• Safety of one intravenous injection of BMT donor derived EBV specific cytotoxic T lymphocytes (CTLs) in BMT recipients at high risk. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
• To compare the antiviral and immunological efficacy of a single dose of CTLs compared to the multiple dose regimens previously employed [ Time Frame: 1 year ] [ Designated as safety issue: No ]

In normal people, the Epstein-Barr (EB) virus infection causes a flu like illness (sometimes called infectious mononucleosis or glandular fever or kissing disease) and usually gets better when the immune system controls the infection. The virus, however, remains hidden in the body for life. After a transplant, while the new immune system is growing back, the EB virus can come out and infect cells and cause them to grow in an uncontrolled manner. Patients can develop fevers, swollen lymph nodes and damage to other organs such as kidneys and lungs.

This infection acts like a cancer because the cells infected with EB virus grow very quickly and there is no known effective treatment. This sort of infection will occur in between 10-30% of patients receiving a transplant from a donor who is not a perfect match, and has been fatal in nearly all these cases.

This infection occurs because the immune system cannot control the growth of the cells. We want to see if we can prevent it from happening or treat it by giving patients a kind of white blood cell called T cells that we have grown from the marrow donor. These cells have been trained to attack EB virus infected cells.

The purpose of this study is to evaluate the effectiveness of using EBV specific T cells grown from a Bone Marrow Transplant (BMT) donor to attack EB virus infected cells.

We will obtain blood from the donor and will first make a B cell line called a lymphoblastoid cell line or LCL by infecting the blood with a laboratory strain of EBV called B95. We will then use this EBV infected cell line (which have been treated with radiation so that they cannot grow) as stimulator cells and mix it with more blood.

This stimulation will train the T cells to kill EBV infected cells and result in the growth of an EBV specific T cell line. We will then test the T cells to make sure that they kill the EBV infected cells and not your normal cells and freeze them.

The marrow donor's T cells will be thawed and injected into the patients intravenous line over a period of 10 minutes. We would give one dose of the cells on or after day 45 following transplant. If the patients EBV DNA levels remain high or they have persistent disease they may be eligible to receive up to 5 additional injections of T cells at the original dose at monthly intervals.

After the patient has received the T cells, they will be contacted by the research nurse or another member of the study team weekly for 6 weeks, then once every three months for a year so that we can check on progress. To learn more about the way the T cells are working, an extra 40 mls (about 8 teaspoonfuls) of blood will be taken every two weeks for six weeks after the T cell infusions, and then every three months for one year.

• Bone Marrow Transplantation
• Epstein-Barr Virus Infections

Inclusion Criteria:

• All patients receiving a T cell depleted BMT from a mismatched family member or unrelated donor will be eligible for this protocol. In addition patients receiving a matched sibling transplant or T replete transplant may be eligible if they are at high risk of developing EBV LPD because of their underlying disease (e.g Wiskott-Aldrich or Ataxia Telangiectasia) or have a past history of EBVLPD or other EBV associated malignancy.

Exclusion Criteria:

• Exclusion criteria for BMT will be as detailed in the relevant protocol

Exclusion criteria at time of administration CTLs.

• GVHD of Grade II or greater.
• Patients with severe renal disease (i.e., creatinine clearance less than half normal for age).
• Patients with severe hepatic disease (bilirubin greater than twice normal, or SGOT greater than 3 x normal).
• Patients with a severe intercurrent infection.
• Life expectancy <6 weeks

• Texas Children's Hospital
• The Methodist Hospital System
• Center for Cell and Gene Therapy