Integrated Radiotherapy-optimized ASCT Sequential CAR-T Therapy for Patients With Relapsed and Refractory B-NHL

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

• Age ≥18 years.
• Histologically confirmed aggressive B-NHL.
• Life expectancy >3 months.
• 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

• 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.

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

• severe hepatic and renal function abnormalities (alanine aminotransferase, bilirubin, creatinine > 2 times the upper limit of normal);
• Presence of organic heart disease with resulting clinical symptoms or abnormal cardiac function (NYHA cardiac function classification ≥ grade 2);
• ECG QTc interval >500 ms;
• active hepatitis B/hepatitis C;
• uncontrolled active infection;
• human immunodeficiency virus infection;
• concurrent other tumors requiring treatment or intervention;
• current or anticipated need for systemic corticosteroid therapy;
• pregnant or lactating women;
• abandonment of consolidation autologous hematopoietic stem cell transplantation for financial reasons;
• other psychological conditions that prevent the patient from participating in the study or signing the informed consent form;
• 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.