Several studies showed that the response rate to standard dose of recombinant Human Erythropoietin (rHuEPO) in MDS patients is generally low, with only few cases presenting a significant increase of haemoglobin (Hb) levels. So, currently, the interest has focused on the use of high dose rHuEPO. The rationale for using high dose rHuEPO was elucidated: residual normal stem cells and/or abnormal clone of MDS stem cells, unresponsive to low levels of endogenous EPO, might respond to high doses of rHuEPO. The aim of this study was to assess the efficacy and safety of high dose rHuEPO treatment. EPO alfa 40.000 IU was given subcutaneously twice weekly for 4 weeks. Twenty-five patients with low-risk MDS (17 RA and 8 RARS) and Hb levels ≤ 10 g/dL were included in this study; sixteen patients were female and 9 male; mean age of enrolled patients was 74 years (range 66 – 85). Twenty-two of 25 patients completed the scheduled treatment and were evaluated for response. At 4 weeks eighteen of 22 patients (81%) showed a Hb mayor response (Hb increase ≥ 2 g/dL); Hb mean value at baseline was 8,15 g/dL (range 7 – 10), at 4 weeks was 13,15 g/dL (range 10 – 14,6). In 4 of 22 patients (19%) the high dose rHuEPO did not induce an increase of Hb levels after 4 weeks of treatment; in addition, these patients needed of RBC transfusions to maintain Hb levels ≥ 8 g/dL. The failure of treatment with rHuEPO occurred in patients with diagnosis of RARS. In our study there were no statistically significant differences between the group of patients with erythroid hyperplasia and the group of patients with normal percent of bone marrow erythroid cells (P = 0,4); no significant difference was noted in response rates between patients with RBC pre-treatment transfusion need and those with stable anaemia without prior transfusion (P = 0,09). In our study, Hb mayor response occurred also in one patient with marked marrow fibrosis. In this study all patients presented defective endogenous EPO production related to their degree of anaemia, with serum EPO levels ≤ 100 mU/ml (mean value 43,5; range 6 – 98). The responder patients need continuous maintenance treatment to maintain their response; EPO alfa 40.000 IU was given subcutaneously once a week; at 12 weeks overall response rate was 77%: 13/18 patients maintained their mayor response, 4/18 patients showed decreased Hb levels in comparison to initial response (Hb decrease > 1 < 2 g/dL), 1 patient progressed on RAEB. Hb mean value at 12 weeks was 11,8 g/dL (range 9,2 – 13,5). The median duration of maintenance of the erythroid response was 7,5 months (range 2 – 24 months). Treatment with high dose of rHuEPO is well tolerated; only one adverse event of arterial hypertension of moderate severity was reported as possible episode related to treatment. In conclusion, our study shows that, in low-risk MDS patients with defective endogenous EPO production, EPO alfa 40.000 IU, given subcutaneous twice weekly for 4 weeks, induces rapid, significant and persistent increase of Hb, without important adverse events; continuous maintenance treatment with 40.000 IU/w is necessary for the majority of the responding patients to maintain their response.

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