PILOT TRIAL OF COMBINED ADMINISTRATION OF ERYTHROPOIETIN AND GRANULOCYTE-COLONY-STIMULATING FACTOR TO CHILDREN UNDERGOING ALLOGENEIC BONE-MARROW TRANSPLANTATION

We carried out a pilot study to evaluate the combined use of recombina nt human erythropoietin (rhEpo) and granulocyte colony-stimulating fac tor (G-CSF) for accelerating marrow engraftment in children given allo geneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Usin g analysis of variance, laboratory and clinical data referring to thes e children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid r epopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receivi ng rhEpo alone and in those receiving combined treatment. These latter , however, showed a further reduction in the total number of red blood cell units required to reach transfusion independence (1.1 +/- 0.7 in the study population vs 2.7 +/- 1.2 in rhEpo group vs 4.2 +/- 2.3 in historical controls; values are mean +/- 1 SD; p < 0.001). Neutrophil engraftment, i.e. time for neutrophils to reach 0.5 x 10(9)/l, was 11 +/- 3 days in children receiving combined treatment, significantly sho rter than that of the control groups (16 +/- 3 and 18 +/- 5, respectiv ely; p < 0.001). Acceleration of neutrophil recovery translated into f ewer infections: days of fever were significantly reduced in the study population (4 +/- 2 vs 11 +/- 8 vs 15 +/- 6, respectively). platelet reconstitution, i.e. time for platelets to reach 50 X 10(9)/l, was 22 +/- 6 days in patients receiving combined treatment, accelerated as co mpared with historical controls (37 +/- 19, p < 0.05), and this was as sociated with a significant reduction in the total number of platelet transfusions (2.4 +/- 1.0 vs 4.4 +/- 2.4 vs 9.5 +/- 7.0, respectively; p < 0.001). There was no toxicity attributable to treatment; in parti cular, graft-versus-host disease was not enhanced. Although these resu lts require confirmation in a randomised trial, they indicate that rhE po and G-CSF can be safely administered in combination and suggest tha t this treatment may acclerate trilineage marrow reconstitution, at le ast in patients without severe transplant-related complications.