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 recombinant human erythropoietin (rhEpo) and granulocyte colony-stimulating factor (G-CSF) for accelerating marrow engraftment in children given allogeneic bone marrow transplantation (BMT). Fifteen consecutive children were enrolled in this study; 13 completed it and were evaluable. Using analysis of variance, laboratory and clinical data referring to these children were compared with those of 15 patients previously treated with rhEpo alone and with those of 16 historical controls. Erythroid repopulation, evaluated sequentially through serum transferrin receptor and reticulocyte count, was similarly accelerated in children receiving 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 ± 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 shorter than that of the control groups (16 ± 3 and 18 ± 5, respectively; p <0.001). Acceleration of neutrophil recovery translated into fewer 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 compared with historical controls (37 ± 19, p <0.05), and this was associated 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 particular, graft-versus-host disease was not enhanced. Although these results require confirmation in a randomised trial, they indicate that rhEpo and G-CSF can be safely administered in combination and suggest that this treatment may accelerate trilineage marrow reconstitution, at least in patients without severe transplant-related complications.