Leukemia May 12, 2003

Meeting Summary

The fourth SOTS meeting on leukemias brought together experts in ALL to discuss important translational science and emerging therapeutic questions to be addressed in future clinical trials. Topics included genetics and gene profiling, apoptosis, pharmacogenomics, minimal residual disease (MRD), preclinical models, classification, allogeneic and autologous stem cell transplant, and treatments for Philadelphia chromosome positive (Ph+) ALL, mature B-cell ALL (Burkitt), T-cell ALL and ALL in adolescents. The afternoon focus in six concurrent working groups was to discuss, develop and prioritize recommendations for ALL research in the areas of MRD, immunotherapeutic approaches with antibodies and vaccines, stem cell transplantation, Ph+ ALL, new agents and drug resistance, and adolescent ALL. The importance of looking at MRD early in therapy was stressed, as were the different approaches for using MRD to direct therapy in adults and children. Discussion of monoclonal antibody (Mab) therapies considered the most promising agents (Rituximab, Campath, Epratuzumab) and utilization strategies (combination or sequential with chemotherapy). Needs were indicated for further data on the level of target antigen expression and the mechanism of action of MAbs in the patient. Discussion of pediatric stem cell transplantation addressed who should be transplanted in CR2 (who will not be cured by chemotherapy), use of unrelated donor vs. sibling donor stem cell sources, and ex vivo manipulations and post-transplant immune modulations. A high priority for adult ALL was to identify those patients that do not need an allogeneic transplant. Other discussion of adult ALL focused on therapy with autologous transplantation followed by non-ablative allogeneic transplantation, the need for increasing reliance on intermediate end points in trials, and research needs on genetics of drug metabolism/toxicity, immunomodulatory genes in GVHD, understanding of GVL, and assessing risk of relapse. Ph+ ALL research priorities were for greater understanding of the disease pathogenesis, prognostic factors, better drugs (e.g., current assessment of Imatinib), and immunotherapeutic approaches with "non-specific" cells. Discussion of new agents for ALL considered FLT3 inhibitors, methylation inhibitors, histone deacetylase inhibitors, liposomal vincristine, methotrexate (with dose intensity), T cell specific agents (FK506, BCX-1777), clofarabine, monoclonal antibodies, MTOR inhibitors, proteasome inhibitors, multi-targeted anti-folates and MDR inhibitors. Evidence that adolescents treated by pediatric oncologists on pediatric protocols have better outcomes, led to the proposal to test the hypothesis that adult oncologists can achieve the same outcomes for adolescents with ALL as pediatric oncologists by using the same treatment regimen.


	Meeting Summary The fourth SOTS meeting on leukemias brought together experts in ALL to discuss important translational science and emerging therapeutic questions to be addressed in future clinical trials. Topics included genetics and gene profiling, apoptosis, pharmacogenomics, minimal residual disease (MRD), preclinical models, classification, allogeneic and autologous stem cell transplant, and treatments for Philadelphia chromosome positive (Ph+) ALL, mature B-cell ALL (Burkitt), T-cell ALL and ALL in adolescents. The afternoon focus in six concurrent working groups was to discuss, develop and prioritize recommendations for ALL research in the areas of MRD, immunotherapeutic approaches with antibodies and vaccines, stem cell transplantation, Ph+ ALL, new agents and drug resistance, and adolescent ALL. The importance of looking at MRD early in therapy was stressed, as were the different approaches for using MRD to direct therapy in adults and children. Discussion of monoclonal antibody (Mab) therapies considered the most promising agents (Rituximab, Campath, Epratuzumab) and utilization strategies (combination or sequential with chemotherapy). Needs were indicated for further data on the level of target antigen expression and the mechanism of action of MAbs in the patient. Discussion of pediatric stem cell transplantation addressed who should be transplanted in CR2 (who will not be cured by chemotherapy), use of unrelated donor vs. sibling donor stem cell sources, and ex vivo manipulations and post-transplant immune modulations. A high priority for adult ALL was to identify those patients that do not need an allogeneic transplant. Other discussion of adult ALL focused on therapy with autologous transplantation followed by non-ablative allogeneic transplantation, the need for increasing reliance on intermediate end points in trials, and research needs on genetics of drug metabolism/toxicity, immunomodulatory genes in GVHD, understanding of GVL, and assessing risk of relapse. Ph+ ALL research priorities were for greater understanding of the disease pathogenesis, prognostic factors, better drugs (e.g., current assessment of Imatinib), and immunotherapeutic approaches with "non-specific" cells. Discussion of new agents for ALL considered FLT3 inhibitors, methylation inhibitors, histone deacetylase inhibitors, liposomal vincristine, methotrexate (with dose intensity), T cell specific agents (FK506, BCX-1777), clofarabine, monoclonal antibodies, MTOR inhibitors, proteasome inhibitors, multi-targeted anti-folates and MDR inhibitors. Evidence that adolescents treated by pediatric oncologists on pediatric protocols have better outcomes, led to the proposal to test the hypothesis that adult oncologists can achieve the same outcomes for adolescents with ALL as pediatric oncologists by using the same treatment regimen.