Department of Hematology and.
Department of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Blood Adv. 2020 Mar 10;4(5):885-892. doi: 10.1182/bloodadvances.2019001157.
Therapy-related myeloid neoplasms (tMN) develop after exposure to cytotoxic and radiation therapy, and due to their adverse prognosis, it is of paramount interest to identify patients at high risk. The presence of clonal hematopoiesis has been shown to increase the risk of developing tMN. The value of analyzing hematopoietic stem cells harvested at leukapheresis before autologous stem cell transplantation (ASCT) with next-generation sequencing and immunophenotyping represents potentially informative parameters that have yet to be discovered. We performed a nested case-control study to elucidate the association between clonal hematopoiesis, mobilization potential, and aberrant immunophenotype in leukapheresis products with the development of tMN after ASCT. A total of 36 patients with nonmyeloid disease who were diagnosed with tMN after treatment with ASCT were included as case subjects. Case subjects were identified from a cohort of 1130 patients treated with ASCT and matched with 36 control subjects who did not develop tMN after ASCT. Case subjects were significantly poorer mobilizers of CD34+ cells at leukapheresis (P = .016), indicating that these patients possess inferior bone marrow function. Both clonal hematopoiesis (odds ratio, 5.9; 95% confidence interval, 1.8-19.1; P = .003) and aberrant expression of CD7 (odds ratio, 6.6; 95% confidence interval, 1.6-26.2; P = .004) at the time of ASCT were associated with an increased risk of developing tMN after ASCT. In conclusion, clonal hematopoiesis, present at low variant allele frequencies, and aberrant CD7 expression on stem cells in leukapheresis products from patients with nonmyeloid hematologic cancer hold potential for the early identification of patients at high risk of developing tMN after ASCT.
治疗相关髓系肿瘤（tMN）发生在暴露于细胞毒性和放射治疗之后，由于其预后不良，因此识别高危患者至关重要。克隆性造血的存在已被证明会增加发生 tMN 的风险。使用下一代测序和免疫表型分析在自体干细胞移植（ASCT）前采集的白细胞分离物中的造血干细胞的价值代表了尚未发现的潜在信息参数。我们进行了一项嵌套病例对照研究，以阐明 ASCT 后 tMN 发展与 ASCT 前白细胞分离物中克隆性造血、动员潜能和异常免疫表型之间的关联。共有 36 例接受 ASCT 治疗后诊断为 tMN 的非髓性疾病患者被纳入病例组。病例组从接受 ASCT 治疗的 1130 例患者队列中确定，并与 36 例未发生 ASCT 后 tMN 的对照组相匹配。病例组在白细胞分离术时的 CD34+细胞动员能力明显较差（P =.016），表明这些患者的骨髓功能较差。在 ASCT 时的克隆性造血（优势比，5.9；95%置信区间，1.8-19.1；P =.003）和 CD7 异常表达（优势比，6.6；95%置信区间，1.6-26.2；P =.004）均与 ASCT 后发生 tMN 的风险增加相关。总之，低变异等位基因频率存在的克隆性造血和非髓性血液恶性肿瘤患者白细胞分离物中干细胞的异常 CD7 表达有可能早期识别 ASCT 后发生 tMN 的高危患者。
