Cytomegalovirus-Specific T-Cell Transfer for Refractory Cytomegalovirus Infection after Haploidentical Stem Cell Transplantation: The Quantitative and Qualitative Immune Recovery for Cytomegalovirus

Abstract

Background The efficiency and mechanisms of adoptive transfer of cytomegalovirus (CMV)specific T cells for refractory CMV infection after haploidentical stem cell transplantation (haplo-SCT) remain largely unknown. Methods Thirty-two patients with refractory CMV infection who accepted treatment with adoptive CMV-specific T-cell infusion following haplo-SCT were prospectively enrolled. Another 32 patients with nonrefractory CMV infection after haplo-SCT were selected as control subjects. The phenotypical and functional characteristics of CMV-specific T cells were analyzed before and after cellular therapy in the refractory cohort, as well as in the nonrefractory cohort. Results In the refractory cohort, 27 of the 32 treated patients exhibited CMV clearance within 4 weeks after adoptive T-cell transfer without recurrence. The in vivo expansion of CMV-specific T cells and improvements in the cytokine production and proliferation ability of the CMV-specific T cells were observed after cellular therapy. Moreover, a reduced expression of programmed death-1 (PD-1) on CMV-specific T cells was observed. However, in the remaining 5 patients who showed CMV recurrence 4 weeks after transfer, neither the quantity nor the function of CMV-specific T cells was restored. Conclusions The adoptive transfer of CMV-specific T cells promotes quantitative and functional recovery of CMV-specific T cells to guard against refractory CMV infection after haplo-SCT.