Teh Benjamin W, Harrison Simon J, Worth Leon J, Spelman Tim, Thursky Karin A, Slavin Monica A
Department of Infectious Diseases, Peter MacCallum Cancer Centre, East Melbourne, Vic., Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Vic., Australia.
Br J Haematol. 2015 Oct;171(1):100-8. doi: 10.1111/bjh.13532. Epub 2015 Jun 24.
We defined the epidemiology and clinical predictors of infection in patients with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs), proteasome inhibitors (PI) and autologous haematopoietic stem cell transplant (ASCT) in a large longitudinal cohort study. Clinical and microbiology records of patients with MM diagnosed between January 2008 and December 2012 were reviewed to capture patient demographics, characteristics of myeloma and infections (type, severity, outcomes). Conditional risk set modelling was used to determine clinical predictors of infection. One hundred and ninety-nine patients with MM with 771 episodes of infection were identified. 44·6% of infections were clinically defined, 35·5% were microbiologically defined and 19·9% were fever of unknown focus. There was a bimodal peak in incidence of bacterial (4-6 and 70-72 months) and viral infections (7-9 and 52-54 months) following disease diagnosis. Chemotherapy regimens high-dose melphalan [hazard ratio (HR) = 2·07], intravenous cyclophosphamide (HR = 1·96) and intensive combination systemic chemotherapy (HR = 1·86) and cumulative doses of corticosteroid (HR = 3·06 at highest dose) were independently associated with increased risk of infection overall (P < 0·05). IMiDs and PI and other clinical factors were not independently associated with increased risk of infection. New approaches to prevention and treatment of infection should focus upon identified periods of risk and treatment-related risk factors.
在一项大型纵向队列研究中,我们确定了接受免疫调节药物(IMiDs)、蛋白酶体抑制剂(PI)和自体造血干细胞移植(ASCT)的多发性骨髓瘤(MM)患者感染的流行病学特征和临床预测因素。回顾了2008年1月至2012年12月期间确诊的MM患者的临床和微生物学记录,以获取患者的人口统计学信息、骨髓瘤特征和感染情况(类型、严重程度、结局)。采用条件风险集模型确定感染的临床预测因素。共识别出199例MM患者,发生771次感染事件。44.6%的感染为临床定义,35.5%为微生物学定义,19.9%为不明原因发热。疾病诊断后,细菌感染(4 - 6个月和70 - 72个月)和病毒感染(7 - 9个月和52 - 54个月)的发病率出现双峰。高剂量美法仑化疗方案(风险比[HR]=2.07)、静脉注射环磷酰胺(HR = 1.96)和强化联合全身化疗(HR = 1.86)以及皮质类固醇的累积剂量(最高剂量时HR = 3.06)与总体感染风险增加独立相关(P < 0.05)。IMiDs、PI和其他临床因素与感染风险增加无独立相关性。感染预防和治疗的新方法应聚焦于已确定的风险期和与治疗相关的风险因素。