A Reciprocal Interaction between Immune Reconstitution and Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Background

Hemorrhagic cystitis (HC) is one of the serious complications of allogeneic hematopoietic stem cell transplants (allo-HSCT), with the potential to cause significant morbidity. However, the underlying mechanism of HC is not yet clear.

Objective

To explore the reciprocal interaction between immune reconstitution and HC after allo-HSCT.

Methods

101 patients undergoing allo-HSCT in our department during July, 2014 to April, 2017 were analyzed. JC virus(JCV), BK virus (BKV), cytomegalovirus (CMV) by quantitative real-time PCR were performed on all blood or urine samples post-HSCT. Non-specific T and B cell immune reconstitution were assessed by the expression of CD3, CD4, CD8, CD56, CD10, CD19, CD20 and CD22 with multiparametric flow cytometry, and specific T cell phenotype and cytokine production were determined by the expression of CD3, CD4, CD8, CD69, IL-2, IFN-gamma and TNF-alpha on PBMCs after the stimulation with one of four BKV peptides (tAg,Tag,VP-1,VP-2,VP-3).

Results

62 out of total 101 patients were male and 39 were female. The median age was 27 years (range, 1-54). 85 patients were diagnosed as malignancy hematologic disease (AML=44, ALL=26, MDS=4, CML=6, NHL=5), while 16 were non-malignancy hematologic disease (SAA = 14, fanconi=1, thalassemia=1). Through the cox regression analysis, the hazard ratio (HR) of HC (95% confidence interval) for BKV viruria was 4.866 (1.908-12.406), with a P-value of 0.001. Those with primary malignance disease also had higher odds of developing HC, with an HR of 5.101. Both of them were independent risk factors in multivariate analysis. There was no significant difference on the expression of CD3, CD4, CD8 and CD56 representative the non-specific T cell immune reconstitution between BK+ and BK- group, but the non-specific B cell immune reconstitution stained with CD19+, CD20+, CD22+ was significant delayed in BK+ group. Moreover, the specific T cell immune reconstitution performed in 6 cases were significant delayed in BK+ group as well compared to that in BK- group.

Conclusion

HC is correlated to BKV viruria and primary malignance disease in allo-HSCT. Poor specific immune reconstitution post-HSCT increased the risk of BK virus reactivation, and BK virus infection delayed the immune reconstitution after transplantation vise versa.