Ann Hematol (1995) 71:65-70 9 Springer-Verlag 1995 A. Torres G6mez 9M. A. Jimenez 9M. A. Alvarez A. Rodriguez 9C. Martin 9M. J. Garcia 9R. Flores J. Sanchez 9 M. J. de la Torre 9C. Herrera J. Roman 9P. Gomez 9F. Martinez Optimal timing of granulocyte colony-stimulating factor (G-CSF) administration after bone marrow transplantation A prospective randomized study Received: 3 March 1995 / Accepted: 8 June 1995 Abstract The positive role of G-CSF in hastening the myeloid recovery of patients undergoing allogeneic bone marrow transplantation (ALLO-BMT) or autolo- gous bone marrow transplantation (ABMT) has recent- ly been established. Considerable knowledge about ad- equate doses and route of administration has been ac- cumulated in the past few years. Nonetheless, the opti- mal time to start growth-factor administration remains undetermined. We have performed a stratified study according to the source of hematopoietic progenitors (ALLO-BMT or ABMT), underlying disease and its stage, and acute graft-versus-host disease (GVHD) pro- phylaxis regimen and randomized patients in two arms: group A, which started G-CSF on day 0 (36 patients), and group B, which started on day +7 post-BMT (39 patients). The same dose (5 ixg/kg/day) and route of ad- ministration were employed in both groups. We found no significant differences in the time to reach an abso- lute neutrophil count (ANC) of 0.1, 0.5, and lx 109/1 and 50• 109 platelets/1 (medians: 10 and 11, 14.5 and 14, 17 and 16, 23 and 24 days, respectively, in groups A and B). We did not find differences in the days of fever or days on antibiotic treatment with less than 1 x 109/1 ANC, rate of bacteriemia, or days of hospitalization in both groups. In contrast, a considerable saving of G- CSF in B group was found (mean days of infusion in group A, 18, versus 11 in group B) (p <0.0001). This is equivalent to a saving of 1120 $US per patient. There- fore, early use of G-CSF after BMT is useless and more expensive and provides no advantage over delayed ad- ministration. A. Torres G6mez ([E~) 9 M. A. Jimenez 9 M. A. Alvarez A. Rodriguez 9 C. Martin - M. J. Garcia 9 R. Flores J. Sanchez - M. J. de la Torre 9 C. Herrera - J. Roman P. Gomez 9 F. Martinez Bone Marrow Transplantation Unit, Department of Hematology, Reina Sofia University Hospital, Avenida Mendndez Pidal, s/n, E-14004 Cdrdoba, Spain Key words Allogeneic bone marrow transplantation 9 Autologous bone marrow transplantation 9 Granulocyte colony-stimulating factor (G-CSF) 9 Hematopoietic recovery Introduction In the past several years, several hematopoietic growth factors (HGFs), such as granulocyte colony-stimulating factor (G-CSF) [17, 19], granulocyte-macrophage colo- ny-simulating factor (GM-CSF) [1, 14], macrophage colony-stimulating factor (M-CSF), [6] and interleukin- 3 [3, 10], have been clinically tested to evaluate their efficacy in shortening the granulocytopenic or pancy- topenic period following allogeneic (ALLO-BMT) or autologous bone marrow transplantation (ABMT). In vitro studies have shown that G-CSF has a positive and synergistic effect on early and, mostly, on late hemato- poietic precursors [5, 12]. This action has been con- firmed in vivo in both phase-HI studies and random- ized clinical trials after conventional therapy or high- dose therapy followed by ABMT or ALLO-BMT [2, 17, 19, 20]. Thus, the use of G-CSF (5-10 ixg/kg/day) has been shown to be effective in reducing the time of granulocytopenia after these therapeutic procedures [7, 8]. Although in the past years considerable clinical knowledge has been accumulated concerning the most effective dose and route of administration of G-CSF and other growth factors, little attention has been paid to the optimal timing and scheduling of this factor after BMT. It is well known that in the days following BMT the restoration of hematopoiesis is dependent on "seeding" and self-renewal of early marrow progenitors (stem cells), followed by subsequent stochastic commitment to proliferation. Nevertheless, once the commitment has occurred, late precursors can be stimulated by li- neage-specific cytokines. A variable period of time seems to be necessary (while seeding, self-renewal,