ASH News Daily - Monday, December 12, 2011 - (Page A-9)

Monday, December 12, 2011 BMT Are We Finally Getting Smarter When It Comes To Stem Cell Transplant? By Michael roSenzweiG, Md, and heather landau, Md D espite significant advances in biologic therapies for hematopoietic malignan- cies, allogeneic hematopoietic stem cell transplantation (HSCT) often remains the only curative modality. However, not only does HSCT cause significant toxicity, but it fails to prevent relapse in 10 to 60 percent of malignant histologies. The aims of allogeneic HSCT are twofold: to reduce the tumor burden with high doses of chemotherapy and to induce the immunologic graft-versus-tumor effect (GVT). The Education Program session, “Hematopoietic Stem Cell Transplantation II: Controversies and Challenges in HSCT,” highlighted novel strategies of immune manipulation to enhance antitumor activity and dampen anti-host toxicity. Dr. David Porter, Abramson Cancer Center, University of Pennsylvania, began the session by discussing the role of reduced-intensity transplantation and donor leukocyte infusion (DLI) to promote a GVT effect and prevent or treat relapsed disease. He discussed methods of ex vivo costimulation of T cells, which can overcome in vivo immunesuppression, as well as the use of adoptively transferred hyperfunctioning haploidentical NK cells that can expand in vivo, overcome self tolerance, and enhance remission in refractory leukemia patients (to be presented by Cooley et al., abstract 355, today at 10:30 a.m.). He highlighted the success of T-cell targeting with bispecific antibodies and updated the results from the series of refractory CLL patients treated with lentiviral vector expressing a chimeric antigen receptor (CAR) with specificity for the B-cell antigen CD19, coupled with CD137 (a costimulatory receptor in T cells) and CD3-zeta (a signal transduction component of the T-cell antigen receptor) signaling domains. He was excited to share that “massive” expansion of engineered cells persisted in vivo for over 12 months. In addition, two CRs are evident by detailed MRD studies, well over 15 months following infusion. Dr. Katayoun Rezvani, Hammer- smith Hospital, Imperial College, London, continued as the second speaker to address strategies to enhance the GVL effect through both active and passive vaccine based immunotherapy. While the target antigen is important, so is optimal timing and modulation of immunosuppressive effector cells. The lymphopenic environment in the post transplant milieu is ideal in this regard, but clinical success will likely require a “hybrid” vaccine approach. Indeed, results from combining antitumor vaccination in the host with donor-derived vaccineprimed lymphocytes are encouraging. Also exciting is the use of vaccine-primed lymphocytes from the patient which are then re-infused following high-dose chemotherapy followed by post-transplant booster immunizations as a way of directing tumor-specific immunotherapy in the autologous setting. Changing the focus from op- timizing GVT to minimizing the complications of HSCT, Dr. Michael Boeckh, Fred Hutchinson Cancer Center, highlighted the current status of optimal CMV prevention, detection, and treatment. In the trans- plant setting, preemptive treatment is typical with ganciclovir or foscarnet but their respective toxicities of myelosuppression and nephrotoxicty are often problematic. Newer agents with even broader activity hold promise, and results from early phase studies using CMX001 and A1C-246 should be forthcoming. The Scientific Program session, “Genomics and Proteomics of »» SMARTER Page A-12 ASH NEWS DAILY Page A–9 ® DANA-FARBER + CHILDREN’S HOSPITAL BOSTON = THE BEST CANCER TREATMENT FOR KIDS We’re proud to be recognized as the nation’s top children’s cancer t reatment center. Dana–Farber/Children’s Hospital Boston combines the strengths of a world–renowned cancer center with the top pediat ric hospital to give kids with cancer and blood diseases the best possible outcomes. And we won’t stop breaking new ground until we find cures for all pediatric cancers. Visit danafarberchildrens.org/usnews. DANA-FARBER/CHILDREN’S HOSPITAL CANCER CENTER

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ASH News Daily - Monday, December 12, 2011

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