CHARM is prognostic of geriatric morbidity and toxicity after allogeneic transplant for older adults: BMT CTN 1704 study

Despite concerns about the toxicity of allogeneic hematopoietic cell transplantation (alloHCT) in older patients, prospective data characterizing prevalence or risk stratification for geriatric morbidity such as disability or frailty are limited. We prospectively assessed the prognostic impact of the novel composite health assessment risk model (CHARM), a score established to predict 1-year nonrelapse mortality (NRM), among 1105 patients aged ≥60 years enrolled on the Bone Marrow Transplant Clinical Trials Network Study 1704. Secondary end points were assessed post-alloHCT at day 100 (D100), D180, and D365 in multivariable models adjusted with predetermined clinical variables. Among alloHCT survivors, the prevalence of disability by instrumental activities of daily living (IADL), frailty by the Physical Frailty Phenotype, and physical function impairment by Patient Reported Measurement Information System (PROMIS) was highest at D100 and lower on D180 and D365. Higher CHARM scores were independently associated with greater disability (coefficient, -0.64; 95% confidence interval [CI], -0.85 to -0.43; P< .001), increased frailty (coefficient, 0.19; CI, 0.081-0.31; P< .001), worse PROMIS physical function, greater PROMIS depression, increased serious organ toxicity by D100, more cognitive decline at D100, and higher mortality after acute graft-versus-host disease (GVHD) but not significantly associated with PROMIS anxiety or acute GVHD. Higher CHARM scores predicted worse disability-free survival (odds ratio [OR], 2.03; CI, 1.66-2.48; P< .001) and lower frailty-free survival (OR, 2.00; CI, 1.61-2.49). In summary, CHARM is an independent prognostic scoring system not only for NRM but also for geriatric morbidity and functional limitation-free survival through 1 year after alloHCT. Pre-alloHCT CHARM is a novel tool to aid shared decision-making for older patients. This trial was registered at www.clinicaltrials.gov as #NCT03992352.

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Journal
Blood Advances
Published
2025-11-21
DOI
https://doi.org/10.1182/bloodadvances.2025018340
Citations
1
Primary Topic
Frailty in Older Adults
Type
article
Field-Weighted Citation Impact
1.22

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article

CHARM is prognostic of geriatric morbidity and toxicity after allogeneic transplant for older adults: BMT CTN 1704 study

Nancy L. Geller, Steven M. Devine, Philip Hollingsworth Imus, Mohamed L. Sorror et al.
1 citations
Blood Advances
Frailty in Older Adults
1.22
article

CHARM is prognostic of geriatric morbidity and toxicity after allogeneic transplant for older adults: BMT CTN 1704 study

Nancy L. Geller, Steven M. Devine, Philip Hollingsworth Imus, Mohamed L. Sorror, Ronald Sobecks, John M. McCarty, William A. Wood, Thomas G. Knight, Lyndsey Runaas, Deborah Mattila, Parastoo Bahrami Dahi, Jennifer N. Saultz, Sarah Wall, Vijaya Raj Bhatt, Laura Johnston, Andrew Artz, Wael Saber, Lawrence E. Morris, Kalyan Nadiminti, Jianqun Kou, Shannon R. McCurdy, Rebecca L. Olin, Asmita Mishra, William J. Hogan, Ryotaro Nakamura, Jeremy D Walston, Joseph Maakaron, Anna Bellach, Mary M. Horowitz, Bailey Protz, Brent R. Logan, Joseph P. Uberti
article en
1 citations

Abstract

Despite concerns about the toxicity of allogeneic hematopoietic cell transplantation (alloHCT) in older patients, prospective data characterizing prevalence or risk stratification for geriatric morbidity such as disability or frailty are limited. We prospectively assessed the prognostic impact of the novel composite health assessment risk model (CHARM), a score established to predict 1-year nonrelapse mortality (NRM), among 1105 patients aged ≥60 years enrolled on the Bone Marrow Transplant Clinical Trials Network Study 1704. Secondary end points were assessed post-alloHCT at day 100 (D100), D180, and D365 in multivariable models adjusted with predetermined clinical variables. Among alloHCT survivors, the prevalence of disability by instrumental activities of daily living (IADL), frailty by the Physical Frailty Phenotype, and physical function impairment by Patient Reported Measurement Information System (PROMIS) was highest at D100 and lower on D180 and D365. Higher CHARM scores were independently associated with greater disability (coefficient, -0.64; 95% confidence interval [CI], -0.85 to -0.43; P< .001), increased frailty (coefficient, 0.19; CI, 0.081-0.31; P< .001), worse PROMIS physical function, greater PROMIS depression, increased serious organ toxicity by D100, more cognitive decline at D100, and higher mortality after acute graft-versus-host disease (GVHD) but not significantly associated with PROMIS anxiety or acute GVHD. Higher CHARM scores predicted worse disability-free survival (odds ratio [OR], 2.03; CI, 1.66-2.48; P< .001) and lower frailty-free survival (OR, 2.00; CI, 1.61-2.49). In summary, CHARM is an independent prognostic scoring system not only for NRM but also for geriatric morbidity and functional limitation-free survival through 1 year after alloHCT. Pre-alloHCT CHARM is a novel tool to aid shared decision-making for older patients. This trial was registered at www.clinicaltrials.gov as #NCT03992352.

Blood AdvancesVol. 10(5)
Northside Hospital (US), University of North Carolina at Chapel Hill (US), City Of Hope National Medical Center (US), Cleveland Clinic (US), National Marrow Donor Program (US), Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa (ZA), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), Johns Hopkins University (US), Oregon Health & Science University (US), University of California, San Francisco (US), Virginia Commonwealth University (US), University of Washington (US), Medical College of Wisconsin (US), Cornell University (US), Johns Hopkins Medicine (US), UW Health University Hospital (US), Susan Thompson Buffett Foundation (US), University of Washington Medical Center (US), Moffitt Cancer Center (US), Fred Hutch Cancer Center (US), The Barbara Ann Karmanos Cancer Institute (US), Levine Cancer Institute (US), University of Wisconsin Carbone Cancer Center (US), National Heart, Lung, and Blood Institute (US), City of Hope (US), Michigan United (US), Mayo Clinic in Arizona (US), Stanford Blood Center (US), University of Minnesota Medical Center (US), Mayo Clinic in Florida (US), Sidney Kimmel Comprehensive Cancer Center (US), UCSF Helen Diller Family Comprehensive Cancer Center (US), The Ohio State University (US), University of Nebraska Medical Center (US), University of Pennsylvania (US), Stanford University (US)
U.S. Department of Health and Human Services, Pfizer, Sanofi, Gilead Sciences, Jazz Pharmaceuticals, Atara Biotherapeutics, MEI Pharma, Incyte, Servier, Swedish Orphan Biovitrum, Health Resources and Services Administration, Genentech, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Daiichi Sankyo Europe
Openalex Percentile: Top 16%
Frailty in Older Adults
1.22
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