Circulating haematopoietic progenitors during treatment of renal anaemia with recombinant human erythropoietin.
The effect of recombinant human erythropoietin (rhEPO) and interleukin 3 (IL3) on circulating haematopoietic progenitors consisting mainly of immature burst-forming-units-erythrocytes (BFU-E), was investigated in ten paediatric patients treated by regular haemodialysis. During a 30-week study rhEPO treatment resulted in a rise of median haemoglobin levels from 6.7 g/dl to > 10 g/dl in all patients. Before initiating rhEPO treatment the number of circulating BFU-E in chronic renal failure patients responded to grading doses of rhEPO in vitro similar to that in control children; however, the dose-response curves were not predictive for the in vivo response to rhEPO. After an initial rise in five patients BFU-E numbers declined by week 30 of rhEPO treatment. BFU-E numbers decreased to 35% of pretreatment values. The number of granulocyte-macrophage colony forming cells (GM-CFC) also decreased during rhEPO treatment. Addition of IL3 to the culture medium containing saturating concentrations of granulocyte-macrophage colony stimulating factor did not stimulate BFU-E numbers of patients before rhEPO treatment or those of controls. However, 2 weeks after start of rhEPO treatment IL3 increased the growth of patient's BFU-E in vitro to 220% of pretreatment levels, followed by a gradual decrease of stimulation until the end of observation. These findings indicate that: (1) long-term recruitment of circulating haematopoietic progenitors during rhEPO treatment is low in children with renal anaemia; (2) rhEPO sensitivity of circulating BFU-E is not predictive for the in vivo response; (3) rhEPO treatment results in enhanced sensitivity of BFU-E to IL3.
Göbel
V
V
Sektion für Onkologie/Immunologie, Universität-Kinderklinik, Heidelberg, Germany.
Hoffmann
H G
HG
Müller-Wiefel
D E
DE
Braun
A
A
Ludwig
R
R
Schärer
K
K
Debatin
K M
KM
D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000209:etiology / Q000628:therapy*; D002648:Child; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D006435:Renal Dialysis
D007377:Interleukin-3; D011994:Recombinant Proteins; D004921:Erythropoietin