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Erythropoietin in AMM (MF)
COMBINATION THERAPY WITH RECOMBINANT HUMAN ERYTHROPOIETIN, INTERFERON ALFA-2b AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN IDIOPATHIC MYELOFIBROSIS by Bourantas, et al, published in Acta Haematologica, issue 96, 1996.
In this Greek study seven patients with idiopathic myelofibrosis (AMM) , aged 48 to 72 years, were treated with a combination of erythropoietin, interferon, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Erythropoietin was chosen for its possible positive effect on anemia; the GM-CSF to reduce neutropenia (three patients presenting with leukocytosis - high white blood cells - were NOT given the GM-CSF). The interferon (IFN) was hoped to suppress bone marrow fibrosis by its inhibition of platelet-derived growth factor (PDGF) and also used to bring about a reduction in the spleen.
Doses given were Epo - 200 U/kg, 3 times per week; IFN - 3 mu/ 3 times per week; and GM-CSF was 250ug/m squared per day for three weeks only. As mentioned, only four of the seven received the GM-CSF.
Results included a hemoglobin increase in all patients (two had been transfusion-dependent). Spleen size decreased in all six patients who had started with splenomegaly. In the four patients treated with GM-CSF, three showed improvement of neutropenia though previous levels returned after the GM-CSF was discontinued (after the three weeks). Bone marrow fibrosis decreased in two patients.
After one year, three patients continued to do well on both Epo and IFN while one continued with the Epo alone. Of the other three patients (after the initial 6 month study), one was lost to follow-up; the other two had discontinued therapy with a subsequent return of splenomegaly and decreased hemoglobin.
The authors note that previous therapies for IMF (AMM) of transfusions, androgens, chemotherapy (for spleen reduction) have not proved particularly helpful. Longer survival is associated with an absence of symptoms at diagnosis. Poor prognostic indicators include organomegaly (enlarged liver or spleen), hemoglobin below 10 g/dl, platelets below 100,000. Better treatment choices are needed and the combination of Epo and IFN, in particular, may be helpful, ESPECIALLY, the authors note, if treatment is started soon after diagnosis. IFN is particularly beneficial when the disease is still proliferative, before extensive fibrosis. GM-CSF with Epo has a synergist effect reducing both anemia and neutropenia.