Aging Phenotypes and Restoring Functional Deficits in Older Adults With Hematologic Malignancy

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  • 1 Division of Hematology,
  • | 2 College of Pharmacy,
  • | 3 Department of Biomedical Informatics,
  • | 4 Department of Molecular Genetics, Cancer Biology and Genetics, and
  • | 5 Cancer Prevention and Control, The Ohio State University, Columbus, Ohio.

Background: Gauging fitness remains a challenge among older adults with hematologic malignancies, and interventions to restore function are lacking. We pilot a structured exercise intervention and novel biologic correlates of aging using epigenetic clocks and markers of immunosenescence to evaluate changes in function and clinical outcomes. Methods: Older adults (n=30) with hematologic malignancy actively receiving treatment were screened and enrolled in a 6-month exercise intervention, the Otago Exercise Programme (OEP). The impact of the OEP on geriatric assessment metrics and health-related quality of life were captured. Clinical outcomes of overall survival and hospital utilization (inpatient length of stay and emergency department use) in relationship to geriatric deficits were analyzed. Results: Older adults (median age, 75.5 years [range, 62–83 years]) actively receiving treatment were enrolled in the OEP. Instrumental activities of daily living and physical health scores (PHS) increased significantly with the OEP intervention (median PHS: visit 1, 55 [range, 0–100]; visit 2, 70 [range, 30–100]; P<.01). Patient-reported Karnofsky performance status increased significantly, and the improvement was sustained (median [range]: visit 1, 80 [40–100]; visit 3, 90 [50–100]; P=.05). Quality of life (Patient-Reported Outcome Measurement Information System [PROMIS]) improved significantly by the end of the 6-month period (median [range]: visit 1, 32.4 [19.9–47.7]; visit 3, 36.2 [19.9–47.7]; P=.01]. Enhanced measures of gait speed and balance, using the Short Physical Performance Battery scores, were associated with a 20% decrease in risk of death (hazard ratio, 0.80; 95% CI, 0.65–0.97; P=.03) and a shorter hospital length of stay (decrease of 1.29 days; 95% CI, −2.46 to −0.13; P=.03). Peripheral blood immunosenescent markers were analyzed in relationship to clinical frailty and reports of mPhenoAge epigenetic analysis are preliminarily reported. Chronologic age had no relationship to overall survival, length of stay, or emergency department utilization. Conclusions: The OEP was effective in improving quality of life, and geriatric tools predicted survival and hospital utilization among older adults with hematologic malignancies.

Submitted June 3, 2020; final revision received November 13, 2020; accepted for publication November 13, 2020.

Published online March 26, 2021.

Author contributions: Study design: Rosko, Sucheston-Campbell, Huang, Burd, Naughton. Patient enrollment: Rosko, Wall, Baiocchi, Benson, Brammer, Byrd, Efebera, Maddocks, Rogers. Research and data analysis: Rosko, Sucheston-Campbell, Tang, Ozer, Huang, Burd. Manuscript preparation: All authors.

Disclosures: Dr. Rosko has reported receiving grant/research support from Janssen, Millennium, and Regeneron. Dr. Rogers has reported receiving grant/research support from Genentech, AbbVie, and Janssen; serving on advisory boards for Acerta Pharma, AstraZeneca, and Pharmacyclics; and receiving travel funds from AztraZeneca. The remaining authors have disclosed that they have not received any financial consideration from any person or organization to support the preparation, analysis, results, or discussion of this article.

Funding: Research reported in this publication was supported by the NCI of the NIH under award number UG1CA189823 Alliance for Clinical Trials in Oncology NCORP Research Base, K23 CA208010-01, and UG1CA233331.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Correspondence: Ashley E. Rosko, MD, Division of Hematology, The Ohio State University, A345 Starling Loving Hall, 320 West 10th Avenue, Columbus, OH 43210. Email: Ashley.Rosko@osumc.edu

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