The role of recombinant human erythropoietin alpha in the treatment of chronic anemia in multiple myeloma.
Chronic anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM) as a consequence of the B cell malignancy. Its pathogenesis is multifactorial. Besides the altered inflammatory cytokine network, other events are held responsible, namely persistent defect of erythropoietin due to the kidney failure, shortening of red cell survival, accumulation of the serum monoclonal component and platelet dysfunction. Our recent studies have demonstrated that excessive erythroblast apoptosis promoted by myeloma cells drives the appearance of anemia, in particular in patients with severely progressive disease. A number of clinical trials have provided evidence for the effectiveness of recombinant human erythropoietin (rHuEPO-alpha: epoetin alpha) in improving the deregulated erythropoiesis in MM, since it acts as a major erythroid growth factor by exerting a specific anti-apoptotic effect. In the majority of these studies, the long-term treatment of MM-associated anemia with rHuEPO-alpha induced a significant improvement of erythropoiesis, as shown by a stable increase of hemoglobin values (> or = 2g/dL) and reduction of transfusion requirements. In a recent trial which included both a double-blind and an open-label phase, we have documented that rHuEPO-alpha induces a stable improvement of anemia in more than 75% of patients and a significant decrease of fatigue, with an overall recovery of the quality of life. Patients receiving a placebo also achieved similar results in the open-label phase, when they were switched to rHuEPO-alpha.
Department of Biomedical Sciences and Human Oncology Section of Internal Medicine and Clinical Oncology, University of Bari, Italy.
Franco
F
Dammacco
Grazia
G
Luccarelli
Marcella
M
Prete
Franco
F
Silvestris
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D001803:Blood Transfusion; D002454:Cell Differentiation / Q000187:drug effects; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000502:physiology; D000068817:Epoetin Alfa; D015672:Erythroid Precursor Cells / Q000187:drug effects / Q000473:pathology; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000627:therapeutic use*; D006801:Humans; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy / Q000523:psychology; D011788:Quality of Life; D011994:Recombinant Proteins; D016896:Treatment Outcome
D016207:Cytokines; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa