In vivo purging and relapse prevention following ASCT

The combination of high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative therapy for patients with relapsed chemosensitive non-Hodgkin's lymphoma (NHL) and is increasingly being considered as a first-line treatment for NHL patients with poor prognosis or poor outcomes from chemotherapy. However, there is a degree of relapse following the latter which is associated with high levels of tumour cell contamination of the stem cells and/or the presence of residual malignant cells in the host following chemotherapy. Reducing the rate of relapse can be achieved by pre-transplant purging of the stem cell graft followed by post-transplant maintenance to minimise residual disease. Various methods of in vitro purging have been shown to reduce, but not eliminate, the level of stem cell contamination and invariably result in a reduced harvest. To date, this has been reflected in disappointing outcomes for the patient. In contrast, in vivo purging with rituximab during the process of stem cell mobilisation and collection does not adversely affect the yield or function of stem cells and shows a significant improvement in the level of tumour cell contamination as measured by bcl-2 clearance. The relapse potential from residual malignant cells in the host can be addressed by a programme of post-transplant rituximab maintenance therapy. In one study 17 patients with follicular lymphoma who underwent ASCT with in vivo rituximab-purged stem cells, followed by rituximab maintenance, have all remained in complete response at a median follow-up of 12.4 months. The optimum in vivo rituximab purging protocol and the precise effect in terms of overall and disease-free survival are currently being evaluated but appear to present an attractive first-line alternative for NHL patients with poor prognosis or poor outcomes following chemotherapy.