Blay J Y, Chauvin F, Le Cesne A, Anglaret B, Bouhour D, Lasset C, Freyer G, Philip T, Biron P
Centre Léon Bérard, Lyon, France.
J Clin Oncol. 1996 Feb;14(2):636-43. doi: 10.1200/JCO.1996.14.2.636.
Febrile grade four (ie, < or = 500/microL) neutropenia (FN) is a frequent life-threatening complication of cancer chemotherapy. Although its incidence correlates to the dose of chemotherapy, FN may occur after almost any cytotoxic regimen. At present, there is no predictive method to identify patients who will experience FN.
Univariate and multivariate analyses of risk factors for FN were performed on a retrospective cohort of 112 consecutive patients treated with various chemotherapy regimens. Two independent risk factors were identified by the logistic regression and used to create a risk model for FN. The validity of the model was tested in three distinct groups of patients: two prospective groups of patients treated in two institutions (Centre Léon Berard [CLB] and Institut G. Roussy [IGR]) and the group of patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) treated with the doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) regimen between 1988 and 1992 at CLB.
Within the retrospective group, 23 of 47 (49%) patients with lymphocyte counts < or = 700/microL at day 5 after chemotherapy experienced FN compared with seven of 65 (11%) of other patients (P = .00002). The type of chemotherapy (high dose v others) was also significantly correlated to FN (48% v 11%, P = .0003). Age, performance status, the number of previous chemotherapy cycles, or polymorphonuclear leukocyte (PMN) counts, were not significantly correlated to the incidence of FN in univariate analyses. Two independent risk factors were identified in the logistic regression: day 5 lymphocyte counts (beta = 1.97 +/- 0.53) and the type of chemotherapy regimen (beta = 1.91 +/- 0.53). The calculated probability to experience FN in patients with none, one, and both of these risk factors was 4.3%, 24.0%, and 68.8%, respectively. The validity of this model was tested in the three groups of patients used as validation samples. The observed incidences of FN in the above defined risk subgroups were 3%, 19%, and 67%, respectively, within the CLB prospective series and 6%, 19%, and 75% within the IGR prospective series. In the ACVBP group, the incidence of FN was 33% and 72%, respectively, in patients from the intermediate- and high-risk groups. In the two prospective groups and in the ACVBP series, the observed numbers of FN in the different risk groups did not differ significantly from those calculated by the model (P = .89, P = .86, and P = .72 for these three groups, respectively).
Day 5 lymphocyte counts < or = 700/microL and the type of chemotherapy regimen enable oncologists to define subgroups of patients treated with chemotherapy as those with a high intermediate, and low risk of FN. These criteria could be used to select subjects in whom prophylactic measures for FN, in particular hematopoietic growth factors, should be proposed.
发热性4级（即≤500/微升）中性粒细胞减少症（FN）是癌症化疗常见的危及生命的并发症。虽然其发生率与化疗剂量相关，但几乎任何细胞毒性治疗方案后都可能发生FN。目前，尚无预测方法来识别会发生FN的患者。
对112例接受各种化疗方案治疗的连续患者的回顾性队列进行FN危险因素的单因素和多因素分析。通过逻辑回归确定了两个独立的危险因素，并用于建立FN风险模型。在三组不同的患者中测试了该模型的有效性：在两个机构（里昂·贝拉尔中心[CLB]和G.鲁西研究所[IGR]）治疗的两组前瞻性患者，以及1988年至1992年在CLB接受阿霉素、环磷酰胺、长春地辛、博来霉素和泼尼松（ACVBP）方案治疗的中高危非霍奇金淋巴瘤（NHL）患者组。
在回顾性队列中，化疗后第5天淋巴细胞计数≤700/微升的47例患者中有23例（49%）发生FN，而其他65例患者中有7例（11%）发生FN（P = 0.00002）。化疗类型（高剂量与其他）也与FN显著相关（48%对11%，P = 0.0003）。在单因素分析中，年龄、体能状态、既往化疗周期数或多形核白细胞（PMN）计数与FN发生率无显著相关性。在逻辑回归中确定了两个独立的危险因素：第5天淋巴细胞计数（β = 1.97 ± 0.53）和化疗方案类型（β = 1.91 ± 0.53）。无、有一个和有这两个危险因素的患者发生FN的计算概率分别为4.3%、24.0%和68.8%。在用作验证样本的三组患者中测试了该模型的有效性。在CLB前瞻性系列中，上述定义的风险亚组中FN的观察发生率分别为3%、19%和67%，在IGR前瞻性系列中为6%、19%和75%。在ACVBP组中，中高危组患者的FN发生率分别为33%和72%。在两个前瞻性组和ACVBP系列中，不同风险组中FN的观察数与模型计算的数无显著差异（这三组的P值分别为0.89、0.86和0.72）。
化疗后第5天淋巴细胞计数≤700/微升和化疗方案类型使肿瘤学家能够将接受化疗的患者定义为FN高、中、低风险亚组。这些标准可用于选择应建议采取FN预防措施（特别是造血生长因子）的患者。
