Sex: U
Vaccine: FLUX
Symptoms: Immunoglobulin therapy, Inspiratory capacity normal, Loss of personal independence in daily activities, Lumbar puncture abnormal, Magnetic resonance imaging spinal abnormal
Clinical narrative: Grade three myalgia secondary to gilteritinib progressed to generalized weakness (grade 3) /acute muscle weakness; Guillain-Barre; Grade three myalgia secondary to gilteritinib progressed to generalized weakness (grade 3) /acute muscle weakness; Worsening peripheral neuropathy (secondary to gilteritinib); Demyelinating disease; MR of spine: suitable hyperintense T2 signal within the central and dosrsal aspect of the cervical and thoracic spinal cord / Caudal dorsal nerve root enhacement; CSF (cerebrospinal fluid) showed elevated protein result of 410 / Albuminocytolic disassociation; Transverse myelitis; Escherichia coli infection; This spontaneous case was received on 21-Mar-2022 from other healthcare professional via Agency (reference number: SEQW22-01003) and concerned a patient of unreported age and gender.  The patient's concurrent conditions included peripheral neuropathy that was managed with Lyrica (pregabalin), de novo acute myeloid leukaemia (AML) and FLT3 gene mutation. The patient's historical procedure included chemotherapy multiple agents systemic (from Sep-2021 until Dec-2021). The patient's concomitant medications were not reported. The patient was enrolled in study   On 29-Oct-2021, the patient was vaccinated with influenza virus vaccine polyvalent (brand not specified; anatomical location, route of administration, dose, indication: not reported). The batch number was not reported.   On an unspecified date in 2021, an unknown amount of time after receiving influenza virus vaccine polyvalent, the patient developed extended spectrum beta-lactamases (ESBL) Escherichia coli infection.   On 22-Dec-2021, the patient started therapy with non-company, co-suspects etoposide and cytarabine at unknown dose, route and frequency, both used for de novo acute myeloid leukaemia and FLT3 gene mutation.  On 26-Dec-2021, the patient received latest dose of etoposide and total dose administered was 1300 mg.  On 27-Dec-2021, the patient started therapy with non-company, co-suspect gilteritinib at unknown dose, route and frequency for de novo acute myeloid leukaemia and FLT3 gene mutation. Also, the patient received latest dose of cytarabine, and total dose administered was 17300 mg.  On an unspecified date in 2021, an unknown amount of time after receiving influenza virus vaccine polyvalent and non-company co-suspect products etoposide, cytarabine and gilteritinib, the patient experienced grade three myalgia secondary to gilteritinib, palliative managed myalgias with around the clock (ATC) MS-Contin (morphine sulfate) and trazodone.  On 20-Jan-2022, the patient was administered with non-company, co-suspects cilgavimab and tixagevimab (reported also as 'monoclonal antibody evusheld') (anatomical location, route of administration, dose, indication: not reported).  On 23-Jan-2022, the patient received latest dose of gilteritinib and total dose administered was 1680 mg.  On 24-Jan-2022, two months and 26 days after receiving influenza virus vaccine polyvalent, 29 days after receiving latest dose of etoposide, 28 days after receiving latest dose of cytarabine, four days after receiving cilgavimab and tixagevimab, and one day after receiving latest dose of gilteritinib, the patient's grade three myalgia secondary to gilteritinib progressed to grade three generalized weakness that appeared to be ascending in nature concerning for possible Guillain-Barre (GBS). Other differential diagnosis of Guillain-Barre included worsening peripheral neuropathy secondary to gilteritinib.   On the same day, as reported the patient was diagnosed with Guillain-Barre and was hospitalized.   On an unspecified date in 2022, neurology was consulted recommended magnetic resonance (MR) of spine which showed subtle hyperintense T2 signal within the central and dorsal aspect of the cervical and thoracic spinal cord and no definite abnormal enhancement or cord expansion were noted. As reported, findings might reflect transverse myelitis or infectious/inflammatory etiology, however, demyelinating disease or malignancy considered less likely but not entirely excluded. Negative inspiratory force was monitored and remained stable.   On 02-Feb-20221, at day 34 as reported, neurology recommended a diagnostic lumbar puncture bone marrow per protocol. Cerebrospinal fluid (CSF) analysis showed elevated protein result of 410 negative for blasts.   On 03-Feb-20221, given radiology confirmed findings of caudal dorsal nerve root enhancement and albuminocytolic disassociation noted in lumbar puncture (LP) a day before, Guillain Barre syndrome (GBS) (Grade 3) was now much higher on the differential. As reported, post monoclonal antibody evusheld and influenza virus vaccine polyvalent, the patient's symptoms became worse.   On an unspecified date in Feb-2022, the patient started with intravenous immunoglobulin therapy (IVIG) with much improvement. The patient continued to work with physical therapy/occupational therapy (PT/OT) with slight improvement of strength and movement and received aggressive inpatient rehab and was discharged with improvement in condition. The patient continued to have physical therapy (PT) two times a week, ambulates with walker and was able to perform activities of daily living (ADL's) except the patient was unable to wipe after a bowel movement.   On 18-Feb-2022, the patient recovered with sequelae from the events of 'Guillain-Barre syndrome' and 'generalized muscle weakness'.  