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Abstract：
Chronic neutrophilic leukemia (CNL) is a rare but potentially aggressive BCR::ABL1 negative myeloproliferative neoplasm, characterized by sustained mature, neutrophilic leukocytosis. The discovery of key driver mutations in the colony-stimulating-factor-3 receptor (CSF3R) gene resulted in the updated World Health Organization (WHO) diagnostic criteria in 2016. A significant number of CNL cases have been associated with plasma cell dyscrasias, predominantly multiple myeloma (MM) and monoclonal gammopathy of unknown significance (MGUS). Compared to pure CNL, mutated CSF3R is infrequently reported in CNL cases associated with monoclonal gammopathies (MG). Until now it remains unclear whether CNL and occurring plasma cell neoplasms are clonally related or CNL is developing secondary to the underlying dyscrasia. Owing to its rarity, currently no standard of care management exists for CNL and MG-associated CNL. In this case series we report the multi-center experience of five MG-associated CNL cases with a median age of diagnosis of 69 years. Three patients (66%) showed predominance of lambda light chain expression. Four (80%) eventually evolved to MM, and one CNL-MGUS patient developed secondary acute myeloid leukemia (AML). Mutated CSF3R was present in the patient who developed AML but was absent in other cases. To assess possible associated genetic aberrations we performed recurrent analysis with next-generation sequencing (NGS). Two patients (40%) deceased with a median time of survival of 8 years after CNL diagnosis. Three (60%) are currently in follow-up with no reoccurring leukocytosis. This case series, followed by a short review, provides a long-term clinical and genetic overview of five CNL cases associated with MG.
摘要：
慢性中性粒细胞白血病（CNL）是一种罕见但潜在侵袭性BCR：：ABL1阴性骨髓增殖性肿瘤，以持续成熟为特征，嗜中性白细胞增多症。集落刺激因子3受体（CSF3R）基因中关键驱动突变的发现导致了2016年世界卫生组织（WHO）更新的诊断标准。相当数量的CNL病例与浆细胞发育不良有关，主要是多发性骨髓瘤（MM）和未知意义的单克隆丙种球蛋白病（MGUS）。与纯CNL相比，突变的CSF3R在与单克隆免疫球蛋白病（MG）相关的CNL病例中很少报道。到目前为止，尚不清楚CNL和发生的浆细胞肿瘤是否与克隆相关，还是CNL继发于潜在的异常。由于它的稀有性,目前对于CNL和MG相关CNL尚无标准的护理管理.在此病例系列中，我们报告了5例MG相关CNL病例的多中心经验，中位诊断年龄为69岁。三名患者(66%)显示λ轻链表达占优势。四个（80％）最终演变成MM，1例CNL-MGUS患者发生继发性急性髓系白血病(AML)。发生AML的患者存在突变的CSF3R，但在其他情况下不存在。为了评估可能的相关遗传畸变，我们使用下一代测序（NGS）进行了反复分析。两名患者（40％）在CNL诊断后死亡，中位生存期为8年。三个（60％）目前正在随访中，没有再次发生白细胞增多症。这个案例系列,接下来是简短的回顾，提供了5例与MG相关的CNL病例的长期临床和遗传概述。
