[Inadequate erythropoietin production (epo) in patients with multiple myeloma]

Anaemia is the most common haematological complication in patients with malignant diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis of this hypoproliferative, normochromic, normocytic anaemia is complex. Results from clinical studies which evaluate the efficacy of recombinant human erythropoietin (rHuEpo) refer to the possibility that patients with multiple myeloma independently of renal function could have Epo deficiency. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with multiple myeloma in order to define clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 42 patients with multiple myeloma were examined. The control group consisted of 25 patients with iron deficiency anaemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and haemoglobin (Hb) in the control group, as well as from O/PEpo ratio as a measure of the degree of adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferin receptors (sTfR) and Hb in the control group, as well as from O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O -- observed sTfR value, P -- predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with multiple myeloma but preserved renal function, which was not the case in patients with renal insufficiency. 43% of patients without renal insufficiency and 85% of patients with renal insufficiency had inadequate Epo response to anaemia. In both patient groups (with and without renal insufficiency) instead of the expected inverse relationship between Hb and sTfR as in the control group, a positive correlation was found. 76% of patients had inadequate sTfR response to anaemia. There is a positive correlation between O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and O/PsTfR in patients with multiple myeloma are significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production, respectively erythropoietic activity. In conclusion, the results from this study show unambiguously that anaemia in patients with multiple myeloma appears because of decreased erythropoiesis as a consequence of bone marrow infiltration with malignant plasma cells as well as inadequate Epo production. Most probably, there are two forms of inadequate Epo production: one because of the renal insufficiency and the other that found in patients with anaemia of chronic diseases the mechanism of which is not clear.