TY - JOUR

T1 - Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT

T2 - a national population-based cohort study

AU - Husby, Simon

AU - Favero, Francesco

AU - Nielsen, Christian

AU - Sørensen, Betina S

AU - Bæch, John

AU - Grell, Kathrine

AU - Hansen, Jakob W

AU - Rodriguez-Gonzalez, Francisco G

AU - Haastrup, Eva K

AU - Fischer-Nielsen, Anne

AU - Andersen, Pernille

AU - Arboe, Bente

AU - Sækmose, Susanne G

AU - Hansen, Per B

AU - Christiansen, Ilse

AU - Clasen-Linde, Erik

AU - Meldgaard, Lene

AU - Ebbesen, Lene H

AU - Segel, Erik K

AU - Josefsson, Pär

AU - Thorsgaard, Michael

AU - El-Galaly, Tarec C

AU - Brown, Peter

AU - Weischenfeldt, Joachim

AU - Larsen, Thomas S

AU - Grønbæk, Kirsten

PY - 2020

Y1 - 2020

N2 - 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).

AB - 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).

U2 - 10.1038/s41375-020-0795-z

DO - 10.1038/s41375-020-0795-z

M3 - Journal article

C2 - 32203146

VL - 34

SP - 3256

EP - 3268

JO - Leukemia

JF - Leukemia

SN - 0887-6924

ER -