Bone Marrow Transplantation (2001) 27, 1287–1292  2001 Nature Publishing Group All rights reserved 0268–3369/01 $15.00 www.nature.com/bmt Myeloid reconstitution Administration of post-autologous PBSCT rhG-CSF is associated with long-term low concentrations of bone marrow hematopoietic progenitor cells MM Osma, F Ortun ˜o, ML Lozano, J Gomez-Espuch, F Ayala, I Sanchez-Serrano, E Perez-Ceballos, JM Moraleda and V Vicente Unit of Hematology and Clinical Oncology, School of Medicine, Hospital General Universitario, Murcia, Spain Summary: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been widely used after autologous peripheral blood stem cell transplant (APBSCT) in an attempt to reduce the duration of neutropenia, but whether this treatment has any influence on long-term engraftment remains unknown. We have retrospectively analyzed data from breast cancer patients to compare post-APBSCT rhG-CSF administration in terms of the short-term benefit and myeloid marrow regeneration after 1 year. Group A included 10 patients not treated with post-APBSCT rhG-CSF, while groups B and C comprised 15 and 13 patients treated with this drug from days +1 and +6, respectively. No differences among the three groups were found in age, diagnosis, previous chemo-radiotherapy, CD34 + /CD71 - cell con- centration in pre-transplant bone marrow (BM), mobil- ization schedule, CD34 + cell yield, conditioning regimen and post-transplant radiotherapy. Post-APBSCT rhG- CSF was shown to accelerate neutrophil recovery, but there were no significant differences in platelet recov- ery, transfusion requirements, days of fever, antibiotic administration or inhospital stay. With regard to BM hematopoietic precursors 1 year after APBSCT, sig- nificantly lower concentrations of total CD34 + cells, committed CD34 + /CD33 + subsets, and more immature CD34 + /CD71 - cells were found in both groups B and C compared with patients not having received the cyto- kine (group A). Thus, post-APBSCT rhG-CSF adminis- tration does not appear to beneficially affect procedure outcome, and might even impair long-term marrow hematopoiesis. Bone Marrow Transplantation (2001) 27, 1287–1292. Keywords: granulocyte colony-stimulating factor (rhG- CSF); breast cancer; autologous peripheral blood stem cell transplantation; long-term hematopoietic recovery Correspondence: Prof V Vicente, Centro Regional de Hemodonacio ´n, C/. Ronda de Garay s/n, 30003 Murcia, Spain Received 19 February 2001; accepted 5 April 2001 A number of reports have indicated that various hematopo- ietic growth factors, including recombinant human granulo- cyte colony-stimulating factor (rhG-CSF), GM-CSF, IL-1, IL-3 and some growth factor combinations can accelerate engraftment when administered after bone marrow (BM) transplantation. 1 Apart from the risk of relapse, one of the major concerns after high-dose therapy followed by auto- logous peripheral stem cell transplantation (APBSCT) is the short-term procedure-related toxicity, particularly life- threatening infections or hemorrhage promoted by delayed engraftment. While there seems to be general consensus on the benefit of rhG-CSF on neutrophil recovery after BMT 2,3 and APBSCT, 4–8 and in some cases a reduction in hospital stay as compared to patients receiving placebo, 6–8 most trials fail to detect any valuable effect of rhG-CSF on plate- let recovery, incidence of infectious complications and clinical outcome. 4–7,9 It is generally accepted that the main effect of rhG-CSF is to stimulate the formation of mature neutrophilic granulocytes, 10 and for that reason, as during the immediate post-transplant period rhG-CSF responsive late-committed neutrophilic progenitors have not been for- med, the administration of early (day +1) vs delayed (day +6) rhG-CSF has no major effects. This has been confirmed in a number of studies analyzing the efficacy of initiating rhG-CSF treatment on day +1 or after day +6 both in BM transplantation, 11 and APBSCT, 9,12 showing no significant differences between both schedules in neutrophil recovery or in clinical outcome. Data concerning the short-term adverse effects of rhG- CSF administration (bone and muscle pains, flu-like symp- toms, headache, fatigue and nausea), have been extensively reported and may be easily controlled with minor analgesia, rarely requiring discontinuation of rhG-CSF treatment. 13 However, there are currently few data evaluating the poten- tial risk of long-term effects related to rhG-CSF adminis- tration, and this issue remains open. 14,15 In this sense, administration of rhG-CSF during the immediate engraftment period might theoretically affect the infused progenitor pool either by stimulating the egress to periph- eral blood or by enhancing their proliferation, potentially leading to a relative loss of precursors with self-renewal capacity and a reduced repopulating ability of the BM. To evaluate the short-term outcome and long-term engraftment, we have retrospectively analyzed data from