One and a half decades of the Lugano International Conference on Malignant Lymphoma: Variations on a theme or true progress?

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attendance. This brief introduction summarizes a few of the highlights of the Sixth Lymphoma Conference and places them in the context of the many achievements and advances in the understanding and treatment of lymphoma over the past decade and a half. In this way, we may better understand both the importance of what has been learned and see more clearly the directions in which these developments are taking us. The first conference, held in 1981, was organized by Cavalli and others. The first four papers were presented by DeVita, Kaplan, Berard, and Bonadonna. The last paper on opening night was delivered by Gianni Bonadonna on the evolution of treatment strategies for malignant lymphomas, a topic that Bonadonna has pursued diligently and for which he was honored during the fifth conference with the San Salvatore Foundation Award when he delivered the 1993 Kaplan Memorial Lecture. During that first conference, various histopathological classifications were discussed extensively. Immunological markers were introduced for routine use, and the Kiel classification found wide acceptance in Europe. Berard gave a preview of the International Working Formulation (IWF). Subsequently, the IWF gained wide clinical use, at least in the United States, for its easy translation of the histopathological findings into clinical entities. By 1994, with the emergence of new entities and more immunological, cytogenetic, and molecular characterization, it was time for a revision, as had become clear from issues raised at the fifth conference the preceding year. Harris and coworkers soon introduced the REAL classification, a detailed histological and immunological system, which leaves room for modification and recognition of yet-to-be identified subgroups. The clinical applicability of the REAL classification and identification of prognostic groups has been reviewed extensively. This new classification appears to be able to group the different lymphomatous diseases into clinically relevant entities, but it will have to be ascertained if it is reproducible on a large scale outside university centers. It offers us the opportunity to categorize lymphomas according to modern immunologic and molecular biologic criteria and allows us to view each subgoup as a discrete entity. Together with the International Prognostic Index, and perhaps the other biologic markers reviewed by Shipp at the most recent conference, the REAL classification may enable prognosis within subtypes. One of the new entities identified in recent years and now classified in the REAL classification is the group of MALT lymphomas. At the sixth conference, one complete session was devoted to these lymphomas. At the preceding conference, in 1993, Wotherspoon had reported regression of gastric MALT lymphomas after eradication of Helicobacter pylori. Indeed, over 90% of low-grade MALT lymphomas in the West are associated with H. pylori. The same year, Cavalli presented the intriguing results of a multicenter study in Italy and southern Switzerland in treating MALTOMAS with amoxicillin, metronidazole, and omeprazole. This treatment has been shown to eradicate over 60% of these lymphomas. Isaacson and Wright had paved the way for this remarkable discovery ten years previously when they described the MALT lymphoma concept. These successes underscore the importance of careful correlative studies that put together clinical and pathologic observations. During the second lymphoma conference in 1984, Riggs and Muggia pointed out in their talks a relationship between AIDS and NHL. Longo gave a paper on AIDS, and Gallo emphasized the role of viruses in lymphoma. Virology has remained an important theme since then, with a multitude of papers on HTLV-1 and HIV at the third conference in 1987. The role of EBV in Hodgkin's disease would be a key issue at the 1990 conference, as highlighted in the introductory lecture by Broder. During the fifth conference in 1993, the pathogenesis of EBV in certain lymphomas was shown by Kieff, Stein, and Diehl, who suggested an important role for the incorporated EBV genome. This work was updated during the 1996 conference by Kieff, who proposed a model for regulation of B-cell growth by LMP-1.