Pegfilgrastim is a granulocyte colony-stimulating factor used in non-myeloid cancer patients to prevent infections and neutropenic fevers. Although this medication is widely used to induce granulocytosis in pancytopenia patients, there are certain instances where such a situation can cause severe side effects. In this case, we present a patient with a history of metastatic colon cancer who is currently taking pegfilgrastim to counter the agranulocytosis caused by his chemotherapy treatment. However, the patient shortly developed localized left-sided jaw swelling, and upon further investigation, the granulocyte colony-stimulating factor revealed an underlying bacteremia. A discussion will also be held regarding the mechanism of action of how pegfilgrastim induced this patient\'s symptoms as well as the risks and benefits.

A 72-year-old man with diffuse large B-cell lymphoma underwent fluorine-18 fluorodeoxyglucose (FDG) PET/CT, revealing lymphoma lesions and no evidence of aortitis. The patient received chemotherapy and was treated with granulocyte colony-stimulating factor (G-CSF) for neutropenia. During chemotherapy, the patient underwent PET/CT again, revealing FDG accumulation and wall thickening at the aortic arch, which suggested aortitis. The patient was only experiencing fatigue. G-CSF-associated aortitis was suspected, and the original G-CSF was switched to another G-CSF while continuing chemotherapy. Three months later, the third round of PET/CT showed that FDG accumulation and wall thickening of the aortic arch vanished. PET/CT may be useful for not only the diagnosis but follow-up of G-CSF-associated aortitis. Radiologists should recognize incidental aortitis on PET/CT in patients receiving G-CSF administration.

With the increased use of granulocyte colony-stimulating factor (G-CSF) preparations, there is concern about the increase in G-CSF-associated large-vessel vasculitis; however, there have been no previous reports of vasculitis caused by multiple types of G-CSF preparations. We experienced a case of drug-induced large-vessel vasculitis caused by two different G-CSF products, which was difficult to diagnose. When treating patients with a history of large-vessel vasculitis caused by pegfilgrastim, we need to pay attention to its recurrence when using other G-CSF preparations.

OBJECTIVE: This study aimed to show the trend of neutrophil counts and frequency of febrile neutropenia after changing pegfilgrastim from 3.6 mg to 1.8 mg.
METHODS: This case-series study was performed between April 2016 and December 2021 at Hyogo Prefectural Amagasaki General Medical Center. All patients who reduced their normal dose of 3.6 mg pegfilgrastim to 1.8 mg due to adverse events or markedly elevated neutrophil counts were included. Any type of chemotherapy was acceptable. Patients who dropped out within 1 month of receiving 1.8 mg pegfilgrastim were excluded. The primary outcome was the neutrophil counts after receiving 1.8 mg pegfilgrastim. The secondary outcome was febrile neutropenia, which was evaluated by the Common Terminology Criteria for Adverse Events v5.0.
RESULTS: The study included seven patients who used a regimen of dose-dense epirubicin and cyclophosphamide, trastuzumab, pertuzumab, and docetaxel, docetaxel, or docetaxel and cyclophosphamide. After using 1.8 mg pegfilgrastim, neutrophil counts changed from a mean of 18,944 [standard deviation (SD)=-7,768] to only 4,447 (SD=1,224). The patients experienced grades 1 to 3 adverse events during the use of 1.8 mg and 3.6 mg pegfilgrastim doses, including febrile neutropenia, and pain. Four patients (57%) complained of grade 1 or 2 fatigue and anorexia. After switching from 3.6 mg pegfilgrastim to 1.8 mg, three patients (42%) experienced adverse events.
CONCLUSIONS: In patients who experienced adverse events due to markedly elevated neutrophil counts with pegfilgrastim, reducing the dose of pegfilgrastim by half may reduce adverse events.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) is increasingly used to prevent chemotherapy-associated febrile neutropenia. Generally, aortitis is not considered a side effect of G-CSF and is thought to be extremely rare. Aortitis is an inflammation of the aorta and occurs mainly in connective tissue diseases (Takayasu arteritis, giant cell arteritis, etc.) and infectious diseases (bacterial endocarditis, syphilis, etc.). We report herein a rare case of G-CSF associated with aortitis in a woman with breast cancer.
METHODS: Here, we present a case involving a 63-year-old woman with luminal type stage IIa breast cancer. The patient\'s treatment was initiated with docetaxel and cyclophosphamide, with pegfilgrastim (PEG-G) as support. After PEG-G administration on day 3, the patient developed an intermittent fever of up to 39.4 °C on day 10 and visited our outpatient clinic on day 13 with persistent high fever. Laboratory tests revealed a high neutrophil count (14,000/μL) and a high C-reactive protein (CRP) level (42.8 mg/dL) without any other abnormalities. Contrast-enhanced computed tomography scanning revealed soft tissue thickening with weak enhancement around the wall of the thoraco-abdominal aorta, aortic arch and left subclavian artery. The patient did not respond to antimicrobial agents. On the basis of these observations, the patient was diagnosed with PEG-G-induced aortitis, and her condition rapidly improved without corticosteroids.
CONCLUSIONS: Clinicians should be aware of aortitis as a potential complication in patients undergoing G-CSF chemotherapy. In cases with persistent high fever after PEG-G administration, and in the absence of infection, aortitis should be suspected.

