Efficacy of Mesenchymal Stromal Cells for Refractory Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

INTRODUCTION Nowadays, the treatment of refractory late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) still faces many difficulties and challenges. Mesenchymal stromal cells (MSCs) possess the capacity to modulate immune or inflammation response, support hematopoiesis and repair tissue. We explore the efficacy of mesenchymal stromal cells for refractory LOHC treatment after allo-HSCT.

METHORDS Twenty-four patients with refractory LOHC from July 2008 to June 2021 received conventional therapy combined with MSCs obtained from bone marrow (BM) of third-party donors. MSCs were given intravenously at a dose of 1×10⁶ cells/kg once weekly until the symptoms improving or LOHC not improving after continuous infusion of four times. The number of BK viruria (BKV)-DNA, JC viruria (JCV)-DNA, cytomegalovirus (CMV)-DNA copies in the urine were detected by real-time quantitative PCR before and at 8 weeks after the MSCs infusion.

RESULTS The median number of MSC infusions for each patient was 3 (range, 2-8). Twenty patients achieved complete response, one partial response after treatment. The overall response rate was 87.5%. With a median follow-up of 397.5 days (range 39-937 days) post-transplantations, 17 patients survived and 7 died. The causes of death included aGVHD (n=1), infections (n=5) and TMA (n=1), respectively. Compared with that before MSCs infusion, the number of BKV-DNA and CMV-DNA copies were significantly lower at 8 weeks after MSCs treatment (12.105×10⁸/mL vs 0.004×10⁸/ml, P=0.041; 3.131×10⁴/mL vs 0.000×10⁴/ml，P=0.008).

CONCLUSIONS The results indicate that MSCs derived from BM of a third-party donor are effective to treat refractory LOHC after allo-HSCT. MSCs might improve LOHC by regulating immune and anti-viral activity.

No relevant conflicts of interest to declare.