Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort
Thrombotic microangiopathy associated with gemcitabine use: Presentation and outcome in a national French retrospective cohort
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DOI：
10.1111/bcp.13808
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发表时间：
2019-02-01
影响因子：
3.4
通讯作者：
Jourde-Chiche, Noemie
中科院分区：
文献类型：
--
作者：
Daviet, Florence;Rouby, Franck;Jourde-Chiche, Noemie
吉西他滨与血栓性微血管病（TMA）有关。我们对吉西他滨相关TMA（G-TMA）进行了一项全国性回顾性研究。方法分析1998年至2015年法国药物警戒网络和法国TMA参考中心报告的所有G-TMA病例，以及探索补体旁路途径异常的病例。结果120例患者确诊为G-TMA，中位年龄61.5岁，中位治疗时间210 d，累积剂量12941 mg m（-2）。吉西他滨适应症为：胰腺癌（52.9%）、肺癌（12.6%）和乳腺癌（7.6%），34.2%的病例为转移性。主要症状为水肿（56.7%）和新发或加重的高血压（62.2%）。大多数患者表现为溶血性贫血（95.6%）和血小板减少症（74.6%）。97.4%的患者报告急性肾损伤，27.8%的患者需要透析。治疗包括：血浆置换（PE; 39.8%）、新鲜冷冻血浆（21.4%）、皮质类固醇（15.3%）和依库珠单抗（5.1%）。TMA完全缓解率为42.1%，血液学缓解率为23.1%，无改善率为34.7%。已知52例患者的生存状态，其中29例死亡（54.7%）。接受PE治疗的患者，尽管急性肾损伤更严重，需要更频繁的透析，但缓解率相当，但不良事件更多。在探索的患者中未记录到补体旁路途径异常。结论本研究证实了G-TMA的严重程度，与严重肾功能衰竭和死亡相关。可监测接受吉西他滨治疗的患者的水肿和高血压，以检测早期TMA。PE或依库珠单抗的获益值得进一步研究。
Aims Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine-associated TMA (G-TMA). Methods From 1998 to 2015, all cases of G-TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results G-TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m(-2). Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new-onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion This large cohort confirms the severity of G-TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation.