It is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-CD19 universal CAR-NK(UCAR-NK) cells therapy combined with HSCT for B cell hematologic malignancies.

Who can participate? Patients who were diagnosed with B cell hematologic malignancies and tumor cells expressing CD19.

How to conduct this study? This study is an interventional clinical study. The intervention in the trial is anti-CD19 UCAR-NK cells, which belong to chimeric antigen receptor modified NK cells. The administration time is 1-7 days after hematopoietic stem cell infusion. Patients were then evaluated for long-term efficacy and safety until 2 years after UCAR-NK cells infusion.

What are the possible benefits and risks of participating? Benefits: The Dual effect of anti-tumor and anti-infection of NK cells may be used to promote the engraftment of hematopoietic stem cell and better disease control.

Risks: Subjects may have adverse reactions to the treatment. These adverse reactions may include abnormal liver injury, fever, thrombocytopenia, thrombotic microangiopathy, and possibly other unknown adverse reactions.

Inclusion Criteria:

1. Patients with indications for hematopoietic stem cell transplantation;
2. Age ≤75 years old;
3. Confirmed B-cell tumor and tumor cells expressing CD19；
4. Expected survival time >12 weeks;
5. Eastern cooperative oncology group (ECOG) score is 0-2;
6. Adequate liver , kidney and cardiopulmonary function;
7. Willingness to complete the informed consent process and to comply with study procedures and visit schedule.

Exclusion Criteria:

1. Had received NK cell therapy or other genetically modified cell therapy within 1 year before screening;
2. At least 14 days or at least 5 half-lives of antitumor therapy had elapsed before screening;
3. Patients who had undergone hematopoietic stem cell transplantation (ASCT), allogeneic hematopoietic stem cell transplantation (HSCT), or solid organ transplantation within 12 weeks before screening; Grade 2 or higher graft versus host disease(GVHD) requiring immunosuppressive therapy occurred within 2 weeks before screening;
4. Patients with atrial or ventricular lymphoma or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression;
5. Have received live attenuated vaccine within 6 weeks before rinsing;
6. Had a cerebrovascular accident or seizure within 6 months before screening;
7. History of deep venous thrombosis or pulmonary embolism within 6 months before screening;
8. A history of myocardial infarction, bypass or stent bypass, unstable angina, or other clinically significant heart disease within 12 months prior to screening;
9. Previous history of Alzheimer's disease;
10. Autoimmune diseases leading to end-organ damage or requiring systemic immunosuppression (e.g. Crohns, rheumatoid arthritis, systemic lupus erythematosus) within 2 years prior to screening;
11. There are uncontrollable infections;
12. Women who are pregnant or breastfeeding; Or women of childbearing age who have positive pregnancy tests during the screening period; Male or female patients who did not wish to use contraception from the time of signing the informed consent to 1 year after receiving the NK cell infusion;
13. Conditions that other researchers deemed inappropriate for participating in the study.