A prospective randomized trial of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in adults

Abstract

Summary:In order to assess the potential clinical benefit of filgrastim (G-CSF) after peripheral blood stem cell (PBSC) autotransplantation a randomized study was begun in our center in July 1997: 62 patients were involved (30 received filgrastim after PBSC infusion and 32, the control group, received no cytokines). All were adults (median 40 years, range 18-65). Patients with one of three different pathologies were recruited: 28 had advanced breast carcinoma, 23 had lymphomas (12 Hodgkin's disease and 11 non-Hodgkin's lymphoma) and 11 had de novo AML. All of them were transplanted using myeloablative chemotherapy conditioning regimens. G-CSF was administered subcutaneously from day +5 in the treated group at a dose of 5 g/kg body weight/day. The numbers of CD34 + and mononuclear (MNC) cells infused were similar in each group. Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data. Faster granulocyte engraftment was evident in the treated group (mean of 10 vs 12 days to achieve Ͼ0.5 × 10 9 /l granulocytes, P = 0.0008), without differences in incidence and severity of infections, days of fever or duration of antibiotic treatment between groups. There was slightly slower platelet engraftment (mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve Ͼ20 × 10 9 /l platelets, P = NS) in this series, but there were no differences in incidence and severity of haemorrhage or platelet transfusion support. Considering the economical costs, the median expenditure per inpatient stay was Eur5961 (range Eur4386-Eur17186) in the G-CSF group compared with Eur5751 (range Eur3676-Eur15640) in the control group (P = 0.47). From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration.

Optimal use of G-CSF administration after hematopoietic SCT

“…Various studies have evaluated the efficacy of using G-CSF in comparison to either placebo 11,16,17 or observation. 10,[18][19][20][21][22][23][24][25][26][27][28][29][30] These studies are summarized in Tables 1-3. Most of the studies involved patients with hematological malignancies (leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma), with some also enrolling patients with nonhematological malignancies.…”

“…Most of the studies involved patients with hematological malignancies (leukemia, Hodgkin's lymphoma, non-Hodgkin's lymphoma and multiple myeloma), with some also enrolling patients with nonhematological malignancies. 10,17,[20][21][22]24,25,27,29,30 Two studies specifically evaluated breast cancer patients undergoing autologous transplantation. 22,25 Most of the studies used filgrastim as a form of G-CSF, whereas three studies used lenograstim at either 263 mg per day 26 or at 150 mg/m 2 per day.…”

“…36 Most of the studies started G-CSF on day þ 1 post transplantation with the exception of a few studies starting on day þ 5. 21,23,24 In addition, some studies compared the control group with the early vs delayed or individualized time to start G-CSF, which is discussed in detail in the next sections. G-CSF was administered on the basis of the patients' body weight in most studies at 5 mg/kg per day as either i.v.…”

“…G-CSF was administered on the basis of the patients' body weight in most studies at 5 mg/kg per day as either i.v. infusion or SQ injection 10,16,[18][19][20]22,[24][25][26]28,30 or at 10 mg/kg per day i.v. or SQ.…”

“…21 Three studies used a BSAbased dosing for filgrastim (50 mg/m 2 per day) or lenograstim (150 mg/m 2 per day), 11,17,27 whereas Lee et al 23 used a fixed dose of filgrastim (300 mg per day) in patients who weighed 70 kg or less and a weight-based dose (5 mg/kg per day) in patients heavier than 70 kg. The criteria for discontinuing G-CSF treatment after PBSCT differed significantly in various studies: when ANC 4500/ ml, 11,20,27 ANC 41000/ml, 21,22 ANC 41500/ml, 16,24 ANC 45000/ml, 19 or WBC 410 000/ml; 25 or after ANC 4500/ml for 2 28 or 3 17,26,29,30 consecutive days; or after ANC 41000/ ml for 2 consecutive days; 23 or after WBC 41000/ml for 3 consecutive days; 18 or was left to the treating physician. 10 Various PBSC mobilization protocols, conditioning regimens and prophylaxis therapies were used in these studies.…”