Stem Cell Transplantation and T-Cell Add-Back to Treat Bone Marrow Malignances

Summary

This study will evaluate the safety and effectiveness of stem cell transplantation in which the donor s T cells (a type of lymphocyte, or white blood cell) have been removed and then added back. Certain patients with bone marrow malignancies undergo transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components white cells, red cells and platelets) to generate new and normally functioning bone marrow. However, T-cells from the donor may see the patient s cells as foreign and mount an immune response to reject them, causing what is called graft-versus-host-disease (GVHD). Therefore, in this study, T-cells are removed from the donor cells to prevent this complication. Nevertheless, there are disadvantages of removing the T-cells, since they are important in fighting viral infections as well as any remaining malignant cells. The attack against the malignant cells is called a graft-versus-leukemia effect. Therefore, donor T cells are given to the patient (added back) later (45 and 100 days after the transplant) when they can provide needed immunity with less risk of causing GVHD.

Patients between 10 and 55 years of age with chronic myelogenous leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, a myelodysplastic syndrome, myeloproliferative disorders, or chronic lymphocytic leukemia may be eligible for this study. Prospective participants and their donors are screened with a medical history and physical examination, blood tests (including a test to match for genetic compatibility), breathing tests, chest and sinus X-rays, and tests of heart function. They also undergo a bone marrow biopsy and aspiration. For this procedure, done under local anesthetic, about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone.

Participants may undergo apheresis to collect lymphocytes for research studies. This procedure involves collecting blood through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and removed by a cell separator machine, and the rest of the blood is returned through a needle in the other arm.

Before treatment begins, patients have a central venous catheter (flexible plastic tube) placed in a vein. This line remains in place during the stem cell transfusion and recovery period for drawing and transfusing blood, giving medications, and infusing the donated cells. Preparation for the transfusion includes irradiation and chemotherapy. Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days. Four days before the transfusion, they begin taking cyclophosphamide, and 9days before the procedure they start fludarabine. These are anti-cancer drugs that kill the cancer cells and prevent rejection of the donated cells. While the patient is receiving chemotherapy, the donor receives daily injections for 6 days of G-CSF, a drug that moves stem cells from the bone marrow into the blood stream. On days 1 and 2 after chemotherapy is completed, the stem cells are infused into the patient through the central line.

Patients usually stay in the hospital about 20 to 30 days after the transplant to recover from treatment side effects, which may include fever, nausea, diarrhea and mouth pain, and receive blood transfusions, if needed. Treatment with cyclosporine, a drug that helps prevents both rejection of donated cells and GVHD, is started on day 44 one day before the first T-cell add-back. Patients return to the clinic for follow-up with various tests, treatments and examinations as required, with a minimum of visits at least once or twice a week for 2 to 4 months after the transplant; then at 4, 6, 9, and 12 months, and then yearly for at least 3 years.

Conditions

• Immunosuppression
• Leukemia

Interventions

DEVICE

SOLEX 300i Stem Cell Selection

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  lead NIH

Principal Investigators

• A. John Barrett, M.D. · National Heart, Lung, and Blood Institute (NHLBI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

10 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2002-01-23

Primary Completion

2007-11-29

Completion

2007-11-29

Countries

• United States

Study Locations