Adoptive Cell Therapy for B-Cell Cancers in Patients After Stem Cell Transplantation

* INCLUSION CRITERIA:

Recipient

1. Patients must have received allogeneic HSCT for B-cell malignancies (BCL), specifically Hodgkin s and non-Hodgkin s lymphomas, chronic lymphocytic leukemias, non T-cell acute lymphoblastic leukemia (B-cell ALL), or multiple myeloma, and must have persistent disease that has failed to respond after a minimum of four weeks to:
2. Donor Engraftment Status: Patients must have had evidence of stable or increasing donor engraftment over the preceding three months and at least 50% donor chimerism in the bone marrow, whole blood and/or circulating CD3+ lymphoid pool.
3. A trial of withdrawal of immunosuppressive therapy, including trials that are discontinued due to development of GVHD
4. Receiving at least one DLI with a minimum T cell dose of 1 x 10(7) CD3+ cells/kg.

   * Patients who have persistent cancer after treatment with an alternative donor alloHSCT (e.g., haploidentical, matched unrelated, umbilical cord blood) or any patient for whom a donor cell product is unavailable and/or timely donor collection is not feasible may be included without failing DLI.
   * Presence of bone marrow involvement with tumor and/or at least one resectable lymph node or other tumor focus that is a minimum of 1.5 cm(3) (estimated size from which at least 1.0 x 106 TNC/kg can be generated):
5. Resectable defined on a case-by-case basis, in collaboration with the Surgical Consult Service.
6. For surgical tumor resection, the expected procedure must be associated with minimal morbidity and minimal hospitalization.
7. In addition to a resectable lesion, there must be at least one other site of disease that permits monitoring for response to therapy.
8. Patients must be 18 75 years of age.
9. ECOG performance status less than or equal to 2 (Karnofsky performance status greater than or equal to 60%).
10. Life expectancy \> 3 months.
11. Minimal to no clinical evidence (Grade 0 to 1) of acute GVHD or limited-stage chronic GVHD while off of systemic immunosuppressive therapy for at least four weeks. Subjects who require continued prophylaxis with steroid-sparing agents, e.g.,cyclosporine, or whose disease is controlled with local therapy, e.g., topical steroids or budesonide, will be eligible for enrollment.
12. Provision for a Durable Power of Attorney.
13. Ability to give informed consent.

1.4 Eligibility of Recipients is not contingent upon enrollment of the donor.

Donor

Note: Donor enrollment is not required to meet the primary objectives of this protocol and will not affect eligibility of recipients.

1. Donor 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 apheresis, or consent to use a temporary central venous catheter for apheresis.
3. Donors must be HIV negative, hepatitis B surface antigen negative, and hepatitis C antibody negative.

EXCLUSION CRITERIA:

Recipients

1. Active infection that is not responding to antimicrobial therapy.
2. Active psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent (as determined by Principal Investigator and/or his designee).
3. Pregnant or lactating. Patients of childbearing potential must use an effective method of contraception. 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.
4. 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. 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 prothombin time \>2 time the upper limit of normal).
5. Minimum absolute neutrophil count of 500 cells/microl, unless attributable to tumor.
6. Untreated leptomeningeal involvement with malignancy.

Donors:

1. History of psychiatric disorder which may compromise compliance with transplant 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. Donors of childbearing potential must use an effective method of contraception.
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 will determine the appropriateness of individuals as donors.