Effects of ruxolitinib on secondary myelofibrosis following chronic neutrophilic leukemia with the CSF3R T618I mutation
Effects of ruxolitinib on secondary myelofibrosis following chronic neutrophilic leukemia with the CSF3R T618I mutation
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鲁索替尼对 CSF3R T618I 突变慢性中性粒细胞白血病继发性骨髓纤维化的影响
DOI：
10.1007/s00277-020-04185-1
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发表时间：
2021
影响因子：
3.5
通讯作者：
Takenaka Katsuto
中科院分区：
文献类型：
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作者：
Ikeda Yuichi;Yamanouchi Jun;Takenaka Katsuto
慢性嗜中性粒细胞白血病（CNL）是一种以成熟中性粒细胞增殖为特征的骨髓增生性肿瘤。根据CSF 3R T618 I突变的存在进行诊断[1，2]。这种疾病的治疗方法尚未确定，但CSF 3R T618 I突变可能激活JAK/STAT通路。已经指出了抑制JAK 2的ruxolitinib的功效。我们报告了1例CSF 3R T618 I突变的CNL后鲁索替尼对继发性骨髓纤维化有效的患者。患者为66岁男性。体检白细胞增多，来我院就诊。初次就诊时外周血白细胞计数为74，900/μL（中性粒细胞96.8%，淋巴细胞1.4%，单核细胞0.8%，嗜酸性粒细胞0.2%，晚幼粒细胞0.6%，成髓细胞0.2%），显示显著增加。成熟的中性粒细胞占较大部分。关于骨髓结果，中性粒细胞占83.7%，表明骨髓增生伴轻度纤维化。腹部计算机断层扫描显示脾肿大（17× 15× 8.5 cm）。使用QIAampDNA Blood Mini Kit（QIAGEN，希尔登，德国）从外周血中提取DNA，并使用聚合酶链反应（PCR）扩增CSF 3R编码区。随后，使用3500遗传分析仪（Applied Biosystems，Tokyo，Japan）进行PCR产物的直接测序以鉴定CSF 3R T618 I基因突变。因此，2016年根据WHO诊断标准诊断为CNL和继发性骨髓纤维化[2]，诊断后给予鲁索替尼10 mg/天。随后，剂量逐渐增加至30 mg/天。在给药后几个月内，脾肿大和血液学数据得到改善。在开始鲁索替尼给药后5个月观察到黑便。ruxolitinib的给药中断了几周，但随后以20 mg重新开始。在开始ruxolitinib给药后16个月，观察到白细胞计数增加和贫血/血小板减少症。给药后17个月发生细菌性肺炎，导致致死性结局（图1）。
Dear Editor, Chronic neutrophilic leukemia (CNL) is a myeloproliferative neoplasm characterized by the proliferation of mature neutrophils. It is diagnosed based on the presence of the CSF3R T618I mutation [1, 2]. Treatment for this disease has not been established, but the CSF3R T618I mutation may activate the JAK/STAT pathway. The efficacy of ruxolitinib, which inhibits JAK2, has been indicated. We report a patient in whom ruxolitinib was effective for secondary myelofibrosis following CNL with the CSF3R T618I mutation. The patient was a 66-year-old male. A health checkup showed leukocytosis, and he consulted our hospital. The peripheral blood leukocyte count on the initial consultation was 74,900/μL (neutrophils 96.8%, lymphocytes 1.4%, monocytes 0.8%, eosinophils 0.2%, metamyelocytes 0.6%, and myeloblasts 0.2%), showing a marked increase. Mature neutrophils comprised the greater portion. Concerning the bone marrow findings, neutrophil cells accounted for 83.7%, suggesting hyperplastic bone marrow with slight fibrosis. Abdominal computed tomography revealed splenomegaly (17× 15× 8.5 cm). DNA was extracted from peripheral blood using a QIAampDNA Blood Mini Kit (QIAGEN, Hilden, Germany), and the CSF3R-coding area was amplified with polymerase chain reaction (PCR). Subsequently, direct sequencing of PCR products was conducted using a 3500 genetic analyzer (Applied Biosystems, Tokyo, Japan) to identify the CSF3R T618I gene mutation. Thus, a diagnosis of CNL and secondary myelofibrosis was made according to the WHO diagnostic criteria in 2016 [2].After diagnosis, ruxolitinib at 10 mg/day was administered. Subsequently, the dose was gradually increased to 30 mg/day. Improvements in splenomegaly and hematological data were achieved in a few months after the administration. Melena was noted 5 months after starting the administration of ruxolitinib. The administration of ruxolitinib was discontinued for a few weeks, but, then, it was resumed at 20 mg. An increase in the leukocyte count and anemia/thrombocytopenia were noted 16 months after the start of ruxolitinib administration. Bacterial pneumonia occurred 17 months after the administration, leading to a fatal outcome (Fig. 1).
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DOI：
10.1056/nejmoa1214514
发表时间：
2013-05-09
期刊：
The New England journal of medicine
影响因子：
--
作者：
Maxson JE;Gotlib J;Pollyea DA;Fleischman AG;Agarwal A;Eide CA;Bottomly D;Wilmot B;McWeeney SK;Tognon CE;Pond JB;Collins RH;Goueli B;Oh ST;Deininger MW;Chang BH;Loriaux MM;Druker BJ;Tyner JW
通讯作者：
Tyner JW
下一代测序技术揭示 MLL-AF9 白血病中 MYB 调节和功能的分子机制
影响因子：
10.1
作者：
Lau I;A. Thomas;J. Kerry;Laura J. Godfrey;C. Nerlov;P. Vyas;T. Milne
通讯作者：
T. Milne
影响因子：
12.8
作者：
Elliott, Michelle A.;Tefferi, Ayalew
通讯作者：
Tefferi, Ayalew
影响因子：
20.3
作者：
Fleischman, Angela G.;Maxson, Julia E.;Tyner, Jeffrey W.
通讯作者：
Tyner, Jeffrey W.