PROGNOSTIC FACTORS IN PATIENTS WITH HIGH-RISK MYELODYSPLASTIC SYNDROME WITH AN INCREASED BLAST COUNT AND TREATED WITH AZACITIDINE

Abstract

Myelodysplastic syndrome（MDS）is a disease entity characterized by ineffective hematopoiesis and a pre-leukemic state. Azacitidine, a DNA demethylating agent, is approved as a first line epigenetic drug medication for high-risk MDS in place of cytotoxic chemotherapy. However, a subset of high-risk MDS with increased myeloblasts（20～30％）（refractory anemia with an excess of blasts（RAEB）can be successfully treated with standard acute myeloid leukemia chemotherapy aiming “kill of every leukemia cell”. To date the molecular basis is not clear to explain the difference of drug sensitivity in MDS with heterogeneous pathogenesis. In the present study, we analyzed 22 patients with high-risk MDS with myeloblasts（20～30％）treated with azacitidine, based on the selection of a group which would likely benefit by azacitidine therapy. By retrospective analysis of the clinical factors and prognosis of these patients, we found the factors which are associated with an increased survival of the patients. Those include age≦80 years old （p＝0.04）, leukocyte counts≦3,000/µl（p＝0.04）, LDH＜normal upper limit（p＝0.003）, serum ferritin≧normal upper limit （p＝0.006）, bone marrow cellularity（p＝0.003）, absence of bone marrow fibrosis（p＝0.04）and early hematological improvement（EHI）（p＝0.009）. Those are possibly important factors in the selection of azacitidine therapy for MDS in daily practice.