ASH 2012 Satellite Symposium

Over 750 participants at the American Society for Hematology 2012 Meeting in Atlanta, Georgia attended the “Changing Faces of MDS and AML” Symposium sponsored by AA&MDSIF and the Cleveland Clinic Center for Continuing Education. The world’s leading researchers in MDS and AML shared in depth of current research related to the biology, prognosis and therapeutic management of MDS and AML.

Research is improving our understanding of the molecular genetics and biology of MDS and AML

This leads to a better ability to predict survival and can help determine the best treatment approach for these conditions. Dr. Guillermo Garcia-Manero, from the MD Anderson Cancer Center, and a member of the AA&MDSIF Medical Advisory Board, reviewed several prognostic scoring systems used in MDS. These include the International Prognostic Scoring System (IPSS), the World Health Organization Prognostic Scoring System (WPSS), the MD Anderson Global MDS Model and the recently validated IPSS-revised, IPSS-R) which includes a more in-depth cytogenetic/chromosomal risk classification.  Dr. Garcia-Manero discussed the increasing importance of these classifications as well as the further identification and recognition of molecular lesions in MDS.  This information may improve a doctor’s ability to predict outcomes and develop more personalized treatments for patients with both high and low risk MDS.

Dr. Ramon Tiu from the Cleveland Clinic explained the latest research on what is known about the impact of mutated genes on diagnosis and treatment of MDS. For example, having mutations in certain genes may be markers of decreased surviva outcome. However, these mutated genes may respond better to certain therapies, such as hypomethylating agents, including azacitidine or decitabine. Dr. Tiu also reviewed recently discovered “spliceosome” mutations (SF3B1, U2AF1, and SRSF2) found in different subtypes of MDS. These may serve as important targets for future therapy.

The rapidly evolving understanding of the biology of MDS leads to progress in treatment. 

Dr. Rena Buckstein from the University of Toronto discussed standard as well as novel non-transplant treatment strategies for MDS. From immunosuppresive therapies such as anthymocyte globulin (ATG) for lower risk MDS to combination therapies with azacitidine for higher risk MDS; there are now many therapeutic options for patients. In addition, there are promising agents on the horizon. These include rigosertib which may have increased effectiveness in patients with a certain chromosomal abnormality (e.g. trisomy 8). Unfortunately, there are few new effective agents for patients who fail hypomethylating therapy.

Dr. Jeffery Lancet from the Lee Moffit Cancer Center presented an in-depth look at AML in the elderly. Although older patients often have co-morbidities which increase the risk of early death during treatment, the risk of death from AML remains most significant. The use of chromosomal and molecular analysis at diagnosis is important in older patients. In reviewing the most recent research on the use of therapies such as hypomethylating agents, clofarabine, and gemtuzumab ozogamicin, there is still little data to identify who best benefits from what type of treatment.

Secondary MDS and AML

As outcomes continue to improve for other cancers and diseases, MDS and AML is increasing as a result of therapy and exposure to radiation and chemotherapy.  Therapy related-MDS and AML (t-MDS/AML) now account for 10-20% of bone marrow myeloid malignancies. Dr. Richard Stone from the Dana-Farber Cancer Institute and a member of the AA&MDSIF Medical Advisory Board,  reviewed the biologic basis, natural history, and risk factors for this type of MDS/AML. T-MDS/AML appear to do worse than “de-novo,” disease (those diseases that did not evolve as a result of prior exposure to chemotherapy or radiation). These lower survival outcomes may be due to factors such as poor bone marrow reserve, morbidity from pre-existing therapy/disease, and poor risk cytogenetics], which is higher in this population, and remains the most powerful predictor of outcome. Treatment related MDS/AML is generally treated similar to de novo MDS/AML with induction chemotherapy and allogeneic transplant being the only curative strategy, especially for those with poor risk cytogenetics. Dr. Stone reviewed promising results of early studies for some novel investigative agents, such as CPX-351, which is a different formulation of two commonly used chemotherapeutic agents in AML.

Discussion of Stem Cell Transplantation

Allogeneic hematopoeitic stem cell transplant remains the only curative strategy for MDS and many acute leukemias. This type of transplantation, on whom and when, presents many unanswered questions that were addressed by Dr. Corey Cutler from the Dana-Farber Cancer Institute. Dana-Farber researchers previously published a decision analysis which predicted better survival outcomes for patients with higher risk MDS who underwent transplant. Those with lower risk MDS performed better without transplantation. Optimal pre-treatment and conditioning regimens prior to transplantation are still not clear. These are being studied in ongoing and future clinical trials. For most patients with AML having a higher risk molecular or cytogenetic profile, Dr. Cutler recommends early referral and transplantation in first remission.