We previously reported that the infusion of ex vivo expanded umbilical cord blood (UCB)-derived natural regulatory T cells (nTregs) infused immediately after UCB transplantation was associated with a reduced incidence of acute graft-vs.-host disease (GVHD) relative to historical controls (1). We did not observe an increased incidence of opportunistic infections or relapse, suggesting that the transient nature of nTreg provided sufficient immune suppression to control GVHD without long-term deleterious effects. However, we hypothesized that early side effects might be heightened and evaluated at specific time points such as when adoptively transferred nTregs were detectable in the peripheral blood of patient. All but one patient, receiving nTreg dose of 10× 106/kg on day+ 1 and 3× 106/kg on day 15, have been reported (1). Patients eligibility, conditioning regimen and immune suppression, and supportive care have been reported (1). In this analysis the historical controls consisted of 65 patient subset of the 108 reported (1) for whom had post-UCB transplantation T cell subset phenotype data available using standard procedures.

In contrast to prior analyses which compared the cumulative incidence of OIs, in this analysis we studied infection density that accounts for multiple infections in an individual patient. We calculated infection density per 1000 patient-days within 180 days by dividing total number of infections within the time period by total patient-day multiplied by 1000 (2). In our initial report we demonstrated that adoptively transferred nTregs were present in the peripheral blood of patients up to 14 days after the infusion of fresh and up to 4 days after the infusion of cryopreserved product (1). Notably, in the current study we found that in this early period (day 0 to+ 30) that nTregs are present, there was significantly higher cumulative density of OI in Treg (18.06 infections/1000 patient-days) as compared to historical controls (7.71 infections/1000 patient-days) patients (univariate RR 5.35, p=. 02)(Figure 1A). These were essentially viral reactivations with no effect on the risk of fungal infections. Thus, it is possible that Treg can increase the risk of infection during the period of time they are detectable. This contrasts with our initial report in which we found no difference on the risk OIs as assessed by the cumulative incidence. In contrast to the first 30 days, between days