BACKGROUND: Pegfilgrastim (PEG) is a sustained-duration pegylated form of filgrastim, a granulocyte-colony stimulating factor agent that is widely used as prophylaxis against febrile neutropenia during chemotherapy. We report the case of a breast cancer patient who developed PEG-induced vasculitis complicated by subarachnoid hemorrhage (SAH) and review the relevant literature.
METHODS: A 48-year-old woman had undergone surgery for breast cancer and was receiving docetaxel and cyclophosphamide as adjuvant chemotherapy (docetaxel 75 mg/m2, cyclophosphamide 600 mg/m2); on day 4 of treatment, PEG had been administered. On day 14, she was admitted to hospital with fever, general malaise, and neck pain, and her C-reactive protein level was found to be high (12.65 mg/dL). Although infection was initially suspected, antimicrobial treatment was ineffective and other laboratory test results were negative for this. Contrast-enhanced computed tomography on day 22 showed thickened vessel walls in the left subclavian artery, the origin of the common carotid artery, and the thoracoabdominal aorta. On day 26, magnetic resonance imaging of the head to investigate possible causes of headache showed signs consistent with SAH, and magnetic resonance angiography images showed irregularity in the basilar artery wall; the findings of both studies were considered to be due to PEG-induced vasculitis. Once treatment with prednisolone 40 mg/day had started, the wall thickening and irregularity improved.
CONCLUSIONS: Although an uncommon adverse effect, vasculitis affecting vessels of various sizes may be caused by PEG. To the best of our knowledge, this report is the first to describe a case of G-CSF-induced vasculitis complicated by SAH. In cases of persistent high fever and elevated inflammatory response after PEG administration and in the absence of infection, clinicians should consider the possibility of drug-induced vasculitis.

Pegfilgrastim is a granulocyte colony-stimulating factor agent used in patients receiving myelosuppressive therapy with chemotherapy or radiation. Two adverse effects associated with this agent include capillary leak syndrome and leukocytosis. To our knowledge, this is the first case of a patient who developed both systemic capillary leak syndrome and leukocytosis greater than 100,000 cells/µL after receiving pegfilgrastim. This patient received early fluid resuscitation, vasopressor support, and methylprednisolone, which improved her clinical course during hospitalization.

