Mismatch Doesn't Mean Misfortune: Quality of Life after HCT in the ACCESS Trial

The ACCESS trial is a multicenter phase II study that evaluated standard dose post-transplant cyclophosphamide in recipients of HLA mismatched unrelated donor (MMUD) hematopoietic cell transplantation (HCT) for hematologic malignancy. This study examines 1-year post-treatment quality of life (QOL) trajectories among 7/8 HLA matched versus <7/8 HLA matched unrelated donor recipients. This longitudinal study included ACCESS (NCT04904588) trial participants who completed at least one patient reported outcome (PRO) for analysis. Patients completed QOL surveys at baseline, day (D)100, D180, and 1-year post-HCT, using the Lee Symptom Scale (LSS), nine Patient Reported Outcome Measurement Information System (PROMIS) domains, and a measure of financial toxicity (FT, COST-FACIT). Clinically meaningful differences were defined as >5 points, with PROMIS and COST-FACIT cut points and published norms used to interpret symptom burden. Fisher exact or Wilcoxon rank-sum test were applied to compare patient characteristics between <7/8 and 7/8 patients. Among the 268 patients enrolled into the ACCESS trial, 232 (87%) submitted at least one survey. Of those patients, 68% (n=158) had a 7/8 MMUD and 31% (n=74) had a <7/8 MMUD. Compared to <7/8 MMUD recipients, patients receiving <7/8 MMUD were younger (median age: 57.6 v. 63.4 years), were more likely to be of racial and/or ethnic minority ancestry (64% v. 42%) and were less likely to be retired (27% v. 43%). At baseline, both cohorts experienced mild FT: 23.9, Grade 1 for <7/8 MMUD recipients and 25.6, Grade 1 for 7/8 MMUD recipients (Fig 1a). At D180 and 1 year, patients receiving <7/8 MMUD continued to report mild financial toxicity while 7/8 MMUD recipients reported no significant financial toxicity at D180 or 1 year. LSS overall scores were similar between groups across all timepoints. PROMIS scores for 7/8 and <7/8 MMUD groups were within the normal limits of symptom burden across all domains except physical and sexual function. At baseline, <7/8 patients had a lower average physical function score (44.1, 95% Confidence interval, CI: 43.3–44.9), indicating mild dysfunction, compared to 7/8 patients (45.7, 95% CI: 44.7–46.7), who were within normal limits (Fig 1b). Both groups showed similar physical function trajectories, with declines at D100 (3.6-point decline for 7/8; 3.9 point decline for <7/8) and recovery to normal ranges by one year (mean 47 for 7/8; mean 46.3 for <7/8). There were no clinically meaningful differences between patients with a 7/8 and <7/8 MMUD on overall QOL. Both cohorts demonstrated similar QOL trajectories, returning to baseline scores at 1-year post-HCT. Small differences involving physical function and FT warrant further study. These findings highlight the expansion of access to HCT through HLA mismatch does not come at the cost of QOL, with equal QOL experienced regardless of HLA match.