Management of the patient with large cell lymphoma

Abstract

Lymphomas are neoplasms of B-lymphocytic (75% of cases) or T-lymphocytic (20% of cases) origin. It is now appreciated that the various sub-types of disease represent counterparts of the normal pathways of lymphoid differentiation and transformation, from resting cells to fully transformed and activated lymphoid cells. The large cell lymphomas represent a group of neoplasms, formerly grouped together and termed ‘histiocytic lymphoma’ which represent transformed lymphocytes, of T- or B-cell derivation. Within the Working Formulation for Clinical Usage, a recently proposed translational tool, these lymphomas fall within the ‘Intermediate’ or ‘High-grade’ disease categories. The initial evaluation of a patient with large-cell lymphoma must include a formal staging procedure, in order to ascertain the precise extent of disease, so that appropriate therapeutic decisions may be made. This evaluation is also useful for defining all sites of lymphomatous disease, so that the results of any given therapeutic intervention can be accurately assessed. For the patient with localized, stage I disease, one option would be to take the patient to formal staging laparotomy, in order to attempt to prove the presence of pathologic Stage I disease. In this instance, wide-field radiotherapy may be employed, with the chance of achieving long-term, disease-free survival of approximately 70%. Alternatively, the patient may be staged less aggressively, and given combination chemotherapy, which is also effective in low-stage disease. In patients with Stage II, III or IV large-cell lymphoma, multi-agent chemotherapy is the expected treatment modality, although some controversy currently exists regarding the optimal regimen(s). The regimens commonly employed in the 1970s, including CHOP (cyclophosphamide, hydroxyldaunamycin, vincristine, prednisone) have resulted in long-term, disease-free survival in approximately 30% of all treated patients, with 10-year follow-up data available. Although newer regimens have recently been proposed which are, for the most part more intensive, these studies have only recently been reported, and large-scale studies which seek to prospectively compare the various regimens are currently in progress. Until these studies have been completed, the true regimen(s) of choice remains undefined. Although various regimens have been reported as effective in the minority of patients who relapse after chemotherapy, the use of autologous and/or allogeneic bone marrow transplantation may provide the best possibility of long-term disease-free survival, especially in younger patients, with low tumor burden, who are not refractory to chemotherapy.