CD19 CAR T Cells in Patients With Resistant or Refractory CD19+ Acute Lymphoblastic Leukemia

Inclusion Criteria: * Patients aged 18 to 70 years with relapsed or refractory CD19 positive ALL(ie, ≥20% blasts CD19-positive) due to receive either salvage 1 or salvage 2 therapy. Ph+ ALL patients must have failed treatment with at least 1 second generation tyrosine kinase inhibitor. * Bone marrow involvement with≥20% lymphoblasts. * Eastern Cooperative Oncology Group (ECOG) Performance status 0-2. * Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum glutamic-oxaloacetic transaminase(SGOT) and serum glutamic pyruvic transaminase(SGPT) ≤ 2.5 x ULN; Creatinine ≤ 1.5 x ULN or any serum creatinine level associated with a measured or calculated creatinine clearance of ≥ 40ml/min. * Patients should sign informed consent form. Exclusion Criteria: * Isolated extramedullary relapse. * Active central nervous system leukemia. * Prior chemotherapy within ≤2 weeks before enrollment with the following exceptions: steroids, hydroxyurea, oral mercaptopurine, methotrexate, vincristine, thioguanine, and tyrosine kinase inhibitors are permitted within 2 weeks of enrollment as maintenance or to reduce the peripheral blood blast count. Patients must have recovered from acute toxicity of all previous therapy prior to enrollment. * Prior allogeneic hematopoietic stem cell transplant (HSCT) ≤ 4 months before enrollment. Patients must have completed immunosuppression therapy prior to enrollment. At enrollment, patients must not have \> grade 2 acute GVHD, or either moderate or severe limited chronic GVHD, or extensive GVHD of any severity. * Peripheral lymphoblasts \> 10,000/μl (treatment with hydroxyurea and/or steroids is permitted within 2 weeks of enrollment to reduce the WBC count). * Known systemic vasculitides, primary or secondary immunodeficiency(such as HIV infection or severe inflammatory disease). * Major surgery within ≤ 4 weeks before enrollment. * Impaired cardiac function:Ejection fraction \< 45 % on MUGA scan. QTc interval \> 450 msec on baseline ECG (using the QTcB formula). If QTcB interval\>450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and then the patient re-screened for QTc. Myocardial infarction within 6 months prior to starting study; other clinically significant heart disease (e.g. unstable angina, congestive heart failure or uncontrolled hypertension, uncontrolled arrhythmias). * Administration of live vaccine ≤ 4 weeks before enrollment. * Other concurrent severe and/or uncontrolled medical conditions: Patients with another primary malignant disease, except those that do not currently require treatment; acute or chronic liver, pancreatic or severe renal disease; another severe and/or life-threatening medical disease. * Evidence of uncontrolled current serious active infection. * Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) male or female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post-menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). * Who is known human deficiency virus (HIV) positive. * Use of any other investigational agent in the last 30 days.