Risk Factors And Treatment Of Hemorrhagic Cystitis After Allogeneic Hematopoietic Stem Cell Transplantation

Objective:To explore the risk factors associated with late-onset hemorrhagic cystitis(LOHC)after allogeneic hematopoietic stem cell transplantation(allo-HSCT),and to evaluate the efficacy and safety of cidofovir.Method:The clinical data of patients with allo-HSCT in our center from March 2013 to June 2018 were retrospectively analyzed.Real-time quantitative fluorescent PCR was used to quantitatively detect BKV,CMV,JCV and other viral DNA in mid-term morning urine.The Gray's test was used to analyze the risk factors of LOHC,and the Fine-Gray model was used for multivariate analysis to determine the independent risk factors affecting the occurrence of LOHC.The clinical data of 14 patients with BK positive LOHC treated with intravenous cidofovir were further analyzed evaluate the efficacy,safety and side effect.Result:231 patients who underwent identical or haploidentical allo-HSCT and successfully obtained leukocyte implantation in the Department of Hematology,Union Hospital of Fujian Medical University from March 2013 to June 2018,were included in the screening and exclusion criteria.Among whom,155 were males(67.1%)and 76 were females(32.9%)with a median age of 24 years(1-61)years.Multivariate analysis showed that age >18 years,neutrophil implantation time >14 days,and aGVHD were independent risk factors for cystitis(all P<0.05).98 cases(71.0%)had urinary BK virus positive,45 cases of them(45.9%)had cystitis,while only 4 cases(10.0%)had cystitis in 40 cases(29.0%)of negative BK virus patients.There was a significant correlation between urinary BK virus and LOHC(P<0.001,HR 5.81,95% CI 2.102-16.062).There was no significant difference in the immune reconstitution of CD3,CD4 and CD8 T cell subsets between BK+ group and BK-group after transplantation(P>0.05).In the B-cell immune reconstitution,the proportion of CD19 +,CD20 + and CD22 + cells in the BK + group was significantly lower than that in the BK-group(P <0.01).The CD19 + and CD22 + cell populations in the BK + group were still significantly decreased 6 months after transplantation(P < 0.05).Fourteen patients with BK positive refractory LOHC were treated with intravenous cidofovir as second-line treatment and the overall response(CR)rate was(78.6%).One patient(7.1%)had irreversible renal impairment.The remaining 2 patients(14.3%)had mild renal impairment,and 7 patients(50%)had varying degrees of leukopenia,which were improved after symptomatic treatment.There was no significant difference in the DNA load of urinary BK virus before and after cidofovir(P=0.615).The overall survival rate of LOHC patients was significantly worse than that of patients without LOHC(P<0.05).Conclusion:The occurrence of LOHC affects the prognosis of allogeneic hematopoietic stem cell transplantation.Age > 18 years,neutrophil implantation time > 14 days,the occurrence of aGVHD,BK virus infection are risk factors for LOHC.B cell immune reconstitution stained at CD19+,CD20+,CD22+ was delayed in BK+ group.Cidofovir is effective in the treatment of refractory LOHC,but its nephrotoxicity needs to be taken seriously and prevented.