Modifications of erythropoiesis in myelodysplastic syndromes treated with recombinant erythropoietin as evaluated by soluble transferrin receptor, high fluorescence reticulocytes and hypochromic erythrocytes.
BACKGROUND
The aim of this study was to evaluate changes in erythropoiesis induced in vivo by recombinant erythropoietin (r-EPO) treatment in myelodysplastic syndromes (MDS), by means of some new, non invasive laboratory parameters.


METHODS
Serum levels of soluble transferrin receptor (STR), a marker of total marrow erythroid activity, and automated detection of high fluorescence reticulocytes (HFR) and hypochromic erythrocytes (HE) (respectively, indexes of effective erythropoiesis and functional iron deficiency) were longitudinally measured in 25 MDS patients treated with r-EPO, and then correlated with conventional clinical and laboratory features.


RESULTS
Stimulation of erythropoiesis was documented in 8 patients, whose serum STR levels showed a significant, early (within 16 days) increase during treatment with r-EPO. However, only 3 of these patients demonstrated a concomitant rise in HFR, and these were the only subjects who experienced a significant clinical response. Two of these patients also developed a functional iron deficiency while on treatment, as documented by an increase in HE, despite normal serum iron, transferrin saturation and even very high levels of ferritin. They needed iron supplementation to maintain the response to r-EPO. No variation in STR, HFR or HE occurred in the remaining 17 unresponsive patients during at least two months of treatment. Serum levels of thymidine kinase, as aspecific marker of cellular proliferative activity, paralleled those of STR. No correlation was found between STR, HFR or HE and serum levels of endogenous EPO, hemoglobin or transfusion requirements in MDS patients.


CONCLUSIONS
These findings suggest that there is a heterogeneous and complex pattern of erythroid response in MDS patients treated with r-EPO. In addition, our results indicate that STR, HFR and HE may provide useful information for the clinical management of these patients.
Musto
P
P
Division of Hematology, Casa Sollievo della Sofferenza Hospital, S. Giovanni Rotondo, Italy.
Modoni
S
S
Alicino
G
G
Savino
A
A
Longo
A
A
Bodenizza
C
C
Falcone
A
A
D'Arena
G
G
Scalzulli
P
P
Perla
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D004912:Erythrocytes / Q000473:pathology*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005453:Fluorescence; D006801:Humans; D007501:Iron / Q000097:blood; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000503:physiopathology*; D011990:Receptors, Transferrin / Q000032:analysis*; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012156:Reticulocytes / Q000473:pathology*; D012995:Solubility
D011990:Receptors, Transferrin; D011994:Recombinant Proteins; D004921:Erythropoietin; D007501:Iron