A. Jacobs

Ferrokinetics and Erythropoiesis in Man: The Measurement of Effective Erythropoiesis, Ineffective Erythropoiesis and Red Cell Lifespan using 59Fe

Existing ferrokinetic methods do not provide a direct and quantitative measurement of effective and ineffective red cell production. A new method is described for calculating the daily uptake of iron by maturing red cells and the mean red cell lifespan. Ineffective erythropoiesis and non‐erythroid iron turnover are also measured. The method involves standard laboratory techniques but the analysis requires access to a computer. The preliminary results suggest that it will be a clinically useful tool for the investigation of erythroid disorders.

Erythropoiesis and the Effect of Transfusion in Homozygous β-Thalassemia

THE erythropoietic abnormality in patients with homozygous β-thalassemia results from a genetically determined defect in globin (β-chain synthesis. Erythroid activity is vastly increased, and estim...

Ferrokinetics and erythropoiesis in man: red-cell production and destruction in normal and anaemic subjects.

Recent advances in the analysis of plasma 59Fe clearance have produced a unified method for measuring effective and ineffective erythropoiesis (Ricketts et al, 1975). We have used this method to investigate the balance between red‐cell production and destruction in normal subjects and in patients with megaloblastic anaemia, iron deficiency anaemia and refractory hypoplastic anaemia. The results show that the normal marrow can maintain an appropriate red‐cell mass by altering red‐cell production to match destruction. In the anaemias we have studied there is an increased rate of either intra‐ or extra‐medullary red‐cell destruction. The response of the marrow may be limited by iron supply, by defective nuclear maturation or by some intrinsic marrow defect.

Ferrokinetics and Erythropoiesis in Man: An Evaluation of Ferrokinetic Measurements

The plasma iron clearance half‐time and plasma iron turnover have usually been interpreted as measures of total erythroid activity and the red‐cell utilization of 59Fe has been equated with effective red‐cell production. Erythrocyte iron turnover has sometimes been calculated as the product of plasma iron turnover and percentage utilization. We have assessed these measurements as estimates of erythroid activity by comparing them with total marrow iron turnover and red‐cell iron turnover determined by the method of Ricketts et al (1975) in 10 normal subjects and 51 patients with an uncomplicated haematological disorder. The results show that the plasma iron clearance half‐time does not reflect erythroid activity and that plasma iron turnover can be particularly misleading in patients with reduced marrow activity. Red‐cell utilization and erythrocyte iron turnover give a distorted reflection of effective erythropoiesis except in patients with erythroid hypoplasia. Marrow iron turnover and red‐cell iron turnover provide more realistic and generally applicable assessments of the degree and effectiveness of erythroid activity.

Clonal growth of haemopoietic progenitor cells from myelodysplastic marrow in response to recombinant haemopoietins

The growth factor requirements of granulocyte-macrophage (GM) and erythroid marrow progenitor cells from 12 myelodysplastic (MDS) patients have been analysed. GM progenitors from two of six patients who grew normal numbers of colonies in response to conditioned medium + erythropoietin (5637CM + Epo) showed defective responses to either GMCSF and/or IL-3. Of all the recombinant factors tested (IL-3, IL-1, GCSF, GMCSF, MCSF), GMCSF was the strongest stimulator of myeloid clonal growth, inducing normal numbers of GM colonies from marrow of six patients (two of whom were neutropenic). Erythroid colonies were low in 5637CM + Epo-supplemented cultures of marrow from all but one patient and remained poor in the presence of any of the haemopoietins. tested. Supraoptimal doses (for normal marrow) of these haemopoietins improved colony growth in only one patient (GM colonies in response to IL-3). Combinations of factors were also largely ineffective at raising myeloid or erythroid colony numbers. These data indicate that the defective response of MDS progenitor cells to growth factors is not amenable to experimental manipulation of recombinant factor levels or combinations. Clonal assays might suggest a role for GMCSF therapy in a subpopulation of neutropenic MDS patients but their potential now needs to be evaluated in association with clinical trials.

Enrichment of haemopoietic progenitor cells from the marrow of patients with myelodysplasia.

Myeloid and erythroid progenitors from myelodysplastic marrows have been separated from accessory cell populations likely to influence their in‐vitro growth. Myeloid colony‐forming cells were enriched 23‐fold and erythroid progenitors 5‐7‐fold but, in both cases, retained their abnormal growth characteristics. After enrichment and removal of lymphocytes and monocytes, erythroid burst formation became markedly more dependent on the addition of 5637 bladder carcinoma conditioned medium as an exogenous source of haemopoietic growth factors. This suggests that lymphocytes and monocytes usually support erythropoiesis in cultures of myelodysplastic marrow and demonstrates that erythroid burst‐forming progenitor cells from myelodysplastic patients can respond to these populations in vitro. Haemopoietic failure in myelodysplasia appears to result from a defect within the preleukaemic clonogenic cell, rather than from an aberration in exogenous factors. The procedure outlined here can be used as a first step towards the isolation of these abnormal progenitors.