Risk of Cytomegalovirus Infection with Post-Transplantation Cyclophosphamide in Haploidentical and HLA-Matched Unrelated Donor Transplantation.

Post-transplantation cyclophosphamide (PTCy) is effective for graft-versus-host disease (GVHD) prevention but is associated with an increased risk of cytomegalovirus (CMV) infection. The effect of PTCy on CMV infection in matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) is unclear, and whether there is any difference in CMV risk with 1 or 2 doses of PTCy is not well established. This study aimed to compare the incidence of CMV infection and the association between T cell recovery in patients who received PTCy-based GVHD prophylaxis and those who received non-PTCy-based GVHD prophylaxis. We conducted a retrospective study to compare the risk of CMV infection in 3 cohorts: cohort A (n = 94), matched related donor (MRD)/MUD HSCT with calcineurin inhibitor-based GVHD prophylaxis; cohort B (n = 103), MRD/MUD HSCT with 1 dose of PTCy, tacrolimus, and mycophenolate mofetil (MMF); and cohort C (n = 28), haploidentical donor HSCT with 2 doses of PTCy, tacrolimus, and MMF. The day +100 cumulative incidence of CMV infection was 29% for cohort A, 39% for cohort B, and 61% for cohort C (P = .009), with no difference among the cohorts in the duration of viremia (P = .46). CD3+ and CD4+ T cell counts were significantly higher in cohort A at day +30 but not at days +60 and +90. Nonrelapse mortality (NRM) trended higher and relapse was significantly lower with PTCy. There was no difference in survival among the 3 cohorts. There is an increased risk of early CMV infection in patients receiving PTCy irrespective of donor type and number of PTCy doses compared with those not receiving PTCy. Strategies focusing on CMV prevention in PTCy recipients to mitigate the risk of NRM may lead to improved long-term outcomes.

Bacterial Dormancy Is More Prevalent in Freshwater than Hypersaline Lakes.

Bacteria employ a diverse array of strategies to survive under extreme environmental conditions but maintaining these adaptations comes at an energetic cost. If energy reserves drop too low, extremophiles may enter a dormant state to persist. We estimated bacterial dormancy and identified the environmental variables influencing our activity proxy in 10 hypersaline and freshwater lakes across the Western United States. Using ribosomal RNA:DNA ratios as an indicator for bacterial activity, we found that the proportion of the community exhibiting dormancy was 16% lower in hypersaline than freshwater lakes. Based on our indicator variable multiple regression results, saltier conditions in both freshwater and hypersaline lakes increased activity, suggesting that salinity was a robust environmental filter structuring bacterial activity in lake ecosystems. To a lesser degree, higher total phosphorus concentrations reduced dormancy in all lakes. Thus, even under extreme conditions, the competition for resources exerted pressure on activity. Within the compositionally distinct and less diverse hypersaline communities, abundant taxa were disproportionately active and localized in families Microbacteriaceae (Actinobacteria), Nitriliruptoraceae (Actinobacteria), and Rhodobacteraceae (Alphaproteobacteria). Our results are consistent with the view that hypersaline communities are able to capitalize on a seemingly more extreme, yet highly selective, set of conditions and finds that extremophiles may need dormancy less often to thrive and survive.