Pascal R Enok Bonong1, Chantal Buteau2, Michel Duval3, Jacques Lacroix4, Louise Laporte5, Marisa Tucci4, Nancy Robitaille6, Philip C Spinella7, Geoffrey D E Cuvelier8, Victor Lewis9, Suzanne Vercauteren10, Caroline Alfieri11, Helen Trottier1. 1. Department of Social and Preventive Medicine, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. 2. Division of Infectious Diseases, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. 3. Division of Hematology-Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. 4. Division of Pediatric Intensive Care Medicine, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada. 5. CHU Sainte-Justine Research Center, Université de Montréal, Montreal, QC, Canada. 6. Division of Hematology-Oncology, Department of Pediatrics, CHU Sainte-Justine, Université de Montréal, Héma-Québec, Montreal, QC, Canada. 7. St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, USA. 8. Pediatric Blood and Marrow Transplant, Department of Pediatric Hematology-Oncology-BMT, Department of Pediatrics and Child Health, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada. 9. Department of Pediatrics and Department of Oncology, Alberta Children's Hospital, University of Calgary, Calgary, AB, Canada. 10. Department of Pathology and Laboratory Medicine, BC Children's Hospital, University of British Colombia, Vancouver, BC, Canada. 11. Department of Microbiology, Infectiology and Immunology, Centre de recherche du CHU Sainte-Justine, Université de Montréal, Montreal, QC, Canada.
Abstract
BACKGROUND: Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. METHODS: We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. RESULTS: Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). CONCLUSION: This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.
BACKGROUND: Epstein-Barr virus (EBV) can cause severe disease following hematopoietic stem cell transplant (HSCT), including post-transplant lymphoproliferative disorder (PTLD). The objective was to analyze risk factors associated with post-transplant EBV outcomes among pediatric allogeneic HSCT recipients. METHODS: We used data from 156 pediatric allogeneic HSCT recipients enrolled in the Canadian multicenter TREASuRE study. Cox and Prentice-Williams-Petersen models were used to analyze risk factors for post-transplant EBV events including occurrence and recurrence of EBV DNAemia, increase in EBV viral load (EBV-VL), and preemptive use of rituximab, an effective therapy against PTLD. RESULTS: Females were at higher risk for increasing EBV-VL (adjusted hazard ratio (HR) = 2.83 [95% confidence intervals (CI): 1.33-6.03]) and rituximab use (HR = 3.08 [1.14-8.30]), but had the same EBV DNAemia occurrence (HR = 1.21 [0.74-1.99]) and recurrence risks (HR=1.05 [0.70-1.58]) compared to males. EBV DNAemia was associated with recipient pre-transplant EBV seropositivity (HR = 2.47 [1.17-5.21]) and with graft from an EBV-positive donor (HR = 3.53 [1.95-6.38]). Anti-thymocyte globulin (ATG) was strongly associated with all EBV outcomes, including the use of rituximab (HR = 5.33 [1.47-19.40]). Mycophenolate mofetil (MMF) significantly decreased the risk of all EBV events including the rituximab use (HR = 0.13 [0.03-0.63]). CONCLUSION: This study in pediatric allogeneic HSCT patients reveals a reduced risk of all EBV outcomes with the use of MMF. Risk factors for EBV events such as EBV-VL occurrence and recurrence include EBV positivity in the donor and recipient, and use of ATG, whereas risk factors for the most severe forms of EBV outcome (EBV-VL and the use of rituximab) include female sex and ATG use.