CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19-negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.

B-cell acute lymphoblastic leukemia is the most common type of leukemia and the prognosis of relapsed/refractory B-ALL is poor. Chimeric Antigen Receptor-transduced T cell (CAR-T) therapy is one of revolutionary targeted immunotherapy. CD19 CAR-T is the most commonly used engineered T cell in B-ALL. The treatment effect is significant and far more than traditional therapy in relapsed/refractory B-ALL. However, the remission time after CD19 CAR-T infusion is short.CD19-positive and CD19-negative B-ALL relapses after CD19 CAR T-cell treatment have occurred in some patients The cause of relapse after CAR-T infusion is minimal residual disease (MRD) which will induce CD19 negative relapse. CD20/CD22/CD10 is still expressed in CD19 negative B-ALL cells which means these CD molecules may become new targets in treatment of CD19 negative relapse of B-ALL. Thus sequential treatment with CD20/CD22/CD10-CART after CD19-CART treatment in relapsed/refractory B-ALL will kill and eliminate CD19 negative B-ALL cells and prolong the remission time.

Inclusion Criteria:

1. Relapsed/Refractory B-ALL patients
2. Did not achieve complete remission after 2 times of standard plan chemotherapy
3. Relapsed after first induction chemotherapy
4. Did not response to chemotherapy before HSCT or relapsed after HSCT
5. Cannot receive allo-HSCT or refuse to receive allo-HSCT
6. Cell phenotype is CD19 and CD20/CD22/CD10/CD70 positive (single or combined)
7. Estimated survival time is more than 3 months in leukemia
8. Volunteered for this clinical trail and signed a consent form

Exclusion Criteria:

1. MRD was negative while the cell phenotype was CD19 expressed
2. Patients with severe insufficient cardiac, pulmonary and hepatorenal functions
3. Patients with severe mental illness, neurological disease or infectious disease
4. Patients with GVHD was taking immunosuppressants
5. Pregnant or lactating women
6. Patients have received other genetic therapy products
7. Transfection efficiency was less than 30%
8. Any situation may do harm to the subjects or interfere the results