Smirnova Svetlana Yu, Al-Radi Lyubov S, Moiseeva Tatyana N, Gemdzhian Eduard G, Yakutik Igor A, Julhakyan Hunan L, Novikov Vyacheslav A, Galstyan Gennady M, Sudarikov Andrey B
National Research Center for Hematology, Moscow, Russia.
National Research Center for Hematology, Moscow, Russia.
Clin Lymphoma Myeloma Leuk. 2021 Jul;21(7):427-430. doi: 10.1016/j.clml.2021.02.005. Epub 2021 Mar 3.
Standard therapy in hairy cell leukemia (HCL) is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications; it is thus a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. Because vemurafenib does not have a myelotoxic effect, we thought that it could be used to treat HCL associated with deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib followed by a standard course of cladribine provided to 22 patients with deep neutropenia/agranulocytosis with or without infectious complications at diagnosis. Vemurafenib was provided to 22 patients with HCL. The response to therapy was evaluated by complete blood cell count (absolute neutrophil count [ANC], hemoglobin concentration, platelet count, absence of hairy cells), spleen size (assessed by ultrasound), and reduce infectious complications. After that, a standard course of cladribine was provided. Among the 22 patients, the male/female sex ratio was 2:1, and median (range) age was 52 (24-78) years. There were 7 patients with severe infectious manifestations admitted to the intensive care unit, including 1 patient during extracorporeal membrane oxygenation. The median (range) ANC at diagnosis was 0.3 (0.04-0.7) × 10/L. Vemurafenib was provided at a dosage of 240 mg 1 or 2 times a day. In 20 patients, vemurafenib was provided for 3 months or more. In 1 case, the effect was not obtained during 1 month of treatment, and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vemurafenib, an increase of ANC was observed and the infectious complications resolved, thus allowing the application of cladribine therapy. After a standard course (0.1 mg/kg per day for 7 days) of cladribine chemotherapy, 18 patients (90%) experienced complete clinical remission and 2 patients (10%) experienced partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy was still ongoing 2 months after initiating therapy. In cases of proven BRAF mutation, vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.
在伴有或不伴有感染并发症的严重中性粒细胞减少/粒细胞缺乏症时，毛细胞白血病（HCL）通常无法进行标准治疗；因此，这是一个复杂的治疗问题。自2012年以来，维莫非尼一直用于治疗难治性HCL。由于维莫非尼没有骨髓毒性作用，我们认为它可作为在使用克拉屈滨治疗前的初始阶段，用于治疗伴有或不伴有感染并发症的严重中性粒细胞减少/粒细胞缺乏症相关的HCL。我们对22例诊断时伴有或不伴有感染并发症的严重中性粒细胞减少/粒细胞缺乏症患者，先使用维莫非尼治疗，随后给予标准疗程克拉屈滨的治疗情况进行了回顾性分析。22例HCL患者接受了维莫非尼治疗。通过全血细胞计数（绝对中性粒细胞计数[ANC]、血红蛋白浓度、血小板计数、无毛细胞）、脾脏大小（通过超声评估）和感染并发症的减少来评估治疗反应。之后，给予标准疗程的克拉屈滨。22例患者中，男女比例为2:1，中位（范围）年龄为52（24 - 78）岁。有7例有严重感染表现的患者入住重症监护病房，其中1例在体外膜肺氧合期间。诊断时的中位（范围）ANC为0.3（0.04 - 0.7）×10⁹/L。维莫非尼的给药剂量为每日240 mg，1次或2次。20例患者接受维莫非尼治疗3个月或更长时间。1例患者在治疗1个月时未获得疗效，在长期粒细胞缺乏期间死于严重感染并发症。在21例接受维莫非尼治疗的患者中，观察到ANC增加且感染并发症得到解决，从而得以应用克拉屈滨治疗。在接受标准疗程（每日0.1 mg/kg，共7天）的克拉屈滨化疗后，18例患者（90%）实现完全临床缓解，2例患者（10%）部分缓解，仍有脾肿大。1例患者在开始治疗2个月后维莫非尼治疗仍在进行。在证实存在BRAF突变的病例中，在使用嘌呤类似物进行标准治疗前，维莫非尼可成功用作伴有或不伴有感染并发症的严重中性粒细胞减少/粒细胞缺乏症患者的有效初始治疗。
