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Impact of geriatric vulnerabilities on allogeneic hematopoietic cell transplantation outcomes in older patients with hematologic malignancies

Abstract

Older patients are at increased risk for complications and death following allogeneic hematopoietic cell transplantation (allo-HCT). Traditional transplant-specific prognostic indices such as hematopoietic cell transplant comorbidity index (HCT-CI) may not capture all underlying geriatric vulnerabilities, and in-depth evaluation by a geriatrician prior to transplant may not always be available. We hypothesize that routine pretransplant interdisciplinary clinical assessment may uncover prognostically important geriatric deficits. Using an institutional database of 457 adults aged 60 years and older who underwent first allo-HCT for hematological malignancies from 2010 to 2017, we examined the prognostic impact of pretransplant deficits in geriatric domains of function, mobility, mood, medication, nutrition, and relevant biochemical markers. We found that impairment in instrumental activities of daily living (IADL) was associated with reduced survival through increased nonrelapse mortality (NRM, HR = 1.82; 95% CI, 1.04–3.19). The combination of IADL impairment with either HCT-CI/age index or disease risk index readily stratified NRM and overall survival, respectively. In addition, we found that even mild renal dysfunction adversely impacted survival in older transplant patients. Our findings establish important geriatric vulnerabilities in older patients prior to allo-HCT and may provide an entry point for prospective, interventional trials to improve their outcomes.

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Acknowledgements

This research was supported in part by National Institutes of Health award numbers P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. RJL received support from the New York State Empire Clinical Research Investigator Program (ECRIP) and the Elsa U. Pardee Foundation for Cancer Research. This work was presented in part at the 60th American Society of Hematology Annual Meeting and Exposition, December 1–4, 2018, San Diego, CA; and at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, May 31-June 4, 2019, Chicago, IL.

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Correspondence to Richard J. Lin or Sergio A. Giralt.

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SAG reports research funding from Amgen, Actinium, Celgene, Johnson & Johnson, Miltenyi Biotec, and Takeda and serves as a consultant for Amgen, Actinium, Celgene, Johnson & Johnson, Jazz Pharmaceuticals, Miltenyi Biotec, Takeda, Novartis, Kite Pharma, and Spectrum Pharmaceuticals. MAP reports honoraria from Abbvie, Bellicum, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, and Takeda. He serves on DSMBs for Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune. He has also received research support for clinical trials from Incyte and Miltenyi Biotec. CSS has served as a paid consultant on advisory boards for: Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite, a Gilead Company and GSK. He has received research funds for investigator-initiated trials from: Juno Therapeutics and Sanofi-Genzyme. All other authors declare that they have no conflict of interest.

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Lin, R.J., Elko, T.A., Devlin, S.M. et al. Impact of geriatric vulnerabilities on allogeneic hematopoietic cell transplantation outcomes in older patients with hematologic malignancies. Bone Marrow Transplant 55, 157–164 (2020). https://doi.org/10.1038/s41409-019-0654-6

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