ten Berge R L, Dukers D F, Oudejans J J, Pulford K, Ossenkoppele G J, de Jong D, Miseré J F, Meijer C J
Departments of Pathology and Haematology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Blood. 1999 Apr 15;93(8):2688-96.
Systemic (nodal) anaplastic large cell lymphoma (ALCL) is a subgroup of T-cell non-Hodgkin's lymphomas with a relatively favorable clinical outcome. Part of systemic ALCLs harbor a genetic aberration (usually the t(2;5)(p23;q35) translocation) containing the anaplastic lymphoma kinase (ALK) gene at 2p23, which results in aberrant expression of the ALK protein. Recently, we have shown that the presence of high percentages of activated cytotoxic T lymphocytes (CTLs) in tumor biopsy specimens of Hodgkin's disease (HD) is associated with a poor prognosis. In the present study, we investigated the prognostic value of percentages of activated CTLs in combination with ALK expression in primary nodal ALCL. Primary nodal biopsies of 42 patients with ALCL were investigated for the percentage of activated CTLs (quantified using Q-PRODIT) and the expression of ALK by immunohistochemistry using monoclonal antibodies (MoAbs) directed against T-cell antigen granzyme B (GrB) and ALK, respectively. These parameters were evaluated for their predictive value regarding progression-free and overall survival time. The presence of a high percentage of activated CTLs (ie, >/=15%) was found to be an unfavorable prognostic marker. In combination with a lack of ALK expression, it was possible to identify a group of patients with a very poor prognosis. In this group, 13 of 16 patients died within 2 years as a result of the disease. Of the remaining 26 patients, only three (all ALK negative) died (P <.0001). Furthermore, the percentage of activated CTLs combined with ALK status appeared to be of stronger prognostic value than the International Prognostic Index (IPI). We conclude that a high percentage of activated CTLs present in biopsy material of patients with primary nodal ALCL is a strong indicator for an unfavorable clinical outcome. The combination of ALK expression and percentage of activated CTLs appears to be more sensitive than the IPI in identifying a group of patients with a highly unfavorable clinical outcome who may be eligible for alternative (high dose) therapy schemes.
系统性（结节性）间变性大细胞淋巴瘤（ALCL）是T细胞非霍奇金淋巴瘤的一个亚组，临床预后相对较好。部分系统性ALCL存在一种基因畸变（通常为t(2;5)(p23;q35)易位），该易位在2p23处包含间变性淋巴瘤激酶（ALK）基因，导致ALK蛋白异常表达。最近，我们发现霍奇金病（HD）肿瘤活检标本中高比例活化细胞毒性T淋巴细胞（CTL）的存在与预后不良相关。在本研究中，我们调查了原发性结节性ALCL中活化CTL百分比与ALK表达相结合的预后价值。对42例ALCL患者的原发性结节活检标本分别使用针对T细胞抗原颗粒酶B（GrB）和ALK的单克隆抗体（MoAbs），通过免疫组织化学法检测活化CTL的百分比（使用Q-PRODIT定量）和ALK的表达。评估这些参数对无进展生存期和总生存期的预测价值。发现高比例活化CTL（即≥15%）的存在是一个不良预后标志物。与ALK表达缺失相结合，有可能识别出一组预后非常差的患者。在该组中，16例患者中有13例在2年内因该病死亡。其余26例患者中，只有3例（均为ALK阴性）死亡（P<0.0001）。此外，活化CTL百分比与ALK状态相结合似乎比国际预后指数（IPI）具有更强的预后价值。我们得出结论，原发性结节性ALCL患者活检材料中高比例活化CTL是不良临床结局的有力指标。ALK表达与活化CTL百分比相结合在识别一组临床结局非常不利、可能适合替代（高剂量）治疗方案的患者方面似乎比IPI更敏感。
