Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study

Leukemia. 2020 Dec;34(12):3256-3268. doi: 10.1038/s41375-020-0795-z. Epub 2020 Mar 20.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is suspected of being a risk factor for patients with cancer. This study aimed to assess the clinical consequences of CHIP in patients with lymphoma intended for high-dose chemotherapy and autologous stem-cell transplantation (ASCT) in a population-based setting. We identified 892 lymphoma patients who had undergone stem cell harvest at all transplant centers in Denmark. A total of 565 patients had an available harvest sample, which was analysed for CHIP by next-generation sequencing, and the median follow-up was 9.1 years. Of the patients who were intended for immediate ASCT, 25.5% (112/440) carried at least one CHIP mutation. In contrast to previous single-center studies CHIP was not associated with inferior overall survival (OS) in multivariate analyses. However, patients with mutations in genes of the DNA repair pathway (PPM1D, TP53, RAD21, BRCC3) had a significant inferior OS (HR after 1 year of follow-up 2.79, 95% confidence interval 1.71-4.56; p < 0.0001), which also was evident in multivariate analysis (p = 0.00067). These patients had also increased rates of therapy-related leukemia and admission to intensive care. Furthermore, in patients who did not undergo immediate ASCT, a significant inferior OS of individuals with DNA repair mutations was also identified (p = 0.003).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Clonal Hematopoiesis / drug effects
  • Clonal Hematopoiesis / physiology*
  • DNA Repair / drug effects
  • DNA Repair / genetics
  • Female
  • Hematopoietic Stem Cell Transplantation / methods
  • Humans
  • Lymphoma / drug therapy
  • Lymphoma / surgery*
  • Lymphoma / therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Transplantation, Autologous / methods

Substances

  • Antineoplastic Agents