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

Simon Husby, Francesco Favero, Christian Nielsen, Betina S Sørensen, John Bæch, Kathrine Grell, Jakob W Hansen, Francisco G Rodriguez-Gonzalez, 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 JosefssonMichael Thorsgaard, Tarec C El-Galaly, Peter Brown, Joachim Weischenfeldt, Thomas S Larsen, Kirsten Grønbæk

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Abstrakt

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).

OriginalsprogEngelsk
Sider (fra-til)3256-3268
Antal sider13
TidsskriftLeukemia
Vol/bind34
Udgave nummer12
Tidlig onlinedato20 mar. 2020
DOI
StatusUdgivet - dec. 2020

Fingeraftryk Udforsk hvilke forskningsemner 'Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study' indeholder.

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