Development of symptoms after axi-cel infusion, diagnostic measures, and therapeutic interventions before discovery of CAR-T-cell DNA in CSF
| . | Symptoms . | Diagnostics . | CAR T-cell DNA copy number per microgram CSF DNA . | Therapeutic interventions . |
|---|---|---|---|---|
| D+262 | Loss of vision | No structural abnormalities of visual organ. Blood test results normal (including inflammatory markers [CRP, ferritin, blood sedimentation], vitamin B1/B6/B12 and folic acid, fibrinogen, triglycerides, and PCR for CMV-/ EBV-/HHV6-/ParvoB19-DNA). Brain MRI normal. CSF results normal (including analysis for HSV1/2, VZV, HHV6, borrelia, FSME, measles, Treponema pallidum, enterovirus, adenovirus, Aspergillus fumigatus, toxoplasma, mycoplasma, LCM virus, and JCV). SARS-CoV-2 negative. | NA | Methylprednisolone 1 g/d for 5 d → no change |
| D+289 | Ataxia of legs and trunk | Blood test results normal (including inflammatory markers [CRP, ferritin, blood sedimentation], fibrinogen, triglycerides, autoimmune panel). Brain MRI normal. CSF results normal (including autoimmune panel, analysis for HSV1/2, VZV, HHV6, borrelia, FSME, measles, T pallidum, enterovirus, adenovirus, A. fumigatus, toxoplasma, mycoplasma, LCM virus, and JCV). PET scan showed lymphoma in complete response, no splenomegaly. Genetic workup for LHON+ is negative. | 86 783* | IV immunoglobulins ceased because of allergic reaction → no change |
| D+309 | Wheelchair user, slight dysarthria, hearing impairment | Blood tests normal (including inflammatory markers [see D+289]). MRI of head and neck normal. CSF: 3 cells per microliter, 20% CD3+; of those 31% CD8+ and 68% CD4+, paraneoplastic antibody panel negative. Electroneurography normal. EEG: slight unspecific general slowing. Metabolic test for porphyrias negative. | NA | Dexamethasone 40 mg/d for 4 days → no change |
| D+326 | Dysarthria, dysphagia, myasthenia | Blood test results normal (including inflammatory markers). Test for acetyl choline receptor antibodies negative. | NA | IV immunoglobulins+100 mg prednisolone stopped because of massive pain attack → no change |
| . | Symptoms . | Diagnostics . | CAR T-cell DNA copy number per microgram CSF DNA . | Therapeutic interventions . |
|---|---|---|---|---|
| D+262 | Loss of vision | No structural abnormalities of visual organ. Blood test results normal (including inflammatory markers [CRP, ferritin, blood sedimentation], vitamin B1/B6/B12 and folic acid, fibrinogen, triglycerides, and PCR for CMV-/ EBV-/HHV6-/ParvoB19-DNA). Brain MRI normal. CSF results normal (including analysis for HSV1/2, VZV, HHV6, borrelia, FSME, measles, Treponema pallidum, enterovirus, adenovirus, Aspergillus fumigatus, toxoplasma, mycoplasma, LCM virus, and JCV). SARS-CoV-2 negative. | NA | Methylprednisolone 1 g/d for 5 d → no change |
| D+289 | Ataxia of legs and trunk | Blood test results normal (including inflammatory markers [CRP, ferritin, blood sedimentation], fibrinogen, triglycerides, autoimmune panel). Brain MRI normal. CSF results normal (including autoimmune panel, analysis for HSV1/2, VZV, HHV6, borrelia, FSME, measles, T pallidum, enterovirus, adenovirus, A. fumigatus, toxoplasma, mycoplasma, LCM virus, and JCV). PET scan showed lymphoma in complete response, no splenomegaly. Genetic workup for LHON+ is negative. | 86 783* | IV immunoglobulins ceased because of allergic reaction → no change |
| D+309 | Wheelchair user, slight dysarthria, hearing impairment | Blood tests normal (including inflammatory markers [see D+289]). MRI of head and neck normal. CSF: 3 cells per microliter, 20% CD3+; of those 31% CD8+ and 68% CD4+, paraneoplastic antibody panel negative. Electroneurography normal. EEG: slight unspecific general slowing. Metabolic test for porphyrias negative. | NA | Dexamethasone 40 mg/d for 4 days → no change |
| D+326 | Dysarthria, dysphagia, myasthenia | Blood test results normal (including inflammatory markers). Test for acetyl choline receptor antibodies negative. | NA | IV immunoglobulins+100 mg prednisolone stopped because of massive pain attack → no change |
CRP, C-reactive protein; D+, days after axi-cel infusion; HSV, herpes simplex virus; EBV, Epstein-Barr virus; FSME, Frühsommer-(tick-borne)meningoencephalitis; HHV6, human herpesvirus 6; JCV, JC virus; LCM virus, lymphocytic choriomeningitis virus; LHON, Leber hereditary optic neuropathy; PET, positron emission tomography; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; VZV, varicella-zoster virus.
Post hoc assessment.