17 Ipilimumab所致血小板减少症:个案报告和文献综述(血液系统)
【附】KOPECKY JINDRICH, TROJANOVA PETRONELA. Treatment possibilities of Ipilimumab-induced thrombocytopenia—case study and literature review[J]. Japanese Journal of Clinical Oncology, 2015, 45(4): 381-384.
Kopecky Jindrich等报道了1例使用Ipilimumab治疗黑色素瘤出现药物诱导的免疫介导的血小板减少症的病例。患者在用药前接受常规检查无异常,第2次用药前常规检测发现Ⅳ度血小板减低,患者未见出血征象。除Ipilimumab外患者同时接受高动脉血压(钙剂和β受体阻滞剂,血管紧张素转换酶抑制剂和保钾利尿剂组合)和高脂血症(阿托伐他汀)的治疗,并且他因过去的短暂性脑缺血发作服用阿司匹林。骨穿排除骨髓肿瘤浸润,诊断为Ipilimumab引起的免疫性血小板减少性紫癜。终止Ipilimumab治疗,予血小板输注,高剂量皮质类固醇静脉治疗有效。患者血小板恢复后因病情进展,换用细胞毒药物化疗。
【精评】孤立性血小板减少症很少与Ipilimumab有关,并且没有这种并发症的标准治疗方法。与使用药物相关的大多数血小板减少症是由针对所施用药物的特定结构的抗体引起的。最常见的情况是在给药后1~2周观察到。诊断基于临床表现和最终排除其他可能的原因,如微血管病性溶血性贫血,血栓性血小板减少性紫癜或弥散性血管内凝血。免疫性血小板减少性紫癜的治疗基于皮质类固醇,最初使用甲泼尼龙冲击治疗和泼尼松龙的维持治疗[1~2mg/(kg·d)]。约70%的患者对泼尼松龙治疗有反应,但持久反应发生率仅为10%~15%,需要长期口服治疗。大多数研究和临床实践认为对治疗有反应定义为血小板数量增加30×109/L和(或)绝对血小板水平超过50×109/L。对皮质类固醇治疗的反应通常发生在治疗前的1~2周。如果在治疗4~6周内没有反应或者反应不是永久性的,则血小板减少症被认为是皮质类固醇的难治性疾病。可使用其他免疫抑制药物,如环孢素,静脉注射免疫球蛋白(1g/kg)。尚无针对Ipilimumab诱导的血小板减少症后重新开始治疗的相关经验,因此在这方面有待更多的病例数据支持。
参考文献
[1] MOMTAZ P, LACOUTURE M E, CHAPMAN P B. Current choices and strategies in the treatment of Metastatic[J]. Melanoma Letter Spring, 2014, 32: 1.
[2] HODI F S, O'DAY S J, MCDERMOTT D F, et al. Improved survival with Ipilimumab in patients with Metastatic melanoma[J]. N Engl J Med, 2010, 363: 711-723.
[3] WEBER J S, KAHLER K C, HAUSCHILD A. Management of immune-related adverse events and kinetics of response with Ipilimumab[J]. J Clin Oncol, 2012, 30: 2691-2697.
[4] AHMAD S, LEWIS M, CORRIE P, et al. Ipilimumab-induced thrombocytopenia in a patient with Metastatic melanoma[J]. J Oncol Pharm Pract, 2012, 8: 287-292.
[5] ASTER R H, CURTIS B R, MCFARLAND J G, et al. Drug induced immune thrombocytopenia: pathogenesis, diagnosis and management[J]. J Thromb Haemost, 2009, 7: 911-918.
[6] STASI R, EVANGELISTA M L, STIPA E, et al. Idiopathic thrombocytopenic purpura: current concept in pathophysiology and management[J]. Thromb Haemost, 2008, 99: 4-13.
[7] CHENG Y, WONG R S, SOO Y O, et al. Initial treatment of immune thrombocy topenic purpura with high-dose dexamethasone[J]. N Engl J Med, 2003, 349: 831-836.
[8] PROVAN D, STASI R, NEWLAND A C, et al. International consensus report on the investigation and management of primary immune thrombocytopenia[J]. Blood, 2010, 115: 168-186.
(邸明一 倪 军 张 力)