Autologous stem cell transplantation in follicular non-Hodgkin's lymphoma

The failure of conventional chemotherapy to improve overall survival rates in follicular non-Hodgkin's lymphoma (NHL) has led to the development of alternative treatment regimens. One such regimen is high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT). In ASCT stem cells, harvested predominantly from peripheral blood, are used to repopulate the haemopoietic system after high-dose chemotherapy. Comparison of failure-free survival rates following ASCT, with those previously obtained with conventional chemotherapy, suggests a benefit for ASCT in patients who have previously responded to chemotherapy. Other factors that adversely influence the outcome of ASCT include large tumour burden and bcl-2 overexpression. Although ASCT in follicular NHL can prolong the period of remission, relapse is still common and can be caused either by contamination of the stem cell harvest with tumour cells, or regrowth of residual malignant cells not eradicated by the high-dose chemotherapy. Several strategies have been developed to reduce the rate of relapse, including in vitro purging of the stem cell product to remove tumour cells and using allogenic stem cells from HLA-matched donors with no history of malignant disease. While both these methods may have some benefit, they also have limitations. In vitro purging is labour intensive, costly and, as yet, the effect on relapse is unclear. Allogenic stem cell transplants have been associated with a reduced risk of relapse, but this is offset by increased transplant-related mortality. The most promising strategy to reduce the rate of relapse following ASCT is in vivo purging using rituximab, a monoclonal antibody to CD20. Rituximab mobilises mechanisms to kill lymphoma cells, and causes a rapid depletion of B cells from peripheral blood. Rituximab has demonstrated good efficacy as monotherapy in patients with both aggressive and indolent lymphoma and has shown very high response rates (>95%) when used in combination with HDT.