This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of anti-CD19 chimeric antigen receptor(CAR)-modified NK cells(CAR-NK-CD19) in patients with relapsed or refractory hematological malignancies.

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can induce substantial toxic effects, and the manufacture of the cells is complex. Natural killer (NK) cells that have been modified to express an anti-CD19 CAR have the potential to overcome these limitations.

Cord blood(CB) derived NK cells from healthy donor are the source for production of CAR-NK-CD19 cells. CB derived NK cells are purified and transduced with a retroviral vector encoding the anti-CD19 CAR and interleukin-15.

This is an investigational study. The objectives are to evaluate the safety and efficacy of CAR-NK-CD19 cells in patients with CD19+ B-cell malignancies.

Inclusion Criteria:

1. Aged ≥ 18 years;

2. Eastern Cooperative Oncology Group score≤ 3;

3. Diagnosed as CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia, chronic lymphocytic leukemia and Non Hodgkin's lymphoma.

4. Patients must relapse or be refractory after at least two lines of therapy.

5. Patient's main organs functioning well:

   A. Liver function: alanine aminotransferase/aspartate aminotransferase < 2.5 times the upper limit of normal (ULN) and total bilirubin≤ 1.5 times ULN; B. Renal function: Creatinine clearance rate ≥ 60ml/min. C. Pulmonary function: Indoor oxygen saturation ≥ 95%. D. Cardiac Function: Left ventricular ejection fraction (LVEF) ≥50%, no clinically-significant ECG findings.

6. Negativity of blood pregnancy test for woman, and participants use effective methods of contraception until last follow-up.

7. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

Exclusion Criteria:

1. Investigators judge the patients with gastrointestinal lymph node and/or central nervous system involvement who may be at high-risk of receiving CAR-NK-CD19 cell treatment.
2. Patients with graft-versus-host reaction and need immunosuppressive agents, or patients with autoimmune diseases.
3. Systemic steroids are used within 5 days before apheresis.
4. Drugs to stimulate the production of bone marrow hematopoietic cells are used within 5 days before apheresis.
5. Patients receive cytotoxic chemotherapy or radiotherapy within 21 days before enrollment(Tyrosine kinase inhibitors or other targeted therapies can be used two weeks before lymphodepleting chemotherapy).
6. History of epilepsy or other central nervous system diseases.
7. Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within five years.
8. Known HIV positive patients.
9. Patients with active infections, including active replication of hepatitis B or active hepatitis C.
10. Patients receive any antitumor treatments within 4 weeks before enrollment, and the toxicity related to previous treatments don't return to < 1 level at enrollment (except for low grade toxicity such as alopecia).
11. Major surgery in the past 4 weeks.
12. Non-compliant patients.
13. Anticoagulants are being used.