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388 Impact of Frailty on Hematopoietic Cell on Early Transplant Outcomes in Older RecipientsClinically Relevant Abstract

Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Transplant Toxicities
Program: Oral and Poster Abstracts
Type: Oral
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Transplant Toxicities: Clinical and Biological Prognostic Markers, Donor Mobilization, Supportive Care
Sunday, December 6, 2015: 5:15 PM
W230, Level 2 (Orange County Convention Center)

Mukta Arora, MD1, Smita Bhatia, MD, MPH2, Todd E. DeFor, MS3*, Manju Nayar1*, Hewan Belete, medical student1*, Troy Lund, MD, PhD1, Bharat Thyagarajan, MD PhD4*, Celalettin Ustun, MD1 and Daniel Weisdorf, MD1

1Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN
2Institute for Cancer Outcomes and Survivorship, University of Alabama at Birmingham, Birmingham, AL
3Adult and Pediatric Blood and Marrow Transplant Program, University of Minnesota, Minneapolis, MN
4Lab Medicine and Pathology, University of Minnesota, Minneapolis, MN

Introduction: With improvements in transplant strategy and supportive care, hematopoietic cell transplantation (HCT) is increasingly being used to treat older patients (60-80 years). Frailty is a well-accepted phenomenon in the geriatric population characterized by diminished physiological reserve and increased vulnerability to stress, with strong associations with falls, disability, hospitalization and mortality. Since HCT is a substantial stressor, we hypothesized that the prevalence of frailty and pre-frailty will increase in the immediate post-transplant period, and that frailty will be associated with early (1y) post-transplant non-relapse mortality (NRM).

Methods: We conducted a prospective, longitudinal study of 96 patients undergoing HCT at age 40y or older between February 2014 and April 2015, and serially performed a multi-domain geriatric assessment (incorporating function, comorbidity, cognition, psychological state, social activity/support, and nutritional status) in additional to demographic, transplant and disease related variables. Frailty was defined by presence of 3 or more of the following criteria: unintentional weight loss, exhaustion, weakness, slow walking speed and low physical activity; pre-frailty was defined by presence of 1 or 2 of the criteria. Geriatric assessments were performed pre-HCT and at 100 days, 6 months and 1 year post HCT. The prevalence of frailty and pre-frailty was evaluated at each time point in older (60-74y, n=48) vs. younger (40-59y, n=48) recipients. Longitudinal assessments (baseline, 100 days, 6 months, 1 year) of ordinal frailty measures were assessed using random effects and non-linear mixed logistic regression models.  Impact of frailty on 1 year NRM was estimated using cumulative incidence estimates.

Results: Older patients were more likely to undergo reduced intensity conditioning, and less likely to be employed at HCT. The prevalence of frailty increased with time since HCT:  The prevalence of frailty was 8% at baseline and increased to 39% by 6 months (<0.01). The prevalence of pre-frailty was 44% at baseline and remained at 45% by 6 months. The prevalence of frailty and pre-frailty did not differ in the younger vs. older age groups at any time point and was independent of the baseline HCT-comorbidity index (HCT-CI).

In the random effects model for frailty, increasing time from transplant was associated with a 3.7 times higher odds of frailty (OR: 3.7, 95% CI: 1.9-7.2, p< 0.01). Other variables associated with a higher odds of frailty were pre-transplant employment status (retired: OR: 7.3, 95% CI: 1.2-46.2, p= 0.03); patients on medical leave or disabled (OR: 11.2, 95% 1.8-67.7, p=0.01), limitations in social activities (OR: 1.04, 95% CI: 1.01-1.07, p< 0.01), and type of HCT (allogeneic vs. autologous: OR: 3.1, 95% CI: 0.9-10.2, P=0.06). Baseline pre-frailty was associated with a 3.1 times odds of subsequently developing frailty (OR: 3.1, 95% CI: 2.3-45.5, P< 0.01)

Despite only limited follow up to date in this recent cohort, we identified a trend towards increasing non-relapse mortality (NRM) in frail patients. The cumulative incidence of NRM at one year was 7% (95% CI: 0-14%) in the non-frail group, 23% (95% CI: 8-38%) in the pre-frail group and 28% (95% CI: 0-57%) in the frail group (p-value for trend= 0.07).

Conclusion: Independent of specific medical co-morbidities or the HCT-CI, frailty was noted in 8%, and pre-frailty in 44% of our HCT population prior to HCT, and was not dependent on age. Frailty is a transitional state and appears to reflect a dynamic progression from robustness to functional decline with time since HCT. It is associated with a higher mortality, indicating a need to identify vulnerable populations and define their need for specific interventions.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH