Tisagenlecleucel In Primary CNS Lymphoma

Inclusion Criteria: Primary CNS Lymphoma in high risk elderly patients * New diagnosis of primary CNS lymphoma. * Voluntarily sign informed consent form(s) * ≥60 years of age at the time of signing informed consent * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 * Have failed or are unable to tolerate definitive first-line methotrexate based therapy as defined by: * Grade 3+ AKI and/or transaminitis preventing repeat treatment exposure and/or, * Failure to achieve a complete response (per IPCG) following two cycles of first line therapy, \--- Definitive first-line therapies must include high dose methotrexate-based therapy but may also include temozolomide, high dose cytarabine, pemetrexed, lenalidomide, ibrutinib and rituximab. * Whole-brain irradiation, lenalidomide monotherapy and ibrutinib monotherapy are considered first line therapy if patient was not eligible for methotrexate-based chemotherapy at time of initial treatment but now meets study eligibility criteria. * Adequate absolute lymphocyte count (ALC \> 500 cells/ul) within one week of apheresis. * Adequate bone marrow function defined by absolute neutrophil count (ANC) \>1000 cells/mm3without growth factor support, and untransfused platelet count \>50,000 mm3 within 7 days. * Left ventricular ejection fraction \>40% * Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<2.5 × upper limit of normal (ULN) and direct bilirubin \<1.5 × ULN * Adequate renal function defined by creatinine clearance \>30 ml/min using the Cockcroft-Gault formula * International ratio (INR) or partial thromboplastin time (PTT) \<1.5 × ULN, unless on a stable dose of anticoagulant for a thromboembolic event. * The effects of tisagenlecleucel T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men with partners of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to leukapheresis for at least 1-year post tisagenlecleucel infusion and until CAR T cells are no longer present by qPCR on two consecutive tests. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men with partners of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to leukapheresis and until 4 months after tisagenlecleucel T cells administration. * Ability and willingness to adhere to the study visit schedule and all protocol requirements Relapsed/Refractory Primary CNS Lymphoma * Diagnosis of relapsed/refractory PCNSL having received at least one prior line of CNS directed therapy. * Voluntarily sign informed consent form(s) * ≥18 years of age at the time of signing informed consent * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Adequate absolute lymphocyte count (ALC \> 500 cells/ul) within one week of apheresis. * Adequate bone marrow function defined by absolute neutrophil count (ANC) \>1000 cells/mm3without growth factor support, untransfused platelet count \>50,000 mm3, and untransfused hemoglobin \>9 g/dL. * Left ventricular ejection fraction \>40% * Adequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<2.5 × upper limit of normal (ULN) and direct bilirubin \<1.5 × ULN * Adequate renal function defined by creatinine clearance \>30 ml/min using the Cockcroft-Gault formula * International ratio (INR) or partial thromboplastin time (PTT) \<1.5 × ULN, unless on a stable dose of anticoagulant for a thromboembolic event. * The effects of tisagenlecleucel T cells on the developing human fetus are unknown. For this reason, women of child-bearing potential and men with partners of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to leukapheresis for at least 1-year post tisagenlecleucel infusion and until CAR T cells are no longer present by qPCR on two consecutive tests. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men with partners of childbearing potential treated or enrolled on this protocol must also agree to use adequate contraception prior to leukapheresis and until 4 months after tisagenlecleucel T cells administration. * Ability and willingness to adhere to the study visit schedule and all protocol requirements Inclusion Criteria for Lymphodepletion/Cell Infusion: * No Active, uncontrolled, systemic bacterial, viral, or fungal infection. * Adequate renal function defined by creatinine clearance \>30 ml/min using the Cockcroft-Gault formula Exclusion Criteria: * Prior treatment with an any investigational cellular therapy. * Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine). Systemic steroids are allowed up to a dose of dexamethasone 4mg daily or equivalent. * Ongoing systemic immunosuppression for acute and/or chronic GVH as a result of previous allogeneic bone marrow transplant. * Significant co-morbid condition or disease which in the judgment of the Principal Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, and/or recent significant traumatic injury. * Active, uncontrolled, systemic bacterial, viral, or fungal infection. * Active hepatitis B or hepatitis C infection. * HIV infection. * Subjects with a history of class III or IV congestive heart failure or non- ischemic cardiomyopathy. * Subjects with second malignancies if the second malignancy has required therapy in the last 3 years or is not in complete remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy other than hormonal therapy. * Pregnant or lactating women * Live virus vaccines within 2 weeks prior to planned start of lymphodepleting chemotherapy.