This study aims to investigate a novel therapeutic strategy of integrated radiotherapy before autologous stem cell transplantation (ASCT) sequential chimeric antigen receptor T-cell(CAR-T) therapy for patients with relapsed/refractory(R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). By evaluating the efficacy and safety of this multimodal approach, we seek to provide a theoretical foundation and clinical data to optimize outcomes for relapsed/refractory aggressive B-NHL patients.

This trial will enroll R/R aggressive B-NHL patients aged ≥18 years who have undergone at least two prior lines of systemic therapy. Participants will be stratified into two cohorts based on post-salvage therapy disease status:

Cohort 1 (PET/CT-, ctDNA+): Patients will receive low-dose radiotherapy (RT) combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.

Cohort 2 (PET/CT+, ctDNA+): Patients will receive high-dose RT combined with reduced-intensity SEAM/TB chemotherapy as a conditioning regimen, followed by ASCT and sequential CAR-T therapy.

All patients completing the combined ASCT-CAR-T protocol will undergo longitudinal follow-up for safety, efficacy survival outcomes .

Inclusion Criteria:

1. Age ≥18 years.

2. Histologically confirmed aggressive B-NHL.

3. Life expectancy >3 months.

4. Appropriate organ function:

   Cardiac function: cardiac ejection fraction ≥50%; Liver function: alanine aminotransferase and glutamic aminotransferase ≤ 2 times the upper limit of normal values; renal function: serum creatinine clearance ≥80 mL/min; serum creatinine <160 mmol/L Lung function: SPO2>91% without oxygen intake

5. Adequate bone marrow reserve defined as:

   hemoglobin ≥90 g/L. platelet count ≥70 x 10^9/L. absolute neutrophil count ≥1.5 x 10^9/L.

6. The patient is capable of understanding and willing to provide written informed consent.

7. Subjects of childbearing or childbearing potential must be willing to practice birth control from the date of enrollment in this study until study follow-up.

Exclusion Criteria:

1. severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);
2. Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);
3. ECG QTc interval >500 ms;
4. active hepatitis B/hepatitis C;
5. uncontrolled active infection;
6. human immunodeficiency virus infection;
7. concurrent other tumors requiring treatment or intervention;
8. current or anticipated need for systemic corticosteroid therapy;
9. pregnant or lactating women;
10. abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;
11. other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;
12. Subjects who, in the judgment of the investigator, are unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or do not meet the requirements for participation in the study.