Relation between S-phase fraction of myeloma cells and anemia in patients with multiple myeloma

In an attempt to define the relation among anemia, tumor mass, and prolifer ative activity of tumor cells in vivo, we measured the proportion and cell cycle distribution of erythropoietic cells and myeloma cells in the bone ma rrow of patients with multiple myeloma using four-parameter flow cytometry, Forty-three bone marrow samples from 33 patients with stage II or III dise ase and normal renal function at diagnosis (n = 9), in partial remission (n = 9), and in progression or relapse after chemotherapy (n = 25) were evalu ated. Early and late erythropoietic cells were discriminated based on publi shed light scatter properties in combination with CD71 expression, Myeloma cells were detected by exploiting their strong CD38 positivity and light sc atter characteristics. Cell cycle distribution of the three cell population s was determined by propidium iodine staining, In the whole group of patien ts, hemoglobin (Hb) concentration was inversely correlated with beta(2)-mic roglobulin (p = 0.03), percentage of marrow CD38(++) cells (p = 0.008), and percentage of CD38++ cells in S phase (S-CD38(++); p < 0.001). Partial cor relation analysis revealed S-CD38(++) to be the only independent predictor of Hb concentration (p < 0.001), No correlation was found between Hb concen tration and the S-phase fraction of erythropoietic cells. In the subgroup o f patients with moderate to severe anemia, defined as Hb concentration <11 g/dL, Hb level correlated negatively only with S-CD38(++) (p < 0.001) but n ot with beta(2)-microglobulin and percentage of marrow CD38++ cells. In add ition, Hb and the S-phase proportion of early erythropoietic cells correlat ed positively (p = 0.029), The strong inverse correlation between Hb concen tration and percentage of myeloma cells in S phase suggests that in multipl e myeloma, tumor proliferative activity may have a more important impact on the development of anemia than tumor mass. The S-phase fraction of tumor c ells appears to be the most important pathogenic factor, especially in anem ic patients. In these patients, the positive relation between Hb concentrat ion and the S-phase fraction of erythro poietic progenitors indicates that development of anemia is associated with inhibition of erythropoiesis. (C) 1999 International Society for Experimental Hematology. Published by Elsevi er Science Inc.