Del Poeta G, Maurillo L, Venditti A, Buccisano F, Epiceno A M, Capelli G, Tamburini A, Suppo G, Battaglia A, Del Principe M I, Del Moro B, Masi M, Amadori S
Cattedra e Divisione di Ematologia, Università Tor Vergata, Ospedale S.Eugenio, Roma, Italy.
Blood. 2001 Nov 1;98(9):2633-9. doi: 10.1182/blood.v98.9.2633.
B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous clinical courses, and several biological parameters need to be added to the current clinical staging systems to predict which patients will experience an indolent or an aggressive outcome. This study analyzed CD38 expression by flow cytometry and soluble APO1/Fas (sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by immunoenzymatic methods to evaluate their effect on the clinical course of 168 unselected B-CLL patients. Intermediate/high risk modified Rai stages were characterized by a higher CD38(+) B-cell number (P =.0002) and higher sCD23 levels (P <.0001). Moreover, CD38(+) B-cell percentages were significantly and directly associated both with beta(2)-microglobulin and sCD23 concentrations (P <.0001 and P =.002, respectively). Both a higher tumor burden (lymphadenopathy/splenomegaly) and a lymphocyte doubling time less than 12 months were significantly associated with higher CD38(+) percentages (P <.0001 and P =.0001, respectively). With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P =.00006) in patients with lower CD38(+) B-cell percentages. Furthermore, the risk of partial or no response to fludarabine increased with increasing CD38 expression (P =.003), and a shorter overall survival (50% versus 92% at 8 years; P <.00001) characterized patients with more than 30% CD38(+) B-cell number. The predictive value of CD38 expression was maintained among the patients within the Rai intermediate risk group and was confirmed in multivariate analysis. Thus, the percentage of CD38(+) B cells appears to be an accurate predictor of clinical outcome and therefore could be used to indicate when more novel chemotherapeutic approaches are needed.
B 细胞慢性淋巴细胞白血病（B-CLL）具有异质性临床病程，需要在当前临床分期系统中加入多个生物学参数，以预测哪些患者会经历惰性或侵袭性病程。本研究通过流式细胞术分析 CD38 表达，并采用免疫酶法检测可溶性 APO1/Fas（sAPO1/Fas）、Bcl-2（sBcl-2）和 CD23（sCD23）蛋白，以评估它们对 168 例未经选择的 B-CLL 患者临床病程的影响。中/高危改良 Rai 分期的特点是 CD38(+) B 细胞数量较多（P = 0.0002）且 sCD23 水平较高（P < 0.0001）。此外，CD38(+) B 细胞百分比与β2-微球蛋白和 sCD23 浓度均呈显著正相关（分别为 P < 0.0001 和 P = 0.002）。较高的肿瘤负荷（淋巴结病/脾肿大）和淋巴细胞倍增时间少于 12 个月均与较高的 CD38(+) 百分比显著相关（分别为 P < 0.0001 和 P = 0.0001）。关于临床结局，CD38(+) B 细胞百分比低的患者无进展生存期显著更长（5 年时为 75% 对 37%；P = 0.00006）。此外，对氟达拉滨部分或无反应的风险随 CD38 表达增加而升高（P = 0.003），CD38(+) B 细胞数量超过 30% 的患者总生存期较短（8 年时为 50% 对 92%；P < 0.00001）。CD38 表达的预测价值在 Rai 中危组患者中得以维持，并在多变量分析中得到证实。因此，CD38(+) B 细胞百分比似乎是临床结局的准确预测指标，因此可用于指示何时需要更新的化疗方法。
