XV. Clinical aspects of transformed lymphoma.

As outlined in the previous sections by Dr. Gascoyne and Dr. Rossi, histologic transformation (HT) refers to the biologic events leading to development of high-grade, aggressive non-Hodgkin’s lymphoma in a patient with an underlying indolent lymphoma. HT is a well-described event in the natural history and clinical course of patients with indolent lymphomas. This phenomenon has been studied most extensively in patients with follicular lymphoma (FL) and subsequent transformation to a diffuse large B-cell lymphoma (DLBCL) [1]. However, HT is not unique to FL, but has been described also in other subtypes of indolent lymphoma including marginal zone lymphoma, lymphoplasmacytic lymphoma, and lymphocyte predominant Hodgkin lymphoma and as in Richter’s syndrome (RS) in small lymphocytic lymphoma/chronic lymphocytic leukemia. HT has a profound impact on the natural history of these usually indolent diseases, and the outcomes of such patients have been historically poor, although survival may be improving in the era of chemoimmunotherapy. The molecular pathogenesis of transformation of lymphoma is described in the accompanying articles, and this review highlights our current concepts of treatment as well as potential future directions of treatment for transformed lymphoma. Much attention has focused on factors that may be used to predict diagnosis at those patients in whom HT will occur. Despite attempts to determine biomarkers and clinical characteristics that might be useful to determine this, there are few useful markers that can be used reliably to predict HT. One possible explanation for this is that recent molecular studies have made it clear that the process of HT is complex and not simply the acquisition of new molecular events within the dominant FL clone, but that HT may occur from new changes within lymphoma progenitor cells [2], or even as second primary