Tandem transplantation in lymphoma

Abstract

Summary:The majority of poor-risk lymphoma patients are not cured with conventional chemotherapy. There is evidence for the superiority of single high-dose chemotherapy in such patients, but many still die from recurrent disease. Strategies to improve survival in these poor-risk patients include dose-intensification with high-dose chemotherapy and PBPC support, tandem autologous HDC with PBPC support, and autologous followed by non-myeloablative allogeneic transplantation. These more aggressive strategies are feasible and tolerable. Whether tandem transplantation will prove more effective than current single high-dose therapy in appropriately selected patients remains to be determined. Bone Marrow Transplantation (2001) 28, 529-535. Keywords: tandem transplantation; lymphoma; autologous; allogeneicThe majority of patients with lymphoma achieve remission with standard therapy. A small percentage of patients are refractory to initial therapy, and approximately one-third of patients with stage III-IV disease will relapse after achieving a complete response. Treatment of minimally responsive or refractory lymphoma patients remains a challenge. Single transplantation and the poor prognosis patientProspective randomized trials show single HDC with autologous transplantation to be superior to standard-dose chemotherapy for relapsed and resistant Hodgkin's disease, 1 for consolidative therapy of poor-risk B cell NHL in first remission 2 and for relapsed chemo-sensitive intermediate or high-grade NHL. 3 An update of the PARMA study reports an 8-year EFS of 36% and OS of 47% for these latter patients. 4 Fewer than 5% of patients with poor-risk NHL or HD who have induction failure and receive conventional salvage chemotherapy are alive at 5 years. NHL patients with induction failure who undergo HDC and autotransplantation have an overall survival at 5 years of 37%. 5 Data from the ABMTR show HD patients with induction Correspondence: DR CS Hesdorffer, Division of Medical Oncology, MHB 6N 435, 177 Ft. Washington Avenue, New York, NY 10032, USA failure who subsequently undergo HDC have progressionfree and overall survivals at 3 years of 38% and 50%, respectively. 6 Data by Sweetenham et al 7 from the EBMT are similar, reporting an actuarial 5-year OS rate of 36% and PFS rate of 32%.Allogeneic transplantation alone does not appear to offer a survival advantage over autologous transplant for lymphoma. 8,9 Studies suggest a graft-versus-lymphoma effect, but this has not translated into increased survival due to the high treatment-related mortality associated with allogeneic transplantation. Further prospective trials, randomized on the basis of HLA-identical donor availability, may provide more reliable data on this issue. 10 While salvage rates of 45-60% are achieved with HDC in patients with relapsed NHL and HD with good prognostic factors, adverse prognostic factors, such as relapse within 1 year of initial treatment, stage III/IV relapse or chemoresistance, portend a poorer outcome, with likely cure in less than 40%. The IP...

High-dose chemotherapy using BEAM without autologous rescue followed by reduced-intensity conditioning allogeneic stem-cell transplantation for refractory or relapsing lymphomas: a comparison of delayed versus immediate transplantation

“…10 Autologous HSCT for tumor debulking followed by RIC HSCT has been advocated as a novel concept for patients with advanced lymphoma, providing the tumor reduction before HSCT and giving the necessary time for the GvL-effect to develop. [11][12][13] Results of a planned interim analysis after 10 patients with relapsed/refractory lymphoma treated with BEAM HDC for initial cytoreduction without autologous stem-cell rescue, followed by RIC allogeneic HSCT at day 28 after BEAM have been previously published. 14 Our report showed that the prolonged aplasia with this regimen was manageable, but infectious complications were frequent.…”

Pilot study of tandem high-dose chemotherapy and autologous stem cell transplantation with a novel combination of regimens in patients with poor risk lymphoma

“…The CR rate for poor-risk and relapsed patients undergoing tandem therapy may be improved, but a clear demonstration of clinical benefit with acceptable long-term toxicity is necessary before tandem transplantation becomes a viable therapeutic choice over the current approaches to poor-risk patients. 20 Although not tested in a randomized fashion, when used as consolidative therapy in responding poor-risk patients, Haioun et al 12 concluded that tandem transplant did not improve on the results of patients receiving a single consolidative HDC regimen. HDC regimens that include newer targeted therapeutic modalities such as rituximab offer the possibility of improved efficacy and decreased toxicity.…”