Recombinant Human Erythropoietin for the Treatment of Anaemia in Patients with Chronic Idiopathic Myelofibrosis

Abstract

Background: Patients with chronic idiopathic myelofibrosis (CIMF) usually present with anaemia. Treatment is often palliative and the majority of patients receive regular red blood cell (RBC) transfusions. Although recombinant human erythropoietin (rhu-EPO) has been proved effective for the treatment of anaemia in several chronic diseases, including haematological malignancies, its role in the treatment of the anaemia in CIMF is not well established. We report the beneficial effect of rhu-EPO administration in 20 patients with CIMF and discuss the parameters predicting favourable response. Patients: Twenty patients with CIMF (9 women and 11 men) regularly treated with supportive RBC transfusions were included in the study. The median age was 70 years (range 45–81 years). Rhu-EPO, 10,000 U, was given subcutaneously 3 times a week. The median duration of therapy was 83 months, ranging from 13 to 87 months. Results: Treatment was considered effective if haemoglobin levels increased over 2 g/dl within 12 weeks after enrolment or the RBC transfusion requirements were reduced by 50% within the same interval. Twelve patients (60%) responded to therapy. Responders were mainly female, had smaller spleen size (p = 0.024), low RBC transfusion requirements (≤1–2 units per month), and significantly lower endogenous serum erythropoietin (EPO) and β₂-microglobulin (β₂-M) levels when compared with non-responders (p < 0.0001 and 0.00001, respectively). Treatment was well tolerated and none of the patients was withdrawn from the treatment protocol because of side effects. Conclusions: Rhu-EPO administration is an effective, safe and well-tolerated treatment for patients with CIMF and anaemia leading to a significant reduction in RBC transfusion requirements. Factors predicting favourable response are low endogenous EPO and β₂-M serum levels and slight to moderate splenomegaly.

Danazol therapy for the anemia of myelofibrosis: assessment of efficacy with current criteria of response and long-term results

“…In responder patients, maintenance danazol dose was 200 mg daily. Median duration of anemia response was 14 months (IQR [10][11][12][13][14][15][16][17][18][19][20][21]. At this writing, 2 patients remained on treatment at 10 and 12 months from danazol start, 8 patients lost the response at 3.2-46 months of its achievement, and 5 definitively discontinued treatment while in response due to toxicity or personal decision.…”

“…Once the abovementioned causes have been ruled out, therapeutic options include erythropoiesis-stimulating agents (ESA), androgens, immunomodulating drugs, and splenectomy. Anemia response to ESA ranges from 23 to 60 %, depending on the criteria of response used, and it is usually restricted to patients with inadequate Epo levels, being less frequent in patients with large spleens or transfusion dependency [14][15][16][17]. With immunomodulating drugs such as thalidomide or lenalidomide, usually given in combination with prednisone, responses are 19 to 35 %, but there is frequent discontinuation due to side effects [18][19][20].…”

Primary myelofibrosis: current therapeutic options

“…Reported overall response rates range from 23% to 60% 25, 26, 27, 28. Hb <10 g/dL, transfusion independence,25, 27 and EPO levels <125 U/L 27 are factors that might confer a better response to treatment.…”

Myelofibrosis: an update on drug therapy in 2016

“…(14) Like in myelodysplastic syndromes (MDS),(47) responses to ESAs are usually restricted to patients with low endogenous erythropoietin levels and lower or no transfusion burden. (48–50) In small studies, response rates have ranged from 40% to 60%. (48–50) Smaller spleen size also predicts for anemia responses to ESAs.…”