From the Guest Editor’s Desk

Masao Tomonaga, MD
Director, Atomic Bomb Disease Institute
Chief, Molecular Medicine Unit,
Nagasaki University Graduate School of Biomedical Sciences
Chief, Department of Hematology, Nagasaki University Hospital

Eighth International
Symposium on Myelodysplastic Syndromes:
An Overview
Nagasaki , Japan , May 12-15, 2005 

The MDS Foundation’s International Symposium was held for the first time in Asia . About 500 doctors and scientists attended, 70% from abroad including twenty doctors from Asian countries other than Japan . There were 72 plenary oral presentations and 124 papers as poster presentations. Dr. John M. Bennett presented the opening address ¾ a concise report on the activities of the MDS Foundation since its establishment in 1994 and information on the previous seven international symposia.

Many new research achievements were highlighted including:

Epidemiology. Dr. David Bowen (UK) showed an interesting figure of gradual

increase in MCV long before hemoglobin began to drop and the diagnosis was established. Dr. Masako Iwanaga ( Japan ) gave new evidence that atomic bomb radiation has been inducing MDS in a distance-dependent manner during the past 25 years.

Diagnosis and Classification. Dr. Akira Matsuda ( Japan ) reported a significant difference in the clinical feature of refractory anemia (RA) between Japan and Germany ; Japanese RA patients were much younger and lived longer. Dr. Ulrich Germing ( Germany ) talked about the usefulness and problems of WHO classification based on a huge number of 2262 registered cases. He also pointed out that the application rate of IPSS to MDS patients remains low in Germany , due to the low rate of chromosome analysis.

Stem Cell Biology. Dr. Tatsutoshi Nakahata ( Japan ), Dr. Koichi Akashi ( Japan ) and Dr. Connie Eaves ( Canada ) gave important overviews on stem cell expansion, plasticity, molecular sequence of myeloid and lymphoid differentiation and model mice for MDS. Dr. Rose Ann Padua ( France ) reported on a reversible two-step animal model of MDS using RAS and BCL2 transgene technique.

Molecular Biology. Many papers were presented on the molecular pathology of MDS. New technologies such as micro-array CGH and proteomics were employed. However, in spite of many new findings disclosed, genuine molecular cause(s) of MDS such as responsible gene(s) for 5q- and 7q- remains unclear. Dr. Stephen D. Nimer (USA) and Dr. H. Phillip Koeffler (USA) gave comprehensive overviews on the mechanism of methylation of genomes and effects of demethylating agents, suggesting important pathways towards new drug development. Dr. Seishi Ogawa ( Japan ) gave results of an extensive analysis of MDS cases using a newly developed high-resolution automatic micro-CGH analyzer. Dr. Kinuko Mitani ( Japan ) succeeded in inducing dysplastic definitive hematopoiesis by establishing AML1/Evi-1 knock-in embryo. Dr. Ying-Wei Lin (USA) established a mouse model for human MDS using NUP98-HOX13 transgenic mice.

Immunosuppressive therapy. Dr. Jeffrey Molldrem (USA) presented a summary of ATG therapy on low-risk MDS and presence of clonal expansion of CD8 T-cells against MDS cells. He also introduced a new vaccination approach against HLA-A2-restricted peptide PR1 that derived from proteinase 3 and elastase of MDS cells. He stressed that CD8 T-cells are a foe of the MDS clone but at the same time a friend of MDS patients if appropriately stimulated with the vaccine to eradicate MDS clones. Dr. Hideki Tsushima ( Japan ) showed a consistent response (41%) of Japanese RA patients to cyclosporine A. Dr. Shinji Nakao ( Japan ) emphasized that the appearance of the PNH clone, at very low frequency, in MDS cases is a good predictor of response to immunosuppressive therapy.

