Similar Overall Survival and Event-Free Survival for Patients Under or over the Age of 14 Years, but More Chronic Graft Versus Host Disease and Non-Relapse Mortality in the “Older” Patients

Purpose: In the prospective, randomized, multinational FORUM trial, total body irradiation and etoposide were statistically more effective than chemoconditioning (Peters et al, JCO 2021; FORUM study; EudraCT: 2012-003032-22; ClinicalTrials.gov: NCT01949129). The multivariate analysis in this cohort showed an inferior overall survival (OS) for patients (pts) over the age of 10 years, HR 1.8 (95% CI, p=0.048). To update these findings, we examine the impact of age at allogeneic hematopoietic stem cell transplantation (HSCT), we analyzed 791 FORUM pts who received TBI and etoposide as conditioning regimen between April 2012 and March 2022 and compared their outcomes according to different age categories. Patients and Methods: Almost all patients were transplanted in second or first complete remission (CR2) (47%, n=370; CR1: 46%, n=361, >CR3: 8%, n=59), from matched unrelated donors (MUD) 70%, n=552, HLA-identical sibling donors (MSD) 30%, n=239, bone marrow (BM) 70%, n=551, or cord blood (CB) 3%, n=26. Median age at HSCT was 10 years (4-21). Median observation time was 2.3 years (0.3 to 8) (Table 1: Basic Characteristics). The conditioning regimen consisted of total body irradiation (TBI) - 6 fractions of 2 Gy on 3 consecutive days followed by 60 mg/kg body weight etoposide (max 1800 mg/m2, total upper dose limit 3.6 g). GVHD prophylaxis was CSA only for MSD receiving bone marrow. ATG/CSA/MTX was used for the MUD HSCT group. Results: 127 evaluable pts were transplanted between 4-6 years (group 1), 249 between 6-10 years (group 2), 231 between 10-14 years (group 3), and > 14 years were 184 pts (group 4) (n.s.) By the 4 age groups, the 5-year OS was 0.83±0.04 (group 1), 0.75±0.04 (group 2), 0.75±0.04 (group 3), and 0.74±0.04 (group 4), respectively, p = 0.133. Five-year event-free survival (EFS) was also similar for all age groups: 0.71 ± 0.06, 0.72 ± 0.04, 0.66 ± 0.05, 0.69 ± 0.04 (p=0.611): Figure 1. The three-year cumulative relapse incidences (CIR) were 0.23±0.04, 0.19±0.03, 0.14±0.03, and 0.17±0.03, respectively (p=0.286). Non-relapse mortality (NRM) was significantly lower in the two younger age groups (0.02 ± 0.01 group 1 and 0.05 ± 0.02 group 2) compared to 0.11 ± 0.02 in both older age groups (p = 0.047). The primary causes of death in the 18/184 pts in group 4 were as follows: infections (fungal, viral, bacterial): n=8, acute and chronic graft versus host disease (aGVHD, cGVHD): n=3, sinusoidal obstruction syndrome, coagulopathies: n=4, multi-organ fa