Clonal hematopoiesis in AML long-term survivors: Risk factors and clinical consequences

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Clonal hematopoiesis (CH) is prevalent in the general population, associated with health risks.
• Its occurrence and implications in acute myeloid leukemia (AML) long-term survivors (LTS) are not well understood.

Purpose of the Study:

• To determine the prevalence and clinical significance of CH in AML LTS.
• To investigate factors influencing CH in AML LTS based on treatment modality.

Main Methods:

• Analysis of CH in 373 AML LTS with a median 11.6-year follow-up.
• Utilized a sensitive targeted sequencing assay employing single-molecule molecular inversion probes.
• Categorized CH based on variant allele frequency (VAF): small-clone CH (<2% VAF) and CH of indeterminate potential (≥2% VAF).

Main Results:

• CH was detected in 61.9% of AML LTS.
• CH prevalence was higher in chemotherapy-only treated survivors (75.7%) versus allogeneic stem cell transplant (alloSCT) recipients (54.0%) and controls.
• CH prevalence correlated with age in chemotherapy-treated survivors and hematopoietic age in alloSCT recipients.
• Specific variants (TP53, PPM1D) were more common in chemotherapy-treated survivors.
• CH variants (≥10% VAF) were associated with increased diabetes risk in alloSCT recipients and secondary neoplasms in chemotherapy-treated survivors.

Conclusions:

• CH is highly prevalent in AML LTS.
• Treatment modality significantly impacts CH prevalence and associated risks.
• CH in AML LTS warrants further investigation for its clinical relevance and management.