Clinical results of recombinant erythropoietin in transfusion-dependent patients with refractory multiple myeloma: role of cytokines and monitoring of erythropoiesis

: 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 consistant 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.