Infusion of cytomegalovirus specific cytotoxic T lymphocytes from a sero-negative donor can facilitate resolution of infection and immune reconstitution.
ABSTRACT We report a stem cell transplant patient with a therapy-refractory cytomegalovirus (CMV) infection who received CMV-specific T cells from his sero-negative stem cell donor. This donor received the Towne strain CMV vaccine, and T cells were expanded using monocytes pulsed with pp65 overlapping peptides. CMV DNA decreased after the CTL infusion, and CMV-specific cytotoxicity increased. This strategy could be implemented in similar situations or with persistent viremia post-transplant.
[Show abstract] [Hide abstract]
ABSTRACT: T-cell response to cytomegalovirus (CMV) is essential in the control of viral replication. Quantification of functional CD4+ and CD8+ T lymphocytes against certain CMV-antigen specificities through flow cytometry, ELISPOT or the QuantiFERON®-CMV kit allows fairly accurate estimation of the risk of active infection and CMV disease in solid organ transplantation (SOT). Combined virological and immunological monitoring of CMV infection could allow antiviral treatments to be individually tailored and optimized in SOT, although clinical experience is currently lacking. The adoptive transfer of CMV-specific T cells before selection with multimer HLA peptides or after activation and expansion ex vivo could be an effective therapeutic alternative in the management of active infection or organic CMV disease refractory to antiviral therapy. Several CMV vaccines have been developed, which have been shown to be safe and immunogenic in preclinical and Phase I clinical trials. However, to date, none of these vaccines has been evaluated in Phase III clinical trials and consequently none has been approved for clinical use.Enfermedades Infecciosas y Microbiología Clínica 12/2011; 29:28–32. DOI:10.1016/S0213-005X(11)70054-4 · 1.88 Impact Factor
Value in Health 05/2005; 8(3):387-387. DOI:10.1016/S1098-3015(10)63044-6 · 2.89 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We conducted a prospective phase II trial utilizing the CliniMACs system to perform CD34(+)-cell selection of PBSCs from haploidentical donors to evaluate engraftment and hematoimmunological reconstitution. In total, 21 children with hematological malignancies or nonmalignant conditions underwent conditioning with 1200 cGy TBI, thiotepa, fludarabine and Thymoglobulin. Patients received megadoses of CD34(+) cells (median: 22 × 10(6)/kg) with a fixed dose of 3 × 10(4)/kg CD3(+) cells/kg, and engraftment occurred in 90% with prompt recovery of neutrophils and platelets. Grade II acute GVHD (aGVHD) was seen in 32% (95% confidence interval (CI), 15-54%) of evaluable patients, there was no grade III-IV aGVHD, and chronic extensive GVHD was seen in 35% (95% CI, 17-59%) of patients. The estimated 2-year EFS was 62% (95% CI, 48-83%) with a median survivor follow-up of 49 months (range: 18-119 months). Patients with nonmalignant diseases had an estimated 2-year EFS of 100% (95% CI, 56-100%) and patients with malignancies in remission had an estimated 2-year EFS of 56% (95% CI, 22-89%). Megadose CD34(+) cells with a fixed CD3(+) cell dose from haploidentical related donors resulted in good outcomes for pediatric patients with nonmalignant diseases and those with malignant diseases transplanted in remission.Bone Marrow Transplantation advance online publication, 26 November 2012; doi:10.1038/bmt.2012.186.Bone marrow transplantation 11/2012; 48(4). DOI:10.1038/bmt.2012.186 · 3.00 Impact Factor