Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study.
Simon HusbyFrancesco FaveroChristian NielsenBetina S SørensenJohn BæchKathrine GrellJakob W HansenFrancisco G Rodriguez-GonzalezEva K HaastrupAnne Fischer-NielsenPernille AndersenBente ArboeSusanne G SækmosePer B HansenIlse ChristiansenErik Clasen-LindeLene MeldgaardLene H EbbesenErik K SegelPär JosefssonMichael ThorsgaardTarec C El-GalalyPeter BrownJoachim WeischenfeldtThomas S LarsenKirsten GrønbækPublished in: Leukemia (2020)
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).
Keyphrases
- dna repair
- high dose
- stem cell transplantation
- dna damage
- high throughput
- end stage renal disease
- stem cells
- circulating tumor cells
- ejection fraction
- newly diagnosed
- chronic kidney disease
- diffuse large b cell lymphoma
- dna damage response
- emergency department
- prognostic factors
- low dose
- computed tomography
- risk assessment
- cell therapy
- patient reported outcomes
- rectal cancer
- climate change
- mesenchymal stem cells
- radiation therapy
- free survival