Clinical Analysis of CAR-T Cell Therapy in Patients with Acute B-Lymphoblastic Leukemia and Central Nervous System Infiltration

Background: Acute B-lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) has traditionally been treated with whole-brain and spinal radiotherapy, combined with intrathecal chemotherapy, systemic chemotherapeutic drugs, and allogeneic hematopoietic stem cell transplantation for long-term survival. There are few reports of clinical cure and long-term survival in patients treated primarily with CAR-T therapy.

Objective: To observe the efficacy of CAR-T therapy in patients with B-ALL and CNSL.Methods and Results:A retrospective analysis was conducted on four cases of relapsed/refractory acute B-lymphoblastic leukemia (R/R B-ALL) with CNSL treated with CAR-T cell therapy at Beijing Boren Hospital from April 2018 to June 2023. Three patients were adult males, and one was a 6-year-old female, with a median age of 33.5 years (range: 6-48 years). Case 1 and 3 had PH+ B-ALL, case 2 had MEF2D-BCL9 fusion gene, and all three relapsed post-transplant. Case 4 relapsed during chemotherapy. Case 1 and 4 had isolated CNSL relapse (50%), case 3 had minimal residual disease (MRD) in bone marrow, and case 2 had hematologic relapse with bone marrow involvement and bilateral kidney and pancreatic infiltration. The clinical outcomes of single and sequential two-course CAR-T cell therapy were observed. The median follow-up for the four patients was 26 months (range: 18-64 months), with all achieving complete remission and a median remission duration of 25 months (range: 17-62 months). The overall survival rate at the end of follow-up was 100% (4/4). Case 1 had a sustained molecular remission for 62 months, case 2 for 21 months, case 3 for 32 months, and case 4 for 18 months. Case 1 experienced reversible ICANS, and the other three had CRS grades 0-1. The event-free survival (EFS) was greater than 18 months (100%), with one case reaching clinical cure criteria. The overall survival rate (OS) was 100%.

Conclusion:CAR-T cell therapy can be considered a primary treatment method for patients with B-ALL and CNSL. In this group of four patients, sustained remission was achieved without cranial radiotherapy or allogeneic hematopoietic stem cell transplantation, thus avoiding radiotherapy-related neurological damage, bone marrow suppression, and graft-versus-host disease (GVHD), improving overall patient quality of life.

No relevant conflicts of interest to declare.