Clinical and pharmacoeconomic analysis of pegylated and nonpegylated forms of colony-stimulating factors after autologous transplantation of hematopoietic stem cells in patients with lymphoproliferative diseases
High-dose chemotherapy (HDCT) with autologous transplantation of peripheral hematopoietic stem cells (auto-HSCT) is complicated by development of the grade IV hematologic toxicity. Among complications in this treatment, the most frequent are infectious conditions. The duration of grade IV neutropenia correlates with the development of severe infectious complications, which can cause death in the early posttransplant period. The use of colony-stimulating factors (CSF) reduces the duration of neutropenia as well as of developing infectious complications. The aim of the study is to evaluate and compare the efficacy, safety and pharmacoeconomic parameters of two forms of CSF, filgrastim and its pegylated form for stimulation leukopoiesis after auto-HSCT in the patients with lymphoproliferative diseases.
Materials and methods
The study included 100 patients: 39 with Hodgkin’s lymphoma, 18 with non-Hodgkin’s lymphomas, 42 with multiple myeloma, 1 acute promyelocytic leukemia; 51 women, 49 men. The median age was 43 years (18-72) (Table 1). The conditioning regimens were Melphalan 200 mg/m2, Melphalan 140 mg/m2, BeEAC, CBV, BEAM, Cytarabine + Melphalan. The patients were randomized into 2 groups: 1 group – patients who received pegylated form of CSF (PEG-CSF) (n=52), 2 group – patients with non- pegylated form of CSF (n=48). Stimulation of leukopoiesis was initiated on D+4. G-CSF was administered daily at dose of 5 μg/ kg/day until the release of agranulocytosis (WBC = 3.0x10 at 9 cells/L). PEG-CSF was administered once in dose of 6 mg (D+4). The pharmacoeconomic analysis included a comparison of economic evaluation of PEG-CSF treatment versus non-pegylated CSF therapy. Costs for PEG-CSF or CSF administered to the appropriate patient in the posttransplant period were taken into account.
Comparative clinical analysis of the use of CSF and PEGCSF was performed using the following parameters: age, number of pre-transplantation chemotherapy lines, number of transplanted CD34 + (mio cells/kg), hemopoiesis recovery, presence of infectious complications (neutropenic fever), duration of hospitalization (Table 2).
Significant differences were obtained by the rate of recovery of leukocyte count (in 1st group, the yield from agranulocytosis was registered significantly earlier). But in the 2nd group, the inhibition of the erythroid line was significantly less. There were no significant differences in other analyzed parameters. Pharmacoeconomic analysis showed that the median amount of money used to purchase PEG-CSF, administered for the treatment of one patient, was 49,042.73 rubles, and for the CSF was 36180.63 rubles. (p <0, 05) (Table 3) .
There were no significant differences in the clinical analysis of the use of pegylated and non- pegylated forms of colony-stimulating factors. Pharmacoeconomic analysis revealed the advantage of non-pegylated form of CSF over PEG-CSF.
Hematopoietic stem cell transplantation, autologous, colony stimulating factor, pegylated form, efficiency, pharmacoeconomics.
Table 1. General clinical characteristics of patients
|Number of patients in group||100|
|Age, median (interval), years||43 (18-72)|
|Men, abs. (%)||49 (49)|
|Women, abs. (%)||51 (51)|
|Non-Hodgkin's lymphomas, abs. (%)||18 (18)|
|Hodgkin Lymphoma, abs. (%)||39 (39)|
|Multiple myeloma, abs. (%)||42 (42)|
|Acute promyelocytic leukemia, abs. (%)||1 (1)|
Table 2. Comparative analysis of PEG-CSF and CSF
|Group CSF||Group PEG-CSF||t-value.||p|
|Age, years (median)||43||41,5||0,12||0.9|
|The number of transplanted CD34 + million/kg, median||2.59||2.65||0.13||0.86|
|Days of agranulocytosis (median)||7||8||-0.93||0.35|
|Day (after TSCC) of the marrow recovery agranulocytosis (median)||11||10||2.17||0.03|
|Day (after TSCC) of febrile neutropenia||4||5||-1.18||0.23|
|Patients with neutropenic fever, abs. (%)||34 (34%)||40 (40%)||0.63||0.52|
|Days of thrombocytopenia below 20х10^9/L (median)||4||5||-1.42||0.15|
|Level of maximum decrease in hemoglobin||95||86||3.34||0.001|
|Number of pre-transplantation chemotherapy lines||2||2||-1.3||0.19|
|Duration of hospitalization||22||22||-0.46||0.64|
Table 3. Results of the cost analysis for the prevention and treatment of febrile neutropenia per 1 person after autograft
for treatment of 1 patient, Rub.
for treatment of 1 patient, Rub.