- INCLUSION CRITERIA:

Inclusion Criteria:

Recipient

1. Recipients (patients with B-cell malignancy) must have received an HLA-identical
sibling allogeneic hematopoietic stem cell transplant, a 1-antigen mismatched related
transplant, or a greater than or equal to 7/8-matched unrelated donor (URD) alloHSCT
for any CD19+ B-cell malignancy. Patients with any CD19+ B-cell malignancy that is
persistent or relapsed after all of the following interventions are eligible:

1. Donor T cell engraftment after alloHSCT (> 50% donor chimerism of the T cell
compartment and a circulating T cell population for at least 12 weeks).

2. A trial of withdrawal of immunosuppressive therapy.

3. At least one donor lymphocyte infusion (DLI) with a minimum T cell dose of 1
times 10(7) CD3+ cells/kg in the case of HLA-identical sibling transplants and
1-antigen mismatched related transplants or 1 times 10(6) CD3+ cells/kg in the
case of greater than or equal to 7/8-matched HLA-matched URD transplants.

Only patients with ALL are eligible after full-donor T cell engraftment and a trial
of withdraw of immunosuppression. Prior DLI is not an eligibility requirement for
patients with ALL.

At least 4 weeks must have elapsed since the latest trial of withdraw of
immunosuppression or DLI until the patient can be deemed to have persistent disease.

2. CD19 expression must be detected on the majority of the malignant cells by
immunohistochemistry or by flow cytometry in the Laboratory of Pathology, CCR, NCI,
NIH. Definition of which cells are malignant must be determined for each patient by
the Laboratory of Pathology using techniques to demonstrate monoclonality such as
kappa/lambda restriction (other techniques can be used to determine monoclonality at
the discretion of the Laboratory of Pathology). The choice of whether to use flow
cytometry or immuohistochemistry will be determined by what is the most easily
available tissue sample in each patient. Immunohistochemistry will be used for lymph
node biopsies and bone marrow biopsies. Flow cytometry will be used for peripheral
blood, fine needle aspirate, and bone marrow aspirate samples.

3. Patients must be 18-75 years of age.

4. Performance status: ECOG less than or equal to 2 (Karnofsky performance status
greater than or equal to 60%)

5. Life expectancy greater than or equal to 3 months.

6. Minimal clinical evidence of acute GVHD and chronic GVHD while off of systemic
immunosuppressive therapy for at least 28 days. Minimal clinical evidence of acute
GVHD is defined as grade 0 to I acute GVHD. Minimal evidence of chronic GVHD is
defined as mild global score chronic GVHD (as defined by the 2005 NIH consensus
project) or no chronic GVHD. Subjects with disease that is controlled to stage I
acute GVHD or to mild global score chronic GVHD with local therapy only, e.g.,
topical cutaneous steroids or oral budesonide, will be eligible for enrollment.

7. Provision for a Durable Power of Attorney.

8. Ability to give informed consent.

9. Prior Therapy: Therapy with monoclonal antibodies and/or chemotherapy must be stopped
at least 7 days prior to anti-CD19 CAR-transduced T cell infusion, and recovery of
treatment-associated toxicity to < grade 2 is required prior to infusion of cells.
For patients that have received prior DLI, the last dose must be at least 28 days
prior to anti-CD19 CAR-transduced T cell administration. Note that patients can be
enrolled on this study at any time after or during therapy, but at least 14 days must
elapse from the time of prior monoclonal antibody administration or chemotherapy
until anti-CD19 CAR-transduced T cells are infused, and at least 28 days must elapse
from the time of withdraw of immunosuppression or DLI until anti-CD19 CAR-transduced
T cells are infused. Systemic immunosuppression must be stopped at least 28 days
prior to protocol entry. There is no time restriction in regard to prior intrathecal
chemotherapy provided there is complete recovery from any acute toxic effects of
such.

10. Recipients of unrelated donor transplants from a National Marrow Donor Program (NMDP)
Center must sign a release of information form to authorize NMDP transfer of
information to the NIH.

11. Previous allogeneic donor must be willing and available to donate again.

12. Patients of childbearing or child-fathering potential must be willing use an
effective method of contraception while being treated on this study and for 4 months
after the last cell infusion.

