Biology Reference
In-Depth Information
Table 4. Features of recombinant human erythropoietin (rHuEPO)-induced pure red cell aplasia
•
Severe transfusion-dependent anemia despite erythropoietic therapy
•
Reticulocyte count 0 to 10 × 10
9
/L
•
Bone marrow shows absence of red cell precursors (<5% erythroblasts), but normal white cell
and platelet maturation
•
Normal circulating white cell and platelet counts
•
Neutralizing antibodies to human erythropoietin (detected by RIP or ELISA)
RIP, radioimmunoprecipitation; ELISA, enzyme-linked immunosorbent assay.
1998, remains unclear. The anti-EPO antibodies, which are mainly of IgG
class, are directed against the protein backbone of the molecule, and they
cross-react with all three erythropoietic agents currently available in Europe,
as well as the endogenous hormone. Management of this condition consists of
immediate cessation of erythropoietic agents, along with possible immuno-
suppressive therapy.
The future of erythropoietic therapy
The future of erythropoietic therapy appears bright. It is well established as a
highly effective treatment and, apart from the recently recognized problem of
pure red cell aplasia, the treatment generally has an excellent safety record.
Large multicenter studies (such as CHOIR, CREATE, and ACORD) are exam-
ining the impact of anemia correction on long-term morbidity and mortality in
dialysis, as well as pre-dialysis, patients. There has recently been a treatment
paradigm shift away from aiming for higher target hemoglobin concentrations
to earlier correction of anemia, particularly in the pre-dialysis phase of treat-
ment. The contribution of other cytokines and growth factors in erythropoiesis
and their interaction with EPO is the subject of ongoing research, as is the
putative role of EPO as a neuroprotective agent. Finally, at a molecular level,
much has still to be learned about mechanisms controlling EPO production,
hypoxic sensing, and gene expression. Novel strategies for stimulating ery-
thropoiesis, such as EPO-mimetic peptides [39] and EPO gene therapy [40],
have been assessed in animal experiments, but their translation into clinical
practice, if ever, is at least a decade away.
References
1 Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correction of the ane-
mia of end-stage renal disease with recombinant human erythropoietin. Results of a combined
phase I and II clinical trial.
N Engl J Med
316:73-78
2 Eschbach JW, Abdulhadi MH, Browne JK, Delano BG, Downing MR, Egrie JC, Evans RW,
Friedman EA, Graber SE, Haley NR et al. (1989) Recombinant human erythropoietin in anemic
