Lymphoma: diagnosis, staging, natural history, and treatment strategies

Non-Hodgkin's lymphoma (NHL) is not a single disease, but a group of closely related B- and T-cell cancers of the lymphatic system. The incidence of NHL is rising, particularly in the countries of the industrialized world. The increased incidence is poorly understood, but several risk factors have been postulated to be associated with NHL, including: exposure to chemicals, viral infections, organ transplantation and blood transfusion, family history, and lifestyle factors. Precise staging of NHL is a prerequisite for the selection of a suitable therapeutic regimen and influences the likelihood of its success. Staging of lymphoma is traditionally conducted using tumor biopsy, imaging (X-ray, computerized tomography [CT], magnetic resonance imaging, lymphangiogram, gallium scan using 67 Ga citrate single photon emission CT [ 67 Ga-SPECT], or positron emission tomography), blood tests, bone marrow examination, and examination of cerebrospinal fluid. CT is the most commonly used imaging technique, but several studies indicate that other techniques, such as 67 Ga-SPECT, are more sensitive and better predictors of response. Low- and high-grade lymphomas differ markedly in prognosis and response to treatment. The management of NHL has been characterized by the increasing recognition that distinct subgroups of NHL respond differently to various therapeutic approaches. In follicular lymphoma (FL), a successful approach has been to combine fludarabine with mitoxantrone (FM), resulting in an overall response rate of 89% (67% complete remission). In an ongoing phase III trial in patients with untreated, advanced, low-grade follicular lymphoma, FM was compared with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) with or without rituximab. Patients previously treated with FM achieved a significantly better complete remission rate (67% v 38%; P = .0013) and a better molecular remission (36% v 20%; P = .049) than patients previously treated with CHOP. Following rituximab treatment, 88% of patients who had received FM achieved clinical and molecular remission compared with 70% who had received CHOP. Strategies using various chemotherapy combinations, including innovative agents such as 90 Y-ibritumomab tiuxetan, show promise in the treatment of NHL, particularly indolent NHL, and hopefully will lead to an improvement in prognosis.