Optimal therapy for small noncleaved cell lymphoma

Small noncleaved cell lymphoma is now well recognized as a specific subtype of non-Hodgkin's lymphoma with distinctive clinicopathologic characteristics. Initial treatment results in children with endemic Burkitt's lymphoma also indicated a unique sensitivity to cytotoxic chemotherapy; to this day, Burkitt's lymphoma remains one of the few human tumors potentially curable with single-agent chemotherapy. However, the development of effective therapy has proved more difficult in nonendemic SNCL, where presentation with advanced stage and large tumor bulk occurs in most patients. The combination chemotherapy regimens currently considered standard for treatment of large-cell lymphoma have usually produced only transient responses in patients (both children and adult) with SNCL. Recently, several regimens of increased dose intensity have yielded encouraging results both in children and adults. High complete response rates and long-term disease-free survival rates in the 60% range have been reported from several institutions using such regimens. At present, we feel that adults without severe coexisting problems should be treated with high dose-intensity regimens, such as those developed at MD Anderson and Vanderbilt. Routine treatment of these patients with standard lymphoma regimens should be avoided, since the cure rate with this approach has been low. Curative therapy for these patients can be of brief duration, and maintenance therapy is not necessary. Although guidelines are unclear, it seems reasonable at present to include meningeal prophylaxis in the treatment of Stage III and IV patients. Since dose intensity has emerged as an important factor in the curative therapy of SNCL, further exploration of this concept in future clinical trials is critical. The role of growth factors is undefined; if the frequently espoused possibility that growth factors can increase curability by allowing intensification of therapy is to be realized in any human tumor, SNCL leads the list of candidates. The role of early high-dose therapy with bone marrow transplantation is also largely unexplored in SNCL. At the other end of the spectrum, the possibility of administering lesser therapy while maintaining a high cure rate in patients with clinical Stage I SNCL needs further investigation. It is likely that continued clinical investigation will continue to improve therapeutic results in this uncommon but highly distinctive lymphoma.