Open AccessPS947 THE SUCCESSFUL APPLICATION OF ANTI‐CD19 CAR‐T THERAPY TO PATIENTS WITH CENTRAL NERVE SYSTEM B‐CELL ACUTE LYMPHOCYTIC LEUKEMIA
Author(s) -
Chen L.,
Zhou H.,
Xue S.,
Sun A.
Publication year - 2019
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/01.hs9.0000562060.85077.cc
Subject(s) - blinatumomab , ponatinib , medicine , acute lymphocytic leukemia , refractory (planetary science) , oncology , chemotherapy , philadelphia chromosome , leukemia , surgery , imatinib , nilotinib , myeloid leukemia , lymphoblastic leukemia , chromosomal translocation , biochemistry , physics , chemistry , astrobiology , gene
Background: Chimeric antigen receptor–modified T cells (CAR‐T) with specificity for CD19 have been demonstrated to have a high efficacy in treating B‐cell hematological malignancy. However, due to the concern of serious neurotoxicity caused by CAR‐T treatment, it remains to be tested for the feasibility of CAR‐T therapy in central nerve system(CNS) B‐cell hematological malignancy. Aims: We aimed to define feasibility, toxicity, treatment response and biological correlates of response in adults with CNS B‐cell hematological malignancy treated with CD19‐CAR T cells. Methods: In this study, CAR‐T cells specify for CD19 with IL‐6 knocking down were prepared. Four adult patients were enrolled, including three with relapsed central nerve system B‐cell acute lymphocytic leukemia showing symptoms of intracranial lesions such as headache, vomiting, seizure, cognitive disorder, visual loss, dysphasia and abducent paralysis, and one without central nervous system leukemia. Of note, bone marrow remissions in all patients were confirmed before CAR‐T therapy. All four patients received fludarabine and cyclophosphamide before infusions of CAR‐T cells with IL‐6 knocking down for three consecutive days at 10%, 30%, 60% of a total dose of 5.0 × 10 6 per kilogram of body weight, respectively. Blood tests, lumbar puncture and imaging examinations were performed during the following days. This trial is registered with ClinicalTrials.gov, number NCT03064269. Results: After CAR‐T treatment, three patients’ symptoms recovered normally except two patients’ visual loss. Magnetic resonance imaging examination showed that leukemic infiltration in brain improved significantly, and leukemic blasts in the cerebrospinal fluid turned negative which is confirmed by cytological and PCR examination. Along with this process, increases in different levels of cytokines and immune cells in the cerebrospinal fluid(CSF) were observed in all patients, even detected minor increase in the patient without central nervous system leukemia. Only grade 1∼2 cytokine release syndrome manifesting fever was noted in three patients and grade 0 in one. Summary/Conclusion: In conclusion, based on our research, CAR‐T cells could migrate into CNS, eradicate leukemic cells with elevated cytokines in CSF and mildly acceptable side effect.