Observational Study

. 2025 Jul 8;9(13):3268-3280.

doi: 10.1182/bloodadvances.2025015793.

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

Mohamed L Sorror^{1

2}, Wael Saber^{3

4}, Brent Logan^{4

5}, Nancy Geller⁶, Anna Bellach⁶, Jianqun Kou^{3

4}, William Wood⁷, John M McCarty⁸, Thomas G Knight⁹, Lyndsey Runaas¹⁰, Laura Johnston¹¹, Jeremy Walston¹², Ryotaro Nakamura¹³, Lori Jarrett¹, Asmita Mishra¹⁴, Joseph Uberti¹⁵, Parastoo B Dahi^{16

17}, Jennifer N Saultz¹⁸, Shannon R McCurdy¹⁹, Lawrence E Morris²⁰, Philip H Imus²¹, William J Hogan²², Kalyan Nadiminti²³, Vijaya Raj Bhatt²⁴, Rebecca Olin²⁵, Joseph Maakaron²⁶, Ronald Sobecks²⁷, Sarah A Wall²⁸, Deborah Mattila^{4

29}, Bailey Protz^{4

29}, Steven M Devine^{4

29}, Mary M Horowitz^{3

4}, Andrew S Artz¹³

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
² Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
³ Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.
⁴ Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
⁵ Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
⁶ The Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, MD.
⁷ Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC.
⁸ Cellular Immunotherapies and Transplant Program, Virginia Commonwealth University Massey Cancer Center, Richmond, VA.
⁹ Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
¹⁰ Cancer Center - Froedtert Hospital, Medical College of Wisconsin, Milwaukee, WI.
¹¹ Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
¹² Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
¹³ Division of Hematology, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
¹⁴ Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
¹⁵ Division of BMT, Leukemia & Lymphoma, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
¹⁶ Adult Bone Marrow Transplant, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁷ David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁸ Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR.
¹⁹ Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA.
²⁰ Northside Hospital Leukemia and BMT Programs, The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA.
²¹ Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
²² Division of Hematology (W10), Mayo Clinic, Rochester, MN.
²³ Carbone Cancer Center, University of Wisconsin Hospitals and Clinics, Madison, WI.
²⁴ Division of Hematology-Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.
²⁵ Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
²⁶ Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN.
²⁷ Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
²⁸ Division of Hematology, The Ohio State University, Columbus, OH.
²⁹ National Marrow Donor Program (NMDP), Minneapolis, MN.

PMID: 40101246
PMCID: PMC12246602
DOI: 10.1182/bloodadvances.2025015793

Observational Study

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

Mohamed L Sorror et al. Blood Adv. 2025.

. 2025 Jul 8;9(13):3268-3280.

doi: 10.1182/bloodadvances.2025015793.

Authors

Affiliations

¹ Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA.
² Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine, Seattle, WA.
³ Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI.
⁴ Center for International Blood and Marrow Transplant Research, Minneapolis, MN.
⁵ Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI.
⁶ The Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, MD.
⁷ Lineberger Comprehensive Cancer Center, University of North Carolina Hospitals, Chapel Hill, NC.
⁸ Cellular Immunotherapies and Transplant Program, Virginia Commonwealth University Massey Cancer Center, Richmond, VA.
⁹ Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute, Atrium Health, Charlotte, NC.
¹⁰ Cancer Center - Froedtert Hospital, Medical College of Wisconsin, Milwaukee, WI.
¹¹ Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
¹² Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
¹³ Division of Hematology, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA.
¹⁴ Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL.
¹⁵ Division of BMT, Leukemia & Lymphoma, Karmanos Cancer Institute, Wayne State University, Detroit, MI.
¹⁶ Adult Bone Marrow Transplant, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁷ David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, NY.
¹⁸ Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, Portland, OR.
¹⁹ Division of Hematology and Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA.
²⁰ Northside Hospital Leukemia and BMT Programs, The Blood and Marrow Transplant Program at Northside Hospital, Atlanta, GA.
²¹ Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD.
²² Division of Hematology (W10), Mayo Clinic, Rochester, MN.
²³ Carbone Cancer Center, University of Wisconsin Hospitals and Clinics, Madison, WI.
²⁴ Division of Hematology-Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE.
²⁵ Helen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA.
²⁶ Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota Medical Center, Minneapolis, MN.
²⁷ Department of Hematologic Oncology and Blood Disorders, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH.
²⁸ Division of Hematology, The Ohio State University, Columbus, OH.
²⁹ National Marrow Donor Program (NMDP), Minneapolis, MN.