13. Normal left ventricular function as evaluated by echocardiograph within 6 weeks of
cell anti-CD19-CAR-transduced T cell infusion.

Inclusion Criteria:

Donor

1. Donors greater than or equal to 18 years of age must be the same individual whose
cells were used as the source for the patient's original stem cell transplant.

2. Adequate venous access for peripheral leukapheresis, or consent to use a temporary
central venous catheter for leukapheresis.

3. Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C
antibody negative.

4. Ability to give informed consent.

5. Donor selection will be in accordance with NIH/CC Department of Transfusion Medicine
(DTM) criteria and, in the case of an unrelated donor from a Transplant Center, the
National Marrow Donor Program (NMDP) standards. When a potentially eligible recipient
of an unrelated donor product from an NMDP Center is identified, the recipient will
complete an NMDP search transfer request to allow NIH NMDP staff to contact the NMDP
Coordinating Center, who will, in turn, contact the donor's prior Donor Center. The
NMDP Policy for Subsequent Donation Requests will be followed and the appropriate
forms (Subsequent Donation Request form) and Therapeutic T Cell Collection
Prescription will be submitted as required.

EXCLUSION CRITERIA:

Exclusion Criteria: Recipients

1. Active infection that is not responding to antimicrobial therapy.

2. Evidence of infection with HIV, Hepatitis B or Hepatitis C. Patients must be HIV
negative, Hepatitis B surface antigen, and Hepatitis C antibody negative. The high
degree of immune suppression that may be used in this study may lead to the
activation or progression of these viral illnesses.

3. Active psychiatric disorder which may compromise compliance with the treatment
protocol, or which does not allow for appropriate informed consent (as determined by
Principal Investigator and/or his designee).

4. Pregnant or lactating. The effects of the immunosuppressive medications that could be
required to treat GHVD are likely to be harmful to a fetus. The effects upon breast
milk are also unknown and may be harmful to an infant.

5. Serum total bilirubin > 2.5 mg/dl, serum ALT and AST values greater than or equal to
2.5 times the upper limit of normal based on age-specific normal values. If the
abnormal liver function is attributable to liver involvement by malignancy, patients
may be eligible with serum total bilirubin up to 5.0 mg/dl, and serum ALT and AST
values up to 5.0 times the upper limit of normal, provided the patient has no
evidence of impending hepatic failure (encephalopathy or prothrombin time > 2 times
the upper limit of normal).

6. Absolute neutrophil count of less than 500 cells/microL.

7. Active cerebrospinal fluid involvement with malignancy or brain metastasis.

8. Platelet count less than 10,000/microL.

9. Anemia (Hb < 9 gm/dl) that cannot be corrected with transfusion. It is not atypical
to have recipients with Hb levels < 9 gm/dl following transplantation, due to
multiple factors (e.g. medications, low serum erythropoietin levels, etc.). As such,
recipients with Hb < 9 gm/dl will be eligible if Hb can be increased and sustained
(> 7days) with transfusion and the case is individually approved by the NIH Blood
Bank. All patients with Hb < 9 gm/dl will undergo full evaluation for anemia.

10. Receiving corticosteroids above physiological dosing within 28 days prior to
anti-CD19-CAR-transduced T cell administration.

Exclusion Criteria: Donors

1. History of psychiatric disorder which may compromise compliance with this protocol or
which does not allow for appropriate informed consent.

2. History of hypertension that is not controlled by medication, stroke, or severe heart
disease (donors with symptomatic angina will be excluded). Donors with a history of
coronary artery bypass grafting or angioplasty who are symptom free will receive a
cardiology evaluation and be considered on a case-by-case basis.

3. Donors must not be pregnant.

4. Anemia (Hb < 11 gm/dl) or thrombocytopenia (platelets < 100,000 per microL).
However, potential donors with Hb levels < 11 gm/dl that is due to iron deficiency
will be eligible as long as the donor is initiated on iron replacement therapy. The
NIH Clinical Center, Department of Transfusion Medicine/NMDP physicians will
determine the appropriateness of individuals as donors.