Optimal timing of G-CSF administration after CD34+immunoselected peripheral blood progenitor cell transplantation

Abstract

Summary:G-CSF accelerates neutrophil recovery after autologous peripheral blood progenitor cell transplantation (aPBPCT), although the optimal timing for its administration is currently unknown. In order to establish the role and the optimal timing of administration of G-CSF after immunoselected CD34 ؉ aPBPCT, we analyzed the data from 21 consecutive patients affected by haematological malignancies. Patients were randomized into three groups according to G-CSF administration after transplantation: day ؉1 (group B); day ؉7 (group C) or no G-CSF (group A). Serum G-CSF level was evaluated until engraftment. The CD34 ؉ cell dose reinfused was similar (P = 0.48). G-CSF significantly reduced time to recovery of PMN Ͼ0.5 × 10 9 /l (11 vs 14 vs 20.5 days) (P = 0.00046); Ͼ1.0 × 10 9 /l (12 vs 15 vs 22) (P = 0.001). No difference was observed in the number of days with PMN Ͻ0.1 × 10 9 /l (5.5 vs 7 vs 8 days). Platelet count Ͼ50 × 10 9 /l and Ͼ100 × 10 9 /l, reticulocytes Ͼ1%, length of hospitalization, non-prophylactic antibiotic therapy, fever, incidence of sepsis and transfusion support did not differ. Early or delayed G-CSF after immunoselected CD34 ؉ aPBPCT significantly accelerated PMN recovery but did not reduce the amount of supportive treatment or the duration of hospitalization. Delaying the initiation of G-CSF did not reduce the length of treatment (11.5 vs 12 days). Early or delayed G-CSF administration resulted in G-CSF peak serum levels 7 (early)-12 (delayed)-fold greater than an endogenous response to neutropenia.

Optimal use of G-CSF administration after hematopoietic SCT

“…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.…”

“…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. 17,29 Filgrastim is derived from Escherichia coli, differing from lenograstim, which is non-glycosylated and has an extra methionine at the N-terminus.…”

“…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.…”

“…Time to neutrophil engraftment was significantly shorter when G-CSF was used after transplantation compared with observation or placebo in most of the studies. 10,11,17,18,[20][21][22][23][24][25][26][27][28][29][30] Only one retrospective and one prospective non-randomized study did not find a statistically significant difference in time to neutrophil engraftment between the group receiving G-CSF and the observation group. 19,21 As all the RCTs with a combined number of more than 100 patients in each group showed the beneficial effects of G-CSF on neutrophil engraftment, 10,11,16,17,[22][23][24]26,29 this was considered level 1A evidence.…”

“…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.…”