Sequential CD19/CD22 CAR-T Cell Therapy Following ASCT

Inclusion criteria

• 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)].*

• Age Restriction: Individuals must be 18 to 70 years old.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 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).]*
• 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).
• Adequate hematopoietic function, defined as:

• Platelet count ≥45 ×10⁹/L;
• Hemoglobin ≥8.0 g/dL;
• Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L.
• Life expectancy ≥3 months.
• 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.
• Willingness to provide written informed consent.

Exclusion criteria

• Prior allogeneic hematopoietic stem cell transplantation or CAR-T cell therapy.
• 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.
• Active hepatitis B (HBsAg positive with detectable HBV DNA) or hepatitis C (anti-HCV positive with detectable HCV RNA) infection at screening.
• Uncontrolled active infection requiring intravenous antimicrobial therapy.
• 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).
• 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)
• HIV infection (positive serology with detectable viral load).
• Pregnancy, lactation, or unwillingness to use effective contraception.
• Any condition that in the investigator's judgment would preclude safe participation.