A randomized trial of granulocyte colony-stimulating factor (Neupogen) starting day 1 vs day 7 post-autologous stem cell transplantation

Abstract

Summary:The purpose of the study was to evaluate the effect of delayed granulocyte colony-stimulating factor (G-CSF) use on hematopoietic recovery post-autologous peripheral blood progenitor cell (PBPC) transplantation. Patients were randomized to begin G-CSF on day +1 or day +7 post transplantation. Thirty-seven patients with lymphoma or myeloma undergoing high-dose therapy and autologous PBPC rescue were randomized to daily subcutaneous G-CSF beginning on day +1 or day +7 post-transplant. Patients р70 kg received 300 g/day and Ͼ70 kg 480 g/day. All patients were reinfused with PBPCs with a CD34 + cell count Ͼ2.0 × 10 6 /kg. Baseline characteristics of age, sex and CD34 + cell count were similar between the two arms, the median CD34 + cell count being 5.87 × 10 6 /kg in the day +1 group and 7.70 × 10 6 /kg in the day +7 group (P = 0.7). The median time to reach a neutrophil count of Ͼ0.5 × 10 9 /l was 9 days in the day +1 arm and 10 days in the day +7 arm, a difference which was not statistically significant (P = 0.68). Similarly, there was no difference in median days to platelet recovery Ͼ20 000 × 10 9 /l, which was 10 days in the day +1 arm and 11 days in the day +7 arm (P = 0.83). There was also no significant difference in the median duration of febrile neutropenia (4 vs 6 days; P = 0.7), intravenous antibiotic use (7 vs 8 days; P = 0.54) or median number of red blood cell transfusions (4 vs 7 units; P = 0.82) between the two arms. Median length of hospital stay was 11 days post-PBPC reinfusion in both groups. The median number of G-CSF injections used was 8 in the day +1 group and 3 in the day +7 group (P Ͻ 0.0001). There is no significant difference in time to neutrophil or platelet recovery when G-CSF is initiated on day +7 compared to day +1 post-autologous PBPC transplantation. There is also no difference in number of febrile neutropenic or antibiotic days, number of red blood cell transfusions or length of hospital stay. The number of doses of G-CSF used per transplant is significantly reduced with delayed initiation, resulting in a significant reduction in drug

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.…”

“…20,22,25,26,29,30,37,47,48 As all the RCTs with a total of more than 100 patients in each group reported the same finding, 22,26,29,37,47,48 this was considered level 1A evidence. In most of the studies, plts 420 000/ml was achieved by day þ 10 to day þ 14.…”

“…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.…”

“…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. 46 In all the studies, patients received on average 42.0 Â 10 6 /kg CD34 þ cells.…”