PURPOSE We determined the safety and efficacy of coadministration of CD19- and CD22-chimeric antigen receptor (CAR) T cells in patients with refractory disease or high-risk hematologic or isolated extramedullary relapse of B-acute lymphoblastic leukemia. PATIENTS AND METHODS This phase II trial enrolled 225 evaluable patients age ≤ 20 years between September 17, 2019, and December 31, 2021. We first conducted a safety run-in stage to determine the recommended dose. After interim analysis of the first 30 patients treated (27 at the recommended dose) showing that the treatment was safe and effective, the study enrolled additional patients according to the study design. RESULTS Complete remission was achieved in 99.0% of the 194 patients with refractory leukemia or hematologic relapse, all negative for minimal residual disease. Their overall 12-month event-free survival (EFS) was 73.5% (95% CI, 67.3 to 80.3). Relapse occurred in 43 patients (24 with CD19+/CD22+ relapse, 16 CD19–/CD22+, one CD19–/CD22–, and two unknown). Consolidative transplantation and persistent B-cell aplasia at 6 months were associated with favorable outcomes. The 12-month EFS was 85.0% (95% CI, 77.2 to 93.6) for the 78 patients treated with transplantation and 69.2% (95% CI, 60.8 to 78.8) for the 116 nontransplanted patients ( P = .03, time-dependent covariate Cox model). All 25 patients with persistent B-cell aplasia at 6 months remained in remission at 12 months. The 12-month EFS for the 20 patients with isolated testicular relapse was 95.0% (95% CI, 85.9 to 100), and for the 10 patients with isolated CNS relapse, it was 68.6% (95% CI, 44.5 to 100). Cytokine release syndrome developed in 198 (88.0%) patients, and CAR T-cell neurotoxicity in 47 (20.9%), resulting in three deaths. CONCLUSION CD19-/CD22-CAR T-cell therapy achieved relatively durable remission in children with relapsed or refractory B-acute lymphoblastic leukemia, including those with isolated or combined extramedullary relapse.

Many studies have sought to construct a substitute to partially replace irreparably damaged meniscus. Only the meniscus allograft has been used in clinical practice as a useful substitute, and there are concerns about its longevity and inherent limitations, including availability of donor tissue and possibility of disease transmission. To overcome these limitations, we developed an acellular xenograft from whole porcine meniscus. Samples were treated with 2% Triton X-100 for 10 days and 2% sodium dodecyl sulfate for 6 days. The DNA content of extracellular matrix (ECM) scaffolds was significantly decreased compared with that of normal porcine menisci (p < 0.001). Histological analysis confirmed the maintenance of ECM integrity and anisotropic architecture in the absence of nuclei. Biochemical and biomechanical assays of the scaffolds indicated the preservation of collagen (p = 0.806), glycosaminoglycan (p = 0.188), and biomechanical properties (elastic modulus and transition stress). The scaffolds possessed good biocompatibility and supported bone marrow mesenchymal stem cells (BMSCs) proliferation for 2 weeks in vitro, with excellent region-specific recellularization in vivo. The novel scaffold has potential value for application in recellularization and transplantation strategies.