Pediatric cases of acute myelopathy following CAR T-cell therapy for B-ALL
| Characteristics . | Patient 2124 . | Patient 2224 . | Patient 2324 . | Patient 2424 . |
|---|---|---|---|---|
| Age at infusion (y) | 7 | 14 | 13 | 2.5 |
| Sex | Female | Male | Male | Male |
| Previous CNS disease | Yes | Yes | No | Yes |
| Previous treatment | Chemotherapy unspecified, tisa-cel, CART22-65s, allo-HSCT, radiotherapy | Chemotherapy unspecified, blinatumomab, tisa-cel | Chemotherapy unspecified | Chemotherapy unspecified, allo-HSCT, inotuzumab, radiotherapy |
| Bridging treatment | Not reported | Not reported | Not reported | Not reported |
| CAR T cells | CD22-directed (CART22-65s) | CD22-directed (CART22-65s) | CD19-directed (huCART19) | Tisa-cel |
| CRS onset | D + 15 | D + 4 | D + 1 | Not reported |
| Max CRS grade | Grade 2 | Grade 2 | Grade 4 | Grade 1 |
| ICANS onset | D + 19 | D + 8 | D + 4 | D + 14 |
| Max ICANS grade∗ | Grade 4 | Grade 4 | Grade 4 | Grade 4 |
| Myelopathy onset | D + 22 | D + 25 | D + 10 | D + 15 |
| Presentation | Areflexic quadriparesis | Areflexic paraparesis, decreased sensation to light touch | Areflexic paraparesis, midchest sensory level | Areflexic quadriparesis |
| Suspected etiology | CAR T-cell– mediated | CAR T-cell–mediated | CAR T-cell–mediated | CMV |
| Treatment | Tocilizumab, dexamethasone, anakinra, carbidopa/levodopa | Tocilizumab, dexamethasone, anakinra | Tocilizumab, dexamethasone, MP, anakinra, IVIG, plasmapheresis, carbidopa/levodopa | Dexamethasone, IVIG, plasmapheresis, valganciclovir, ganciclovir, foscarnet, carbidopa/levodopa |
| Clinical improvement | No | No | No | Partial |
| Best oncologic response | Refractory | Refractory | CR | CR |
| LA | D + 31 | D + 30 | 15 mo | D + 189 |
| Oncologic response at LA | PD, death | PD, death | CR | Relapse, death |
| Characteristics . | Patient 2124 . | Patient 2224 . | Patient 2324 . | Patient 2424 . |
|---|---|---|---|---|
| Age at infusion (y) | 7 | 14 | 13 | 2.5 |
| Sex | Female | Male | Male | Male |
| Previous CNS disease | Yes | Yes | No | Yes |
| Previous treatment | Chemotherapy unspecified, tisa-cel, CART22-65s, allo-HSCT, radiotherapy | Chemotherapy unspecified, blinatumomab, tisa-cel | Chemotherapy unspecified | Chemotherapy unspecified, allo-HSCT, inotuzumab, radiotherapy |
| Bridging treatment | Not reported | Not reported | Not reported | Not reported |
| CAR T cells | CD22-directed (CART22-65s) | CD22-directed (CART22-65s) | CD19-directed (huCART19) | Tisa-cel |
| CRS onset | D + 15 | D + 4 | D + 1 | Not reported |
| Max CRS grade | Grade 2 | Grade 2 | Grade 4 | Grade 1 |
| ICANS onset | D + 19 | D + 8 | D + 4 | D + 14 |
| Max ICANS grade∗ | Grade 4 | Grade 4 | Grade 4 | Grade 4 |
| Myelopathy onset | D + 22 | D + 25 | D + 10 | D + 15 |
| Presentation | Areflexic quadriparesis | Areflexic paraparesis, decreased sensation to light touch | Areflexic paraparesis, midchest sensory level | Areflexic quadriparesis |
| Suspected etiology | CAR T-cell– mediated | CAR T-cell–mediated | CAR T-cell–mediated | CMV |
| Treatment | Tocilizumab, dexamethasone, anakinra, carbidopa/levodopa | Tocilizumab, dexamethasone, anakinra | Tocilizumab, dexamethasone, MP, anakinra, IVIG, plasmapheresis, carbidopa/levodopa | Dexamethasone, IVIG, plasmapheresis, valganciclovir, ganciclovir, foscarnet, carbidopa/levodopa |
| Clinical improvement | No | No | No | Partial |
| Best oncologic response | Refractory | Refractory | CR | CR |
| LA | D + 31 | D + 30 | 15 mo | D + 189 |
| Oncologic response at LA | PD, death | PD, death | CR | Relapse, death |
All patients, except patient number 24, had evidence of active disease at CAR T-cell infusion. None of the patients had CNS involvement at the time of CAR T-cell infusion. None of the patients have been reported to develop IEC-HS. However, because of a lack of data, we cannot exclude the possibility that some cases were associated with this complication.
Abbreviations are explained in Table 1.
Allo-HSCT, allogeneic hematopoietic stem cell transplantation; PD, progressive disease.
The ICANS grade was defined based on the ASTCT consensus grading. According to this definition, deep focal motor weakness, such as hemiparesis or paraparesis, is classified as grade 4.