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)

Abstract

Abstract Background: Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for many hematologic malignancies, yet survivors often face persistent physical and psychological challenges. Post-HCT care remains focused on relapse surveillance and graft-versus-host disease (GVHD) detection, with limited integration of patient-reported outcomes (PROs). Methods: We analyzed 422 adult HCT recipients who completed the MD Anderson Symptom Inventory-Bone Marrow Transplantation (MDASI-BMT) at defined intervals post-HCT (median 360; range 30-2922 days). This 13-item tool assesses physical, psychologic and systemic symptoms from 0-10; moderate distress is defined as scores 4–6 and severe distress as ≥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 approximately 115, 155, 161, and 132 evaluable patients at 3, 6, 12, and 24 months, symptom burden was common and persistent. Moderate-to-severe distress in ≥1 domain was reported in 61.7%, 75.5%, 65.2%, and 57.6% of patients at each timepoint. Severe symptoms were seen in 23.4-38.4% across all timepoints. Multi-domain burden was also sustained: ≥3 symptom domains with scores ≥4 were reported in 33.0%, 38.8%, 45.9%, and 27.9%; ≥4 domains in 27.7%, 33.6%, 41.3%, and 25.0%; ≥5 domains in 22.3%, 26.9%, 32.1%, and 19.1%; and ≥6 domains in 19.6%, 23.1%, 26.6%, and 16.2% at 3, 6, 12, and 24 months respectively, indicating substantial morbidity with limited improvement over time. Notably, 12.8% of patients at 12 months and 7.4% at 24 months reported ≥9 abnormal domains, highlighting a small but vulnerable subset facing severe, multi-system morbidity. Symptoms evolved over time. Fatigue was the most prevalent throughout (31.6% at 3 months, peaking at 35.4% at 6 months, and persisting at 29.6% at 2 years). At 3 months, symptoms reflected acute post-HCT effects: physical weakness (24.4%), dry mouth (17.5%), drowsiness (20.9%), and appetite loss (13.9%). By 2 years, the burden shifted toward psychosocial and chronic domains: sexual dysfunction (20.6%), cognitive difficulty (19%), sleep disturbance (19.9%) and neuropathy (19.8%). Sadness (11.5%) and distress (11.4%) persisted at 2 years, suggesting long-term psychosocial burden. Multivariable modeling identified no consistent association between symptom burden and relapse, TBI, GVHD or conditioning intensity. GI and oral symptoms improved over time including appetite (2y vs 3m OR0.16, p<0.0001), diarrhea (OR0.18, p<0.0001), and nausea (OR0.2, p=0.005), along with muscle weakness (OR0.37, p=0.004). In contrast, others worsened, including sexual dysfunction (1y v 3m OR2.41, p<0.0001), neuropathy (OR2.61, p<0.0001), joint stiffness (OR2.69, p=0.02), and cognitive difficulties (OR2.26, p=0.049). Importantly, domains such as fatigue, sadness, distress, pain, and shortness of breath showed no significant improvement at any timepoint, reflecting chronic persistence rather than resolution. GVHD was significantly associated with eye problems (OR3.06, p<0.0001), dry mouth (OR2.82, p=0.004), and sleep disturbance (p<0.0001), but not with psychological burden or fatigue. Conclusion Despite improvement in acute symptoms, most HCT survivors experience persistent, multi-domain symptom burden years post-HCT. Chronic emotional, musculoskeletal, neurologic, and sexual symptoms underscore the need for structured long-term supportive care. These findings support routine integration of PROs into survivorship care and the need for proactive, longitudinal symptom management.