EFFECT OF GRANULOCYTE COLONY STIMULATING FACTOR ON NEUTROPENIA INDUCED BY CYTOTOXIC CHEMOTHERAPY

doi:10.1016/S0140-6736(88)91475-4

The Lancet

Volume 331, Issue 8587, 26 March 1988, Pages 667-672

https://doi.org/10.1016/S0140-6736(88)91475-4 Get rights and content

Abstract

A phase I/II study of granulocyte colony stimulating factor (G-CSF) was undertaken in patients with advanced malignancy receiving melphalan to determine the granulocyte response, side-effects, and pharmacokinetics. Patients received doses of 1-60 μg/kg intravenously. There were 3 patients at each dose level. Before chemotherapy the immediate effect of G-CSF was a transient depression in circulating neutrophils followed by a dose-dependent rise. Neutrophil counts up to 80 × 10⁹/l were achieved. G-CSF administration following melphalan reduced the period of neutropenia caused by melphalan. G-CSF was well tolerated and the only clinical observation that appeared related to G-CSF administration was slight bone pain during some infusions. G-CSF was rapidly cleared from the blood with a mean half-life of 110 min for the second phase. Reductions in the number of days of neutropenia following cytotoxic chemotherapy may reduce the morbidity and mortality of chemotherapy.

