[Analysis of causes for anemia in patients with multiple myeloma]

Pathogenetic mechanism of myeloma (MM) associated anaemia may involve: decreased level of erythropoietin (Epo) production, insufficient response to this hormone, bone marrow replacement by tumour cells, and cytokine mediated suppressive effect on erythropoiesis (ACD type of anaemia). We evaluated some possible causes of MM associated anaemia in a group of MM patients before treatment, using tests of in vitro culture of erythroid precursors and determination of the level of selected cytokines and evaluation of patient sera and media conditioned by patient cells for haematopoietic growth in vitro inhibitory/stimulatory activity. The study group included 15 patients with advanced MM at III clinical stage (according Durie and Salmon classification) prior treatment with a median age 61.8 women and 7 men. Diagnostic work-up included cytogenetics and serum Epo level as well as routine tests. We determined number of CFU-E, BFU-E and CFU-GM in the bone marrow of patients and healthy donors after mononuclear and T cell depletion in serum free culture under different conditions: 1) with conditioned medium (CM) by patients T cells, 2) CM by T cells of healthy donors and 3) without CM. IL-6, IL-1 alpha and TNF-alpha level in the serum and CM was determined. All patients were slightly anaemic--mean Hb 6 mmol/l (9.6 g/dl), transferrin level was increased--mean 1612 pmol/l (732 ng/ml) whereas iron level was normal. The average frequency of erythropoietic cells in myelogram was decreased (12%), however, the frequency of plasmocytes was increased (32%). Epo serum level was decreased in comparison with degree of anaemia (mean 22.2 U/ml). The average number of CFU-E/10(5) was slightly lower--212 and in the cultures containing CM by patient T cell and CM-by T cells of healthy donor decreased significantly to 138 and 183, accordingly. This phenomenon was not observed in cultures containing normal bone marrow cells. IL-6 level was increased in patients' serum and CM by patients T cells (27 ng/ml and 51 ng/ml, respectively).

The results of this study support the notion on the multifactorial origin of anaemia in myeloma patients. The factors specified in this study include 1. defective response of Epo to the degree of anaemia 2. decreased number of committed erythroid cells in the marrow 3. suppression of erythropoiesis by IL-6.