The purpose of this study is to assess the feasibility, safety and efficacy of anti-CD19/22 bi-specific CAR-T cell therapy in patients with CD19 and/or CD22 positive B cell malignancies. Another goal of the study is to learn more about the safety and function of the anti-CD19/22 bi-specific CAR-T cells and their persistency in patients.

Patients with refractory and/or recurrent B cell malignancies have poor prognosis despite complex multimodal therapy. Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Further, more than 40% patients with progressive large B cell lymphoma (LBCL) experienced reduced or lost expression of CD19 on the tumor cells after CAR19 treatment; low surface CD19 density before treatment was associated with progressive disease. Therefore, novel curative approaches are needed. The investigation attempts to use genetically modified T cells to express a 4th generation lentiviral anti-CD19/22 bi-specific CAR (bi-4SCAR-CD19/22). The CAR molecules enable the T cells to recognize and kill tumor cells through the recognition of a surface antigen, CD19 or CD22, which is expressed at high levels on tumor cells but not at significant levels on normal tissues.

To overcome tumor escape of single target antigen and enhance in vivo CAR-T efficacy, a novel bi-specific CD19/22 CAR-T therapy regimen is developed to include booster and consolidation CAR-T applications to target highly-refractory B cell cancer. The aim is to evaluate safety and long term efficacy of the bi-CAR-T therapy strategy in CD19 and/or CD22 positive cancer patients.

Inclusion Criteria:

1. age older than 6 months.
2. malignant B cell surface expression of CD19 or CD22 molecules.
3. the KPS score over 80 points, and survival time is more than 1 month.
4. greater than Hgb 80 g/L.5. no contraindications to blood cell collection.

Exclusion Criteria:

1. accompanied with other active diseases and difficult to assess patient response.
2. bacterial, fungal, or viral infection, unable to control.
3. living with HIV.4. active HBV or HCV infection.

5. pregnant and nursing mothers. 6. under systemic steroid treatment within a week of the treatment. 7. prior failed CD19 and CD22 CAR-T treatment.