A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation

Abstract

Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT. Fifty-four patients with hematologic malignancies undergoing a related, HLA-matched allogeneic BSCT were randomly assigned to receive daily filgrastim at 10 μg/kg or placebo starting on the day of transplantation. A minimum of 3 × 106 CD34+ cells/kg in the allograft was required for transplantation. All patients received a standard preparative regimen and a standard regimen for the prevention of graft-versus-host disease (GVHD). The median time to achieve an absolute neutrophil count greater than 0.5 × 109/L was 11 days (range, 9-20 days) for patients who received filgrastim compared with 15 days (range, 10-22 days) for patients who received placebo (P = .0082). The median time to achieve a platelet count greater than 20 × 109/L was 13 days (range, 8-35 days) for patients who received filgrastim compared with 15.5 days (range, 8-42 days) for patients who received placebo (P = .79). There were no significant differences for red blood cell transfusion independence, the incidence of acute GVHD, or 100-day mortality between the groups. The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT.

A Phase 3, Randomized, Placebo‐controlled Trial of Filgrastim in Patients with Haematological Malignancies Undergoing Matched‐related Allogeneic Bone Marrow Transplantation

“…reported a significantly faster neutrophil recovery [8]. Furthermore, in a randomized double‐blind trial of G‐CSF 10 µg/kg/day (N = 26) vs. placebo (N = 24) administered after allogeneic BMT, G‐CSF also resulted in significantly more rapid neutrophil recovery (11 vs. 15 days for placebo, P = 0.008) [4]. More recently, a retrospective database analysis by Khoury et al.…”

“…Additional risk factors for mortality include infections that arise as a result of neutropenia and prolonged immune deficiency. Recombinant human granulocyte colony‐stimulating factor (G‐CSF) or granulocyte macrophage colony‐stimulating factor (GM‐CSF) may be administered after allogeneic transplantation of either bone marrow or peripheral blood stem cells to enhance engraftment [2–7]. Some authors report that patients receiving growth factors post allogeneic stem cell transplant experience faster neutrophil recovery and no adverse effects in terms of graft versus host disease (GvHD) [4,8].…”

“…Recombinant human granulocyte colony‐stimulating factor (G‐CSF) or granulocyte macrophage colony‐stimulating factor (GM‐CSF) may be administered after allogeneic transplantation of either bone marrow or peripheral blood stem cells to enhance engraftment [2–7]. Some authors report that patients receiving growth factors post allogeneic stem cell transplant experience faster neutrophil recovery and no adverse effects in terms of graft versus host disease (GvHD) [4,8]. Nevertheless, the effects of G‐CSF on longer‐term outcomes in this setting are not well defined and have been the subject of debate [9–11].…”

Effectiveness of daily versus non‐daily granulocyte colony‐stimulating factors in patients with solid tumours undergoing chemotherapy: a multivariate analysis of data from current practice

“…Daily G-CSFs, such as filgrastim or lenograstim, should be administered daily until the expected neutrophil nadir is passed and the neutrophil count has recovered to the normal range, which usually requires up to 2 weeks of treatment. In clinical trials where daily G-CSFs were continued until either the neutrophil count reached Ն10 ¥ 10 9 /L or for up to 14 days, whichever occurred first, the mean duration of G-CSF prophylaxis was up to 10-11 days (Dale et al 1993;Muhonen et al 1996;Bishop et al 2000;Holmes et al 2002b;Green et al 2003;Siena et al 2003). However, several observational studies have reported that in most patients treated in the clinical practice, duration of prophylaxis with daily G-CSFs is less than 7 days, and that a short duration of daily G-CSF treatment is associated with worse neutropenia-related clinical outcomes (Weycker et al 2006;Morrison et al 2007).…”

Administration of G‐CSF from day +6 post‐allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings

“…In allogeneic HSCT, the use of GCSF leads to an improvement in neutrophil engraftment of 1-4 days in comparison with observation (13)(14)(15)(16)(17)(18)(19)(20) or placebo (9,21). This is borne out in both PBSCT and BMT studies, with only one retrospective BMT study not supporting this Abbreviations: ASCO, American Society of Clinical Oncology; BMT, bone marrow transplantation; GCSF, granulocyte colony stimulating factor; GMCSF, granulocyte macrophage colony stimulating factor; GvHD, graftversus-host disease; HSCT, hematopoietic stem cell transplant; IV, intravenous; PBSCT, peripheral blood stem cell transplant; SC, subcutaneous; TPN, total parenteral nutrition; TRM, transplant-related mortality.…”