Delayed G-CSF after autologous progenitor cell transplantation: a prospective randomized trial

Abstract

G-CSF is given after autologous progenitor cell transplantation to accelerate neutrophil engraftment. Historically, G-CSF has been started on the day of progenitor cell infusion. To study the timing of the initiation of G-CSF after autologous peripheral blood progenitor cell (PBPC) transplantation, we conducted a prospective, randomized trial comparing the initiation of G-CSF therapy on day 0, day +3 or day +5 after autologous PBPC transplantation. Seventy patients with diagnoses of breast cancer, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma were prospectively randomized to one of the three treatment arms. All patients were treated with a chemotherapy (only) preparative regimen. The source of hematopoietic reconstitution was PBPC alone (without autologous marrow), and all patients yielded a minimum of 2 x 10(6) CD34+ cells per kilogram. Times to neutrophil engraftment and platelet engraftment were identical in the three treatment groups, with neutrophil engraftment occurring at a median of 10, 11 and 11 days when starting G-CSF on day 0, day 3 or day 5, respectively. Time to platelet transfusion independence was 14, 11 and 14 days by treatment group. We conclude that delaying the initiation of G-CSF from day 0 to day +5 does not affect engraftment and results in cost savings.

Optimal use of G-CSF administration after hematopoietic SCT

“…In comparing the time to neutrophil engraftment (ANC 4500/ml), most of the studies did not find statistically significant differences between early (day 0 to day þ 4) and delayed (Xday þ 5) G-CSF administration. 20,25,26,29,30,37,47,48 In one of the studies, the number of CD34 þ cells infused was significantly less in the delayed administration group compared with the early G-CSF treatment group. 37 However, this difference did not significantly affect the time to neutrophil engraftment.…”

“…Most of the studies enrolled patients with hematological malignancies, with some also including patients with solid tumors. 20,29,30,37,48,49 Two studies Significant difference from other groups.…”

“…49 In addition, in the study conducted by deAzevedo et al, 46 the benefit of early G-CSF (day þ 1) compared with late G-CSF (day þ 5) in reaching ANC 4500/ml was only evident in a subgroup of patients who received melphalan as a conditioning regimen and received 43.0 Â 10 6 per kg CD34 þ cells. When only the RCTs were evaluated, five studies with a combined number of over 100 patients showed no difference in ANC recovery with delayed initiation of G-CSF, 26,29,37,47,48 whereas two studies with a total of o100 patients in each group reported delayed neutrophil engraftment with starting G-CSF later than day þ 5. 22,46 Therefore, delayed G-CSF initiation was considered to be equally effective for early initiation in terms of neutrophil engraftment (level 1B).…”

“…With this in mind, several studies have analyzed the optimal time to start G-CSF after autologous PBSCT. 20,22,25,26,29,30,37,[46][47][48][49] The summary of these studies is provided in Table 2. Most of the studies enrolled patients with hematological malignancies, with some also including patients with solid tumors.…”

“…29 Filgrastim was administered on the basis of weight in most studies at 5 mg/kg per day as either i.v. infusion or SQ injection, 20,22,25,30,46,48,49 whereas a fixed dose of G-CSF (filgrastim 300 or 480 mg per day) was used in some studies. 37,47 The criteria for discontinuing G-CSF treatment after PBSCT varied significantly in various studies: on the day of ANC 4500/ml, 20,47 ANC 41000/ml, 22 or WBC 410 000/ml; 25 or after ANC 4500/ml for 2 37,48 or 3 consecutive days; 26,29,30,49 or after ANC 41500/ml for 3 consecutive days.…”