Adoptive Cell Therapy for B-Cell Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation With Costimulated, Tumor-Derived Lymphocytes

Background:

• After allogeneic (donor) stem cell transplantation, a new immune system grows in the patient from the transplanted donor stem cells and lymphocytes (type of immune cell). Donor lymphocytes, unlike the patient s own lymphocytes, often can recognize the patient s tumor cells as being foreign and destroy them.
• It is thought that tumor shrinkage after stem cell transplantation is the result of donor T lymphocytes, or T cells. Some studies show that patients with tumors that have T cells are better able to keep tumor growth in check.
• Patients who have had donor stem cell transplantation may have donor T cells in their tumors that can recognize and fight their cancer. Compared with donor T cells taken directly from the donor and infused into the patient, donor T cells found in patients tumors may be specific for the cancer cells and thus better able to attack tumor. Also, because the T cells found their way to the tumor, they may be less likely to recognize and attack non-tumor tissues than the T cells given in donor lymphocyte infusions.
• The T cells may be especially effective at controlling tumor if they are given an additional stimulus to become active. Costimulation is the name of the body s natural process for providing an extra stimulus, and can be performed on cells in the laboratory. Costimulation can produce large numbers of activated cells that may be able to attack cancer cells and shrink tumors.

Objectives:

-To evaluate the ability of lymphocytes found in tumors from patients who have received donor stem cell transplants to control their tumor growth.

Eligibility:

-Patients between 18 and 75 years of age with a B-cell cancer that has continued to grow or recurred after remission following allogeneic stem cell transplantation. This includes patients who have received transplants from unrelated donors and cord blood.

Design:

• Immune cells are collected from patients blood and blood from their stem cell donor.
• Patients undergo surgery to remove their tumor and a small piece of skin. In the laboratory, donor T cells are isolated from the tumor and costimulated to expand the number of cells and activate them.
• The expanded, activated T cells as infused into the patient.
• Patients have a needle biopsy and possibly surgery to remove a sample of remaining tumor for research studies.
• Patients are followed at the NIH clinic 48 hours after the cell infusion, and again at 1, 2, 4, 8 and 12 weeks after the infusion. Tumor size is monitored every month with CT scans, and possibly also with a PET or bone marrow aspiration and biopsy, for the first 3 months after the cells are infused. Thereafter, visits are less frequent (every 3 months, then every 6 months, and then yearly) during a minimum 5-year follow-up.