title: Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis.
abstract: Recombinant erythropoietin (r-EPO) was administered to 37 patients with advanced, transfusion-dependent and chemo-resistant multiple myeloma (MM), at the fixed dose of 10,000/U s.c., 3 times a week, for 2 months. Thirteen patients (35.1%) achieved a significant response in terms of complete abolition of red cell transfusions. Factors significantly predictive of response were: a) inappropriate production of endogenous EPO, as expressed by a reduced observed/predicted ratio; b) presence of a consistent number of circulating erythroid precursors BFU-E; c) low serum levels of tumor necrosis factor (TNF) and interleukin-1 (IL-1), cytokines with inhibitory activity on erythropoiesis; d) a single line of previously received chemotherapy. Renal failure, bone marrow plasma cell infiltration, serum levels of IL-6 and other main clinical and laboratory parameters did not affect significantly the response to r-EPO. High fluorescence reticulocytes (HFR) and soluble transferrin receptor (sTfR) values were useful to detect an early stimulation of erythropoiesis in responders, while a high percentage of circulating hypochromic erythrocytes (HE), as assessed by an automated counter, identified those patients developing functional iron deficiency during r-EPO treatment. We conclude that about one-third of severely anemic patients with advanced MM, unresponsive to chemotherapy, may benefit by r-EPO therapy. The clinical management of these patients can be accomplished using non-invasive parameters, such as sTfR, HFR and HE.
authors.affiliation: Division of Hematology, IRCCS Casa Sollievo della Sofferenza Hospital S. Giovanni Rotondo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Musto
authors.forename: A
authors.initials: A
authors.lastname: Falcone
authors.forename: G
authors.initials: G
authors.lastname: D'Arena
authors.forename: P R
authors.initials: PR
authors.lastname: Scalzulli
authors.forename: R
authors.initials: R
authors.lastname: Matera
authors.forename: M M
authors.initials: MM
authors.lastname: Minervini
authors.forename: G F
authors.initials: GF
authors.lastname: Lombardi
authors.forename: S
authors.initials: S
authors.lastname: Modoni
authors.forename: A
authors.initials: A
authors.lastname: Longo
authors.forename: M
authors.initials: M
authors.lastname: Carotenuto
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000150:complications / Q000188:drug therapy; D001803:Blood Transfusion; D004341:Drug Evaluation; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications / Q000628:therapy*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin