Burden and Impact of Geriatric Syndromes in 2-Year, Progression-Free Survivors of Older Allogeneic Hematopoietic Cell Transplant Recipients – a Landmark Analysis

Introduction/Methods The trajectory of functional decline and the prevalence of geriatric syndromes have not been examined among long-term survivors of older allo-HCT recipients. We previously described significant burden and adverse impact of post-transplant geriatric syndromes, delirium and fall, among older allogeneic recipients. We report here theprevalence and impact of geriatric syndromes in 2-year, progression-free survivors among this cohort of patients using our institutional database. Baseline characteristics, transplant outcomes, geriatric assessment domains, and geriatric syndromes were obtained and analyzed as previously described. Results We identified 199 2-year, progression-free survivors of patients allografted at age ≥60 years from 2001 to 2016, including 111 out of 241 patients on the CD34+ selection platform (46%), and 88 out of 231 T-cell replete patients (38%). The median age at allo-HCT was 65.4 years (range 60 – 78.7); 73% had myeloid malignancies; 69% had high/very high risk HCT-CI/age; 14% had a mismatched donor; and 56% had a CD34+ selected graft. With a median follow-up of 5.7 years for survivors, the 3-yr OS and RFS from the 2-year landmark was 86% (95% CI, 80 – 91) and 83% (95% CI, 78 – 89). Thirty-three patients died, including 8 from relapse/disease progression, and 25 from non-relapse mortality (6 each from secondary neoplasm, organ failure, and infections). The 3-year cumulative incidence of new functional impairment (FI), defined as new admission to skilled nursing facility, fall, or assisted walking device from the 2-year landmark, was 20% (95% CI, 15 – 27). In addition, the 3-year cumulative incidence of new psychiatric illness and cognitive decline was 6% (95% CI, 3 – 11) and 5% (95% CI, 3 – 10), respectively (Figure 1). We examined factors associated with new FI and found that, among others, patients who were transplanted with a CD34+ selected graft had lower incidence of new FI in univariate (hazard ratio [HR]=0.49, 95% CI 0.28 – 0.86, P=0.014) and multivariate analysis with borderline significance (HR=0.53, 95% CI 0.27 – 1.02, P=0.056). In 2-year landmark analyses, both high/very high HCT-CI/age index and mismatched donor were significantly associated with inferior OS and RFS (Table 1). Conclusion While limited by the single institution, retrospective design, heterogenous transplant approach, and likely under-reporting, our findings nevertheless illustrate the high prevalence of FI among older allo-HCT survivors, which maybe attenuated by the CD34+ selection platform. In addition, the impact of graft-versus-host disease on the development of geriatric syndromes merits closer examination. While requiring prospective confirmation, long-term functional impairment should be considered as an important secondary outcome when comparing curative strategies to other less intense approaches in older patients with hematologic malignancies.