By Mary Jo Lechowicz, MD
The Education Program Session on allogeneic transplantation in the lymphoproliferative disorders will provide an overview of the innovations in transplant from graft selection to conditioning regimens, particularly in adult ALL, CLL, and follicular lymphoma. Each discussant will review the evidence for graft-versus-leukemia/lymphoma (GVL) effects, the role of reduced-intensity conditioning (RIC), and the detection and management of minimal residual disease (MRD). The education session is being held again this morning in La Nouvelle Ballroom AB from 9:30 to 11:00 a.m.
The adult ALL transplantation session will be presented by Dr. Anthony Goldstone from University College London Hospital, who will discuss the results of the International ALL Trial conducted by the Medical Research Council (MRC) in the United Kingdom and the Eastern Cooperative Oncology Group (ECOG). The trial recruited nearly 2,000 patients between 1993 and 2006; over this period of time, there were improvements in unrelated donor selection, and RIC evolved. In this MRC/ECOG study, the importance of the GVL effect in adult ALL was demonstrated, with a reduction in relapse by an allogeneic effect. The study surprisingly did not show a significant improvement in survival with transplant in the high-risk group, which may partially be explained by an increase in treatment-related mortality in high-risk patients. Additional questions regarding the definition of high-risk adult ALL, particularly whether Philadelphia-chromosome-positive patients are still high-risk in the era of tyrosine kinase inhibitors, will be the focus of future trials.
In CLL, Dr. Peter Dreger of Universitätsklinikum Heidelberg reviewed the studies on MRD kinetics and the ability to achieve long-term MRD negativity after allogeneic transplantation. A major challenge is that those MRD responses are typically only temporary. Many authors have speculated about the cause of this resistance development. This occurrence has been described using both RIC and myeloablative-conditioning regimens. Future research will facilitate the identification of mechanisms that lead to this resistance and alternative treatment strategies for these patients.
Progress in indolent lymphoma and allogeneic transplantation is the topic of the presentation by Dr. Koen van Besein from the University of Chicago Medical Center. Data previously suggested that, although remissions could be achieved in patients with indolent lymphoma, a high risk of TRM in allogeneic transplantation limited its use to patients who had refractory or end-stage disease. IBMTR data from 1990 through 1999 show decreasing TRM over time, likely due to improved supportive care and donor selection. Now with the advent of RIC, indolent lymphomas were postulated to be a good target for this approach. The data to date, particularly in the follicular lymphoma patients, show that indolent disease and availability of a related donor predict a better outcome. The future of transplantation in these patients will include improved GVH prophylaxis with mTOR inhibitors and novel conditioning regimens.
Improvements in supportive care, conditioning regimens, GVH prophylaxis, new agents, and understanding of immune manipulation in the transplant setting are all the ingredients for great New Orleans gumbo, transplant style.
Dr. Lechowicz indicated no relevant conflicts of interest.
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