ArticleFrontiers in immunology2025
Early intrathecal dexamethasone and methotrexate as an effective approach for immune effector cell-associated neurotoxicity syndrome after CAR-T cell therapies.
Article in Frontiers in immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Bispecific CD37-Siglec6 CAR‑T cells exhibit enhanced anti‑leukemic activity and reduced exhaustion in acute myeloid leukemia xenograft models.Journal of translational medicine · 2026Article
- Repurposing mitochondrial-targeting drugs for management of ICANS in CAR T-cell therapy: a novel steroid-sparing approach.Frontiers in pharmacology · 2026Article
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9 authors.
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Abstract
Introduction: Chimeric antigen receptor T (CAR-T) cell therapies have demonstrated remarkable success in treating relapsed and refractory (R/R) B-cell hematological malignancies. Although the application of CAR-T therapy in acute myeloid leukemia (AML) is still restricted, we and other institutions have also demonstrated high complete remission rate of CAR-T targeting C-type lectin-like molecule 1 (CLL1) for R/R AML. However, CAR-T cell related toxicities such as steroid-refractory and severe immune effector cell-associated neurotoxicity syndrome (ICANS) can be life-threatening. Previous cases have reported potential efficacy of intrathecal corticosteroids alone or in combination with chemotherapy. Theoretically, intrathecal corticosteroids combined with intrathecal chemotherapy can control ICANS faster and better. Whether intrathecal dexamethasone and methotrexate (IDM) is beneficial for the patient with steroid-refractory or severe ICANS remains unclear. Methods: We retrospectively analyzed the clinical data of 13 patients with severe or steroid-refractory ICANS, and evaluated the effect of IDM in the treatment of severe ICANS or steroid-refractory ICANS by analyzing the changes in ICANS grade, ICE score, and laboratory indicators. Grade 3-4 ICANS downgraded to grade 1 and grade 1-2 ICANS recovery to an ICE score of 10 points is considered ICANS remission. Results: Among the 13 patients, there were 7 cases of AML, 3 cases of ALL, 1 case of MM, 1 case of B-cell lymphoma, and 1 case of blastic plasmacytoid dendritic cell neoplasm, with a median age of 39 (11-65) years. The median number of prior lines of therapy was 7(1-16). There were 6 CAR-T products targeting CD19, CLL1, CD7, CD123, BCMA, and CD19-CD22, respectively. The median CAR-T cell infusion dose was 2.0×10 Conclusion: Our data suggest that early administration of IDM may contribute to a rapid resolution of severe or steroid-refractory ICANS after CAR-T cell therapies, which may create opportunities for subsequent treatments in these patients. Larger sample and multicenter clinical trials are warranted to further validate these findings.
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