Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma (1) and follows an aggressive course, resulting in the death of patients within months without treatment (2). Researchers, when using anthracycline-based combination chemotherapy, have found that 80 to 85% of patients respond, with more than 50 to 76% achieving a complete response, that is, no disease identifiable 4 or more weeks after the end of treatment (3,4). Unfortunately, in nearly half of responders, their lymphoma returns, with only a minority being cured by more intensive retreatment (5). Thus, at 5 yr from the diagnosis of DLBCL, less than 50% of patients remain alive, disease-free (1). The best, validated predictor of response and outcome to treatment to date is a crude index based upon five clinical variables termed the International
From: Methods in Molecular Medicine, Vol. 115: Lymphoma: Methods and Protocols Edited by: T. Illidge and P. W. M. Johnson © Humana Press Inc., Totowa, NJ
Prognostic Index (IPI ). The IPI stratifies patients into low-, intermediate-, high-intermediate, and high-risk groups, with the respective 5-yr overall survival of each group being 73, 51, 46, and 32%. Because most patients fall into the intermediate group, the IPI fails to define their risk any better than the risk for all patients considered together. Therefore, the ability to predict which patients will respond to treatment and be cured of their lymphoma and which will ultimately die of their DLBCL still cannot be performed accurately for the majority.
The variability in clinical response and course of DLBCL and the recognition of morphological subtypes and nuances has led to the hypothesis that DLBCL is in fact composed of several distinct subtypes with differing outcomes to treatment. Because such subtypes cannot be successfully reproduced on the basis of morphological appearance alone, the search for molecular methods of subdividing DLBCL into meaningful clinical subtypes has long been the goal of lymphoma clinicians and scientists.
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