Stem-cell transplantation in non-Hodgkin's lymphoma: improving outcome.
High-dose therapy with stem-cell transplantation is a potentially curative therapy for younger patients with relapsed aggressive non-Hodgkin's lymphoma (NHL) and is also under investigation in relapsed indolent NHL. There are, however, risks associated with this treatment strategy. Autologous stem-cell transplantation (ASCT) continues to be associated with a high risk of relapse, while graft-versus-host disease is a major limiting factor with allogeneic stem-cell transplantation. The presence of minimal residual disease (MRD) in the harvested, re-infused stem cells, or remaining in the patient following chemotherapy, is associated with relapse after ASCT. As a result, monitoring and eradicating MRD has become a major focus of many studies in NHL. Rearrangement and overexpression of the bcl-1 and bcl-2 genes are the hallmarks of mantle-cell and follicular lymphoma, respectively, and evidence suggests that they are promising surrogate markers of MRD. Polymerase chain reaction analysis is a sensitive methodology used to monitor the status of occult lymphoma cells bearing these genetic aberrations, and results from trials of ASCT have shown that clearance of bcl-1/JH- and bcl-2/JH-positive cells following treatment is associated with a significant improvement in outcome. Rituximab, the anti-CD20 monoclonal antibody, is increasingly used for in vivo purging and can effectively eradicate bcl-1/JH- and bcl-2-positive cells. If the encouraging preliminary results with rituximab are maintained with a longer follow-up, this agent could play a pivotal role in improving outcome after stem-cell transplantation in NHL.
Gianni
Alessandro M
AM
Division of Medical Oncology and Bone Marrow Transplant, Milan Cancer Institute, Milan, Italy. Alessandro.Gianni@unimi.it
Berinstein
Neil L
NL
Evans
Paul A S
PA
López-Guillermo
Armando
A
Solano
Carlos
C
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D016465:Bone Marrow Purging; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D006086:Graft vs Host Disease / Q000517:prevention & control; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000628:therapy*; D018365:Neoplasm, Residual; D016133:Polymerase Chain Reaction; D000069283:Rituximab; D033581:Stem Cell Transplantation
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000069283:Rituximab