In Vitro Expanded Allogeneic Epstein-Barr Virus Specific Cytotoxic T-Lymphocytes (EBV-CTLs) Genetically Targeted to the CD19 Antigen in B-cell Malignancies

Inclusion Criteria:

- History of CD19+ malignancy with evidence of relapse or persistent MRD following
autologous or allogenic hematopoietic stem cell transplantation. (cohort 1)

- Relapse on this protocol is detection of CD19+ malignancies in bone marrow ≥ 5% or
extramedullary lesion by morphology cytogenetics, molecular, radiographic and/or flow
cytometry.

- Persistent minimal residual disease after transplantation must be demonstrated by
morphology karyotype, FISH, flow cytometry or RT-PCR.

- History of relapsed or refractory CD19+ malignancies (e.g. Non Hodgkin Lymphoma) who
have failed prior treatment and require autologous hematopoietic stem cell transplant.
Evidence of disease not required. (cohort 2)

- No age restriction for patients

- KPS or Lansky score > or = to 50

- Renal function (measured prior to conditioning chemotherapy)

- Hepatic function (measured prior to conditioning chemotherapy):

- AST ≤ 5 x the institutional ULN Elevation secondary to leukemic involvement is not an
exclusion criterion. Leukemic involvement will be determined by the presence of
progressive relapse defined by escalating bone marrow or peripheral blood leukemia
blasts within the previous month and the absence of initiation of know hepatotoxic
medication (e.g. azoles).

- Total bilirubin ≤ 2.5 x the institutional ULN

- Adequate cardiac function (e.g. LVEF ≥ 40%) as assessed by ECHO or MUGA or other
similar cardia imaging performed within 1 month of treatment.

- Pulmonary function (measured prior to treatment):

- Oxygen saturation ≥ 90% on room air

Donor Eligibility:

- The patient's HSCT donor, or if HSCT donor is not available a third party donor, must
consent to a leukapheresis or whole blood donation(s) obtained at one or more
phlebotomies which, in aggregate, will total approximately 250 ml for adults and no
more than 5ml/kg per draw from pediatric donors.

- Related donors <18 years of age requiring placement of a leukapheresis catheter will
donate peripheral blood collected by phlebotomy (including a unit of blood if weight
permits) and shall not undergo catheter placement for leukapheresis as this is
considered above minimal risk to the donor.

- There is no upper age limit for a donors. However, the minimum age for a related donor
is 7 years as this is the youngest age a person can be considered capable of giving
assent to participate in a research study.

- Evidence of prior sensitization to EBV by EBV serology testing (seropositive)

- Donor's high resolution HLA typing must be available for review

- CBC within one week of donation. Results of tests must be within a range that would
not preclude donating blood or undergoing leukapheresis.

- Serologic testing for transmissible diseases will be performed as per institutional
guidelines adopted from extant NMDP and FACT guidelines. Donors should be considered
eligible to donate leukapheresis or blood based on these guidelines (i.e. blood
donation guidelines)

Exclusion Criteria:

- Patients with active HIV, hepatitis B or hepatitis C infection.

- Patients with any concurrent active malignancies as defined by malignancies requiring
any therapy other than expectant observation.

- Females who are pregnant.

- Patients will be excluded if they have isolated extra-medullary relapse of ALL.

- Previous infusion of CD19 CAR T cells at another institution

- Patients with active (grade 2-4) acute graft versus host disease (GVHD), chronic GVHD
or an overt autoimmune disease (e.g. hemolytic anemia) requiring glucocorticosteroid
treatment (>0.5 mg/kg/day prednisone or its equivalent) as treatment

- Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic
evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia
(i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28
days of treatment. Prophylactic intrathecal medication is not a reason for exclusion.

- Adult patients (≥18 years old) with the following cardiac conditions will be excluded:

- New York Heart Association (NYHA) stage III or IV congestive heart failure

- Myocardial infarction ≤ 6months prior to enrollment

- History of clinically significant ventricular arrhythmia or unexplained syncope, not
believed to be vasovagal in nature or due to dehydration.

- History of severe non-ischemic cardiomyopathy with EF ≤20%

- Uncontrolled, symptomatic, intercurrent illness including but not limited to
infection, psychiatric illness, or social situations that would limit compliance with
study requirements or in the opinion of the treating investigator would pose an
unacceptable risk to the subject.

- Prior neurologic toxicity to previous immunotherapy

- Preceding and/or ongoing organ dysfunction or other co-morbidity including but not
limited to uncontrolled infection that would impair the patient's ability to endure
known side effects of cytokine release syndrome or neurological toxicity

- Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion.

- Recent prior therapy: Systematic chemotherapy less than 2 weeks prior to infusion.
Exceptions:

- There is no time restriction in regard to prior intrathecal chemotherapy provided
tere is complete recovery from any acute toxic effects of such.

- Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled
provided there has been no increase in dose for at least 2 weeks prior to
starting apheresis or treatment

- Subjects receiving steroid therapy at physiological replacement doses only are
allowed provided there has been no increase in dose for at least 2 weeks prior to
subject starting apheresis or treatment.

- Subjects must have recovered from the acute side effects of their prior therapy,
such that eligibility criteria are met. Cytopenias deemed to be disease-related
and not therapy-related are exempt from this exclusion.

- Rapidly progressive disease that in the estimation of the treating physician would
compromise ability to complete study therapy.