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 - 2020/12
Y1 - 2020/12
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).
UR - http://www.scopus.com/inward/record.url?scp=85082878611&partnerID=8YFLogxK
U2 - 10.1038/s41375-020-0795-z
DO - 10.1038/s41375-020-0795-z
M3 - Journal article
C2 - 32203146
SN - 0887-6924
VL - 34
SP - 3256
EP - 3268
JO - Leukemia
JF - Leukemia
IS - 12
ER -