By David P. Steensma, MD

2008-12-06

One of the most remarkable stories surrounding the ASH annual meeting in recent years has been the dramatic growth of interest in the myelodysplastic syndromes (MDS). In the 1990s, MDS-related programs were held in small rooms in difficult-to-find corners of convention centers, and there were usually at least a few empty chairs. But better understanding of disease biology, and especially increased availability of efficacious treatments, has changed all that.

At last year’s meeting in Atlanta, more than 3,000 people attended the MDS education session, the MDS-related scientific sessions were standing-room only, and an exciting MDS-related observation about ribosomal protein S14 was featured in the Plenary Scientific Session. This year’s MDS education sessions — despite their 7:30 a.m. start time today and Sunday — will also draw large (and presumably heavily caffeinated) crowds, so they will be held in Halls B and C of the Moscone Center.

In the May 15, 2008, issue of Blood, as part of series of review articles celebrating the 50th anniversary of ASH, Dr. Stephen Nimer, of Memorial-Sloan Kettering Cancer Center, prepared a valuable and provocative summary of the current state of the MDS field. At the MDS education sessions today and tomorrow, Dr. Nimer will focus on the stem cell abnormalities that may contribute to the development of MDS, especially lower-risk forms of MDS where the stem cell defect is more difficult to understand, such as the peculiar 5q- syndrome that has generated so much recent interest. Although Dr. Nimer points out that immunological abnormalities and defects in the bone marrow microenvironment are also likely to be important in MDS pathobiology, his presentation will reflect the fact that most research work has focused on the hematopoietic stem cell/progenitor cell compartment.

The session will be chaired by Dr. Eva Hellström-Lindberg, from the Karolinska Institutet in Stockholm, who recently served as president of the European Hematology Association (EHA). Dr. Hellström-Lindberg will discuss the significance of the JAK2 V617F kinase activating mutation for MDS. The discovery of JAK2 V617F in 2005 was an important advance in myeloid disease biology and in the clinical care of patients with myeloproliferative neoplasms (MPNs), but JAK2 is also relevant to MDS — especially in patients with features of both MDS and MPNs, such as those with both ring sideroblasts and thrombocytosis. Dr. Hellström-Lindberg has a long-standing interest in refractory anemia with ring sideroblasts (RARS), and her laboratory group has published key observations concerning mitochondria-mediated apoptosis and accumulation of mitochondrial ferritin in erythroid precursor cells with MDS, upon which she will elaborate.

Although the roster of non-transplant therapeutic options for patients with MDS is growing, rather risky allogeneic stem cell transplantation (SCT) remains the only routinely curative treatment. Transplant expert Dr. Nicolaus Kröger, of University Hospital Hamburg-Eppendorf in Hamburg, will review evolving approaches to SCT in MDS, including updates of reduced-intensity conditioning regimens and a discussion of ways to approach patients relapsing after SCT. Professor Kröger will also discuss possible roles for DNA methyltransferase inhibitors azacitidine and decitabine in SCT, including how these drugs might be used to prepare patients for SCT — or maintain remission achieved by SCT, since relapse is so common.

Since all three of these presenters hail from at least three time zones to the east of San Francisco, they should already be wide awake at 7:30 a.m., leading to a dynamic session. For those of us in the audience who might not be quite as energetic that early, this lineup is well worth setting the alarm clock for.

Dr. Steensma indicated no relevant conflicts of interest.

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