Associations between Symptom Severity and Distress with Functional Status after Allogeneic Hematopoietic Cell Transplantation

Functional status after allogeneic hematpoietic stem cell transplant (allo-HCT) is a critical predictor of morbidity and mortality, particularly in older or frail adults. While symptom burden impacts quality of life, its association with functional status post-HCT is less understood. To examine the impact of HCT on functional status and the association between symptom burden and changes in functional status post-HCT. We used data from the ACE-BMT study, an ongoing longitudinal, randomized seamless phase II/III trial, that enrolled adult patients considered for allo-HCT who were either age of ≥65 years, had HCT-CI scores of ≥3, or were frail. The study randomized patients into four arms: palliative care, clinical management of comorbidities, both approaches combined, or standard of care. We used multiple linear regression to test the association between baseline MD Anderson Symptom Inventory mean scores for total symptom burden, and severity and distress subscales, with functional status 3 months post-HCT based on the 6-minute walk test (meters, m), timed get-up-and-go test (seconds, s), and grip strength (kilograms, kg). Of 381 participants (mean age 66, 38% female), significant declines in functional status were observed from baseline to 3 months post-HCT. On average, the 6-minute walk distance decreased by 17 m (P<0.001), grip strength declined by 3.5 kg (P<0.001), and the time to complete the get-up-and-go test increased by 0.32 s (P<0.001). The mean (SD) total symptom, symptom severity, and symptom distress scores at baseline were 1.8 (1.5), 1.5 (1.3), and 2.3 (2.2), respectively. After adjustment for age, randomization group, and HCT-CI score, total symptom burden and symptom severity scores at baseline were associated with declines in functional status (Figure). For each additional point on the total and severity symptom scales, 6-minute walk distance was lower by 5.12 (95% CI: -9.74, -0.64) and 6.10 (95% CI: -11.1, -1.11) m, respectively. Get-up-and-go time was slower by 0.11 (95% CI: 0.05, 0.19) and 0.14 (95% CI: 0.06, 0.22) s per each additional point in symptom burden and severity scores. Greater symptom distress was associated with a slower get-up-and-go time (b: 0.11, 95% CI: 0.01,0.11 s). Individually, pain, fatigue, nausea, shortness of breath, and sleep disturbance were statistically significantly associated with poorer 6-minute walk distance and get-up-and-go test (P < 0.05). Symptom burden was not associated with grip strength at 3-months post-HCT. Higher symptom burden and severity at baseline are associated with greater declines in functional status 3 months post-HCT, particularly mobility and endurance. Symptoms like pain, fatigue, and sleep disturbance had the greatest impact on functional decline. Further research should explore strategies for managing these symptoms to enhance recovery post-HCT.