The outcome of other events was not reported.  The reporter assessed the events of 'Guillain-Barre syndrome' and 'muscle weakness' as related to influenza virus vaccine polyvalent. The investigator of study considered that influenza virus vaccine, Escherichia coli infection, cilgavimab and tixagevimab had possible attribution factor and peripheral neuropathy had unlikely attribution factor for GBS. Also, the investigator considered that influenza virus vaccine, peripheral neuropathy, cilgavimab and tixagevimab had possible attribution factor and Escherichia coli infection had unlikely attribution factor for muscle weakness acute.   The events of 'Guillain-Barre syndrome', 'peripheral neuropathy aggravated', 'myelitis transverse', 'demyelination', 'myalgia', 'cerebrospinal fluid protein increased', 'magnetic resonance imaging spinal abnormal', 'cerebrospinal fluid protein increased' and 'muscle weakness' were assessed serious due to seriousness criteria of hospitalization. Additionally, the events of 'Guillain-Barr syndrome', 'peripheral neuropathy aggravated', 'myelitis transverse', 'demyelination' and 'cerebrospinal fluid protein increased' were considered to be medically significant by a Physician within Seqirus' Pharmacovigilance and Risk Management Department.  Company comment: A patient of unreported age and gender was vaccinated with the suspect product influenza virus vaccine polyvalent. An unknown amount of time after vaccination the patient developed ESBL producing E. Coli infection. The patient developed also myalgia for which chronology is unclear. As reported myalgia was secondary to treatment with gilteritinib. Two months and 26 days following vaccination the patient's myalgia progressed to generalized weakness that appeared to be ascending in nature concerning for possible Guillain-Barre syndrome (GBS). Differential diagnosis additionally included worsening peripheral neuropathy secondary to gilteritinib treatment and transverse myelitis. Additionally, demyelinating disease or malignancy were considered less likely but were not entirely excluded. Cerebrospinal fluid (CSF) analysis showed albuminocytolic disassociation. Magnetic resonance imaging showed subtle hyperintense T2 signal within the central and dorsal aspect of the cervical and thoracic spinal cord caudal, and caudal dorsal nerve root enhancement. However, from the provided information it is not clear what the final diagnosis is. Treatment with co-suspect products etoposide, cytarabine, cilgavimab and tixagevimab, and gilteritinib confounds causality. Causality for the event E. Coli infection is assessed as not related based on biological implausibility. Causality for the events GBS, muscular weakness, demyelination and associated diagnostic findings is assessed as not related based on implausible temporal relationship. Causality for the event worsening of peripheral neuropathy is assessed as not related based on unsuggestive temporal relationship and presented confounder gilteritinib. Inconclusive information provided preclude causality assessment for transverse myelitis. Causality for the event myalgia is unassessable due to unclear temporal relationship.; Reporter's Comments: The investigator of study considered that influenza virus vaccine, Escherichia coli infection, cilgavimab and tixagevimab had possible attribution factor and peripheral neuropathy had unlikely attribution factor for GBS. Also, the investigator considered that influenza virus vaccine, peripheral neuropathy, cilgavimab and tixagevimab had possible attribution factor and Escherichia coli infection had unlikely attribution factor for muscle weakness acute.; Sender's Comments: A patient of unreported age and gender was vaccinated with the suspect product influenza virus vaccine polyvalent. An unknown amount of time after vaccination the patient developed ESBL producing E. Coli infection. The patient developed also myalgia for which chronology is unclear. As reported myalgia was secondary to treatment with gilteritinib. Two months and 26 days following vaccination the patient's myalgia progressed to generalized weakness that appeared to be ascending in nature concerning for possible Guillain-Barre syndrome (GBS). Differential diagnosis additionally included worsening peripheral neuropathy secondary to gilteritinib treatment and transverse myelitis. Additionally, demyelinating disease or malignancy were considered less likely but were not entirely excluded. Cerebrospinal fluid (CSF) analysis showed albuminocytolic disassociation. Magnetic resonance imaging showed subtle hyperintense T2 signal within the central and dorsal aspect of the cervical and thoracic spinal cord caudal, and caudal dorsal nerve root enhancement. However, from the provided information it is not clear what the final diagnosis is. Treatment with co-suspect products etoposide, cytarabine, cilgavimab and tixagevimab, and gilteritinib confounds causality. Causality for the event E. Coli infection is assessed as not related based on biological implausibility. Causality for the events GBS, muscular weakness, demyelination and associated diagnostic findings is assessed as not related based on implausible temporal relationship. Causality for the event worsening of peripheral neuropathy is assessed as not related based on unsuggestive temporal relationship and presented confounder gilteritinib. Inconclusive information provided preclude causality assessment for transverse myelitis. Causality for the event myalgia is unassessable due to unclear temporal relationship.