Bone marrow transplantation in low-grade non-Hodgkin's lymphoma

The low-grade histologic types constitute one quarter of all non-Hodgkin's lymphomas (NHL). Conventional chemotherapy and chemo-radiation therapy have failed to significantly alter the course of this disease, and most patients eventually succumb to lymphoma. Despite the fact that NHLs exhibit a steep dose-response relation to cytotoxic therapy, fewer than 30% of eligible patients undergo bone marrow transplantation. Reasons for fewer patients receiving this course of treatment include: elderly patient population, extensive previous chemotherapy and/or radiation therapy, high incidence of bone marrow involvement, and transformation to higher grade NHLs. In recent years, improvements in several areas have enhanced the therapeutic index for bone marrow transplantation. These advances include the use of more effective preparative regimens, recombinant hematopoietic growth factors, extended-spectrum antibiotics, and an increased expertise in blood transfusion techniques and practices. Other, more effective strategies include sophisticated in vitro bone marrow purging approaches and peripheral blood progenitor cell collection. As a result, more patients have been able to receive dose-intensive therapy followed by hematopoietic cellular rescue. Although follow up is short in most series, encouraging results have stimulated some centers to begin transplanting responding patients earlier in their disease course; in more than 200 patients treated in this fashion, long-term disease-free survival has been achieved in nearly 70% of patients, some patients for a period of greater than 6 years. The new purine analogues fludarabine, pentostatin, and 2-chlorodeoxyadenosine also have shown promise in both initial and salvage treatment of low-grade NHLs. It remains to be determined whether this group of drugs will be complimentary to the bone marrow and/or peripheral blood progenitor cell transplant approach.