Factors associated with frailty in vulnerable hematopoietic cell transplantation candidates.

6552 Background: Allogenic hematopoietic cell transplantation (allo-HCT) is increasingly offered to older patients and those with comorbidities. Frailty, characterized by reduced muscle strength and functional decline, is associated with lower quality of life, increased mortality, and higher hospitalization after allo-HCT. However, frailty prior to allo-HCT remains understudied. The study investigated factors associated with frailty in allo-HCT candidates prior to transplant. Methods: This cross-sectional analysis utilized data from the ACE-BMT study, an ongoing longitudinal, unblinded, randomized seamless phase II/III trial, that enrolled adult patients allo-HCT candidates either age of ≥65 years, with HCT comorbidity index (HCI-CI) score of ≥3, or 4-meter walk speed test <0.8 m/s. We classified frailty in participants at baseline using the Fried frailty phenotype: 1) unintentional weight loss, 2) low energy (Patient Health Questionnaire 9-item [PHQ-9]), 3) grip strength or stand-up time below standard, 4) 4-meter walk test < 0.8m/s, and 5) the lowest 20% of physical functioning (Medical Outcomes Study Physical Health). Participants were classified as frail (≥3), pre-frail (1-2), or not frail (0). We assessed pre-HCT variables including demographics, comorbidities, and self-reported social support (ENRICHED Social Support Instrument), symptom severity and interference with daily life (MD Anderson Symptom Inventory), depression (PHQ-9), cognitive impairment (Bless Orientation Memory Concentration), quality of life (Euro Quality of Life 5-Dimensions), and functional status (Karnofsky Performance Status). We compared baseline characteristics based on frailty status and conducted a multivariable logistic regression to identify the factors associated with frailty. Results: Among 381 patients (mean age 65.49, 38.32% female) included in the analysis, 81.7% were pre-frail and frail at baseline. Compared to non-frail, participants as frail were younger (mean age 66.49 vs 61.49), more likely to be female (35.7% vs. 48.7%), to have cardiovascular disease (1.3% vs. 9.2%) and diabetes (9.8% vs. 23.7%), and a HCT-CI score ≥3 (39.3% vs. 61.8%). They also self-reported greater depression, symptom severity and interference, cognitive impairment, and poorer quality of life. In a multivariable logistic regression model, older age (OR: 0.98, 95% CI: 0.95, 1.00), higher symptom interference (OR: 1.04, 95% CI: 1.01-1.08), and depression (OR: 1.14, 95% CI: 1.03-1.27) were significantly associated with frailty. Conclusions: Frailty prior to allo-HCT is associated with symptom burden and depression, underscoring the importance of addressing these factors pre-HCT. These findings provide preliminary support for psychological screening and symptom-focused interventions. Future analyses will examine the incidence and risk factors of post-HCT frailty and its association with clinical outcomes.