THE SUCCESSFUL APPLICATION OF ANTI-CD19 CAR-T THERAPY TO PATIENTS WITH CENTRAL NERVE SYSTEM B-CELL ACUTE LYMPHOCYTIC LEUKEMIA
Author(s): ,
Liyun Chen
Affiliations:
Hematology,The First Affiliated Hospital of Soochow University,Suzhou,China;Hematology,Jiangsu Institute of Hematology,Suzhou,China
,
Haixia Zhou
Affiliations:
Hematology,The First Affiliated Hospital of Soochow University,Suzhou,China;Hematology,Jiangsu Institute of Hematology,Suzhou,China
,
Shengli Xue
Affiliations:
Hematology,The First Affiliated Hospital of Soochow University,Suzhou,China;Hematology,Jiangsu Institute of Hematology,Suzhou,China
Aining Sun
Affiliations:
Hematology,The First Affiliated Hospital of Soochow University,Suzhou,China;Hematology,Jiangsu Institute of Hematology,Suzhou,China
EHA Library. Chen L. Jun 15, 2019; 267248; PS947
Liyun Chen
Liyun Chen
Contributions
Abstract

Abstract: PS947

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

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 5.0×106 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. 

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.

Session topic: 2. Acute lymphoblastic leukemia - Clinical

Keyword(s): Acute lymphoblastic leukemia, CD19, Cellular therapy

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