Background Relapsed and refractory (R/R) Burkitt's lymphoma is characterized by its aggressive nature and poor prognosis. Autologous hematopoietic stem cell transplantation (ASCT) has demonstrated limited efficacy in treating R/R Burkitt lymphoma. Similarly, CD19 chimeric antigen receptor T-cell (CAR-T) therapy has shown ineffectiveness for these patients. Emerging evidence suggests that the combination of ASCT with dual-target CAR-T therapy (CD19/CD22) may enhance therapeutic outcomes. Methods This study analyzed 13 patients with R/R Burkitt lymphoma from July 2020 to May 2025, all enrolled in a single-center clinical trial investigating sequential ASCT followed by CD19/CD22 CAR-T therapy for R/R B-cell lymphoma (NCT05206071). Comprehensive assessments, including MYC FISH, TP53 FISH, and gene mutation detection, were performed on all participants. After enrollment, bridging therapies included local radiotherapy targeting large masses. The initial ASCT regimen was BEAM until 2022; it was then modified to Be+IDA+FLU+Ara-C+melphalan (BIFAM). CD19 and CD22 CAR-T cells were infused simultaneously at a median interval of 5 days post-ASCT (range: 2-11 days), with dosages of 2*10^6/kg for CD19 and 1*10^6/kg for CD22. Therapeutic effects were evaluated through bone marrow examinations and imaging studies (CT, MRI, PET-CT) conducted one month, two months, and three months after CAR-T cell infusion; subsequent evaluations occurred every three months thereafter. One month post-infusion of CAR-T cells, maintenance therapy with a CD20 monoclonal antibody and chidamide (an histone deacetylase inhibitors, HDACi) was initiated. Results: There were 9 males and 4 females, with a median age of 29 years (range: 4 to 44). FISH analysis revealed TP53 deletion or mutation in 8 out of the 10 cases (80%). Among the patients, there were 3 in Clinical Stage II and 10 in Stage IV. Large masses were present in 8 patients (61.5%), while bone marrow or central nervous system (CNS) invasion occurred in 5 patients (38.5%). Radiotherapy was administered to 7 patients (53.8%). Three patients received BEAM therapy, and ten cases underwent BIFAM for ASCT regimen. The median stem cell infusion dose was calculated at 5.7×10^6/kg(range:2.5-17.4×10^6/kg). All patients completed treatment safely. CD19 CAR-T and CD22 CART cell amplification peaks occurred on days 10 (8.9%) and day 15 (16.3%), respectively. Adverse events included grade I/II cytokine release syndrome (CRS) observed in twelve cases (92.3%); no instances of grade III CRS or immune effector cell-related neurotoxicity syndrome (ICANS) were reported. The overall response rate (ORR)within three months was76.9% (10/13), with CR of 61.5% (8/13). One and two-year OS rates were both 65.6% (95%CI 38.2-93.1), while one and two-year progression-free survival (PFS) rates were 56.3% (95%CI 27.2-85.3). Subgroup analyses indicated that there were no significant differences in 2-year OS and PFS based on the presence of large masses versus their absence (57.1% vs. 80%), bone marrow ±CNS involvement (53.3% vs. 71.4%), TP53 abnormalities (71.4% vs. 50%), bridging therapy with radiotherapy versus without it (71.4% vs. 53.3%), BEAM versus BIFAM regimens (66.7% vs. 66.7%) (all p>0.05). Conclusion This clinical trial confirmed the efficacy and safety of ASCT followed by CD19/CD22 CAR-T therapy for R/R Burkitt lymphoma, demonstrating a 2-year OS rate of 65.6% and a 2-year PFS rate of 56.3%. This treatment protocol effectively addresses high-risk factors such as TP53 abnormalities, large tumor masses, and involvement of bone marrow or CNS. It is suggested that incorporating radiotherapy for large masses, optimizing the ASCT regimen with idarubicin and fludarabine, as well as implementing maintenance therapy with CD20 antibodies and HDACi following CAR-T treatment may enhance therapeutic outcomes. Nevertheless, there remains a need to further optimize the treatment strategy. Additionally, the small sample size in this study necessitates validation in larger cohorts to confirm these findings.

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2025
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