Influence of recombinant human granulocyte colony-stimulating factor (filgrastim) on hematopoietic recovery and outcome following allogeneic bone marrow transplantation (BMT) from volunteer unrelated donors

Abstract

Summary:Effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) on hematopoietic recovery and clinical outcome in patients undergoing allogeneic bone marrow transplantation (BMT) from volunteer unrelated donors (VUD) were analyzed retrospectively. Additionally, the influence of baseline patient and transplant characteristics on hematopoietic recovery was evaluated. From January 1994 to March 1996, 47 consecutive adult patients received VUD-BMT. GVHD prophylaxis was cyclosporin A/short course methotrexate/prednisolone, and in four patients additional ATG. Post-transplantation, cohorts of patients received rhG-CSF (5 g/kg/day) (n ‫؍‬ 22) or no rhG-CSF (n ‫؍‬ 25) in a non-randomized manner. The patient groups with and without rhG-CSF were rather comparable with respect to baseline patient and transplant characteristics. Median time to neutrophil counts (ANC) Ͼ500/ l was 14 days with rhG-CSF vs 16 days without rhG-CSF (P ‫؍‬ 0.048), to ANC Ͼ1000/ l was 15 vs 18 days (P ‫؍‬ 0.084). Neutrophil recovery was accelerated in patients receiving more than the median MNC dose of 2.54 ؋ 10 8 /kg with a median time to ANC Ͼ1000/ l of 13 days vs 19 days (P ‫؍‬ 0.017). RhG-CSF did not influence platelet recovery and incidence of infectious complications. Incidence of acute GVHD II-IV was 50% with rhG-CSF and 28% without rhG-CSF (P ‫؍‬ 0.144), but death before acute GVHD II-IV occurred in 9% of patients with and 20% of patients without rhG-CSF. The median follow-up time was 38 and 36 months in patients with and without rhG-CSF, respectively. Survival at 2 years post-transplant was 39% (95% confidence interval (18%, 60%)) in patients with rhG-CSF and 24% (95% confidence interval (7%, 41%)) in patients without rhG-CSF. Administration of rhG-CSF after VUD-BMT may lead to more rapid neutrophil recovery, but did not influence the incidence of

Optimal use of G-CSF administration after hematopoietic SCT

“…56,58,60,62 However, one retrospective study found a delayed engraftment by 2 days with the use of G-CSF vs observation in BMT patients. 55 The authors did not speculate on the reason for their contradictory result. In three RCTs in patients undergoing PBSCT, the time to plt engraftment was not significantly different in patients who received G-CSF vs those who did not; 12,57,61 this was considered level 1B evidence because of a combined number of o100 in each group.…”

“…Three non-randomized studies evaluating outcomes in BMT patients showed similar findings. 55,58,62 However, one retrospective study found a slight but statistically significant delay in plt engraftment when G-CSF was used in both PBSCT and BMT patients. 60 This delay in plt engraftment in the study by Ringden et al 60 was presumed to be a result of G-CSF increasing plt aggregation and creating an accelerated intravascular consumption of plts.…”

“…infusion or SQ injection, with the dose ranging from 5 to 10 mg/kg per day. 12,13,55,57,58,62 Some studies did not report the route or dose used in their studies. 56,60 The criteria for discontinuing G-CSF treatment after allogeneic transplant was variable in these studies: on the day of ANC 4500/ml; 58 or after ANC 4500/ml  2 days; 62,63 or after ANC 4500/ml  3 days 13,60 or ANC 41000/ml  3 days 12,57,64,65 or ANC 43000/ml  1 day.…”

“…Several studies have analyzed the efficacy of using G-CSF compared with control to decrease the number of neutropenic days after allogeneic transplantation in patients receiving either peripheral blood or BM cells. 12,13,[55][56][57][58][59][60][61][62] The outcomes from these studies are summarized in Table 5. Most of these studies included patients with hematological malignancies, whereas some also enrolled patients with solid tumors.…”

“…56,60 The criteria for discontinuing G-CSF treatment after allogeneic transplant was variable in these studies: on the day of ANC 4500/ml; 58 or after ANC 4500/ml  2 days; 62,63 or after ANC 4500/ml  3 days 13,60 or ANC 41000/ml  3 days 12,57,64,65 or ANC 43000/ml  1 day. 55 Owing to the small number of studies, we overlooked the variability of the parameters mentioned above in various studies and assume that the outcomes analyzed below are not influenced by this variability.…”