Thrombopoietin mimetic offers aplastic anemia hope

By Lynda Williams

Eltrombopag significantly improves blood counts in some patients with refractory severe aplastic anemia, suggests research published in TheNew England Journal of Medicine.

In the phase II study conducted in 25 patients unresponsive to immunosuppression, treatment with the oral thrombopoietin mimetic elicited a hematologic response in at least one lineage in 11 patients after 12 weeks.

Nine patients no longer required platelet transfusion after achieving a median increase in platelets of 44,000 per mm3. In addition, six patients experienced a significant increase in hemoglobin levels (median 4.4 g/dL), three of whom no longer required transfusion. Nine patients significantly increased their neutrophil count, by a median 1350 per mm3.

"These findings, which suggest that eltrombopag stimulates hematopoiesis at the level of primitive hematopoietic cells, are consistent with the results of previous laboratory studies," say Cynthia Dunbar (National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA) and co-authors.

Overall, seven of the 11 patients with a response, who began on an initial daily dose of 50 mg, increasing up to 150 mg, continued with treatment for a median of 16 months. During this time, blood counts continued to show clinically significant improvements, with one patient meeting criteria in two lineages and six patients meeting criteria in three lineages.

Four patients discontinued treatment due to a neutrophil-only response or toxicity. Of the 23 patients examined for bone marrow fibrosis, none had increases in fibrosis or reticulin.

In an accompanying editorial, Donald Metcalf (Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia) comments: "If confirmed, the implication of these intriguing results is that in many patients with aplastic anemia, the hematopoietic stem cells and their progenitor-cell progeny may have acquired defective MPL [myeloproliferative leukemia virus oncogene] receptors that are unresponsive to thrombopoietin but remain able to be activated by eltrombopag."

He notes: "a recent study in which patients with familial aplastic anemia were shown to have nonsense mutations in the MPL gene. Time will tell whether the hematopoietic cells in other patients with aplastic anemia will also prove to have defective MPL signaling."

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