Abstract
BACKGROUND: Despite initial responses, resistance to tyrosine kinase inhibitors (TKIs) and disease relapse remain major challenges in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL). Given the efficacy of chimeric antigen receptor T (CAR-T) cell therapy in Relapsed/Refractory (R/R) ALL, we aimed to evaluate the long-term outcomes of co-administration of CD19 and CD22 CAR-T cell therapy for pediatric patients with R/R Ph(+) ALL. METHODS: We conducted a retrospective subanalysis of patients with R/R Ph(+) ALL to assess the long-term outcomes of co-administration of CD19 and CD22 CAR-T cell therapy. Complete hematologic remission (CHR), measurable residual disease-negative complete remission (MRD(-)CR), complete molecular remission (CMR), relapse-free survival (RFS), and overall survival (OS) were among the important outcomes that were evaluated with a data cutoff of October 1, 2025. RESULTS: Within 1 month after CAR-T cell infusion, all patients achieved CHR, with MRD(-)CR and CMR of 100 and 77.8%, respectively. Two patients underwent consolidative allogeneic stem cell transplant (allo-HSCT). Notably, six patients achieved sustained CHR without allo-HSCT. At a median follow-up of 54.93 months (range, 16.83-71.6 months), the 4-year OS and RFS were 91.7 and 66.7%. No treatment-related deaths occurred from CAR-T toxicity. CONCLUSION: These preliminary findings suggest that CD19 and CD22 CAR-T cell therapy may provide long-term survival benefits in pediatric patients with R/R Ph(+) ALL, with manageable toxicity. However, these results should be considered hypothesis-generating and require validation in larger, controlled studies. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=52403, ChiCTR2000032211.