Tandem Stem Cell Transplantation for Non-Hodgkin's Lymphoma

The approach to recurrent or primary refractory non-Hodgkin's lymphoma has been to treat patients with second-line chemotherapy (usually 2-3 courses) for the purposes of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells have been mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease. In a group of 17 patients with transformed lymphoma who received autologous transplants at Stanford University, the median EFS and OS were 1.48 and 2.7 years respectively with a 7-year survival of only 20%. In comparison, patients with chemosensitive follicular lymphoma who received the same regimen also had a poor median EFS of 1.3 years, but the median survival was 6.7 years. The outcomes for patients with chemotherapy-resistant relapsed NHL is also poor with EFS in the range of 20% in many studies of autologous transplantation. These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that we have taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. In addition, there are limited reports of using an autologous/allogeneic approach for lymphoma patients using non-myeloablative allogeneic transplants. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide, cytarabine and melphalan with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.