Significantly Increased Risk of Grade II-IV Acute Gvhd in Adolescent and Young Adult (AYA) Recipients (ages 13 years) Vs Childhood Recipients (ages 2-12 years) with Acute Leukemia Following Matched Unrelated Donor (MUD) Stem Cell Transplantation (SCT): The Children's Oncology Group Experience

Background Adolescent and young adult (AYA) acute leukemia patients have inferior outcomes in comparison to their younger counterparts, related to higher risk disease and increased toxicity (Hochberg J, et al., BJH, 2013). AYA recipient age (≥13 years) vs children (ages 2-12 years) has been associated with increased acute and chronic graft versus host disease (GVHD) in matched sibling donor SCT (Qayed M, et al., BBMT, 2017). Objective To determine the association between recipient age (age ≥13 years vs age 2-12 years) and risk of acute grade II-IV and chronic GVHD following MUD SCT in acute leukemia recipients. Methods We reviewed all pediatric and young adult recipients receiving a MUD SCT enrolled on Children\u0027s Oncology Group clinical trials ASCT0431, AAML03P1, AAML0531, AAML1031 from 2004-present. Variables assessed included age at transplant, sex, race, performance score, leukemia type (ALL vs AML), remission (CR1 vs CR2), stem cell source, donor/recipient ABO, CMV, and sex matching, GVHD prophylaxis, year of transplant, time from diagnosis to transplant. Overall survival (OS), event-free survival (EFS), acute and chronic GVHD were assessed with Kaplan-Meier curves, cumulative incidence curves, and multivariable Cox proportional hazard models. Results Four-hundred eighty-six children and young adults underwent transplant on these trials, including 205 patients undergoing MUD SCT. For the MUD population, 8% were under age 2 years, 58% were age 2-12, and 34% were age 13-29. Seventy-one percent of patients had AML in CR1; 8% had ALL in CR1; 21% had ALL in CR2. Stem cell source included bone marrow (48%), peripheral blood stem cells (14%), and cord blood (38%). Complete HLA match in 60%, 1 allele HLA mismatch in 27%, 2+ HLA mismatches in 13%. Five-year OS and EFS rates (± standard error) for MUD were 48.4±3.8% and 44.6±3.6%, respectively. In multivariable analysis, older recipient age was associated with a significant increase in grade II-IV acute GVHD, hazard ratio or HR (95% CI) =2.03(1.28, 3.22) for age ≥13 vs age 2-12, p=0.004 (see Figure 1). HLA mismatches (≥2) were associated with grade II-IV acute GVHD, HR=2.35(1.30, 4.24) for ≥2 HLA mismatches vs matched, p=0.039 (see Figure 2). Older recipient age was not associated with chronic GVHD (p=0.83). However, significant association was found between chronic GVHD vs leukemia type and remission status (p=0.007; see Figure 3), with ALL in CR2 having more chronic GVHD than did AML in CR1 (HR=3.54(1.56, 8.03)). Acute GVHD, as expected, was a risk factor for the development of chronic GVHD (HR=2.18(1.03, 4.60), p=0.040). Conclusion Older recipient age (ages ≥13 years vs ages 2-12 years) was associated with significantly increased risk of grade II-IV acute GVHD in patients with acute leukemia following MUD SCT. Further evaluations of differential toxicity of AYA vs younger pediatric patients undergoing MUD SCT are underway.