ABSTRACT
BACKGROUND: Bacterial septicemia remains the leading cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (AlloHCT). While murine studies have found acute gastrointestinal graft-vs-host disease (aG-GVHD) to be associated with increased incidence of enteric bacterial bloodstream infections (EB-BSI), this association has not been studied in humans. We hypothesized that in patients who developed aG-GVHD, the EB-BSI density after onset of aG-GVHD would be higher than before onset and higher than in patients without acute GVHD (aGVHD). METHODS: We retrospectively reviewed data collected on 264 pediatric AlloHCT recipients with malignant and nonmalignant disease. We calculated and compared EB-BSI densities in the following 3 subgroups: patients without aGVHD and patients with aG-GVHD, both before and after onset of aG-GVHD. We also examined the effect of aG-GVHD onset on the first episode of EB-BSI using Cox proportional hazards models. RESULTS: The overall incidence of aG-GVHD was 28.8% (n = 76). Analyses done both at 120 and 180 days post-AlloHCT showed that the EB-BSI density increased after aG-GVHD onset (0.95 infections/person-year before aG-GVHD vs 2.7 infections/person-year after aG-GVHD at day 120 [P = .006]; 0.95 infections/person-year before aG-GVHD vs 2.26 infections/person-year after aG-GVHD at day 180 [P = .033]). On multivariate analysis, the onset of aG-GVHD had a positive hazard ratio of 1.47 (P = .077) on time to first EB-BSI. CONCLUSIONS: Our results support the theory that aG-GVHD predisposes pediatric AlloHCT recipients to EB-BSI. Prophylactic agents such as probiotics should be studied prospectively in patients with aG-GVHD.
Subject(s)
Bacteremia/epidemiology , Graft vs Host Disease/epidemiology , Hematopoietic Stem Cell Transplantation/adverse effects , Transplantation, Homologous/adverse effects , Adolescent , Bacteremia/mortality , Child , Child, Preschool , Female , Graft vs Host Disease/mortality , Humans , Male , Retrospective StudiesABSTRACT
Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/analogs & derivatives , Siblings , Tacrolimus/administration & dosage , Transplantation Conditioning , Acute Disease , Adolescent , Adult , Child , Child, Preschool , Disease-Free Survival , Female , Graft vs Host Disease/mortality , Graft vs Host Disease/prevention & control , Humans , Infant , Male , Mycophenolic Acid/administration & dosage , Neoplasms/mortality , Neoplasms/therapy , Retrospective Studies , Survival RateABSTRACT
HHV-6 is an evolving pathogen in the field of AlloHCT. However, the impact of HHV-6 on AlloHCT outcomes remains to be elucidated. We studied the incidence and clinical impact of HHV-6 viremia in children following AlloHCT. One hundred consecutive children were monitored weekly by plasma PCR for the first 180 days following AlloHCT for HHV-6, CMV, EBV, and ADV. HHV-6 viremia was defined as plasma PCR >1000 viral copies/mL. The median age was nine yr. Following AlloHCT, 19% (95% CI 11.3-26.7%) of patients had HHV-6 viremia, with the highest incidence of reactivation (14/19, 73%) occurring during day +15-day +98. The proportion of platelet engraftment by day +180 was lower in patients with HHV-6 viremia (58%) than in those without HHV-6 viremia (82%), p = 0.028. Delay in neutrophil and platelet engraftment was not associated with HHV-6 viremia in multivariate analysis. Similarly, HHV-6 viremia was not associated with TRM in multivariate analysis (p = 0.15). In summary, HHV-6 viremia is prevalent in pediatric AlloHCT recipients. Based on our study results, we recommend that HHV-6 PCR should only be performed on clinical suspicion.