CMV Specific T Cell Therapy After Allogeneic Stem Cell Transplantation.

Inclusion criteria

• Patients:

• All underlying diseases that form an indication for allogeneic stem cell transplantation
• Underwent allogeneic stem cell transplantation with a donor that fulfills the following criteria:
• CMV-seropositive at the time of transplant and
• Age 18-70 years 3) Having a CMV reactivation or primary infection or disease with the following characteristics: CMV PCR at least twice positive AND CMV infection relapsing after 3 successful treatment episodes with gancyclovir OR Refractory to treatment with available antiviral drugs which is defined as follows: Persistent positive CMV PCR > detection limit 14 days after initiation of antiviral treatment OR increasing CMV viral load 7 days after initiation of antiviral treatment 4) Informed consent given
• Donor:

• Is identical to donor of the previous stem cell transplant
• The donor will be pre-screened for the presence of sufficient numbers of CMV-specific T cells:
• IFNgamma producing T cells upon CMVpp65 stimulation are at least twice the background level (unstimulated cells)
• At least 10 events of IFNgamma positive T cells are measured
• IFNgamma producing T cells upon CMVpp65 stimulation are equal or higher than 0,1% of the viable CD4+ and CD8+ cell population If the donor shows sufficient number of circulating CMV-specific cells, according to the test described in 2 3) Only if the donor shows sufficient number of circulating CMV-specific cells, according to the test described in 2:
• Donor has positive IgG serology for CMV, IgM negative or positive
• Donor has signed informed consent for the donation of donor lymphocyte cells
• Donor is found fit for donation by a medical doctor according to selection criteria conform KB annex II (C-2009/18414)
• Donor is negative for infectious disease markers including HCV, HBV and HIV-NAT testing: HBs antigen, HBc/HBs antibodies, Syphilis (TPHA or equivalent), HVC and HIV antibodies.
• Additional testing should be performed and negative when relevant: malaria, west nile virus, trypanosomiasis, HTLV conform KB annex II (C-2009/18414)
• HCG negative within 7 days of apheresis

Exclusion criteria

• Patients:

• HIV, HCV, HBV positive (HbSAg positivity after vaccination is allowed)
• Life expectancy severely limited by disease other than malignancy or viral infection
• Administration of cytotoxic agent(s) for cytoreduction within three weeks prior to initiation of the treatment or to be expected within 8 weeks after administration of the treatment
• Terminal organ failure except for renal failure (dialysis acceptable)
• Uncontrolled other infection than the one being treated
• Karnofsky performance score < 60%
• Patient is a fertile man or woman who is unwilling to use contraceptive techniques during and for 12 months following treatment
• Patient is a female who is pregnant or breastfeeding
• Patient with active aGVHD grade 3 or more
• Patient with severe chronic GVHD
• Patient on corticosteroids > 0.5mg/kg. Patient can still be on therapeutic doses of immunosuppressive therapy, but these will be tapered to the lowest possible dose, as is part of standard care in case of CMV reactivation.
• Patient that has received ATG < 1 month prior to infusion or Campath < 1 year prior to infusion
• Any condition not fulfilling inclusion criteria
• Donor:

• Any condition not fulfilling inclusion criteria