Therapy-related myeloid neoplasms (t-MN) are aggressive leukemia that develops as a complication of prior exposure to DNA-damaging agents. Clonal cytopenia of undetermined significance (CCUS) is a precursor of de novo myeloid neoplasms. Characteristics of CCUS that develop following cytotoxic therapies (therapy-related clonal cytopenia, t-CC) and outcomes following t-CC have not been described. We identified 33 patients with t-CC and compared to a cohort of the WHO-defined t-MN (n = 309). t-CC had a distinct genetic and cytogenetic profile: pathogenic variants (PV) in TET2 and SRSF2 were enriched in t-CC, whereas TP53 PV was more common in t-MN. Ten (30%) t-CC patients developed a subsequent t-MN, with a cumulative incidence of 13%, 23%, and 50% at 6 months, 1, and 5 years, respectively. At t-MN progression, 44% of evaluable patients had identifiable clonal evolution. The median survival following t-CC was significantly superior compared all t-MN phenotype including t-MDS with <5% bone marrow blasts (124.5 vs. 16.3 months, P < 0.001) respectively. The presence of cytogenetic abnormality and the absence of variants in DNMT3A, TET2, or ASXL1 (DTA-genes) were associated with a higher likelihood of developing a subsequent t-MN and an inferior survival. We describe a putative precursor entity of t-MN with distinct features and outcomes.

与治疗相关的髓系肿瘤 (t-MN) 是侵袭性白血病，是先前暴露于 DNA 损伤剂的并发症。意义未明的克隆性血细胞减少症 (CCUS) 是新发髓系肿瘤的前兆。尚未描述细胞毒性治疗后发生的 CCUS 的特征（治疗相关的克隆性血细胞减少症，t-CC）和 t-CC 后的结果。我们确定了 33 名 t-CC 患者，并与 WHO 定义的 t-MN 队列（n  = 309）进行了比较。t-CC 具有独特的遗传和细胞遗传学特征：TET2和SRSF2中的致病变异 (PV)在 t-CC 中富集，而TP53PV 在 t-MN 中更常见。10 名 (30%) t-CC 患者随后出现 t-MN，在 6 个月、1 年和 5 年的累积发病率分别为 13%、23% 和 50%。在 t-MN 进展时，44% 的可评估患者具有可识别的克隆进化。t-CC 后的中位生存期显着优于所有 t-MN 表型，包括分别具有 <5% 骨髓原始细胞的 t-MDS（124.5 与 16.3 个月，P  < 0.001）。DNMT3A、TET2或ASXL1 ( DTA ) 中存在细胞遗传学异常和不存在变异-genes）与更高的发展后续 t-MN 的可能性和较差的生存率相关。我们描述了一个假定的 t-MN 前体实体，具有不同的特征和结果。