BACKGROUND: Pegfilgrastim is a modified version of granulocyte-colony stimulating factor (G-CSF), with a polyethylene glycol (PEG) that prolongs its half-life in peripheral blood. It is prophylactically administered during chemotherapy to prevent severe febrile neutropenia. G-CSF-related aortitis is a rare side effect but reports of this disease have been increasing in recent years, probably due to PEGylation. Herein, we report a case who developed pegfilgrastim-induced aortitis, localized to the right subclavian artery, during adjuvant chemotherapy. Her condition recovered without the use of steroids.
METHODS: A 58-year-old woman was diagnosed with invasive ductal carcinoma of the left breast. She had a medical history of contralateral breast cancer and pyelonephritis. Following curative surgery for her left breast cancer, she received adjuvant chemotherapy. Two days after the first course of dose-dense paclitaxel, pegfilgrastim was used as planned. Eight days after the administration of pegfilgrastim, she developed a high fever of 38 °C and visited the emergency outpatient clinic 3 days after. Blood tests revealed an increased inflammatory response, and contrast-enhanced computed tomography (CT) revealed a wall thickening of the subclavian artery, suggesting aortitis caused by pegfilgrastim. She was hospitalized on day 15 when CRP increased to 21.5 mg/dL and the high fever continued. Blood and urine culture tests were negative throughout. Pegfilgrastim-induced aortitis was suspected and she was observed without the use of steroids. Seven days later, her fever abated. A contrast-enhanced CT scan on day 26 showed the subclavian artery wall thickening had disappeared. The patient continues to be afebrile and is currently on weekly paclitaxel without use of G-CSF.
CONCLUSIONS: The onset of this disease is known to usually occur within 2 weeks after the first pegfilgrastim administration. Aortitis localized to the subclavian artery is relatively rare with the most frequent site being the aortic arch. Clinicians should be aware of the timing and location of onset of this disease.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) is increasingly been used to prevent febrile neutropenia (FN) associated with the administration of chemotherapy for various cancers. The most common adverse effects of G-CSF are bone pain and injection-site reactions and aortitis has rarely been reported. We report herein a rare case of G-CSF associated with aortitis in a woman with advanced breast cancer.
METHODS: A 72-year-old woman with estrogen receptor-negative human epidermal growth factor 2-positive breast cancer with distant metastases in the lung was admitted. Her treatment was initiated with docetaxel in combination with trastuzumab and pertuzumab followed by the supportive use of a long-acting G-CSF, pegfilgrastim. After administration of pegfilgrastim on day 5, the patient had an intermittent fever (body temperature up to 39.6 °C) on day 9 which continued irrespective of taking levofloxacin. She visited our outpatient clinic on day 13 with no objective symptoms other than fever. Laboratory tests revealed a high neutrophil count (15,000/μl) and a high C-reactive protein (CRP) level (46.35 mg/dl) without any other abnormalities. There was no response upon administration of antimicrobial agents. An 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) revealed thickening of the wall of the descending thoracic aorta and left pleural effusion. Therefore, thoracic aortitis induced by pegfilgrastim was suspected. On day 19, the fever resolved spontaneously followed by a gradual reduction in the neutrophil count and CRP level. In the follow-up CT, the aortic wall thickness and pleural effusion had disappeared.
CONCLUSIONS: G-CSF may cause aortitis due to stimulation of the production of inflammatory cytokines. In case of high continuous fever after administration of pegfilgrastim, aortitis should be suspected unless there are other infectious findings.

BACKGROUND: Sweet\'s syndrome is an acute neutrophilic dermatosis characterized by abrupt onset of skin lesions accompanied by fever, arthralgia, leukocytosis and diffuse neutrophilic infiltration of the dermis, as well as an excellent response to corticosteroid therapy.
METHODS: A 46-year-old patient with myelodysplastic syndrome was admitted for chemotherapy. On the eighth day of chemotherapy, he received a single dose of pegfilgrastim. Three days later, he developed pyrexia, conjunctivitis, arthralgia and erythematous and painful papulo-nodular lesions. Broad-spectrum empiric antibiotic therapy was started but the patient\'s condition deteriorated. Biology showed pancytopenia and inflammatory syndrome. Microbiological tests, autoimmune serologies and chest-computed tomography were negative. Cutaneous biopsy was compatible with Sweet\'s syndrome. A diagnosis of Sweet\'s syndrome induced by pegfilgrastim was made and intravenous corticosteroid therapy was started with a rapid favorable outcome.
CONCLUSIONS: Sweet\'s syndrome is a rare adverse effect of G-CSF.