若在中性粒细胞减少性发热出现的最初 48 小时内不进行处理,其死亡率可达到 50%。[3]Bodey GP, Jadeja L, Elting L. Pseudomonas bacteremia. Retrospective analysis of 410 episodes. Arch Intern Med. 1985;145:1621-1629.http://www.ncbi.nlm.nih.gov/pubmed/3927867?tool=bestpractice.com 因此,这是肿瘤科急症,且自 1971 年起,在缺乏明确感染证据的情况下,给予经验性抗生素治疗已经是治疗标准。[4]Schimpff S, Satterlee W, Young VM, et al. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971;284:1061-1065.http://www.ncbi.nlm.nih.gov/pubmed/4994878?tool=bestpractice.com 及时给予抗生素使反应率高达 60%-70%,并降低死亡率至 10%。[4]Schimpff S, Satterlee W, Young VM, et al. Empiric therapy with carbenicillin and gentamicin for febrile patients with cancer and granulocytopenia. N Engl J Med. 1971;284:1061-1065.http://www.ncbi.nlm.nih.gov/pubmed/4994878?tool=bestpractice.com
中到高风险患者的住院时间
第一次出现中性粒细胞减少性发热的患者中,约 80% 需要住院,住院时间为 1-10 天不等(40%<5 天,42%为 5-10 天),住院的中位时间为 11.21 天。住院时长可能随着中性粒细胞减少性发热的反复发生而增加。[66]Lyman GH, Kuderer NM. Filgastrim in patients with neutropenia: potential effects on quality of life. Drugs. 2002;62:65-78.http://www.ncbi.nlm.nih.gov/pubmed/12479595?tool=bestpractice.com[67]Lyman GH, Kuderer N, Greene J, et al. The economics of febrile neutropenia: implications for the use of colony-stimulating factors. Eur J Cancer. 1998;34:1857-1864.http://www.ncbi.nlm.nih.gov/pubmed/10023306?tool=bestpractice.com
中性粒细胞减少性发热的住院时长及并发症也与年龄>65 岁、晚期疾病、中性粒细胞减少的时间和程度、并存疾病和器官功能不全、损伤的体力状态和白蛋白水平低相关。[7]Talcott JA, Finberg R, Mayer RJ, et al. The medical course of cancer patients with fever and neutropenia. Clinical identification of a low-risk subgroup at presentation. Arch Intern Med. 1988;148:2561-2568.http://www.ncbi.nlm.nih.gov/pubmed/3196123?tool=bestpractice.com[8]Klastersky J, Paesmans M, Rubenstein EB, et al. The Multinational Association for Supportive Care in Cancer risk index: a multinational scoring system for identifying low-risk febrile neutropenic cancer patients. J Clin Oncol. 2000;18:3038-3051.http://www.ncbi.nlm.nih.gov/pubmed/10944139?tool=bestpractice.com
此外,患有低血压、菌血症或肺炎的中性粒细胞减少性发热患者,发生包括死亡在内的并发症的风险较高。[68]Gonzalez-Barca E, Fernandez-Sevilla A, Carratala J, et al. Prognostic factors influencing mortality in cancer patients with neutropenia and bacteremia. Eur J Clin Microbiol Infect Dis. 1999;18:539-544.http://www.ncbi.nlm.nih.gov/pubmed/10517190?tool=bestpractice.com[69]Malik I, Hussain M, Yousuf H. Clinical characteristics and therapeutic outcome of patients with febrile neutropenia who present in shock: need for better strategies. J Infect. 2001;42:120-125.http://www.ncbi.nlm.nih.gov/pubmed/11531318?tool=bestpractice.com[70]Darmon M, Azoulay E, Alberti C, et al. Impact of neutropenia duration on short-term mortality in neutropenic critically ill cancer patients. Intensive Care Med. 2002;28:1775-1780.http://www.ncbi.nlm.nih.gov/pubmed/12447522?tool=bestpractice.com[71]Elting LS, Rubenstein EB, Rolston KV, et al. Outcomes of bacteremia in patients with cancer and neutropenia: observations from two decades of epidemiological and clinical trials. Clin Infect Dis. 1997;25:247-259.http://www.ncbi.nlm.nih.gov/pubmed/9332520?tool=bestpractice.com[72]Carratala J, Roson B, Fernandez-Sevilla A, et al. Bacteremic pneumonia in neutropenic patients with cancer: causes, empirical antibiotic therapy, and outcome. Arch Intern Med. 1998;158:868-672.http://archinte.ama-assn.org/cgi/content/full/158/8/868http://www.ncbi.nlm.nih.gov/pubmed/9570172?tool=bestpractice.com[73]Lyman GH, Kuderer NM. Cost-effectiveness of myeloid growth factors in cancer chemotherapy. Curr Hematol Rep. 2003;2:471-479.http://www.ncbi.nlm.nih.gov/pubmed/14561391?tool=bestpractice.com
复发性中性粒细胞减少性发热的风险
中性粒细胞减少性发热史预示后续的中性粒细胞减少性发热发作,因此美国临床肿瘤学会 (ASCO)、美国国立综合癌症网络 (NCCN) 和欧洲癌症研究和治疗组织 (EORTC) 指南推荐在后续化疗中预防性使用集落刺激因子。