Ala Abudayyeh1, Amir Hamdi1, Maen Abdelrahim2, Heather Lin3, Valda D Page4, Gabriela Rondon5, Borje S Andersson5, Aimaz Afrough5, Charles S Martinez5, Jeffrey J Tarrand6, Dimitrios P Kontoyiannis7, David Marin5, A Osama Gaber8, Betul Oran5, Roy F Chemaly7, Sairah Ahmed5, Islam Abudayyeh9, Amanda Olson5, Roy Jones5, Uday Popat5, Richard E Champlin5, Elizabeth J Shpall5, Katayoun Rezvani5. 1. Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 2. Division of Medical Oncology, Duke University School of Medicine, Durham, NC, USA. 3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Emergency Medicine and Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 5. Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 7. Department of Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 8. Department of Transplant Surgery, Houston Methodist Hospital, Houston, TX, USA. 9. Division of Cardiology, Interventional Cardiology, Loma Linda University Health, Loma Linda, CA, USA.
Abstract
BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
BACKGROUND:BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyVinfection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyVinfection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.
Authors: Hannah Imlay; Hu Xie; Wendy M Leisenring; Elizabeth R Duke; Louise E Kimball; Meei-Li Huang; Steven A Pergam; Joshua A Hill; Keith R Jerome; Filippo Milano; W Garrett Nichols; Phillip S Pang; Hans H Hirsch; Ajit P Limaye; Michael Boeckh Journal: Blood Adv Date: 2020-02-25