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The Role of Filgrastim
Published in Howard J.A. Carp, Recurrent Pregnancy Loss, 2020
Fabio Scarpellini, Marco Sbracia
Filgrastim is often used clinically to increase the number of stem cells after organ transplant or to activate the reconstruction of the vascular bed after heart ischemia, and in neurology to treat patients with severe degenerative diseases [1–14]. In our study, a significant increase of β-hCG levels was observed in ongoing pregnancies from the fifth through the ninth gestational week in filgrastim-treated pregnancies when compared to control pregnancies [26]. These data showed a direct effect of filgrastim on the trophoblast, with the mobilization and activation of placental stem cells. Another mechanism of action may be the effect of G-CSF on lymphocytes; several studies have shown that G-CSF promotes the mobilization and proliferation of several lymphocyte and dendritic cells, in particular Treg and DC2 cells [39,40]. Our unpublished data show that women with RPL treated with filgrastim had a significant increase in the number of peripheral blood Treg cells when compared to normal pregnancy. Furthermore, in women with RPL treated with filgrastim who subsequently miscarried again due to embryonic aneuploidy, there was still an increase of Treg cells in the decidua compared to the controls. These data suggest that G-CSF may mobilize and differentiate stem cells and immune cells enhancing trophoblast function.
Linezolid
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Two case reports have been published regarding myelosuppression in children receiving linezolid: a case of pure red cell precursor toxicity after 14 days of therapy, which resolved after treatment cessation (Taketani et al., 2009), and a child who became neutropenic after several months of linezolid for tuberculosis. The latter received an off-label dose of filgrastim, with sufficient count recovery to continue linezolid treatment (Hernández Segurado et al., 2013).
Integrative hyperthermia treatments for different types of cancer
Published in Clifford L. K. Pang, Kaiman Lee, Hyperthermia in Oncology, 2015
Clifford L. K. Pang, Kaiman Lee
The patient presented myelosuppression of degree IV 10 days after chemotherapy; the minimum was 0.3 × 109/L, and the platelet count was a minimum of 10 × 109/L, accompanied by pulmonary infection. Filgrastim was given to increase WBCs. Antibiotics were applied for anti-infection. The patient’s myelogram was completely remissed after 1 week, and the second cycle of chemotherapy was carried out as scheduled. Thereafter, the patient received six cycles of whole-body chemotherapy, combined with herbal medicines, chelation detoxification (a total of 28 times), and intravenous medical ozone (a total of 32 times) treatment for consolidation. The patient survived the marrow inhibitory period after chemotherapy, and chemotherapy was completed on time. After discharge, the patient adhered to whole-body medium-low temperature hyperthermia, chelation detoxification, medical ozone, and TCM treatment once every month. The condition remained stable, as was shown by periodic reviews. The patient could work as usual. After the platelets of the patient returned to normal, acupuncture was conducted on acupoints such as Qihai, Zusanli, Feishu, Sanyinjiao, Shenshu, Taixi, Pishu, Xuehai, Yanglingquan, Linggu, and Dabai. Mild reinforcing–reducing method was used with needle retention of 20 minutes, once per day. Took 2 days off after five acupuncture treatments. Moxibustion and auricular therapy remained unchanged.
Looking for the phoenix: the current research on radiation countermeasures
Published in International Journal of Radiation Biology, 2023
Vojtěch Chmil, Alžběta Filipová, Aleš Tichý
A PEGylated form of filgrastim (pegfilgrastim) is branded Neulasta. It acts similarly by inducing proliferation and differentiation of neutrophils from their respective progenitors. However, compared to filgrastim, pegfilgrastim is negligibly eliminated by the kidneys, so its effective concentration in the body remains for a prolonged time period (Yang B-B and Kido 2011). Neulasta is indicated for febrile neutropenia and H-ARS treatment (FDA 2002). Wang X et al. (2021) performed a comparative study of pegfilgrastim in 43 patients who underwent autologous hematopoietic stem cell transplantation. The results were compared to a retrospective study of 129 patients treated with filgrastim. The incidence of febrile neutropenia in patients treated with filgrastim was 50.39%, while in those treated with pegfilgrastim only 18.6%. The pegfilgrastim group also had a shorter mean time to absolute neutrophil count engraftment, namely 8.72 days compared to 9.87 days in the filgrastim group. The cost of treating one patient with pegfilgrastim was lower by 15%.
Advances in engineering and delivery strategies for cytokine immunotherapy
Published in Expert Opinion on Drug Delivery, 2023
Margaret Bohmer, Yonger Xue, Katarina Jankovic, Yizhou Dong
NKTR-214 is not the only example of PEGylated IL-2. A study published in 2021 developed a new recombinant human IL-2 (rhIL-2) by incorporating synthetic nucleosides, dNAM and dTPT3, to create distinct codons [38]. These manufactured codons were then translated into synthetic, click chemistry-compatible amino acids. mPEG, attached to the linker DBCO, was subsequently bound to the synthetic amino acids via click chemistry. This PEGylated IL-2 variant, termed THOR-707, could effectively accumulate in the B16-F10 melanoma tumors and reduce tumor growth. The PEGylation of THOR-707 enabled it to stay in circulation for longer periods, resulting in higher accumulation in the tumor tissues and enhanced anti-tumor activity [38]. PEGylation has been applied to various other cytokines beyond IFNs and IL-2. A PEGylated form of filgrastim, pegfilgrastim, was FDA-approved in 2002 for neutropenia induced by myelosuppressive chemotherapy and radiation [39–41]. Filgrastim, first approved in 1991, is a recombinant human granulocyte colony-stimulating factor (G-CSF), a cytokine that stimulates neutrophil proliferation in bone marrow [42]. Since filgrastim is short-acting, the PEGylated version was designed to be long-lasting, decreasing administration frequency [43]. Binding mPEG-aldehyde to filgrastim was speculated to create a larger conjugate that evades kidney clearance and stays in circulation [18,44]. Multiple clinical trials reflected this prediction; in every chemotherapy cycle, a single dose of pegfilgrastim effectively replaced daily filgrastim treatments [45–49].
G-CSF primary prophylaxis use and outcomes in patients receiving chemotherapy at intermediate risk for febrile neutropenia: a scoping review
Published in Expert Review of Hematology, 2022
Kim Campbell, Nidhi Chadha, Seema Dimri, Weijia Wang, Edward Li
Table 2 provides a summary of G-CSF PP use and FN incidence reported in the studies. In seven studies, all patients receiving the intermediate-risk chemotherapy regimen received G-CSF PP. In the first study by Furuya et al., all patients with breast cancer receiving the fluorouracil, epirubicin, cyclophosphamide-docetaxel (FEC-D) regimen were administered prophylactic filgrastim on day 3 [34]. Two small studies in prostate cancer, both retrospective analyses, included patients treated with cabazitaxel and prophylactic G-CSF support [31,32]. The fourth study, a retrospective analysis of claims data by Weycker et al., evaluated FN risk with early discontinuation of G-CSF prophylaxis and thus included only patients who received first-cycle pegfilgrastim prophylaxis [38]. The other three studies included all patients who received the rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) regimen and G-CSF PP support [33,37,41]. Among the remaining 16 studies, G-CSF PP use ranged from 22.6% to 62.9%, with two studies reporting G-CSF PP use by a proportion of chemotherapy cycles (FEC and D portions [in the FEC-D regimen] delivered with G-CSF PP support) [42,43].