Recombinant human granulocyte colony-stimulating factor (filgrastim) following high-dose chemotherapy and peripheral blood progenitor cell rescue in high-grade non-Hodgkin's lymphoma: clinical benefits at no extra cost

Abstract

Summary In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor (G-CSF, filgrastim) following peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy (HDCT), 23 consecutive patients aged less than 60 years with poor-prognosis, high-grade non-Hodgkin's lymphoma (NHL) were entered into a prospective randomized trial between May 1993 and September 1995. Patients were randomized to receive either PBPC alone (n = 12) or PBPC+G-CSF (n = 11) after HDCT with busulphan and cyclophosphamide. G-CSF (300 gg day-') was given from day +5 until recovery of granulocyte count to greater than 1.0 x 109 1-1 for 2 consecutive days. The mean time to achieve a granulocyte count > 0.5 x 1091-1 was significantly shorter in the G-CSF arm (9.7 vs 13.2 days; P<0.0001) as was the median duration of hospital stay (12 vs 15 days; P= 0.001). In addition the recovery periods (range 9-12 vs 11-17 days to achieve a count of 1.0 x 1091-1) and hospital stays (range 11-14 vs 13-22 days) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median. There were no statistically significant differences between the study arms in terms of days of fever, documented episodes of bacteraemia, antimicrobial drug usage and platelet/red cell transfusion requirements. Taking into account the costs of total occupied-bed days, drugs, growth factor usage and haematological support, the mean expenditure per inpatient stay was £6500 (range £5465-£81 01) in the G-CSF group compared with £8316 (range £5953-£15 801) in the group not receiving G-CSF, with an observed mean saving of £1816 per patient (or 22% of the total cost) in the G-CSF group. This study suggests that after HDCT and PBPC rescue, the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay. Furthermore, and despite the additional costs for G-CSF, these clinical benefits are not translated into increased health care expenditure.

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.…”

“…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.…”

“…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.…”

“…In most of the studies, ANC 4500/ml was achieved by day þ 9 to day þ 11 when G-CSF was used. The difference in days to neutrophil engraftment between the groups receiving or not receiving G-CSF ranged from 2 to 9.5 days, 10,11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] showing that the use of G-CSF was beneficial in terms of earlier neutrophil engraftment. In addition, several studies noted that even though the high number of CD34 þ cells infused correlated with earlier neutrophil engraftment, the benefit of using G-CSF was independent of the number of CD34 þ cells infused.…”

“…24,[38][39][40][41] However, there was no significant difference in time to plts engraftment (plts 420 000/ml) between the group receiving G-CSF and the control group in most studies. 10,11,[17][18][19][20][21][22][23][24][25][26][27][28][29][30] Only one randomized, single-blind, placebo-controlled study showed a significant increase in plts engraftment when G-CSF was used (starting on day þ 5) compared with placebo. 16 As eight out of nine RCTs (o90%) with well over 100 patients in each group showed no significant difference in plts engraftment with the use of G-CSF, 10,11,17,[22][23][24]26,29 this was considered level 1B evidence.…”