Development of virus-specific immunocellular therapy after cord blood transplantation

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The one of crucial questions in cord blood transplantation (CBT) is whether naivity of cord blood lymphocytes could gain antigen-specific cellular immunity during early phase of transplant. Cytomegalovirus (CMV) infection is serious clinical problem in allogeneic transplant recipients and T cell immunity has known to have an important. role in control of virus replication and prevention.During 1998 and 2006, 111 adults has received myeloablative regimens including 12 Gy of total body irradiation followed by CBT and a standard cyclosporine and methotrexate combination as GVHD prophylaxis in our institute. Patients also received intravenous immunoglobulin from day -3 to day 120 if the immunoglobulin level in the serum was less than 500 mg/dl. CMV antigenemia assay was performed twice a week after neutrophil recovery until day 120. Once CMV antigenemia is positive, patients received 5 mg/kg ganciclovir (GCV) once daily for at least 2 weeks as preemptive therapy. Ninety-two patients achiev … More ed engraftment with full donor chimerism and survived without disease relapse at the time of 120 days after CBT (82.8%). None of these 92 recipients had CMV disease during first 4 months after CBT.We have investigated the association of CMV reactivation status and their immune reconstitution process for 4 months after CBT in 39 patients who received CBT from 2002 to 2006 in our institute. CMV-specific CD4^+ and CD8^+ T cell recoveries were assessed by detection of interferon-g (IFN-g) producing cells with CMV antigen stimulation using intracellular cytokine staining. The positive was defined as more than 0.1% IFN-g positive cells among CD4^+ or CD8^+ T population.Six of 39 patients were CMV sero-negative and 33 patients were sero-positive. None of 6 CMV sero-negative recipients and 31 of 33 CMV sero-positive recipients observed CMV reactivation and received GCV therapy within the first 4 months. CMV-specific CD4^+ T cells were detected in 30 of 31 recipients with positive CMV antigenemia (% positive:55% at 1 month and 85% at 2 month), on the other hand, CMV-specific CD8^+ T cells were detected in 14 out of 31 cases (% positive:14% at 1 month and 22% at 2 month), both of which were comparable to post-bone marrow or peripheral blood transplants (CMV-specific CD4^+ T cells were detected 18 of 21 recipients with positive CMV antigenemia and CMV-specific CD8^+ T cells were detected in 12 out of 21).These data suggest that post-thymic naive T lymphocytes in cord blood might obtain memory and effector function in vivo with antigen-specific manner during early phase of post-transplant. Less