P Rossi Ferrini — Page 4

PubMedDate not supplied

In vivo administration of stem cell factor enhances both proliferation and maturation of murine megakaryocytes.

BACKGROUND: Stem cell factor (SCF) has already been shown to participate in the regulation of erythro- and granulopoiesis. The aim of this study was to define the possible role of SCF in the regulation of megakaryocytopoiesis. METHODS: Stem cell factor activity has been assessed in an in vivo murine model, in which different doses of the factor were either given alone or in association with recombinant human erythropoietin (rhEpo). Mice were sacrificed after a six-day treatment to evaluate the effect of SCF on the number of bone marrow and spleen colony-forming units-megakaryocyte (CFU-Mk), and after a two-day treatment for evaluation of thrombopoietin-like activity. RESULTS: We found that SCF induces a dose-related increase in the number of CFU-Mk in both the bone marrow and spleen of the treated mice, and that in the range of the doses used (from 25 to 200 mg/kg/day) the greatest activity was observed when a dose of 200 mg/kg/day was injected. The effect was enhanced by adding rhEpo to optimal SCF concentrations. SCF also stimulated megakaryocyte maturation as assessed by the megakaryocyte number, the size of acetylcholinesterase-positive cells, 35Sulphur (35S) incorporation into the newly formed platelets. All these parameters were only minimally affected by the addition of rhEpo. CONCLUSIONS: These data suggest that SCF participates in the regulation of megakaryocytopoiesis and that its administration might have a role in the treatment of disorders of platelet production.

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PubMedDate not supplied

High doses of recombinant human erythropoietin fail to accelerate platelet reconstitution in allogeneic bone marrow transplantation. Results of a pilot study.

BACKGROUND AND OBJECTIVE: The effectiveness of recombinant human erythropoietin (rhEpo) in accelerating erythroid engraftment in patients undergoing allogeneic bone marrow transplantation (BMT) has been demonstrated in previous studies. On the other hand, there are experimental data suggesting that high doses of rhEpo might also exert a stimulatory effect on thrombopoiesis. METHODS: We carried out a pilot study on the use of high doses of rhEpo (500 U/kg/day for 30 days after transplant) in ten patients (HD-Epo group) receiving BMT to evaluate the effects on both erythroid and platelet (Plt) engrafment. This group was compared to ten BMT patients who had not received the hormone (Placebo group). RESULTS: The HD-Epo group patients showed signs of accelerated erythropoietic recovery; in fact, the time required to reach a reticulocyte count higher than 30 x 10(9)/L was significantly shorter than in the Placebo group, while the number of high RNA content reticulocytes (HFR) was about three times greater. Circulating transferrin receptor (TfR) levels 30 days after BMT were also significantly higher in the HD-Epo group than in the other. Finally, the number of red blood cell (RBC) transfusions in the first 30 days following BMT was about twofold lower in the HD-Epo group; moreover, 4/10 patients who were treated with HD-Epo did not require any RBC units. No significant effects on the engraftment of platelets or on the number of Plt transfusions were observed in the HD-Epo as compared to the Placebo group. No adverse effect was noted on granulocytopoiesis, nor were any adverse clinical experiences found in patients who had been treated with erythropoietin at high dosages. INTERPRETATION AND CONCLUSIONS: These data confirm that rhEpo may stimulate erythroid reconstitution after BMT, while its effects on Plt engraftment and on Plt transfusion requirements are minimal.

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