Diehl Volker, Stein Harald, Hummel Michael, Zollinger Raphael, Connors Joseph M
Medizinische Klinik I, University of Cologne, Cologne, Germany.
Hematology Am Soc Hematol Educ Program. 2003:225-47. doi: 10.1182/asheducation-2003.1.225.
Hodgkin's lymphomas belong to the most curable tumor diseases in adults. About 80% of patients in all anatomical stages and of all histological subtypes can be cured with modern treatment strategies. In spite of the great clinical progress, the pathogenesis of this peculiar lymphoproliferative entity has not been elucidated completely up until now. In Section I Drs. Stein, Hummel, and Zollinger describe the different pro-proliferative and antiapoptotic pathways and molecules involved in the transformation of the germinal center B-lymphocyte to the malignant Hodgkin-Reed-Sternberg cell. They use a comprehensive gene expression profiling (Affymetrix gene chip U133A) on B- and T-Hodgkin cell lines and state that the cell of origin is not the dominant determinant of the Hodgkin cell phenotype, but the transforming event. H-RS cells lack specific functional markers (B-T-cell receptors) and physiologically should undergo apoptosis. Why they do not is unclear and a matter of intensive ongoing research. In Section II Dr. Diehl summarizes the commonly used primary treatment strategies adapted to prognostic strata in early, intermediate and advanced anatomical stages using increasing intensities of chemotherapy (two, four, eight courses of chemotherapy such as ABVD) and additive radiation with decreased doses and field size. ABVD is without doubt the gold standard for early and intermediate stages, but its role as the standard regimen for advanced stages is challenged by recent data with time- and dose-intensified regimens such as the escalated BEACOPP, demonstrating superiority over COPP/ABVD (equivalent to ABVD) for FFTF and OS in all risk strata according to the International Prognostic Score. In Section III, Dr. Connors states that fortunately there is a considerably decreased need for salvage strategies in Hodgkin's lymphomas since primary treatment results in a more than 80% tumor control. Nevertheless, a significant number of patients experience either a tumor refractory to therapy or an early or late relapse. Therefore, one of the continuing challenges in the care for Hodgkin's lymphomas today is to find effective modes for a second tumor control. High-dose chemotherapy followed by autologous stem cell support has proved to be the treatment of choice when disseminated tumors recur after primary chemo- and or radiotherapy. Nodal relapses respond well to local radiation when they recur outfield of primary radiation without B-symptoms and in stages I-II at relapse. Allogeneic stem cell support needs further intensive evaluation in controlled studies to become an established alternative.
霍奇金淋巴瘤属于成人中最可治愈的肿瘤疾病。在所有解剖分期和所有组织学亚型中，约80%的患者可通过现代治疗策略治愈。尽管取得了巨大的临床进展，但这种特殊的淋巴增殖性疾病的发病机制至今尚未完全阐明。在第一部分，斯坦因博士、胡默尔博士和佐林格博士描述了生发中心B淋巴细胞转化为恶性霍奇金-里德-斯特恩伯格细胞过程中涉及的不同促增殖和抗凋亡途径及分子。他们对B和T霍奇金细胞系进行了全面的基因表达谱分析（Affymetrix基因芯片U133A），并指出细胞起源并非霍奇金细胞表型的主要决定因素，而是转化事件。霍奇金-里德-斯特恩伯格细胞缺乏特异性功能标记（B-T细胞受体），从生理角度讲应发生凋亡。它们为何不发生凋亡尚不清楚，是正在深入研究的问题。在第二部分，迪尔博士总结了根据预后分层，在早期、中期和晚期解剖分期采用强度递增的化疗（如ABVD化疗两、四、八个疗程）以及剂量和照射野缩小的附加放疗等常用的初始治疗策略。ABVD无疑是早期和中期的金标准，但随着时间和剂量强化方案（如强化的BEACOPP）的出现，其作为晚期标准方案的作用受到挑战，根据国际预后评分，强化的BEACOPP在所有风险分层的无进展生存期（FFTF）和总生存期（OS）方面均显示出优于COPP/ABVD（等同于ABVD）。在第三部分，康纳斯博士指出，幸运的是，由于初始治疗能实现超过80%的肿瘤控制，霍奇金淋巴瘤对挽救策略的需求大幅降低。然而，仍有相当数量的患者出现治疗难治性肿瘤或早期或晚期复发。因此，当今霍奇金淋巴瘤治疗中持续存在的挑战之一是找到有效的二次肿瘤控制模式。当播散性肿瘤在初次化疗和/或放疗后复发时，大剂量化疗后自体干细胞支持已被证明是首选治疗方法。当结内复发发生在原发放疗野外、无B症状且复发时处于I-II期时，对局部放疗反应良好。异基因干细胞支持需要在对照研究中进一步深入评估，以成为一种既定的替代方法。
