If the patient and their donor are eligible, we will take 100-120 ml (20-24 teaspoonfuls) of blood from the donor 3-4 weeks before the transplant. We will only take as much blood as is safe for the patient and their donor. We will use this blood to grow T cells. We will first infect the peripheral blood mononuclear cells with a specially produced human virus adenovirus) that carries part of the CMV gene to the monocytes which will stimulate the T cells. This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface. If this approach is insufficient to stimulate T cells which will kill the pp65 from the CMV virus then we will grow a special type of cell called dendritic cells which will stimulate the T cells and we will put the specially produced human virus (adenovirus) that carries the parts of the CMV gene (called pp65) into the dendritic cells. These dendritic cells will then be treated with radiation so they cannot grow. They will then be used to stimulate T cells. This stimulation will train the T cells to kill cells with the pp65 from the CMV virus on their surface. We will then grow these CMV specific CTLs by more stimulation with EBV infected cells (which we will make from the blood of the donor by infecting them with EBV in the laboratory). We will also put the adenovirus that carries the CMV pp65 gene into these EBV infected cells so that they too have CMVpp65. These EBV infected cells will be treated with radiation so they cannot grow. Once we have made sufficient numbers of T cells we will test them to make sure they kill cells with CMVpp65 on their surface. To make sure that these cells won't attack the patients tissues, we test these cells against the lymphoblasts that we grow in the laboratory. These will be used to check if the CMV CTL can attack them. Alternatively, we could take a small piece of skin from the patient to grow skin cells which can also be used to check if CMV CTL can attack them. The skin biopsy can be done at the same time of another procedure such as a bone marrow. The donor's CMV CTL cells will be thawed and injected into the patients intravenous line for a period of 10 minutes after the patient received Benadryl and Tylenol. The patient will receive the dose of CMV CTL cells on or after day 30 following their transplant if they agree and are well enough. We will not give antiviral medications during this study but we will monitor the CMV levels weekly for at least 30 days after the transplant. If after the initial dose of CMV CTL cells the patient develops a viral infection, then they may be eligible to receive one additional injection of CTLs at the same dose as the first injection. If the CMV levels in the blood continue to rise after the dose of T cells then the patient will receive treatment with Ganciclovir, Foscarnet, or Cidofuvir. The patient will continue to be followed in the BMT clinic after the injection. They will be seen in the clinic, in the hospital or contacted by the research nurse and have blood tests (to monitor the blood counts, the kidney and liver function and to monitor for viruses) weekly for the first 60 days after the CTL infusion, then at 3, 6, 9 and 12 months. To learn more about the way the T cells are working in the body, an extra 20-40 mls (4-8 teaspoons) of blood will be taken before the infusion and then 24 hours after the infusion (optional depending on the patients preference), and then at 1, 2, 4 and 6 weeks after the infusion. After this, blood will be taken every 3 months for 1 year. The amount of blood taken in the first 12 months will be 260-460mls (1-2 cups). Total time participation for this study will be 1 year.
Inclusion criteria: * Recipients of allogeneic donor stem cell transplants at risk for CMV reactivation with a CMV seropositive stem cell donor and at least 30 days post transplant. * Recipients can have early evidence of CMV reactivation with greater than 2 leukocytes but less than 10 leukocytes positive for the CMV Ag per 100,000 cells. * No evidence of graft-versus-host disease (GVHD) \> Grade II at time of enrollment. * Life expectancy \> 30 days * No severe intercurrent infections * Lansky/Karnofsky scores greater than or equal to 60 * Absence of severe renal disease (Creatinine \> x 3 normal for age) * Absence of severe hepatic disease (direct bilirubin \> 3 mg/dl or SGOT \> 500) * Not receiving Ganciclovir, Foscarnet, or Cidofovir or other antiviral therapy for CMV reactivation * Patient/guardian able to give informed consent Exclusion Criteria: * Patients with CMV negative stem cell donors * Patients with GVHD Grades III-IV * Patients receiving antiviral therapy for CMV reactivation or other viral infections such as adenovirus or herpes viruses * Patients with significant CMV reactivation. Significant CMV reactivation is defined as one CMV Antigenemia reading with \>10 leukocytes positive for the CMV Ag per 100,000 cells * Patients with less than 50% donor chimerism in either peripheral blood or bone marrow or patients with relapse of original disease
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