Survivors of pediatric cancer may have an increased risk of clonal hematopoiesis at any age, according to research published in Cancer Discovery.

Researchers found a higher rate of clonal hematopoiesis in pediatric cancer survivors than in matched control individuals. Past treatment with an alkylating agent, radiation, or bleomycin was associated with an increased risk of clonal hematopoiesis. 

The researchers conducted this retrospective study using data from 2860 pediatric cancer survivors and 324 demographic-matched community control individuals without a history of cancer. 

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The median age of the cancer survivor cohort was 31.6 (range, 6.0-66.4) years, and the median age of the control individuals was 34.6 (range, 18.3-70.2) years. The median follow-up was 23.5 years.

The researchers performed targeted sequencing of 39 cancer-predisposing genes or genes associated with hematologic malignancy. They identified 540 validated clonal hematopoiesis variants, with a median variant allele frequency of 0.4%.

The overall prevalence of clonal hematopoiesis was significantly higher in the cancer survivor cohort than in the control cohort — 15% and 8.6%, respectively (P =1.44 × 10-3).

In both cohorts, the prevalence of clonal hematopoiesis was associated with age. However, the pediatric cancer survivors were more likely than control individuals to have clonal hematopoiesis at any age. 

In a multivariate analysis, treatments that were associated with a greater risk of clonal hematopoiesis included alkylating agents (odds ratio [OR], 1.3; P <.001), radiation (OR, 1.2; P < .01), and bleomycin (OR, 1.1; P <.05). 

Survivors of Hodgkin lymphoma (HL), soft tissue sarcoma, germ cell tumor, rhabdomyosarcoma, neuroblastoma, non-Hodgkin lymphoma, or acute lymphoblastic leukemia had an increased risk of clonal hematopoiesis (P =1.83 x 10-57). The researchers noted that all of these patients were more likely to have been treated with an alkylating agent.

The researchers also found significant enrichment for STAT3 mutations, particularly the Y640F mutation, among survivors of HL. The proportion of patients with STAT3 mutations was 9.3% among HL survivors, 1.4% among survivors of other cancers (P =9.21 x 10-14 for HL survivors vs other survivors), and 0.6% in the control cohort (P =.426 for other survivors vs control individuals). 

“This first comprehensive CH [clonal hematopoiesis] analysis in long-term survivors of pediatric cancer presents the elevated prevalence and therapy-exposures/diagnostic spectrum associated with CH,” the researchers wrote. “Due to the contrasting dynamics of clonal expansion for age-related versus therapy-related CH, longitudinal monitoring is recommended to ascertain the long-term effects of therapy-induced CH in pediatric cancer survivors.” 


Hagiwara K, Natarajan S, Wang Z, et al. Dynamics of age- versus therapy-related clonal hematopoiesis in long-term survivors of pediatric cancer. Cancer Discov. Published online February 8, 2023. doi:10.1158/2159-8290.CD-22-0956