Protocol Number: 04-H-0112

Title:

Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation Followed by T Cell Add-Back for Hematological Malignancies - Effect of Peritransplant Cyclosporine on Chimerism

Number:

04-H-0112

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) are removed and then added back. Certain patients with bone marrow malignancies undergo transplantation of donated stem cells 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 protocol, T-cells are removed from the donor cells to prevent this complication. However, because T-cells are important in fighting viral infections as well as any remaining malignant cells (called graft-versus-leukemia effect), the donor T-cells are given to the patient (added back) at a later time after the transplant when they can provide needed immunity with less risk of causing GVHD.

Patients between 10 and 55 years of age with acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome 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 For this procedure, done under local anesthetic, about a tablespoon of bone marrow is withdrawn through a needle inserted into the hipbone.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 have dental and eye examinations. They 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 intravenous line (flexible plastic tube) placed in a vein in the chest. This line remains in place during the stem cell transplant and recovery period for drawing and transfusing blood, giving medications, and infusing the donated cells. Preparation for the transfusion includes high-dose radiation and chemotherapy. Patients undergo total body irradiation in 8 doses given in two 30-minute sessions a day for 4 days. Eight days before the transplant, they begin taking fludarabine, and 3 days before the procedure they start cyclophosphamide. These are anti-cancer drugs that kill the cancer cells and prevent rejection of the donated cells. Patients with aggressive leukemia will also receive etoposide - a powerful anti-leukemic drug - 3 days before the transplant. While the patient is receiving chemotherapy, the donor receives daily injections for 5 days of G-CSF, a drug that moves stem cells from the bone marrow into the blood stream, and the white cells are then collected by apheresis. The day after chemotherapy is completed, the stem cells are infused into the patient through the central line.

Patients usually stay in the hospital about 4 weeks after the transplant to recover. Treatment with cyclosporine, an immune-suppressing drug that helps prevents both rejection of donated cells and GVHD, is given 6 days before the transplant until 21 days post-transplant. It is then stopped to allow the donor immunity to function and is resumed on day 59 post-transplant (1 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 5 years.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: No longer recruiting/follow-up only

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria: This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Special Instructions:

Currently Not Provided

Keyword(s):

Chronic Myelogenous Leukemia

Acute Lymphoblastic Leukemia

Acute Myelogenous Leukemia (AML)

Chronic Lymphocytic Leukemia

Myelodysplastic Syndromes

Peripheral Blood Stem Cells

Graft-Versus Leukemia/Myeloma

Graft-Versus-Host Disease

Cyclosporine

Fludarabine

Recruitment Keyword(s):

Leukemia

Myelodysplastic Syndrome

Myeloproliferative Syndrome

Non-Hodgkin Lymphoma

ALL

CML

Condition(s):

Leukemia

Bone Marrow Transplantation

Investigational Drug(s):

None

Investigational Device(s):

None

Interventions:

Device: Isolex 300i Magnetic Cell Selector

Supporting Site:

National Heart, Lung and Blood Institute

Contact(s):

This study is not currently recruiting new subjects. If you have questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.

Citation(s):

Barrett AJ. Antilymphocyte globulin and its use in skin diseases. Int J Dermatol. 1977 Nov;16(9):738-9. No abstract available.

Barrett AJ. Bone marrow transplantation. Arch Dis Child. 1980 Oct;55(10):750-2. No abstract available.

Barrett AJ. Bone marrow transplantation. Practitioner. 1980 Oct;224(1348):1009-15. No abstract available.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department Clinical Research Informatics, CC.

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