BK-viruria and haemorrhagic cystitis are more frequent in allogeneic haematopoietic stem cell transplant patients receiving full conditioning and unrelated-HLA-mismatched grafts

Abstract

The influence of conditioning regimen, donor background and HLA matching on development of BK virus (BKV)-associated haemorrhagic cystitis (HC) was examined in 175 allogeneic haematopoietic stem cell transplant (HSCT) patients, undergoing 179 HSCT events. Twentyseven patients presented late-onset HC, and BK viruria was verified in 23/27 HC events. Seventy-one (40%) HSCTs were performed with myeloablative conditioning (MC), 108 (60%) were performed with reduced intensity conditioning (RIC), 66 (37%) were performed with a related donor (RD) grafts and 113 (63%) with an unrelated donor (URD) graft. BK viruria was more common during HC, than non-HC events, after MC as compared to RIC (both Po0.001), and with an HLA-mismatched donor (Po0.01). By multivariate logistical regression analysis, independent risk factors for HC were BKV (OR 6.7; 95% CI 2.0-21.7; P ¼ 0.001), MC (OR 6.0; 95% CI 2.1-17.3; Po0.001) and URD (OR 3.4; 95% CI 1.1-10.6; P ¼ 0.03). However, when analysing HSCT performed with URD or RD grafts separately, BKV (OR 8.5; 95% CI 1.8-19.3; P ¼ 0.004) and MC (OR 5.9; 95% CI 1.3-11.3; P ¼ 0.009) increased the risk for HC only with a URD, but not with an RD graft.

Hemorrhagic cystitis after allogeneic hematopoietic stem cell transplants is the complex result of BK virus infection, preparative regimen intensity and donor type

“…Use of such preparative regimens has previously been demonstrated to be a risk factor for cystitis (mostly of early onset), although not all investigators confirmed this association while others saw no difference in late onset hemorrhagic cystitis incidence between reduced intensity conditioning and ablative regimens. 11,13,15,[19][20][21] The association of BK viruria and hemorrhagic cystitis has been under investigation for many years, but we failed to document a correlation between viral load and hemorrhagic cystitis (or severity of cystitis) as previously suggested. 11,12,[22][23][24] The proportion of patients with hemorrhagic cystitis was very similar in all quartiles of urinary viral load.…”

High burden of BK virus-associated hemorrhagic cystitis in patients undergoing allogeneic hematopoietic stem cell transplantation

“…Regarding the conditioning regimen, most studies except one 1 show that MAC favors the occurrence of BKV-HC in comparison with RIC. [10][11][12]15,23 Our study fails to demonstrate the impact of MAC, likely attributable to the low proportion of RIC in our cohort. Moreover, the ubiquitous use of BU may also explain the lack of difference as other studies have proven BU to be a risk factor of HC development.…”

“…22 Another issue is the role of HLA mismatching as a cofactor for BK viruria as previously shown. 15 Although we showed that HLA mismatching and unrelated donor are cofactors in univariate analysis, multivariate analysis did not confirm it as independent risk factors. Regarding the conditioning regimen, most studies except one 1 show that MAC favors the occurrence of BKV-HC in comparison with RIC.…”

“…7 In the HSCT setting, the risk factors associated with BKV-HC development are allogeneic versus autologous HSCT, 8,9 myeloablative conditioning, [10][11][12] unrelated donor transplants, [11][12][13] cord blood transplantation 10 and pretransplantation BKV serology measured by a quantitative method. 14 Discrepancies are found in studies regarding other factors such as recipient age, 10,13 HLA mismatching and 1,15 GvHD. 10,16 Around half of allo-HSCT patients present BKV viruria at some point after HSCT.…”

“…Transient BK viruria occurs in all allo-HSCT patients 19 with 4-25% of the patients developing sustained BKV-HC. 8,15,17,19,20,[26][27][28][29] A peak in BK viruria X3 to 6-log correlates with the occurrence of HC. 1,18,29,30 Consistent with these data, all the patients in our study had a BK viruria higher than 10 8 copies/mL indicating that BK viruria may not be the most relevant factor for the prediction of BKV-HC severity.…”