BK Virus (BKV) Associated Haemorrhagic Cystitis Is Associated with Graft Versus Host Disease (GVHD) and Significant Morbidity Post Haematopoietic Stem Cell Transplant (HSCT).

Abstract

3040 The Polyomavirus hominis 1 BK virus (BKV) is a non-encapsulated DNA virus, which infects up to 90% of the world's population, and may reactivate at times of severe immunosuppression, including post haematopoietic stem cell transplantation (HSCT). The significance of BK virus reactivation post Haematopoietic Stem Cell Transplant (HSCT) remains unclear. We collected retrospective data on viruria, viraemia, haemorrhagic cystitis (HC) and acute/chronic graft versus host disease (a/cGVHD) in patients at our institution over the period 2006 to 2011. We compared with a multivariate matched control group of 38, who did not reactivate BK. The groups were matched for age, sex, donor source and conditioning regimen including use of Alemtuzumab. Global BK reactivation incidence was 32% (38/118) of allogeneic HSCT during this period. 73% (28/38) of those who reactivated received volunteer unrelated donor (VUD) grafts, and 50% (18/38) received Alemtuzumab. Patients were sub-divided into those with high grade viraemia (HGV, VL >104 copies/ml), 47% (18/38) or low grade viraemia (LGV, VL<104 copies/ml), 53% (20/38). HGV was present in 57% of VUD transplants and 20% of sibling recipients, compared to LGV in 29% of VUDs and 70% of siblings. HGV influenced 1 year EFS; 18% versus 55% in LGV. Median OS was 173 days in HGV versus 345 days in LGV. Cumulative mortality rate in the BK group was 71% (27/38) as compared to 55% (21/38) in the control group (not significant). Relapse related mortality in the BK group was 22% (6/27) versus 57% (12/21) in the control group, at a median follow up of 229 days (p=0.088), indicating the high incidence of non-relapse causes of mortality in the BK group. 79% (30/38) of patients reactivating BK developed aGVHD, including 83% (15/18) with HGV, compared to 57% (21/37) in the control group (p=0.039). The number of patients who developed grade II-IV aGVHD in the BK group was 30/38 (79%) and 11/37 (20%) in the control group (p <0.001), figure 1. In 33% of patients BK reactivation preceded aGVHD by a mean of 12 days. 84% (27/32) of patients developed cGVHD, compared to 30% (18/30) in control group (p=0.05). Moderate-severe (NIH grade) cGVHD was more prevalent in patients reactivating BK, compared to control group; 75% (24/32) versus 3% (1/30) (p<0.001), figure 2. This data suggests the association of BK with an increased incidence of acute and chronic GVHD, and significant morbidity. Notably 10 patients developed severe complications including grade 4 HC (5/10), obstructive hydronephrosis and bladder wall dysfunction requiring invasive intervention. 7/10 (70%) of these patients had HGV; 2 patients reactivated early, failed treatment, developed obstructive renal failure and died. These patients had an increased rate of mortality compared to the whole study group (p=0.005), and all failed to achieve an EFS of over 1 year. Of note, 8.5% of all allografts developed grade 4 HC and 90% of these subsequently died. BK reactivation strongly correlates with acute and chronic GVHD and an increase in non relapse mortality. Routine surveillance for BK with risk scoring may allow earlier detection and reduced morbidity of BK and GVHD. Further prospective studies are required to understand the impact of the reactivation of the virus. Figure 1: Cumulative Incidence of acute GVHD Grade II-IV: Figure 1:. Cumulative Incidence of acute GVHD Grade II-IV: p <0.001 Figure 2: Cumulative Incidence of chronic GVHD moderate-severe: Figure 2:. Cumulative Incidence of chronic GVHD moderate-severe: p <0.001 Disclosures: No relevant conflicts of interest to declare.