Pegylated human granulocyte colony stimulating factor(Shandong Kexing Bioproducts)

A 55-yr-old woman presented to the emergency department at a general hospital in Japan with a 3-day history of fever and upper back pain.She was diagnosed with metastatic pancreatic cancer and underwent systemic chemotherapy with a modified FOLFIRINOX regimen (oxaliplatin 65 mg/m2, leucovorin 200 mg/m2, irinotecan 150 mg/m2, fluorouracil 400 mg/m2 given as a bolus followed by 2400 mg/m2 given as a 46-h continuous infusion).She had received the third cycle of chemotherapy 12 days before her visit to the hospital and a single dose of PEG-G-CSF 7 days before her visit to hospital.Her blood test showed her leukocyte count was 15 600 cells/μL and her C-reactive protein level was 11·0 mg/dL.On the following day of her stay in hospital, contrast CT scan revealed contrast-enhanced wall thickening of the aortic arch and descending aorta (figure).Thus, the diagnosis of G-CSF-associated aortitis was made, and treatment with 60 mg of i.v. methylprednisolone (1·0 mg/kg/day) was initiated.The methylprednisolone dose was successfully tapered to 40 mg per day on the 11th day of her stay in hospital without any flare-up of her symptoms.In conclusion, it is essential to consider the possibility of G-CSF-associated aortitis in patients on chemotherapy.Systemic glucocorticoid therapy is an option in the management of G-CSF-associated aortitis, but the treatment plan should be individualized according to the patient's condition.

Pegfilgrastimis a recombinant PEGylated human granulocyte colony-stimulating factor (G-CSF) analog filgrastim (trade names Neulasta® or G-Lasta®) that stimulates the production of white blood cells (neutrophils). It is employed as an alternative to filgrastim (G-CSF) for chemotherapy-induced neutropenia in patients due to its longer half-life. In clinical settings, PEG-G-CSF is administered to cancer patients via both the s.c. and i.v. routes. In a murine study, we showed that, regardless of administration route, initial doses of PEG-G-CSF above 0.06 mg/kg elicited anti-PEG immune response in a dose-dependent manner. I.v. administration elicited higher levels of anti-PEG IgM than the s.c. route. Initial doses of PEG-G-CSF (6 mg/kg) that were high enough to trigger production of anti-PEG IgM, did not trigger the accelerated clearance of a lower subsequent dose (0.06 mg/kg) that was similar to i.v. clinical doses of PEG-G-CSF, but when the subsequent dose of PEG-G-CSF was raised to (6 mg/kg), the initial dose triggered the accelerated clearance of the second dose via an anti-PEG IgM-mediated complement activation. Similar observations were noted when an increased PEG-OVA dose was given as the second dose, indicating that pre-existing and/or treatment-induced anti-PEG antibodies might compromise the therapeutic activity and/or reduce tolerance of other PEGylated formulations. To the best of our knowledge, this is the first report to suggest the induction of the ABC phenomenon upon repeated injections of pegfilgrastim. In the clinic, cancer patients, receiving multiple cycles of chemotherapy, receive multiple cycles of pegfilgrastim to avoid infections and substantial morbidity. The ABC phenomenon to pegfilgrastim appears to be the cause of loss of clinical benefit of sequential treatments with pegfilgrastim in patients.