Since 1974, a group of consecutive adult patients with non-Hodgkin's lymphoma have been prospectively analyzed for tumor-surface membrane-marker phenotype and histopathologic correlation with response to treatment and survival. The results are reported in a subset of 35 patients with advanced (Stages III-IV) large-cell variants, most of whom would be classified by Rappaport criteria as histiocytic. An attempt has been made to define those marker characteristics that will identify long-term survivors in this diverse group who remain in continuous disease-free remission. There were ten patients with complete remissions with intensive treatment. The most common subgroup within the complete responders were patients with cells that were nonexpressive (null) and were classified by Lukes-Collins criteria as the large, noncleaved follicular center cell variant. Currently there are seven patients remaining in complete remission, five of whom have been in continuous disease-free remission for more than two years (total survival 34+-42+ months) following cessation of all treatment. Of those five, four were in the null group and four were classified as large non-cleaved. The actuarial survival curve for all null patients is characterized by a rapid initial decline and a subsequent plateau, which contains four of the long survivors. In contrast, the B-derived group has a more graded decline in survival with time; this curve currently contains the remaining long survivor. Although the overall prognosis of B-derived tumors appears to be superior to that of the null subset, the subgroup with the potential for cure at this point in our study includes patients with both null and B-derived tumors, particularly those classified by Lukes-Collins criteria as the large noncleaved follicular center cell variant.

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