Effects and long‐term follow‐up of using umbilical cord blood–derived mesenchymal stromal cells in pediatric patients with severe BK virus‐associated late‐onset hemorrhagic cystitis after unrelated cord blood transplantation

Abstract

This is a retrospective study to evaluate the efficacy and safety of umbilical cord blood–derived mesenchymal stromal cells (MSCs) for the treatment of pediatric patients with severe BK virus–associated late‐onset hemorrhagic cystitis (BKV‐HC) after unrelated cord blood transplantation (UCBT). Thirteen pediatric patients with severe BKV‐HC from December 2013 to December 2015 were treated with MSCs. The number of MSCs transfused in each session was 1 × 106/kg once a week until the symptoms improved. The median follow‐up time was 1432 (89‐2080) days. The median frequency of MSC infusion was 2 (1‐3), with eight cured cases and five effective cases; the total efficacy rate was 100%. The copy number of urine BKV DNA was 4.43 (0.36‐56.9) ×108/mL before MSC infusion and 2.67 (0‐56.3) ×108/mL after MSC infusion; the difference was not significant (P = .219). There were no significant differences in the overall survival, disease‐free survival, and the incidence of relapse and acute and chronic graft‐versus‐host disease between the MSC infusion group and non‐MSC infusion group. There was also no significant difference in the cytomegalovirus, Epstein‐Barr virus (EBV), and fungal and bacterial infection rates between the two groups. Although umbilical cord blood–derived MSCs do not reduce the number of BKV DNA copies in the urine, the cells have a high efficacy rate and minimal side effects in treating severe BKV‐HC after UCBT among pediatric patients. MSCs do not affect the rates of relapse, long‐term infection, or survival of patients with leukemia.

Management of BK virus-associated haemorrhagic cystitis in allogeneic stem cell transplant recipients

“…62 These patients exhibited similar overall survival and GVHD incidence compared to those who did not receive MSCs. 62…”

Dynamic Culture of Mesenchymal Stromal/Stem Cell Spheroids and Secretion of Paracrine Factors

“…Moreover, MSCs have emerged as critical modulators of innate and adaptive immune responses ( Ma et al, 2014 ; Xie et al, 2014 ; Luk F et al, 2015 ; Gao et al, 2016 ). They have been used to treat autoimmune and inflammation-associated diseases, including graft-versus-host disease ( Le Blanc et al, 2008 ), rheumatoid arthritis ( Tanaka 2015 ), multiple sclerosis (Cohen, Imrey et al, 2018), osteoarthritis (OA) ( Pers et al, 2016 ), and systemic lupus erythematosus ( Wang et al, 2014 ), among other serious complications, such as hemorrhagic cystitis ( Tong et al, 2020 ) and acute respiratory distress syndrome ( Hamdan et al, 2021 ; Ringdén et al, 2022 ). The cellular and molecular mechanisms underlying the therapeutic properties of MSCs are still not completely understood.…”

Fluoroquinolones for BK viral complication after transplantation: Meta‐analysis

“…Early‐onset HC is mainly due to conditioning regimens such as cyclophosphamide, while late‐onset HC is generally related to viral infections. Adenovirus, BKV, and JC polyomavirus are well known to cause late‐onset HC, of which BKV is the most common pathogen 2 . The severely immunosuppressive state after HSCT enhances BKV replication, leading to BKV viruria in about 50% and BKV‐HC in 10%‐25% usually within 2 months, often resulting in renal dysfunction and increased mortality 1 .…”

“…After HSCT, hemorrhagic cystitis (HC) is a common complication and can be classified as early-onset and late-onset HC. 2 Early-onset HC is mainly due to conditioning regimens such as cyclophosphamide, while late-onset HC is generally related to viral infections. Adenovirus, BKV, and JC polyomavirus are well known to cause late-onset HC, of which BKV is the most common pathogen.…”

“…Adenovirus, BKV, and JC polyomavirus are well known to cause late-onset HC, of which BKV is the most common pathogen. 2 The severely immunosuppressive state after HSCT enhances BKV replication, leading to BKV viruria in about 50%…”