New Focus on Myeloproliferative
Disorders - Top to Bottom

The spectrum of myeloproliferative disorders includes many different diseases, most of which have not received the attention they are due — so says ASH, the NHLBI, and the NCI. But together, we are trying to change this problem. A request for grant applications has been issued by the NIH to explore the pathogenetic mechanisms driving these disorders (see sidebar).

And, even if you exclude all of the advances made in recent years in CML (which, in case you forgot, is a myeloproliferative disorder), we are also witnessing major advances and changes in the treatment of other disorders in this category. Evidence for this is the fact that at last year’s plenary session there was an abstract discussing the role of aspirin in polycythemia vera, while at yesterday’s plenary session there was a presentation of the Medical Research Council Primary Thrombocythemia PT1 trial in essential thrombocythemia. In what is probably the largest randomized trial ever conducted for any type of myeloproliferative disorder besides CML, the Medical Research Council accrued 809 essential thrombocythemia patients judged to be at high risk of thrombosis. These patients were randomized to either hydroxyurea plus aspirin (75-100 mg daily) or anagrelide plus aspirin (same doses as on the hydroxyurea arm). By nine months, control of platelet count in these high risk patients was equivalent in both arms. But, there were significantly more events in the anagrelide arm including arterial thrombosis, TIA, and major hemorrhage. Plus, there was an increased risk for the development of myelofibrosis in the anagrelide arm while the risk for leukemogenesis was equivalent in both arms. This large trial clearly demonstrates that essential thrombocytosis patients at high risk of thrombosis should receive hydroxyurea and low dose aspirin as initial therapy, and anagrelide should be reserved for second line use. Many, many questions and comments ensued after this, the last of the plenary abstract presentations. Other fireworks over the myeloproliferative disorders also went off on Saturday. In case you missed it, there was a good old fashioned duel between Drs. Spivak and Tefferi regarding present day use of diagnostics tests for polycythemia vera. The only thing missing from this duel were the pistols.

Further, an Education Session over the weekend presented a wide spectrum of what’s new in myeloproliferative diseases. Dr. Stephen O’Brien discussed optimizing therapy for CML patients. He talked about the four different monitoring tests and how best to apply them. There was also discussion about how frequently monitoring should be applied. Can we ever stop Gleevec therapy? Dr. Ayalew Tefferi updated attendees on the current thinking of myelofibrosis, both in terms of pathogenesis and treatment. Myelofibrosis is clearly a clonal process with a secondary stromal reaction resulting in myelofibrosis. But what starts things off in the first place? Are there any conventional agents worth trying in myelofibrosis? In the current age of reduced intensity stem cell transplantation and with the data that marrow fibrosis can actually reverse (albeit slowly) after allogeneic transplantation, is it time to refer more of these patients for transplant consideration? All worthwhile questions still awaiting answers. Finally, Drs. Valent and Metcalfe discussed mast cell proliferative disorders. Are these really myeloproliferative diseases or just close cousins? They discussed the full spectrum of c-kit gene mutations. They also covered the spectrum of indolent and aggressive systemic mastocytosis as well as those rare mast cell sarcomas. Overall a very elucidating talk, but after hearing all this talk about mast cells one couldn’t help but feel an itch or two, whether it was real or perceived.

NIH RFA Funding Opportunity