Rorije, N.M.G. (Nienke) (2012) BK Virus Disease following Allogeneic Stem Cell Transplantation: a Cohort Analysis. thesis, Medicine.
Full text available on request.Abstract
Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an increasingly used modality for the treatment of hematological disorders that causes a state of immunosuppression. Infection is a major cause of morbidity and mortality in HSCT recipients. Reactivation of BK virus (BKV), a human polyomavirus, following allogeneic HSCT affects the genitourinary (GU) tract with manifestations ranging from asymptomatic viruria to severe hemorrhagic cystitis. Knowledge about epidemiology, morbidity and clinical spectrum of BKV disease is limited in this population. Aim of this study was to assess and quantify incidence, severity, risk factors and outcome of BKV disease following allogeneic HSCT. Patients and Methods: Patients that underwent a first allogeneic HSCT between January 1, 2010 and December 31, 2011 at BWH/DFCI were included in this study. Medical records were reviewed for patient and HSCT characteristics. BKV disease was defined as detection of BKV by PCR testing in association with GU symptoms. BKV disease was considered severe when patients had at least 1 of the following characteristics: hematuria with clot formation, imaging compatible with BKV disease, need for invasive GU interventions, or hospitalization for BKV disease management. Time at risk was censored at time of death, second HSCT or on July 1, 2012. Fisher's exact or Wilcoxon test were used to compare variables between patients with BKV disease and patients without BKV disease. Cox modeling was used to analyze potential risk factors for BKV disease. Results: BKV disease occurred in 88 (17.9%) of 491 patients who underwent HSCT during the study period for an overall incidence rate of 0.54/1000 patient days (95% CI, 0.43 – 0.67). Severe BKV disease occurred in 31 patients for an overall incidence rate of 0.17 per 1000 patient days (95% CI, 0.12 – 0.25). Dysuria, hematuria and frequency were the most frequent experienced symptoms among patients with BKV disease during their first BKV disease episode. Symptoms lasted a median of 31 days (range, 2 – 385; IQR 9-67 days). Cohort characteristics associated with increased BKV disease risk included myeloablative conditioning (p=0.01), cyclophosphamide conditioning (p=0.0008), cord blood HSCT (p=0.03), GVHD prophylaxis with mycophenolate (MMF, p=0.0006) and acute GVHD (aGVHD) grades II-IV (p< 0.0001). On multivariate Cox modeling, time-dependent aGVHD (adjusted HR [aHR] 3.60, 95% CI 2.20 – 5.89), MMF use (aHR 3.15, 95% CI 1.79 – 5.56), and cyclophosphamide use (aHR 1.96, 95% CI 1.26 – 3.06) remained significant predictors of BKV disease. Time-dependent aGVHD grade III-IV (aHR 8.74, 95% CI 3.93 – 19.40) and cord blood HSCT (aHR 4.47, 95% CI 1.65 – 12.14) were independent risk factors for severe BKV disease. Conclusion: BKV disease is a common complication of HSCT, associated with significant and prolonged morbidity, especially in the setting of aGVHD, cyclophosphamide and MMF use. Prospective studies are needed to better define the morbidity of BKV disease and to properly inform the impact of future prophylaxis and treatment trials.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor Groningen: and Kallenberg, Professor C.G.M. MD and Department of Rheumatology and Clinical Immunology and University Medical Center Groningen and Chairman of the GIPS-M Committee |
| Supervisor name: | Supervisor Boston: and Marty, F.M. MD and Department of Medicine and Division of Infectious Disease and Brigham and Women’s Hospital and Dana-Farber Cancer Institute |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:54 |
| Last Modified: | 25 Jun 2020 10:54 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1470 |
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