1.
Microbiota Predict Infections and Acute Graft-Versus-Host Disease after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation
Margolis, E. B., Alfaro, G. M., Sun, Y., Dallas, R. H., Allison, K. J., Ferrolino, J., Ross, H. S., Davis, A. E., Jia, Q., Turner, P., et al
The Journal of infectious diseases. 2023
Abstract
BACKGROUND Despite intensive prophylactic and pre-emptive measures, infections remain an important cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Disruption of the gut microbiota has been linked to clinical outcomes after adult allo-HCT. This study evaluated whether these or differing microbiota disruptions or signatures were associated with risk of infection in pediatric allo-HCT. METHODS In a prospective observational study, fecal samples from 74 children were collected prior to conditioning and at the time of neutrophil recovery and profiled by means of 16S ribosomal rRNA sequencing. The associations between microbiome signatures and infections or acute graft-versus-host disease (aGVHD) were examined using Cox proportional-hazards analysis. RESULTS Previously associated indices of microbiome disruption in adults, including diversity and butyrate producer frequency, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (e.g. Lachnoclostridium, Parabacteroides, Clostridium spp.) prior to conditioning predicted likelihood of bacteremia (cox hazards ratio 3.89) in first year post HCT. A distinct ratio of oral (e.g. Rothia, Veillonella spp.) to colonic anaerobes (e.g. Anaerobutyricum, Dorea, Romboutsia spp.) at neutrophil recovery predicted likelihood of bacterial infections (cox hazards ratio 1.81) and viral enterocolitis (cox hazards ratio 1.96) through first year post transplant. CONCLUSIONS Interactions between medical interventions, pediatric hosts and microbial communities may be responsible for these consistent microbiota signatures that predict infections. A future multi-center investigation will be needed to demonstrate whether these ratios can be generalized to other pediatric cohorts.
2.
Unrelated donor peripheral blood stem cell transplantation for patients with beta-thalassaemia major based on a novel conditioning regimen
Sun, L., Wang, N., Chen, Y., Tang, L., Xing, C., Lu, N., Shi, Y., Ma, Y., Lin, F., Yu, K., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only available curative treatment for patients with beta-thalassemia major (beta-TM). However, the problem of finding a suitable sibling donor (SD) with well-matched human leukocyte antigens (HLAs) is still a major obstacle to curing these patients. With the progress in high-resolution HLA typing technology and supportive care, outcomes after allo-HSCT from a HLA-well-matched unrelated donor (UD) now approach those of well-matched SDs. However, UD-HSCT is hampered by an increased risk of graft-versus-host disease (GVHD) and transplant-related mortality (TRM). Here we report the outcome of transplantation in beta-TM patients using a novel WZ-14-TM transplant protocol, based on cyclophosphamide, intravenous busulfan, fludarabine, and antithymocyte globulin, in our center. Forty-eight patients between 2 and 11 years of age with beta-TM received HLA-well-matched UD peripheral blood stem cell transplantation (PBSCT) following the WZ-14-TM protocol. All of the transplanted patients achieved donor engraftment. The incidences of grade II-IV acute and chronic GVHD were 8.3% and 8.3%, respectively. The overall survival (OS) and thalassaemia-free survival (TFS) rates were both 100%. This encouraging result suggests that the WZ-14-TM protocol is a feasible and safe conditioning regime for beta-TM patients undergoing UD-HSCT.
3.
Rotavirus Infection in Pediatric Allogeneic Hematopoietic Cell Transplant Recipients: Clinical Course and Experience Using Nitazoxanide and Enterally Administered Immunoglobulins
Flerlage, T., Hayden, R., Cross, S. J., Dallas, R., Srinivasan, A., Tang, L., Sun, Y., Maron, G.
Pediatric Infectious Disease Journal. 2018;37(2):176-181
Abstract
BACKGROUND Rotaviruses may produce prolonged and severe disease in allogeneic hematopoietic cell transplant (HCT) recipients. Nitazoxanide and enterally administered human immunoglobulins are potential therapeutic options. This retrospective study describes the clinical course of rotavirus infection in pediatric allogeneic HCT recipients and a single-center experience with nitazoxanide and oral immunoglobulins as potential treatment options. METHODS We identified 36 patients who had positive stool rotavirus antigen assays after allogeneic HCT from May 30, 2012, to July 31, 2015. Clinical, microbiologic and treatment data were collected and analyzed using descriptive statistics. RESULTS Forty-nine discrete episodes of rotavirus infection were identified among these 36 patients for a cumulative incidence of 19.7%. For these 49 episodes, the median day to infection after HCT was day 82, and the median duration of diarrhea was 17.5 days (range 4-122). Nitazoxanide and enteral immunoglobulins were prescribed for 41 episodes. The median duration of clinical symptoms after initiation of nitazoxanide was 11 days (range 2-85), 23 days (range 10-107) after enteral immunoglobulins and 26 days (range 6-90) after a combination of nitazoxanide and enteral immunoglobulins (P = 0.1). No adverse effects of either treatment were documented, but efficacy could not be assessed in this patient population. CONCLUSIONS In pediatric HCT recipients, the clinical illness produced by rotaviruses is prolonged compared with otherwise healthy children. Nitazoxanide appears safe, but its efficacy for this indication requires further study.