Salzberger B, Bowden R A, Hackman R C, Davis C, Boeckh M
Fred Hutchinson Cancer Research Center and University of Washington, Seattle 98109-4417, USA.
Blood. 1997 Sep 15;90(6):2502-8.
To determine risk factors, frequency, time patterns, and outcome of ganciclovir-related neutropenia in allogeneic marrow transplant recipients, 278 consecutive patients receiving ganciclovir from engraftment until day 100 were studied. In this cohort, 159 patients (57%) had absolute neutrophil counts (ANC) less than 1,500/microL, 112 (41%) had an ANC less than 1,000/microL, 87 (31%) less than 750/microL, and 56 (21%) less than 500/microL for at least 2 consecutive days. Statistically significant risk factors for neutropenia in a Cox model were low marrow cellularity between day 21 and 28 (relative risk [RR] 2.4, P = .0002), hyperbilirubinemia > or =6 mg/dL during the first 20 days (RR 2.5, P = .0001), and elevation of serum creatinine > or =2 mg/dL after day 21 after transplant (RR 2.1, P = .001). Restriction to factors present at engraftment resulted in a similar model with low marrow cellularity, hyperbilirubinemia > or =6 mg/dL, and elevated serum creatinine as significant risk factors. Patients with no risk factor had an incidence of neutropenia of 21%, an incidence of 31% for one risk factor, and of 57% for two or more risk factors (RR 3.8, P = .001). Neutropenia was a negative predictor of overall (RR 2.0, P = .0001) and event-free survival (RR 2.1, P < .0001), and a predictor of relapse (RR 1.7, P = .03) and nonrelapse mortality (RR 2.1, P = .003). Thus, early liver dysfunction, elevated serum creatinine, and low marrow cellularity are risk factors for ganciclovir-related neutropenia. Neutropenia in ganciclovir recipients after marrow transplantation is an independent risk factor for mortality.
为了确定异基因骨髓移植受者中更昔洛韦相关中性粒细胞减少的危险因素、发生率、时间模式及转归，我们对278例从植入至第100天接受更昔洛韦治疗的连续患者进行了研究。在这个队列中，159例患者（57%）的绝对中性粒细胞计数（ANC）低于1500/μL，112例（41%）低于1000/μL，87例（31%）低于750/μL，56例（21%）至少连续2天低于500/μL。在Cox模型中，中性粒细胞减少的统计学显著危险因素为第21至28天骨髓细胞减少（相对危险度[RR] 2.4，P = 0.0002）、前20天内胆红素血症≥6mg/dL（RR 2.5，P = 0.0001）以及移植后第21天血清肌酐升高≥2mg/dL（RR 2.1，P = 0.001）。将因素限制为植入时存在的因素，得到一个类似的模型，其中骨髓细胞减少、胆红素血症≥6mg/dL以及血清肌酐升高为显著危险因素。无危险因素的患者中性粒细胞减少发生率为21%，有一个危险因素的发生率为31%，有两个或更多危险因素的发生率为57%（RR 3.8，P = 0.001）。中性粒细胞减少是总生存（RR 2.0，P = 0.0001）和无事件生存（RR 2.1，P < 0.0001）的负性预测指标，也是复发（RR 1.7，P = 0.03）和非复发死亡率（RR 2.1，P = 0.003）的预测指标。因此，早期肝功能障碍、血清肌酐升高和骨髓细胞减少是更昔洛韦相关中性粒细胞减少的危险因素。骨髓移植后更昔洛韦接受者中的中性粒细胞减少是死亡的独立危险因素。
