The goal of this clinical trial is to learn if sequential CD19/CD22 CAR-T cell therapy following autologous stem cell transplantation (ASCT) works to treat relapsed or refractory large B-cell lymphoma (LBCL) in adults. It will also learn about the safety of this treatment combination. The main questions it aims to answer are:

Does ASCT followed by sequential CD19/CD22 CAR-T therapy improve complete response rates in participants with relapsed/refractory LBCL? What medical problems do participants have when receiving this treatment combination? Researchers will evaluate the safety and efficacy of ASCT followed by sequential CD19/CD22 CAR-T therapy to determine if this treatment approach works to improve outcomes for patients with relapsed/refractory LBCL.

Participants will:

Undergo two separate apheresis procedures for stem cell collection and CAR-T cell manufacturing.

Receive conditioning chemotherapy followed by autologous stem cell infusion on day 0.

Receive sequential CD19 and CD22 CAR-T cell infusions over 3 days within one week post-transplant.Visit the clinic regularly for checkups and tests to monitor their response to treatment and any potential side effects.

Keep a record of their symptoms and any adverse events experienced during the treatment period.

Inclusion Criteria:

1. Patients with relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy.

   *[Note: LBCL includes: diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS); diffuse large B-cell lymphoma transformed from follicular lymphoma (FL-DLBCL); grade 3b follicular lymphoma (FL); primary mediastinal large B-cell lymphoma (PMBCL); high-grade B-cell lymphoma with rearrangements of MYC and BCL-2 and/or BCL-6 (double-hit/triple-hit lymphoma, DHL/THL)].*

2. Age Restriction: Individuals must be 18 to 70 years old.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

4. Presence of at least one measurable target lesion. *[Note: A target lesion is defined as ≥1 lesion with a longest diameter (LD) >1.5 cm and a longest perpendicular diameter (LPD) ≥1.0 cm, as assessed by computed tomography (CT) or magnetic resonance imaging (MRI).]*

5. Adequate organ function, defined as:

   • Left ventricular ejection fraction (LVEF) ≥50% by echocardiography;
   • Creatinine clearance ≥30 mL/min;
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN).

6. Adequate hematopoietic function, defined as:

   • Platelet count ≥45 ×10⁹/L;
   • Hemoglobin ≥8.0 g/dL;
   • Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L.

7. Life expectancy ≥3 months.

8. For women of childbearing potential, a negative pregnancy test is required. Both male and female patients must agree to use effective contraception during treatment and for 1 year thereafter.

9. Willingness to provide written informed consent.

Exclusion Criteria:

1. Prior allogeneic hematopoietic stem cell transplantation or CAR-T cell therapy.

2. Use of immunosuppressive agents or systemic corticosteroids (equivalent to >10 mg prednisone daily) within 2 weeks prior to leukapheresis, or requirement for continued use after enrollment.

3. Active hepatitis B (HBsAg positive with detectable HBV DNA) or hepatitis C (anti-HCV positive with detectable HCV RNA) infection at screening.

4. Uncontrolled active infection requiring intravenous antimicrobial therapy.

5. History of other malignancies within 2 years prior to enrollment (except adequately treated basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ).

6. Significant comorbidities that may compromise study participation or patient safety, including:

   • Severe cardiovascular disease (NYHA Class III/IV heart failure, myocardial infarction within 6 months, unstable arrhythmias, or angina)
   • Severe pulmonary dysfunction (FEV1 or DLCO ≤50% predicted, or requiring supplemental oxygen)

7. HIV infection (positive serology with detectable viral load).

8. Pregnancy, lactation, or unwillingness to use effective contraception.

9. Any condition that in the investigator's judgment would preclude safe participation.