New Treatment. Dr. Alan F. List (USA) highlighted the most recent results on lenalidomide (Revlimid®) focusing on the effects on 5q- syndrome (WHO classification) patients. Cytogenetic effects in this group of MDS patients was again confirmed with 44% complete response, but the effect was found much wider including other MDS subtypes with single 5q- or 5q- plus other chromosome abnormalities (complex). This new drug also induced erythroid response (51%) in non-(5q-) patients. Dr. Martin Jaderson ( Sweden ) observed a selective inhibition in vitro of (5q-)-carrying erythroid components by lenalidomide for the first time. Dr. Richard M. Stone ( USA ) gave an excellent overview on new therapy for MDS and emphasized the importance of more research into the molecular pathology of MDS to further promote drug development. The effects of demethylating drugs, 5-azacytidine (Vidaza®) and decitabine (Dacogen®), were summarized by Dr. Lewis Silverman (USA), Dr. Pierre W. Wijermans ( Netherlands ) and others. Although complete response rate by these drugs in single use is not high, around 25%, there was an accumulation of data of consistent effects providing a prolongation of overall survivals. Future studies will be designed by combining a demethylating drug and other drug(s) with different mechanisms of action. Dr. Michael L ü bbert ( Germany ) reported cytogenetic remission with 5-azacytidine in patients with complex karyotypes that were almost always resistant to conventional drugs. Dr. Norbert Vey ( France ) reported on the effects of arsenic trioxide (Trisenox®), but showed a low response rate (21%). As a cytokine therapy, dalbopoietin, a highly glycosylated form with longer half-life in blood was reported by the French group to have very promising effects on MDS patients with lower EPO levels.

Iron chelation. Development of new oral iron chelators was another highlight in this symposium. At a satellite symposium, an international consensus meeting was held with 60 doctors participating, discussing the importance of oral chelation therapy in the management of MDS patients who are transfusion-dependent for the long term. Dr. Peter Jensen ( Denmark ) gave an excellent overview on iron overload and oral chelator development. Dr. Norbert Gattermann ( Germany ) summarized the above mentioned consensus meeting. Dr. Peter Greenberg chaired a very nice session for a new oral iron chelator, ICL670 (Exjade), with these speakers.

Intensive chemotherapy. Dr. Arnold Ganser ( Germany ) and Dr. Elihu Estey ( USA ) summarized the positioning of intensive chemotherapy for high-risk MDS.

Stem Cell Transplantation. Drs. Theo de Witte ( Netherlands ) and Ghulam Mufti ( UK ) presented their summary data of non-myeloablative therapy on MDS patients ages 50 to 65. Overall results are still unsatisfactory but they viewed this data as important progress and raised several key points to further improve non-relapse survivals. For ablative transplant, Dr. Joachim Deeg (USA) reported on the Fred-Hutchinson experience and stressed that the policy of waiting until progression of MDS among low-risk patients is an important factor to gain longer overall survival. Dr. Miguel Sanz ( Spain ) introduced the European experience of cord blood transplant to treat adult MDS patients suggesting a promising result in the near future. Dr. Shin-ichiro Okamoto ( Japan ) reported on the overall results of the Japan Marrow Donor Program and ongoing results of non-myeloablative transplant and showed similar results in the elderly population.

Susanne Fleischman Memorial Lecture. Dr. Timothy E. Quill, University Rochester Medical Center , Center for Palliative Care and Clinical Ethics, gave the most informative lecture on palliative care and quality-of-life for MDS patients by presenting a case with RAEB.

Report from International Working Group (IWG) on Morphology of MDS. At the final plenary session, Drs. Bennett and Mufti reported on the aim and the results of two meetings held in Lisbon and Nagasaki . Recognizing that the WHO classification is a major step forward in the classification of MDS, this IWG is trying to improve diagnostic accuracy by establishing morphological criteria for minimal dysplastic changes. Dr. Masao Tomonaga ( Japan ), the President of this symposium, gave a summary talk. He emphasized that MDS researchers are now passing an important time with several new drugs that suppress MDS clones or reduce ineffective hematopoiesis of MDS clones, achieving even a complete cytogenetic remission as seen in CML with Gleevec or actual incremental improvement of Hgb value. This is a real dawn of practical drug therapy for MDS to prolong overall survival of MDS patients in the near future. Moreover, as a sole curative therapy at this moment, HSCT is rapidly being applied to the increasing number of elderly patients with MDS. We are thus entering a promising era towards longer survival or even a cure for MDS that was seen in the AML field some 30 years ago. The 9 th International MDS Symposium will be held in Florence, Italy and chaired by Professor Mario Cazzola will surely present an acceleration of such a progress in 2007.   

The abstracts of the 8 th International Symposium on MDS published by Leukemia Research are now available upon request by contacting the MDS Foundation at 800-637-0839.

Symposium Highlights

Nagasaki Brick Hall
The Mayor of Nagasaki, Iccho Itoh; and President of the Organizing Committee, Masao Tomonaga, MD.	International Working Group on MDS Morphology participating in microscopic research.