Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study
Ibrutinib-associated invasive fungal diseases in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: An observational study
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DOI：
10.1111/myc.13001
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发表时间：
2019-12-01
期刊：
影响因子：
4.9
通讯作者：
Lachish, Tamar
中科院分区：
文献类型：
--
作者：
Ruchlemer, Rosa;Ben-Ami, Ronen;Lachish, Tamar
背景侵袭性真菌病（IFD）是一种危及生命的感染，最常见于急性白血病患者，伴长期中性粒细胞减少，而在淋巴组织增生性疾病患者中不常见。目的：在开始使用伊克替尼治疗慢性淋巴细胞白血病后不久诊断出曲霉病的初步报告后，开展了一项调查，以寻找伊克替尼治疗期间IFD的其他病例。方法联系当地和国际医生和团体了解相关病例。如果患者符合以下标准，则将其纳入：诊断为慢性淋巴细胞白血病/非霍奇金淋巴瘤;确诊或可能的IFD;以及在诊断IFD之日接受过伊鲁替尼治疗。使用REDCap软件采集临床和实验室数据。结果来自8个国家的22个中心的35例IFD患者报告：26例（74%）患有慢性淋巴细胞白血病。IFD发生前，伊鲁替尼治疗的中位持续时间为45天（范围1-540天）。22例（63%）患者中鉴定出曲霉菌属，9例（26%）患者中鉴定出隐球菌属。69%的患者发生肺部受累，60%发生颅骨受累，60%发生播散性疾病。确诊21例（69%），死亡率69%。使用来自以色列的关于接受伊鲁替尼治疗的患者的数据评价2.4% IFD的患病率。结论：慢性淋巴细胞白血病/非霍奇金淋巴瘤患者接受伊曲替尼治疗后IFD的患病率似乎高于预期。这些患者通常表现出不寻常的临床特征。本研究中IFD的死亡率较高，表明迫切需要进行额外的研究以确定存在伊匹替尼相关IFD风险的患者。
Background Invasive fungal diseases (IFD) are life-threatening infections most commonly diagnosed in acute leukaemia patients with prolonged neutropenia and are uncommonly diagnosed in patients with lymphoproliferative diseases. Objectives Following the initial report of aspergillosis diagnosed shortly after beginning ibrutinib for chronic lymphocytic leukaemia, a survey was developed to seek additional cases of IFD during ibrutinib treatment. Methods Local and international physicians and groups were approached for relevant cases. Patients were included if they met the following criteria: diagnosis of chronic lymphocytic leukaemia/non-Hodgkin lymphoma; proven or probable IFD; and ibrutinib treatment on the date IFD were diagnosed. Clinical and laboratory data were captured using REDCap software. Result Thirty-five patients with IFD were reported from 22 centres in eight countries: 26 (74%) had chronic lymphocytic leukaemia. The median duration of ibrutinib treatment before the onset of IFD was 45 days (range 1-540). Aspergillus species were identified in 22 (63%) of the patients and Cryptococcus species in 9 (26%). Pulmonary involvement occurred in 69% of patients, cranial in 60% and disseminated disease in 60%. A definite diagnosis was made in 21 patients (69%), and the mortality rate was 69%. Data from Israel regarding ibrutinib treated patients were used to evaluate a prevalence of 2.4% IFD. Conclusions The prevalence of IFD among chronic lymphocytic leukaemia/non-Hodgkin lymphoma patients treated with ibrutinib appears to be higher than expected. These patients often present with unusual clinical features. Mortality from IFD in this study was high, indicating that additional studies are urgently needed to identify patients at risk for ibrutinib-associated IFD.