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

Research output: Contribution to journalJournal articleResearchpeer-review

  • Christian Nielsen
  • Betina S Sørensen
  • John Bæch
  • Eva K Haastrup
  • Anne Fischer-Nielsen
  • Pernille Andersen
  • Bente Arboe
  • Susanne G Sækmose
  • Per B Hansen
  • Ilse Christiansen
  • Erik Clasen-Linde
  • Lene Meldgaard
  • Lene H Ebbesen
  • Erik K Segel
  • Pär Josefsson
  • Michael Thorsgaard
  • Tarec C El-Galaly
  • Thomas S Larsen

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).

Original languageEnglish
Pages (from-to)3256-3268
Number of pages13
Publication statusPublished - 2020

ID: 238428793