Cancer Therapy and Clonal Hematopoiesis, MSK, Blood Adv 2023

Overview

Cohort of 42,714 MSK patients with nonhematologic cancer who had matched-normal peripheral blood sequencing as the germline comparator for MSK-IMPACT tumor profiling. Built to characterize clonal hematopoiesis (CH) genotypes — including “silent” synonymous/noncoding variants — associated with subsequent hematologic malignancy PMID:38147626.

Composition

  • 42,714 patients with nonhematologic cancer profiled by MSK-IMPACT; 39,510 were alive without a hematologic diagnosis within 2 weeks of sequencing and had follow-up beyond that PMID:38147626.
  • Hematologic malignancy events identified via a hybrid NLP (CEDARS) + manual chart review pipeline, adjudicated by board-certified hematologists/oncologists PMID:38147626.
  • 26 patients had paired post-diagnosis sequencing for VAF trajectory analysis PMID:38147626.

Assays / panels (linked)

Papers using this cohort

  • PMID:38147626 — Stonestrom et al., High-risk and silent clonal hematopoietic genotypes in patients with nonhematologic cancer, Blood Advances 2024.

Notable findings derived from this cohort

  • Any CH conferred HR = 1.93 (95% CI 1.45–2.57, P<.001) for subsequent hematologic malignancy after adjustment for age, sex, and solid cancer type PMID:38147626.
  • JAK2, RUNX1, and XPO1 identified as high-risk CH genotypes PMID:38147626.
  • Silent CH (synonymous/noncoding) predicts hematologic malignancy risk, especially with multiple variants or high VAF PMID:38147626.
  • At hematologic malignancy onset, JAK2 and TP53 VAFs expanded while DNMT3A and silent CH VAFs mostly decreased PMID:38147626.

Sources

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