Search

Background: Cytomegalovirus (CMV) is associated with morbidity and mortality following allogeneic hematopoietic cell transplantation (alloHCT). Letermovir is a novel antiviral agent that prevents CMV reactivation in alloHCT patients, with limited data regarding influence on post‐alloHCT outcomes. Methods: We retrospectively examined 273 alloHCT recipients, 158 in the non‐letermovir cohort (NLC), and 115 in the cohort using letermovir prophylaxis (LC). Patients that received letermovir were CMV‐seropositive and met criteria for high risk of CMV reactivation. Results: Median start of letermovir was 21 days post‐alloHCT, median duration of prophylaxis was 86 days. Letermovir prophylaxis demonstrated a statistically significant reduction in first CMV reactivation (at 200 days post 63.9% in the NLC vs. 35.7% in the LC; p <.001). On univariate analysis at 1 year, overall survival (OS) for NLC was 79.6% and 79.5% for LC (p =.54). Non relapse mortality (NRM) at 1 year for NLC was 12% and 12.3% for LC (p =.69). Cumulative incidence of relapse (CIR) at 1 year was 13.9% for NLC versus 17.1 for the LC (p =.27). On multivariable analysis, there was no significant difference between the two cohorts for OS, NRM, and CIR. Conclusions: Letermovir prophylaxis started at day +21 post‐alloHCT reduced CMV reactivation, with no impact on posttransplant outcomes. [ABSTRACT FROM AUTHOR]

We explore risk factors and impacts of post-transplant EBV-Reactivation (EBV-R) and PTLD in 270 patients that underwent RIC alloHCT using ATG-PTCy and cyclosporine for GVHD prophylaxis. Twenty-five (12%) patients had probable (n = 7) or proven (n = 18) PTLD. Patients were managed with reduction of immunosuppression and 22 with weekly rituximab (375 mg/m2 IV). ORR was 84%; 8 (32%) recipients died, and one-year OS and NRM of patients with PTLD was 59.7% and 37%, respectively. One hundred seventy-two (63.7%) recipients had EBV-R. One-year OS and RFS of patients with EBV-R were 68.2% and 60.6%, and of EBV-Negative patients were 62.1% and 50.1%, respectively. High incidence but low mortality of EBV-R and PTLD was documented. EBV-R induced a protective effect on RFS in multivariable analysis (HR 0.91, p =.011). Therefore, EBV-R may have a protective effect on RFS in this setting. Further research is necessary to evaluate the interplay of EBV-R, immune reconstitution, and post-transplant outcomes. [ABSTRACT FROM AUTHOR]

Graft-versus-host disease (GVHD) represents a major contributor to morbidity and mortality in recipients of allogeneic hematopoietic cell transplants (HCT). Several strategies exist for GVHD prophylaxis and include post-transplant cyclophosphamide (PTCY) and anti-thymocyte globulin (ATG). While several groups have described the use of PTCY in younger patients, there is a paucity of data about the efficacy of PTCY in older individuals, particularly when combined with ATG. We investigated the effect of PTCY and ATG combination on transplant outcomes in older patients at Princess Margaret Cancer Centre, Toronto, Canada. Compared to those patients who received other forms of GVHD prophylaxis, individuals who received ATG-PTCY combination had higher 2-year overall survival (OS), 57% (95% confidence interval, 44-69) vs 37% (26-49), P = 0.02; higher 2-year graft-vs-host- and relapse-free survival (GRFS), 27% (17-39) vs 12% (6-21), P = 0.01; lower 2-year non-relapse mortality (NRM), 21% (12-32) vs 45% (33-56), P = 1.00 × 10-3; lower 100-day incidence of grade 2-4 acute GVHD (aGVHD), 11% (5-21) vs 28% (18-39), P = 0.02; and lower 100-day incidence of grade 3-4 aGVHD, 0% vs 7% (3-15), P = 0.02 without an increase in the 2-year cumulative incidence of relapse (CIR), 31% (20-43) vs 21% (12-32), P = 0.14. Therefore, in older HCT recipients, use of PTCY combined with ATG is associated with improved OS, lower NRM, decreased risk of aGVHD, and improved GRFS without a significant increase in relapse risk. Therefore, the PTCY with ATG combination represents an effective strategy for GVHD prophylaxis in older allogeneic HCT recipients. [ABSTRACT FROM AUTHOR]

Pediatric protocols for allogeneic hematopoietic SCT have been altered during the last two decades. To compare the outcomes in children (<18 yr old), who underwent SCT at our center during 1992-2002 (P1) and 2003-2013 (P2). We retrospectively analyzed 188 patients in P1 and 201 patients in P2. The most significant protocol changes during P2 compared with P1 were a decrease in MAC protocols, particularly those containing TBI, an increase in RIC protocols, and altered GvHD prophylaxis. In addition, P2 had more patients with nonmalignant diagnoses (p = 0.002), more mismatched ( MM) donors (p = 0.01), and more umbilical CB grafts (p = 0.03). Mesenchymal or DSCs were used for severe acute Gv HD during P2. Three-yr OS in P1 was 58%, and in P2, it was 78% (p < 0.001). Improved OS was seen in both malignant disorders (51% vs. 68%; p = 0.05) and nonmalignant disorders (77% vs. 87%; p = 0.04). Multivariate analysis showed that SCT during P2 was associated with reduced mortality ( HR = 0.57; p = 0.005), reduced TRM ( HR = 0.57; p = 0.03), unchanged relapse rate, similar rate of GF, less chronic Gv HD ( HR = 0.49; p = 0.01), and more acute Gv HD ( HR = 1.77, p = 0.007). During recent years, OS has improved at our center, possibly reflecting the introduction of less toxic conditioning regimens and a number of other methodological developments in SCT. [ABSTRACT FROM AUTHOR]

Invasive mold infections (IMIs) are major complications after allogeneic hematopoietic stem cell transplantation (HSCT) with high mortality. We retrospectively investigated incidence and risk factors for IMI after 797 HSCTs in a center with high autopsy frequency, trying to identify patient groups that would potentially benefit from mold-active prophylaxis. The cumulative 1-year incidence of IMI was 2.1% in patients aged 21 to 40, 7.1% in patients aged 41 to 60, and 16.4% in patients > 60 years of age ( P  < .01 for patients aged 21 to 40 versus 41 to 60, P  < .001 for patients aged 21 to 40 versus patients > 60). Risk factors for a new IMI in multivariate analysis were older age, grades II to IV acute graft-versus-host disease (GVHD) (risk hazard, 4.1; 95% CI, 1.9 to 8.8; P  < .001), treatment with mesenchymal stromal cells (risk hazard, 4.0; 95% CI, 2.1 to 7.8; P < .001), transplantation with female donor to male recipient (risk hazard, 2.2; 95% CI, 1.1 to 4.3; P = .02), and hematopoietic stem cell transplantation–specific comorbidity index over 5 (risk hazard, 2.8; 95% CI, 1.1 to 6.8; P = .03). In patients with grade II acute GVHD, no IMI was seen after onset of acute GVHD in 109 HSCTs performed in patients < 40 years of age, as compared with 14 IMIs in 97 HSCTs (14%) performed in patients > 40 years of age ( P  < .001). To conclude, older age is an important risk factor for developing IMIs, and patients < 40 years of age with grade II acute GVHD do not appear to need mold-active prophylaxis unless receiving prolonged treatment with corticosteroids. [ABSTRACT FROM AUTHOR]