NEJM EvidencePrediction of Risk for Myeloid Malignancy in Clonal Hematopoiesis

A Clonal Hematopoiesis Risk Score (CHRS) to Identify High-Risk CHIP/CCUS Patients

A recent study has developed a new prognostic framework, the Clonal Hematopoiesis Risk Score (CHRS), to predict the risk of myeloid neoplasms (MN) in patients with Clonal Hematopoiesis of Indeterminate Potential (CHIP) and Clonal Cytopenia of Undetermined Significance (CCUS).

HCN Medical Memo
The CHRS provides a simple yet effective tool for healthcare professionals to identify high-risk CHIP/CCUS patients who are more likely to progress to MN. This could significantly aid in clinical management and research.

Study Design

• The study analyzed sequenced exomes of healthy UK Biobank participants (N=438,890) in separate derivation and validation cohorts.
• Genetic mutations, laboratory values, and MN outcomes were used in conditional probability–based recursive partitioning and Cox regression to determine predictors of incident MN.
• Independent CHIP/CCUS patient cohorts were used to test the prognostic capability of the CHRS in the clinical setting.

AML was diagnosed in more than 21,000 people and resulted in nearly 11,000 deaths in the US in 2019. The incidence of AML has increased 3.7% per year from 2006 to 2015.

Key Findings

• Recursive partitioning distinguished patients with CHIP/CCUS with 10-year probabilities of MN ranging from 0.0077 to 0.85.
• Key features, including single DNMT3A mutations, high-risk mutations, two or more mutations, a VAF of 0.2 or more, 65 years of age or older, having CCUS versus CHIP, and red blood cell indices, influenced MN risk in a variable direction.
• CHRS was used to define low-risk (n=10,018 [88.4%]), intermediate-risk (n=1196 [10.5%]), and high-risk (n=123 [1.1%]) groups.
• In clinical cohorts, most MN events occurred in high-risk patients with CHIP/CCUS.

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