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New Treatments for Essential Thrombocythemia and Myeloid Metaplasia with Myelofibrosis

Myeloid metaplasia with myelofibrosis. This term is interchangeable with extramedullary hematopoiesis. In reference to this disease, it refers to the extramedullary hematopoiesis which occurs in the spleen. So this is splenic extramedullary hematopoiesis with bone marrow fibrosis. This state can occur de novo, and you would call it agnogenic myeloid metaplasia.

So what can you do? Well, quality of life is bad. Survival is short. Try to cure it. Because palliating it is not going to take you anywhere and they have done that. Initially there was a concern about the fibrotic marrow not accepting the graft. This has been refuted now. As you can see, over 90% of the patients engrafted well. So first thing, patients with myelofibrosis can engraft. That’s not the problem. Second, you can actually, 50% of the patients, can survive meaning the other 50% are dead. Patients have to remember this and as you can see, the first essential thrombocythemia, myeloid metaplasia with myelofibrosis.

So what can you do? In that group of patients, at this point, we only palliate their symptoms. And what are their symptoms? Anemia is one of the major problems with myelofibrosis. This is a cocktail that I use; Halotestin 10 mg twice a day along with about 30-40 mg of prednisone.

The second thing that you have to palliate them is the big spleen. What can you do about it? Use hydroxyurea, about 500 mg three times a day, combined with Procrit 40,000 units once a week. Minimize the anemic side effect of hydroxyurea. When that fails, go to splenectomy and if they are not good surgical candidates for splenectomy.

After splenectomy, the average survival is about two years, but we have patients who have survived over ten years. What good did it do? Well, those bad constitutional symptoms, almost all of them get improved and that improvement is pretty durable. If you have transfusion-requiring anemia you can expect that 25% of your patients will have a durable improvement.

How about splenic irradiation? It’s very effective. It will shrink it; they will feel better. It’s usually transient but the interesting thing is you can do it again and get exactly the same response. Splenic irradiation causes severe myelosuppression and I think this is what historically has been known as abscopal effect. Basically there is a lot of stem cell progenitors.

There are two pathogenetic mechanisms here. First is this clonal myeloproliferation, which involves the megakaryocytes and probably involves the monocytes and histiocytes. Then there’s the reactive stromal reaction, which includes fibrosis, ineffective hematopoiesis, osteosclerosis, and believe it or not, angiogenesis. We’ve got tons of data now showing severe increase in micro-vessel density in these patients. So the question is, we know that this stromal reaction is probably cytokine mediated.

We implicate the megakaryocytes and the monocytes. We are trying to sort this out and believe me, it is hard. But that’s what we are trying to do, is to see if we can identify some cytokines.