Search

Objectives: Cytomegalovirus (CMV) infection is one of the most common complications in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. The classic antiviral treatments have shown clinical efficacy but are often associated with drug resistance. Reconstitution of CMV-specific cellular immunity is essential in controlling CMV infection; therefore, adoptive transfer of CMV-specific T cells is a promising treatment option. We treated a patient with a multidrug resistant CMV infection after haploidentical HSCT with CMV-specific T cells. Methods: The T cells were derived from the HSCT donor who was CMV seropositive. We generated the T cells by a short-term Good Manufacturing Practice (GMP) grade protocol in which a leukapheresis product of the HSCT donor was stimulated with the immunodominant antigen pp65 and interferon-γ secreting cells were isolated. A total of 5 × 10 5  T cells were administered to the patient within 30 hours after leukapheresis. Results: The patient was closely monitored for reconstitution of antiviral T cell immunity and viral replication after adoptive T cell transfer. We observed an in vivo expansion of both CD4 + and CD8 + CMV-specific T cells associated with a significant decrease in viral burden and clinical improvement. Conclusion: This case report further supports the feasibility and effectiveness of adoptive donor T cell transfer for the treatment of drug resistant CMV infections after allo-HSCT.

Background: Bone marrow CD133-positive (CD133+) cells possess high hematopoietic and angiogenic capacity. We tested the feasibility, safety, and functional effects of the use of enriched CD133+ progenitor cells after intracoronary administration in patients with recent myocardial infarction., Methods and Results: Among 35 patients with acute myocardial infarction treated with stenting, 19 underwent intracoronary administration of CD133+ progenitor cells (12.6+/-2.2 x 10(6) cells) 11.6+/-1.4 days later (group 1) and 16 did not (group 2). At 4 months, left ventricular ejection fraction increased significantly in group 1 (from 45.0+/-2.6% to 52.1+/-3.5%, P<0.05), but only tended to increase in case-matched group 2 patients (from 44.3+/-3.1% to 48.6+/-3.6%, P=NS). Likewise, left ventricular regional chordae shortening increased in group 1 (from 11.5+/-1.0% to 16.1+/-1.3%, P<0.05) but remained unchanged in group 2 patients (from 11.1+/-1.1% to 12.7+/-1.3%, P=NS). This was paralleled by reduction in the perfusion defect in group 1 (from 28.0+/-4.1% to 22.5+/-4.1%, P<0.05) and no change in group 2 (from 25.0+/-3.0% to 22.6+/-4.1%, P=NS). In group 1, two patients developed in-stent reocclusion, 7 developed in-stent restenosis, and 2 developed significant de novo lesion of the infarct-related artery. In group 2, four patients showed in-stent restenosis. In group 1 patients without reocclusion, glucose uptake shown by positron emission tomography with 18fluorodeoxyglucose in the infarct-related territory increased from 51.2+/-2.6% to 57.5+/-3.5% (P<0.05). No stem cell-related arrhythmias were noted, either clinically or during programmed stimulation studies at 4 months., Conclusions: In patients with recent myocardial infarction, intracoronary administration of enriched CD133+ cells is feasible but was associated with increased incidence of coronary events. Nevertheless, it seems to be associated with improved left ventricular performance paralleled with increased myocardial perfusion and viability.