[Large volume, isovolemic erythrocytapheresis in treatment of polycythemia vera. Effect of massive iron depletion of proliferation behavior of erythroid precursor cells (BFU-E)].

BACKGROUND

Isovolemic large volume erythrocyte-apheresis (EA) is a rapid, effective and well-tolerated treatment modality for red blood cell (RBC) depletion in patients with polycythaemia vera (PV). According to clinical observations its long lasting effect (median interval from EA to EA about 6 months) may, at least in part, be due to the associated loss of iron.

METHODS

Therefore we investigated the influence of EA on the proliferative capacity of erythroid (BFU-E) and granulocyte-macrophage (GM-CFU) progenitor cells and on the erythropoietin-(EPO-)independent, spontaneous in vitro growth of BFU-E in particular. In six patients RBC and iron parameters as well as the proliferative capacity of hematopoietic progenitor cells were determined before and after EA.

RESULTS

RBC parameters (in median) were before/after EA: RBC 7.64/5.93 x 10(6)/microliter; Hct 53/40%; Hb 15.5/12.0 g/dl and remained at reduced levels for several months; serum iron and ferritin levels decreased, while transferrin levels and transferrin receptor expression on peripheral mononuclear cells were enhanced. Serum EPO-levels were temporarily but only slightly increased. In all patients there was a significant inhibition of the growth of BFU-E detectable after EA while the GM-CFU were less affected. Within 3 to 6 weeks, the inhibition of endogenous BFU-E ranged from 53% to 100% and of EPO-dependent BFU-E from 31% to 74%. The inhibition of EA associated BFU-E growth could be reduced by in vitro addition of FeCl3. On the other hand, in vitro exposure of progenitor cells to an equivalent concentration of the iron chelator DFO (deferoxamine mesylate) resulted in a total suppression of progenitor cell growth.

CONCLUSION

Our data suggest that the long lasting effect of EA is not only due to the high volume removal of RBC itself, but also to the growth inhibition of EPO-independent and -dependent BFU-E which is obviously mediated by the considerable loss of iron by EA.