Cancer patients with clonal hematopoiesis die from primary malignancy or comorbidities despite higher rates of transformation to myeloid neoplasms

Q: What is clonal hematopoiesis (CH) and what subtypes does it include?

CH refers to somatic mutations in a hematopoietic cell subpopulation without a morphological hematologic diagnosis. It includes CH of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS).

Q: How were CHIP and CCUS defined in the study?

CHIP was defined as CH without cytopenia or morphologic findings of hematologic malignancy. CCUS was defined as CH with cytopenia using criteria such as persistent anemia, neutropenia, or thrombocytopenia for at least 4 months.

Q: Which factors were associated with transformation to a myeloid neoplasm?

Transformation was associated with variant allele frequency ≥0.2 and hemoglobin <10 g/dL, based on multivariate analysis.

Sep 21, 2026

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Clonal hematopoiesis (CH), marked by somatic mutations without overt hematologic disease, includes CHIP and CCUS and has been linked to both blood cancers and systemic comorbidities, yet its impact in patients who also have malignancies is unclear. A retrospective evaluation at a tertiary cancer center analyzed CH patient characteristics, mutational profiles, and outcomes, reporting overall survival, causes of death, and transformation risk across risk strata.

LanguageEnglish

CategoryHealthcare

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Pages12

Reading Time30 min

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Abstract

Background

Methods

Results

Conclusions

Introduction

Methods

Study design and participants

Assessment of somatic mutation

DOI: 10. 1002/cam4 .7093 RESEAR CH ARTICLE Cancer patients with clonal hematopoiesis die from primary malignancy or comorbidities despite higher rates of transformation to myeloid neoplasms Kelly S. Chien1 | Faustine Ong1 | Kunhwa Kim1 | Ziyi Li2 | Rashmi Kanagal-Shamanna3 | Courtney D. DiNardo1 | Koichi Takahashi1 | Guillermo Montalban-Bravo1 | Danielle Hammond1 | Koji Sasaki1 | Sherry A. Pierce1 | Hagop M. Kantarjian1 | Guillermo Garcia-Manero1 1Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA Correspondence Kelly S. Chien, Department of Leukemia, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA. [Email:](Email: kchien@mdanderson.org)[ kchien@mdanderson.org](Email: kchien@mdanderson.org) Funding information University of Texas MD Anderson Cancer Center, Grant/Award Number: MDS/AML Moon Shot Program and Support Grant CA016672 Abstract Background: The occurrence of somatic mutations in patients with no evidence of hematological disorders is called clonal hematopoiesis (CH) . CH, whose subtypes include CH of indeterminate potential and clonal cytopenia of undetermined significance, has been associated with both hematologic cancers and systemic comorbidities. However, CH's effect on patients, especially those with concomitant malignancies, is not fully understood. Methods: We performed a retrospective evaluation of all patients with CH ata tertiary cancer center. Patient characteristics, mutational data, and outcomes were collected and analyzed. Results: Of 78 individuals included, 59 (76%) had a history of cancer and 60 (77%) had moderate to severe comorbidity burdens. DNMT3A, TET2, TP53, and ASXL1 were the most common mutations. For the entire cohort, the 2-year overall survival rate was 79%(95% CI: 70, 90), while the median survival was not reached. Of 20 observed deaths, most were related to primary malignancies (n = 7, 35%), comorbidities (n = 4, 20%), or myeloid neoplasms (n = 4, 20%) . Twelve patients (15%) experienced transformation to a myeloid neoplasm. According to the clonal hematopoiesis risk score, the 3-year transformation rate was 0% in low-risk, 15% in intermediate-risk (p = 0.098), and 28% in high-risk (p = 0.05) patients. By multivariate analysis, transformation was associated with variant allele frequency ≥0.2 and hemoglobin <10 g/dL. Conclusions: In a population including mostly cancer patients, CH was associated with comorbidities and myeloid transformation in patients with higher | Kelly S. Chien and Faustine Ong have contributed equally to this work.
Data from this study were presented at the 2022 SOHO Annual Meeting and 2023 ASCO Annual Meeting. | | --- | | This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | Cancer Medicine. 2024;13:e7093 . [https://doi.org/10.1002/cam4.7093](https://doi.org/10.1002/cam4.7093) [wileyonlinelibrary.com/journal/cam4](wileyonlinelibrary.com/journal/cam4) 1 of 12 mutational burdens and anemia. Nevertheless, such patients were less likely to die of their myeloid neoplasm than of primary malignancy or comorbidities. KEYWORDS clonal hematopoiesis, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, CHIP, CCUS 1 | INTRODUCTION The presence of somatic mutations in a subpopulation of hematopoietic cells in individuals without a morphological diagnosis is known as clonal hematopoiesis (CH) . CH includes patients with CH of indeterminate potential (CHIP) and th

FAQs

What is clonal hematopoiesis (CH) and what subtypes does it include?

CH refers to somatic mutations in a hematopoietic cell subpopulation without a morphological hematologic diagnosis. It includes CH of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS).

How were CHIP and CCUS defined in the study?

CHIP was defined as CH without cytopenia or morphologic findings of hematologic malignancy. CCUS was defined as CH with cytopenia using criteria such as persistent anemia, neutropenia, or thrombocytopenia for at least 4 months.

Which factors were associated with transformation to a myeloid neoplasm?

Transformation was associated with variant allele frequency ≥0.2 and hemoglobin <10 g/dL, based on multivariate analysis.

Sep 21, 2026

Upload by Finn