Gascoyne R D, Aoun P, Wu D, Chhanabhai M, Skinnider B F, Greiner T C, Morris S W, Connors J M, Vose J M, Viswanatha D S, Coldman A, Weisenburger D D
Departments of Pathology and Laboratory Medicine, Medical Oncology, and Epidemiology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada.
Blood. 1999 Jun 1;93(11):3913-21.
Anaplastic large cell lymphoma (ALCL) is an aggressive lymphoma that is frequently associated with the t(2;5)(p23;q35), resulting in expression of a fusion protein, nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which can be detected by either monoclonal or polyclonal antibodies to the ALK protein. The clinical features of adults with ALCL are incompletely described, and the prognostic factors that are useful for predicting survival remain unclear. This report describes the clinical and laboratory findings in 70 adults with systemic ALCL who were treated with curative intent. We attempted to identify the clinical and pathological factors of prognostic importance, including the International Prognostic Index (IPI), immunophenotype, and expression of the ALK protein. The median age of the patients was 49 years (range, 15 to 75). There were 26 women and 44 men with a median follow-up of 50 months for living patients. Advanced stage was present in 56% and B symptoms were noted in 70% of the patients. Immunostains showed that 46% of the cases had a T-cell phenotype, 36% a null phenotype, and 18% a B-cell phenotype. The expression of ALK protein was found in 51% of the cases. The IPI factors were evenly distributed between the ALK+ and ALK- groups, except that the ALK+ patients were younger (median age, 30 v 61 years; P <.002). The ALK+ cohort included cases with null (44%), T-cell (42%), and B-cell (14%) phenotypes. All 10 cases with cytogenetic or molecular evidence of a t(2;5) were ALK+. The 5-year overall survival (OS) of the entire cohort was 65%. The 5-year OS of the ALK+ and ALK- cases was 79% and 46%, respectively (P <.0003). Analysis of only the T-cell/null cases (n = 57) showed a 5-year OS of 93% for the ALK+ cases and only 37% for the ALK- cases (P <.00001). Univariate analysis of the clinical features showed that age </=60 years (P <.007), a normal serum lactate dehydrogenase (LDH) (P <.00001), a good performance status (Eastern Cooperative Oncology Group [ECOG] <2) (P <.03), </=1 extranodal site of disease (P <.012), and an IPI score </=3 (P <.00001) were associated with improved OS. Although a younger age correlated with ALK positivity, multivariate analysis showed that only a normal serum LDH (P <. 00001), an IPI score of </=3 (P <.0005), and ALK protein expression (P <.005) predicted independently for an improved OS. We conclude that ALCL is a heterogeneous disorder. However, ALK protein expression is an independent predictor of survival and serves as a useful biologic marker of a specific disease entity within the spectrum of ALCL.
间变性大细胞淋巴瘤(ALCL)是一种侵袭性淋巴瘤,常与t(2;5)(p23;q35)相关,导致融合蛋白核磷蛋白-间变性淋巴瘤激酶(NPM-ALK)的表达,可通过针对ALK蛋白的单克隆或多克隆抗体检测到。成人ALCL的临床特征描述不完整,对预测生存有用的预后因素仍不清楚。本报告描述了70例接受根治性治疗的成人系统性ALCL的临床和实验室检查结果。我们试图确定具有预后重要性的临床和病理因素,包括国际预后指数(IPI)、免疫表型和ALK蛋白的表达。患者的中位年龄为49岁(范围15至75岁)。有26名女性和44名男性,存活患者的中位随访时间为50个月。56%的患者处于晚期,70%的患者有B症状。免疫染色显示,46%的病例具有T细胞表型,36%为无表型,18%为B细胞表型。51%的病例中发现ALK蛋白表达。IPI因素在ALK+和ALK-组之间均匀分布,只是ALK+患者更年轻(中位年龄,30岁对61岁;P<.002)。ALK+队列包括无表型(44%)、T细胞(42%)和B细胞(14%)表型的病例。所有10例有t(2;5)细胞遗传学或分子证据的病例均为ALK+。整个队列的5年总生存率(OS)为65%。ALK+和ALK-病例的5年OS分别为79%和46%(P<.0003)。仅对T细胞/无表型病例(n=57)分析显示,ALK+病例的5年OS为93%,而ALK-病例仅为37%(P<.00001)。临床特征的单因素分析显示,年龄≤60岁(P<.007)、血清乳酸脱氢酶(LDH)正常(P<.00001)、良好的体能状态(东部肿瘤协作组[ECOG]<2)(P<.03)、≤1个结外疾病部位(P<.012)和IPI评分≤3(P<.00001)与OS改善相关。虽然年龄较小与ALK阳性相关,但多因素分析显示,只有血清LDH正常(P<.00001)、IPI评分≤3(P<.0005)和ALK蛋白表达(P<.005)可独立预测OS改善。我们得出结论,ALCL是一种异质性疾病。然而,ALK蛋白表达是生存的独立预测因素,并且是ALCL谱系内特定疾病实体的有用生物学标志物。