWP registry

This retrospective registry-based study investigated the role of acute GvHD in the largest reported pediatric population with acute lymphoblastic leukemia (ALL) undergoing allogeneic stem cell transplantation (HSCT). The study included 3328 children. Median age was 9.6 years (IQR 6–13.9 and range 0.4–18). Forty-nine percent were transplanted from an MSD, 37% from MUD, 14% from MMUD; 68% received a TBI-based conditioning. CSA alone or in combination with methotrexate/MMF was administered as GVHD prophylaxis in 94%. The 100-day cumulative incidence of grade II–IV acute GVHD (aGVHD) was 35% (95% CI: 34–37), while that of grade III–IV was 11% (95% CI: 10–12). Two-year cumulative incidence of chronic GVHD (cGVHD) was 17% (95% CI: 15–18)/extensive cGVHD 8% (95% CI: 7–9). With a median follow-up of 3.1 years, OS, leukemia-free survival (LFS), and GVHD-free/relapse-free survival were 74% (95% CI 72–76), 65% (95% CI 64–67) and 51% (95% CI 49–53), respectively. Using multivariable Cox models in 100-day landmark analysis, any degree of aGVHD was associated with reduced risk of relapse; grade III–IV significantly increased NRM and reduced OS; grade II aGVHD offers the best chances of achieving prolonged LFS (HR = 0.78 (0.64–0.94), p = 0.008). Overall, these data confirm that grade II aGvHD prevents the occurrence of leukaemia relapse without causing unacceptable mortality.