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Clinical impact of clonal hematopoiesis in patients with lymphoma undergoing ASCT: a national population-based cohort study
Leukemia ( IF 11.4 ) Pub Date : 2020-03-20 , DOI: 10.1038/s41375-020-0795-z
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 Josefsson , Michael Thorsgaard , Tarec C. El-Galaly , Peter Brown , Joachim Weischenfeldt , Thomas S. Larsen , Kirsten Grønbæk

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).



中文翻译:

一项全国性人群队列研究表明,克隆性造血对接受ASCT的淋巴瘤患者的临床影响

怀疑潜在的克隆性造血功能(CHIP)是癌症患者的危险因素。这项研究旨在评估CHIP在以人群为基础的大剂量化疗和自体干细胞移植(ASCT)淋巴瘤患者中的临床后果。我们确定了在丹麦所有移植中心接受干细胞采集的892名淋巴瘤患者。共有565位患者有可用的收获样品,并通过下一代测序对其进行了CHIP分析,中位随访时间为9.1年。在打算立即进行ASCT的患者中,有25.5%(112/440)携带至少一种CHIP突变。与以前的单中心研究相反,在多变量分析中,CHIP与总体生存率(OS)较低无关。然而,PPM1DTP53RAD21BRCC3)的OS明显较差(随访1年后的心率2.79,95%置信区间1.71-4.56;p  <0.0001),这在多变量分析中也很明显(p  = 0.00067)。这些患者的治疗相关白血病和接受重症监护的比例也有所增加。此外,在未接受立即ASCT的患者中,还发现具有DNA修复突变的个体的OS明显较差(p  = 0.003)。

更新日期:2020-04-24
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