Novel composite health assessment risk model for older allogeneic transplant recipients: BMT-CTN 1704

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models' performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P < .0001) and worse OS (HR, 2.09; P < .0001). Bootstrap bias-corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

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Publication Details

Journal
Blood Advances
Published
2025-03-18
DOI
https://doi.org/10.1182/bloodadvances.2025015793
Citations
13
Primary Topic
Cancer survivorship and care
Type
article
Field-Weighted Citation Impact
13.59
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article

Novel composite health assessment risk model for older allogeneic transplant recipients: BMT-CTN 1704

Nancy L. Geller, Steven M. Devine, Philip Hollingsworth Imus, Mohamed L. Sorror et al.
13 citations
Blood Advances
Cancer survivorship and care
13.59
article

Novel composite health assessment risk model for older allogeneic transplant recipients: BMT-CTN 1704

Nancy L. Geller, Steven M. Devine, Philip Hollingsworth Imus, Mohamed L. Sorror, Ronald Sobecks, John M. McCarty, Louise Jarrett, William A. Wood, Thomas G. Knight, Lyndsey Runaas, Brent R. Logan, 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 Walston, Joseph Maakaron, Anna Bellach, Mary M. Horowitz, Bailey Protz, Joseph P. Uberti
article en
13 citations

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for older adults with hematologic malignancies. Concerns on nonrelapse mortality (NRM) in older adults limit allo-HCT utilization. We executed a prospective, observational study BMT-CTN 1704 (Blood and Marrow Transplant Clinical Trials Network) enrolling allo-HCT recipients aged ≥60 years from 49 centers in the United States. We analyzed associations between 13 measurements of older adult health and NRM within 1 year to construct a comprehensive health assessment risk model (primary-CHARM) using multivariate Fine-Gray model and grouped penalized variable selection. Two machine learning (ML) models (Cox and pseudo-value boosting) were also explored. Models' performances were compared using area under the curve (AUC), with bootstrap and cross-validation sampling to correct for optimism, decision curve analysis (DCA), calibration, and Brier scores. Among 1105 patients with median age of 67 (range, 60-82) years who received allo-HCT, NRM was 14.4% and overall survival (OS) 71.7% at 1 year. Factors statistically selected for inclusion in primary-CHARM were higher comorbidity burden, lower albumin, higher C-reactive protein, older age, higher weight-loss percentage, lower patient-reported performance score, and cognitive impairment. Primary-CHARM scores were independently associated with higher NRM (hazard ratio [HR], 2.72; P < .0001) and worse OS (HR, 2.09; P < .0001). Bootstrap bias-corrected AUC for primary-CHARM was 0.591. Comparing primary-CHARM with HCT-comorbidity index and 2 ML-CHARM models, calibration, Brier score, and DCA analysis favored primary-CHARM. Primary-CHARM, with mostly simple and readily available parameters, risk stratifies older adults for allo-HCT. Adopting primary-CHARM in practice may promote broader use of HCT by quantifying risk and enhance the design of strategies to improve outcomes. This trial was registered at www.ClinicalTrials.gov as #NCT03992352.

Blood AdvancesVol. 9(13)
Northside Hospital (US), University of North Carolina at Chapel Hill (US), City Of Hope National Medical Center (US), Froedtert Hospital (US), Cleveland Clinic (US), National Marrow Donor Program (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), University of Wisconsin–Madison (US), Johns Hopkins University (US), Oregon Health & Science University (US), University of California, San Francisco (US), Virginia Commonwealth University (US), Medical College of Wisconsin (US), Johns Hopkins Medicine (US), UW Health University Hospital (US), University of Minnesota System (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), University of North Carolina Hospitals (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)
Good health and well-being
Openalex Percentile: Top 1%
Cancer survivorship and care
13.59
DOIOpen Access PDFOpenAlex
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