How I treat How I treat patients with diffuse large B-cell lymphoma

The disease we now call diffuse large B-cell lymphoma has gone by many names in the past. These have included reticulum cell sarcoma,1 diffuse histiocytic lymphoma,2 and, more recently, diffuse mixed lymphoma, diffuse large cell lymphoma, or immunoblastic lymphoma—terms from the Working Formulation.3 Early studies of therapy for patients with diffuse large B-cell lymphoma contained some patients with aggressive T-cell lymphoma, as these were lumped together in the Working Formulation and some older classifications. The correct diagnosis today is diffuse large B-cell lymphoma, as used in the World Health Organization (WHO) classification (Table 1).4 However, we know that this is still a heterogenous group that includes lymphomas with a wide variety of morphologic appearances (Table 2), protein-expression patterns, and gene-expression patterns. For example, patients with diffuse large B-cell lymphoma can be divided into at least 3 clinically relevant groups using gene-expression profiling.5-7 These include the germinal-center type, the activated B-cell type, and mediastinal large B-cell lymphoma (Table 3). A few patients will not easily be classified into these categories.8 Mediastinal large B-cell lymphoma represents less than 10% of all large B-cell lymphomas, occurs primarily in young women, and always presents with a mediastinal mass. The gene-expression profile is similar to that seen in classical Hodgkin disease.7,9 The other 2 types of diffuse large B-cell lymphoma, and those not easily classified, have a median age at presentation in the 60s, a male predominance, and can present at essentially any site in the body.8 They will be the major focus of this paper. Lymphomas are the fifth most common systemic cancer, with the most common subtype being diffuse large B-cell lymphoma followed by follicular lymphoma and Hodgkin lymphoma. Diffuse large B-cell lymphoma represents approximately 30% of all lymphomas and is the most common subtype throughout the world. This is in contrast to many other types of lymphoma, which have striking geographic variation in frequency of occurrence.10 Diffuse large B-cell lymphoma can be seen after histologic transformation of most other types of B-cell lymphoma. This is particularly frequent in patients with follicular lymphoma and is recognized clinically in up to 50% of patients.11,12 Although much less frequent, this transformation occurring in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma has the eponym Richter transformation.13,14 In general, patients with diffuse large B-cell lymphoma seen after histologic transformation have a poorer response to therapy and prognosis than those with a de novo appearance, particularly if the patient were treated for the preceding lymphoma. This manuscript will focus on the treatment of patients with primary diffuse large B-cell lymphoma.