PMID: 40101246
PMCID: PMC12246602
DOI: 10.1182/bloodadvances.2025015793

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.

Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.

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Conflict of interest statement

Conflict-of-interest disclosure: M.L.S. reports receiving consultancy and receiving honoraria from JAZZ Pharmaceuticals for giving educational talks and receiving research funding from BlueNote. W.W. reports receiving research support from Pfizer and Genentech; having equity and providing consulting to Koneksa Health; and providing consulting for Teladoc Health, Quantum Health, and American Society of Hematology Research Collaborative. A.M. reports receiving grant support from Novartis. P.H.I. reports receiving research support from Janssen. V.R.B. reports participating in the Safety Monitoring Committee for Protagonist; serving as an Associate Editor for the journal, Current Problems in Cancer; serving as a contributor for BMJ Best Practice; providing consultancy for Imugene, Sanofi, and Taiho; receiving research support from MEI Pharma, Actinium Pharmaceutical, Sanofi U.S. Services, AbbVie, Pfizer, Incyte, Jazz, and National Marrow Donor Program; and receiving drug support (institutional) from Chimerix for a trial. R.O. reports receiving research support from Cellectis and providing consulting for Servier and Riger. J.M. reports receiving research support from Gilead, Atara, CRISPR, Precision Biosciences, Scripps Research Institute, VOR Bio, and Affimed. S.A.W. reports serving on the speaker bureau for Sobi. A.S.A. reports having advisory role for AstraZeneca and Magenta Therapeutics and providing consulting to AbbVie. The remaining authors declare no competing financial interests.

Figures

**Figure 1.**
**DCA plot of net benefit vs threshold probability for NRM.** All plots are bias-corrected using cross-validation to generate predicted probabilities. This figure reveals that CHARM exhibited higher net benefit compared with a “treat all” or “treat none” and that benefit was higher than that per the HCT-CI approach with a wide range of threshold probability for NRM.

**Figure 2.**
**CONSORT diagram describing study flow.**

**Figure 3.**
**Primary-CHARM tertiles stratifying for NRM.**

**Figure 4.**
**Stratification of outcomes per primary CHARM tertiles.** Primary-CHARM tertiles stratifying for (A) overall survival and (B) relapse.

See this image and copyright information in PMC

References

1. Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2013. https://seer.cancer.gov/csr/1975_2013/ Accessed 1 January 2025.
1. Thein MS, Ershler WB, Jemal A, Yates JW, Baer MR. Outcome of older patients with acute myeloid leukemia: an analysis of SEER data over 3 decades. Cancer. 2013;119(15):2720–2727. - PMC - PubMed
1. Cornelissen JJ, van Putten WL, Verdonck LF, et al. Results of a HOVON/SAKK donor versus no-donor analysis of myeloablative HLA-identical sibling stem cell transplantation in first remission acute myeloid leukemia in young and middle-aged adults: benefits for whom? Blood. 2007;109(9):3658–3666. - PubMed
1. McDonald GB, Sandmaier BM, Mielcarek M, et al. Survival, non-relapse mortality, and relapse-related mortality after allogeneic hematopoietic cell transplantation: comparing 2003-2007 versus 2013-2017 cohorts. Ann Intern Med. 2020;172(4):229–239. - PMC - PubMed
1. Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127–1138. - PMC - PubMed

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

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

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Conflict of interest statement

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