1.
HLA-DP mismatch and CMV reactivation increase risk of aGVHD independently in recipients of allogeneic stem cell transplant
Ghobadi, A., Milton, D. R., Gowda, L., Rondon, G., Chemaly, R. F., Hamdi, A., Alousi, A., Afrough, A., Oran, B., Ciurea, S., et al
Current research in translational medicine. 2019
Abstract
HLA-DP mismatched allogeneic hematopoietic stem cell transplantation (allo-HCT) is associated with increased risk of aGVHD and decreased risk of relapse with no effects on overall survival (OS). It has been proposed that CMV-reactivation induces expression of HLA-DP molecules on GVHD target tissues by releasing inflammatory cytokines. We hypothesized that the increased GVHD incidence in HLA-DP mismatched allo-SCTs correlates with recipient CMV serostatus or CMV reactivation. In addition, CMV reactivation is associated with increased risk of GVHD with an unknown mechanism. Here, we analyzed the association between HLA-DPB1 and CMV reactivation on cumulative incidence of aGVHD and relapse as well as OS in 613 patients with AML and MDS who underwent matched related or unrelated allo-HCT at MD Anderson Cancer Center from 2005 to 2011. In multivariable analysis, HLA-DPB1 mismatching was associated with increased risk of aGVHD (hazard ratio (HR): 1.53, P < 0.001) independent of CMV serostatus and CMV reactivation. Additionally, HLA-DPB1 mismatching was associated with decreased risk of relapse and no effect on OS. CMV reactivation increased risks of aGVHD (HR: 5.82, P < 0.001) independent of HLA-DP mismatching with no effect on relapse or OS. In conclusion, our data suggests that HLA-DPB1 mismatching and CMV reactivation increase risk of aGVHD independently.
2.
Characterization of viral infections following antithymocyte globulin-based conditioning in adults undergoing allogeneic hematopoietic stem cell transplantation
Figgins, B., Hammerstrom, A., Ariza-Heredia, E., Oran, B., Milton, D. R., Yeh, J.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Antithymocyte globulin (ATG) has been shown to reduce the incidence of graft-versus-host-disease (GVHD) following matched related (MRD) and unrelated (MUD) hematopoietic stem cell transplantation (HCT) [1-6]; however, due to increased risks of infection and relapse, use has not translated into a significant improvement in post-transplant survival. The goal of this single-center, retrospective cohort analysis was to quantify the incidence of viral reactivation and viral end organ disease within the first 100 days following MUD HCT with ATG-based conditioning compared to MRD HCT without ATG. Fifty-nine adult patients underwent ATG-based MUD HCT compared to 64 patients receiving MRD HCT without ATG. CMV reactivation was the most frequent event in both groups (65% MUD vs 61% MRD), followed by BKV reactivation (26% vs 24%), and EBV reactivation (20% vs 9%). A higher percentage of MUD patients experienced viral end organ disease (EOD) by day +100 when compared to MRD patients (34% vs 16%, p=0.022). This was most notable for EOD involving BKV (15% vs 6%, p=0.14) and EBV (7% vs 0%, p=0.050). Correspondingly, more patients in the MUD group experienced virus-related complications, including hospitalization (24% vs 3%, p < 0.001), intensive care unit (ICU) admission (10% vs 6%, p=0.19), and mortality (8% vs 4%, p=0.44). There were no significant differences in either RFS (62% vs 78%, p=0.07) or OS (72% vs 86%, p=0.07) at 6 months post-HCT. However, when utilizing the final time point of 21 months in the MUG/ATG group and 23 months in the MRD/No ATG group, MUD patients who received ATG had inferior survival (OS: 27% vs 77%, p=0.009; RFS: 40% vs 59%, p=0.042). Our results add to and further quantify the infectious risks associated with the use of ATG in MUD transplants, as well as promote the implementation of more intensive pre-emptive viral monitoring practices in patients receiving ATG-based MUD transplants.
3.
Prevention of Cytomegalovirus Reactivation in Haploidentical Stem Cell Transplantation
Hammerstrom, A. E., Lombardi, L. R., Pingali, S. R., Rondon, G., Chen, J., Milton, D. R., Chemaly, R. F., Champlin, R. E., Gulbis, A., Ciurea, S. O.
Biology of Blood & Marrow Transplantation. 2017
Abstract
Cytomegalovirus (CMV) infection can increase the morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Because of a higher degree of immunosuppression, haploidentical transplant recipients may be at an increased risk of viral infections, particularly CMV. We retrospectively analyzed 86 haploidentical HCT recipients at our institution to determine whether a more intensified antiviral strategy would reduce the incidence of CMV reactivation compared with a traditional antiviral prophylaxis regimen. According to practice changes over time in antiviral prophylaxis at our institution, patients were divided into the following 3 groups: hybrid (n=15), traditional (n=26), and intermediate dose (n=45). The hybrid group received valganciclovir from admission to day -2 followed by standard-dose valacyclovir. The traditional group received standard-dose valacyclovir starting on day -1. The intermediate-dose group received ganciclovir from admission through day -2, followed by intermediate-dose valacyclovir. The hybrid and intermediate-dose groups were combined into an intensified group for further analysis. We found the cumulative incidence (CI) of CMV reactivation within 100 days post-HCT was higher for patients receiving the traditional strategy compared with the hybrid and intermediate-dose strategy groups (81% versus 53% versus 71%, respectively; P=.08) and was significantly higher when the traditional group was compared against the intensified group (81% versus 67%, respectively; P=.032). Median time to CMV reactivation was also shorter in the traditional group versus the intensified group (31 versus 41 days, respectively). Moreover, the CI of CMV disease by day 100 was significantly worse for patients receiving the traditional prophylaxis strategy among the 3 groups (8% traditional versus 0% hybrid versus 0% intermediate dose; P=.032). Renal toxicity did not differ between the traditional and intensified group. In conclusion, an intensified approach to prevention of CMV reactivation was associated with lower incidence of CMV reactivation and less CMV disease without increased toxicity. Because the most benefit was observed in the intensified group, further studies are needed to assess which antiviral intervention is the most beneficial on lowering the rates of CMV viremia and disease. Copyright © 2017. Published by Elsevier Inc.