{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T23:16:22Z","timestamp":1794266182925,"version":"4.9.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u20134 ICANS downgraded to grade 1 and grade 1\u20132 ICANS recovery to an ICE score of 10 points is considered ICANS remission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\u00d710\n                      <jats:sup>6<\/jats:sup>\n                      \/kg. The median bone marrow blasts before lymphocyte depletion was 33.23%(5.34%-78.50%) and 9 patients had CNS involvement. All patients developed grade 1\u20132 CRS. Of the 13 patients, 5 had grade 3\u20134 ICANS and 8 had grade 1\u20132 ICANS. The median onset time of ICANS after CAR-T was 11(3-20) days. The median time of first IDM after ICANS was within 12 hours, and the median number of IDM was 1(1-3). The median time to ICANS remission was 1(1-7) days, with a response rate of 92.3% (12\/13 patients). IDM significantly reduced CAR-T cells and tended to reduce protein and IL-6 levels in cerebrospinal fluid. As of June 30, 2025, the median OS and median PFS were 6 months and 5 months, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1716317","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T05:20:57Z","timestamp":1765948857000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Early intrathecal dexamethasone and methotrexate as an effective approach for immune effector cell-associated neurotoxicity syndrome after CAR-T cell 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