Persistent Symptom Burden and Unmet Needs in Long-Term Survivors of Allogeneic Hematopoietic Cell Transplantation: an Analysis Using the MD Anderson Symptom Inventory (MDASI-BMT)

Background Allogeneic transplantation (HCT) offers cure for hematologic malignancies, yet survivors face persistent physical and psychological challenges. Post-HCT care remains focused on relapse and graft-versus-host disease (GVHD) detection, with limited integration of patient-reported outcomes (PROs). Methods We analyzed 422 adult HCT recipients with completed MD Anderson Symptom Inventory-BMT (MDASI-BMT) at defined intervals post-HCT (median 360; range 30-2922 days). This 23-item tool rates physical and psychologic symptoms from 0-10; moderate distress is 4–6 and severe distress is ≥7. Multivariable mixed effects logistic regression modeled symptom burden by time and clinical variables including age, GVHD, relapse, conditioning intensity, and total body irradiation (TBI). Results Among 115,155,161 and 132 evaluable patients at 3,6,12 and 24mo, moderate-to-severe distress in ≥1 domain occurred in 62%, 76%, 65%, and 58% of patients at each timepoint. Severe symptoms were seen in 23-38%. Multi-domain burden persisted: at 3,6,12 and 24mo, ≥3domains with scores≥4 were reported in 33%, 39%, 46% and 28%; ≥4 in 28%, 34%, 41%, and 25%; ≥5 domains in 22%, 27%, 32%,and 19% and ≥6 in 20%, 23%, 27%, and 16%, indicating substantial morbidity with limited improvement over time. 13% of patients at 12mo and 7% at 24mo reported ≥9 abnormal domains, highlighting a small but vulnerable subset with severe morbidity. Fatigue was the most persistent (32% at 3mo, peaking at 35% at 6mo, and persisting at 30% at 2yrs).At 3mo, symptoms reflected acute effects: physical weakness (24%), dry mouth (18%), drowsiness (21%), and appetite loss (14%). By 2yrs, the burden shifted toward chronic domains: sexual dysfunction (21%), cognitive difficulty (19%), sleep disturbance (20%) and neuropathy (19.8%). Sadness (12%) and distress (11%) persisted at 2yrs, suggesting long-term psychosocial burden.Multivariable modeling found no association between symptom burden and relapse, TBI, GVHD or conditioning intensity. GI and oral symptoms improved over time including appetite (OR0.16,p<0.0001), diarrhea (OR0.18,p<0.0001), and nausea (OR0.2,p=0.005), and muscle weakness (OR0.37,p=0.004). In contrast, sexual dysfunction(OR 2.41,p<0.001), neuropathy(OR2.61,p<0.0001), joint stiffness(OR2.69,p=0.02), and cognitive difficulties(OR2.26,p=0.049) worsened. Importantly, fatigue, sadness, pain and dyspnea showed no improvement at any timepoint. GVHD was significantly associated with eye problems, dry mouth and sleep disturbance, but not with psychological burden or fatigue. Conclusion Despite resolution of acute symptoms, most survivors experience persistent, multi-domain morbidity years post-HCT including emotional, sexual and musculoskeletal effects. Symptoms underscore the need for structured long-term supportive care and routine integration of PROs into survivorship care.