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Treatment-Induced Bone Marrow Enhancement at MRI in Breast Cancer Patients Receiving Granulocyte-Colony Stimulating Factor Adjunct to Chemotherapy
2023, Academic Radiology
Granulocyte-colony stimulating factor (G-CSF) induces the reconversion of fatty bone marrow to hematopoietic bone marrow. The bone marrow changes are detectable as signal intensity changes at MRI. The aim of this study was to evaluate sternal bone marrow enhancement following G-CSF and chemotherapy treatment in women with breast cancer.
This retrospective study included breast cancer patients who received neoadjuvant chemotherapy with adjunct G-CSF. The signal intensity of sternal bone marrow at MRI on T1-weighted contrast-enhanced subtracted images was measured before treatment, at the end of treatment, and at 1-year follow-up. The bone marrow signal intensity (BM SI) index was calculated by dividing the signal intensity of sternal marrow by the signal intensity of the chest wall muscle. Data were collected between 2012 and 2017, with follow-up until August 2022. Mean BM SI indices were compared before and after treatment, and at 1-year follow-up. Differences in bone marrow enhancement between time points were analyzed using a one-way repeated measures ANOVA.
A total of 109 breast cancer patients (mean age 46.1 ± 10.4 years) were included in our study. None of the women had distal metastases at presentation. A repeated-measures ANOVA determined that mean BM SI index scores differed significantly across the three time points (F[1.62, 100.67] = 44.57, p < .001). At post hoc pairwise comparison using the Bonferroni correction BM SI index significantly increased between initial assessment and following treatment (2.15 vs 3.33, p < .001), and significantly decreased at 1-year follow-up (3.33 vs 1.45, p < .001). In a subgroup analysis, while women younger than 50 years had a significant increase in marrow enhancement after G-CSF treatment, in women aged 50 years and older, the difference was not statistically significant.
Treatment with G-CSF as an adjunct to chemotherapy can result in increased sternal bone marrow enhancement due to marrow reconversion. Radiologists should be aware of this effect in order to avoid misinterpretation as false marrow metastases.
Severe, Reversible Acute Lung Injury During Autologous Hematopoietic Stem Cell Mobilization After Filgrastim in a Child With Neuroblastoma: A Case Report
2020, Transplantation Proceedings
Peripheral blood hematopoietic stem cell mobilization is widely performed in a variety of clinical facilities and is believed to be a safe outpatient procedure. In this report, we describe a child with neuroblastoma who developed an extremely severe acute lung injury after granulocyte colony-stimulating factor was used for peripheral hematopoietic stem cell mobilization.
A 3-year-old boy with a medical history of patent foramen ovale and secundum atrial septal defect was diagnosed with an MYCN-amplified neuroblastoma and treated with chemotherapy. During stem cell mobilization with filgrastim, the boy was in very good clinical condition, with a peripheral white blood cell (WBC) count of 57.17 K/μL, but he suddenly deteriorated, and nausea, seizures, and nystagmus were observed. The patient developed dyspnea with hemoptysis, and lung computed tomography showed bilateral asymmetrical pulmonary opacification demonstrating an anteroposterior density gradient. Because of rapidly progressing circulatory and respiratory failure, the child was hospitalized in the intensive care unit. Corticosteroid therapy, broad-spectrum antibiotic therapy, and cardiovascular support with mechanical ventilation were immediately instituted, and the child recovered without sequelae.
The presented case emphasizes that life-threatening complications can occur during granulocyte colony-stimulating factor administration, and patient surveillance is warranted, especially if high leukocyte counts are observed or the patient exhibits cardiopulmonary signs.
Comparing granulocyte colony–stimulating factor filgrastim and pegfilgrastim to its biosimilars in terms of efficacy and safety: A meta-analysis of randomised clinical trials in breast cancer patients
2018, European Journal of Cancer
Citation Excerpt :
Current treatment guidelines from the American Society of Clinical Oncology [1], the National Comprehensive Cancer Network [2], the European Organisation for Research and Treatment of Cancer [3], the European Society for Medical Oncology [4] and Canadian supportive care guidelines [5] recommend the prophylactic use of granulocyte colony–stimulating factors (G-CSFs) in patients receiving chemotherapy when the risk of FN is ≥ 20%, and in patients with FN risk between 10–20% who have additional risk factors such as age ≥65 years, poor performance status and prior FN. In clinical trials and daily practice, primary and secondary prophylaxis with G-CSF has been shown to reduce FN incidence, its complications and improve outcomes of cancer treatment [6–11]. The G-CSF class of therapeutic agents was developed by isolating, purifying, and cloning this haematopoietic regulatory factor [12].
Granulocyte colony–stimulating factors (G-CSFs) are widely used to prevent neutropenia in cancer patients undergoing myelosuppressive chemotherapy. Several biosimilar medicines of G-CSF are now available, with their development involving a step-wise series of comparisons to demonstrate similarity to reference biologics. Randomised clinical trials (RCTs) are considered confirmatory, and for G-CSF biosimilars, patients with breast cancer (BC) undergoing myelosuppressive chemotherapy are the most sensitive population in which to confirm similarity. This meta-analysis aimed to compare the clinical efficacy and safety of approved or proposed G-CSF biosimilars (filgrastim or pegfilgrastim) with reference G-CSF in patients with BC.
A Medline literature search up to March 2017 identified RCTs comparing biosimilar G-CSF to reference in BC patients. The primary efficacy end-point was mean difference in duration of severe neutropenia (DSN). Secondary efficacy end-points were differences in depth of absolute neutrophil count (ANC) nadir, time to ANC recovery and incidence of febrile neutropenia. Safety analyses included calculation of risk ratios for bone pain events, myalgia events and serious adverse events. Random effect models were fitted to obtain the pooled estimates of the mean difference for continuous outcomes and the risk ratio for dichotomous outcomes and their corresponding 95% confidence intervals (CIs).
Eight eligible RCTs were included in this meta-analysis. Overall difference in DSN between reference and biosimilar medicines was not statistically significant (0·06 d [95% CI −0·05, 0·17]). The analysis of secondary efficacy end-points showed no significant differences between reference biologics and biosimilar medicines, as well as the analysis of bone pain events, myalgia events and serious adverse events.
This meta-analysis showed no significant differences in clinical efficacy and safety between biosimilar and reference G-CSF in BC patients.
Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?
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Improving the Therapeutic Potential of G-CSF through Compact Circular PEGylation Based on Orthogonal Conjugations
2023, Biomacromolecules
Semimechanistic pharmacokinetic–pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy
2023, CPT: Pharmacometrics and Systems Pharmacology

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EFFECT OF GRANULOCYTE COLONY STIMULATING FACTOR ON NEUTROPENIA INDUCED BY CYTOTOXIC CHEMOTHERAPY

Abstract

J Biol Chem

Blood

Blood

Biochem Biophys Res Comm

High-dose melphalan with autologous bone marrow transplantation for multiple myeloma Blood

Principles of chemotherapy in cancer

Autologous bone marrow transplantation: present status and future prospects

Aust NZ J Med

Bacterial infections in neutropenic patients in supportive care

The molecular biology and function of the granulocyte-macrophage colony stimulating factors

Blood

Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells

Int J Cancer

Granulocyte colony-stimulating factor and differentiation-induction in myeloid leukemic cells

Int J Cell Cloning

Identification of the human analogue of a regulator that induces differentiation in murine leukaemic cells

Nature

Separation of functionally distinct human granulocyte-macrophage colony-stimulating factors

Blood