Aagaard Theis, Reekie Joanne, Jørgensen Mette, Roen Ashley, Daugaard Gedske, Specht Lena, Sengeløv Henrik, Mocroft Amanda, Lundgren Jens, Helleberg Marie
Centre of Excellence for Health, Immunity and Infections (CHIP), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, University College London, London, UK.
Cancer Med. 2020 May;9(9):3033-3042. doi: 10.1002/cam4.2955. Epub 2020 Mar 7.
Febrile neutropenia (FN) is a critical complication of chemotherapy associated with increased in-hospital mortality. However, associations with increased mortality and intensive care unit (ICU) admissions during longer follow-up are not established. Patients treated with standard first-line chemotherapy for solid cancers at Rigshospitalet, Denmark in 2010-2016 were included. Incidence rate ratios (IRR) of all-cause, infectious and cardiovascular mortality, and ICU admissions after FN were analyzed by Poisson regression. Risk factors at the time of FN were analyzed in the subpopulation of patients with FN; all-cause mortality was further stratified by the time periods 0-30, 31-365, and 366+ days after FN. We included 9018 patients with gastric (14.4%) and breast (13.1%) cancer being the most common, 51.2% had locally advanced or disseminated disease and the patients had a median Charlson Comorbidity Index score of 0 (interquartile range, 0-0). During follow-up, 845 (9.4%) experienced FN and 4483 (49.7%) died during 18 775 person-years of follow-up. After adjustment, FN was associated with increased risk of all-cause mortality, infectious mortality, and ICU admissions with IRRs of 1.39 (95% CI, 1.24-1.56), 1.94 (95% CI, 1.43-2.62), and 2.28 (95% CI, 1.60-3.24). Among those with FN, having a positive blood culture and low lymphocytes were associated with excess risk of death and ICU admissions (predominantly the first 30 days after FN), while elevated C-reactive protein and low hemoglobin predicted mortality the first year after FN. The risk of death varied according to the time since FN; adjusted IRR per additional risk factor present for the time periods 0-30, 31-365, and 366+ days after FN were 2.00 (95% CI, 1.45-2.75), 1.36 (95% CI, 1.17-1.57), and 1.17 (95% CI, 0.98-1.41). FN was associated with increased mortality and risk of ICU admissions. An objectively identifiable subgroup of patients among those with FN carried this excess risk.
发热性中性粒细胞减少症（FN）是化疗的一种严重并发症，与住院死亡率增加相关。然而，在更长的随访期内，其与死亡率增加及重症监护病房（ICU）收治之间的关联尚未明确。纳入了2010年至2016年在丹麦里格霍斯皮塔尔接受实体癌标准一线化疗的患者。通过泊松回归分析FN后全因、感染性和心血管死亡率以及ICU收治的发病率比值（IRR）。在FN患者亚组中分析FN发生时的危险因素；全因死亡率按FN后0至30天、31至365天和366天及以后的时间段进一步分层。我们纳入了9018例患者，其中胃癌（14.4%）和乳腺癌（13.1%）最为常见，51.2%患有局部晚期或播散性疾病，患者的Charlson合并症指数中位数为0（四分位间距，0至0）。在随访期间，845例（9.4%）发生FN，在18775人年的随访中有4483例（49.7%）死亡。调整后，FN与全因死亡率、感染性死亡率及ICU收治风险增加相关，IRR分别为1.39（95%CI，1.24至1.56）、1.94（95%CI，1.43至2.62）和2.28（95%CI，1.60至3.24）。在FN患者中，血培养阳性和淋巴细胞计数低与死亡及ICU收治的额外风险相关（主要在FN后的前30天），而C反应蛋白升高和血红蛋白降低可预测FN后第一年的死亡率。死亡风险根据距FN的时间而有所不同；在FN后0至30天、31至365天和366天及以后的时间段，每增加一个额外危险因素的调整后IRR分别为2.00（95%CI，1.45至2.75）、1.36（95%CI，1.17至1.57）和1.17（95%CI，0.98至1.41）。FN与死亡率增加及ICU收治风险相关。在FN患者中，有一个可客观识别的亚组存在这种额外风险。
