Clinical Analysis of CAR-T Cell Therapy in Patients with Relapsed Acute B-Lymphoblastic Leukemia after Second Allogeneic Hematopoietic Stem Cell Transplantation

**Background:** Patients with relapsed acute B-lymphoblastic leukemia (B-ALL) after a second allogeneic hematopoietic stem cell transplantation (allo-HSCT) have limited treatment options and low remission rates. This study explores the efficacy of CAR-T cell immunotherapy in these patients.

**Objective:** To observe the efficacy of CAR-T therapy in patients with relapsed B-ALL after a second allo-HSCT and to evaluate the effect of maintenance therapy with demethylating agents and targeted drugs in patients who achieve remission after CAR-T therapy.

**Methods:** The study included eight patients treated at Beijing Boren Hospital from February 2021 to July 2024. Follow-up continued until July 16, 2024. All patients had relapsed after a second allo-HSCT and received CAR-T therapy. Patients who achieved remission after CAR-T therapy received sequential CAR-T treatment and maintenance therapy with targeted drugs.

The cohort consisted of four males and four females, aged between 5 and 58 years, with a median age of 29 years. Two patients did not respond to CAR-T therapy, while the remaining six achieved varying degrees of remission. The shortest remission duration was 1.3 months, and the longest was 20 months (as of July 16, 2024), with a median remission duration of 9.5 months.

**Results:** Among the eight patients, six achieved minimal residual disease (MRD)-negative remission (75%) after CAR-T therapy, while two did not respond (25%). The overall survival (OS) ranged from 1.3 months to 20 months (as of July 16, 2024). Among the six patients who achieved remission, one received two different CAR-T treatments, one received four different CAR-T treatments, and the remaining four received one CAR-T treatment each. During the first CAR-T treatment, all patients experienced cytokine release syndrome (CRS) with a 100% incidence rate. Five patients had grade 1 CRS (62.5%), and one patient had grade 3 CRS (37.5%). No patients experienced grade 3 or higher CRS or ICANS (immune effector cell-associated neurotoxicity syndrome).

**Conclusion:**

1. CAR-T therapy shows a significant remission rate, minimal side effects, and high safety in patients with relapsed B-ALL after a second allo-HSCT, effectively prolonging disease-free survival.

2. Combining CAR-T therapy with BCL2 inhibitors and demethylating agents may improve patient outcomes and extend survival, providing a new treatment approach for patients with relapsed/refractory B-ALL after a second allo-HSCT.

No relevant conflicts of interest to declare.