Combination Therapy with Recombinant Human Erythropoietin, Interferon-α-2b and Granulocyte- Macrophage Colony-Stimulating Factor in Idiopathic Myelofibrosis

Abstract

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-α-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 × 10⁶/U 3 times weekly, and that of GM-CSF was 250 μg/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.

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

“…The effectiveness of rhu-EPO treatment in CIMF has been studied in relatively small series of patients [6, 11, 14, 25, 26] and the response rates significantly vary among these reports [11,24,25,26,27]. …”

“…Cytotoxic drugs, such as hydroxyurea, busulphan, melphalan and 2-chlorodeoxyadenosine, have been reported to be effective for the control of leucocytosis, thrombocytosis and splenomegaly [6,7,8,9,10]. Interferon-α alone or in combination with growth factors has been used for the inhibition of bone marrow fibrosis [11]. …”

“…In previous decades, recombinant human erythropoietin (rhu-EPO) was used effectively for the treatment of anaemia related to chronic diseases, such as chronic renal failure, solid tumours, malignant and non-malignant haematological disorders, such as lymphoproliferative disorders, myelodysplastic syndromes and myeloproliferative disorders, anaemia due to prematurity, sickle cell anaemia, β-thalassaemia and sickle/β-thalassaemia [11, 14,17,18,19,20,21,22,23]. …”

“…Data regarding the efficacy of rhu-EPO administration in patients with CIMF are limited, although several series of patients treated with rhu-EPO have been reported [11,24,25,26,27,28]. A recent study, which also included previously published results, suggests that rhu-EPO may be an effective treatment for anaemia in CIMF [29].…”

Modern management of myelofibrosis

“…In this sense, it must be pointed out that most patients with IM have serum erythropoietin levels appropriate to the degree of anaemia (Barosi et al, 1993a). The experience with erythropoietin therapy in IM is limited, with only a few small series having been reported (Aloe-Spiriti et al, 1993;Tefferi & Silverstein, 1994;Bourantas et al, 1996;Rodríguez et al, 1998;Hasselbalch et al, 2002). Response rates range from 33 to 100%, although the criteria of response employed are not uniform.…”