Mesenchymal Stromal Cells as an Adjuvant Treatment for Severe Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The management of severe late-onset hemorrhagic cystitis (LO-HC) after allogeneic hematopoietic stem cell transplantation (HSCT) is still challenging. Because mesenchymal stromal cells (MSCs) possess anti-inflammatory and tissue repair-promoting properties, we retrospectively analyzed the efficacy and safety of MSC infusions in 7 of 33 patients with severe LO-HC after allogeneic HSCT. During treatment, each patient received at least one MSC infusion of Wharton's jelly derived from the umbilical cord of a third-party donor. In 6 patients, MSC treatment was initiated within 3 days of gross hematuria onset, while the 7th patient received an infusion 40 days later. The median dose was 1.0 (0.8-1.6) × 10⁶/kg. Five of 7 patients responded to treatment. Notably, gross hematuria promptly disappeared in 3 patients after 1 infusion, with a time to remission not seen in patients without MSC infusion. Two patients showed no response even after several infusions. No acute or late complications were recorded. Our findings indicate that MSC transfusion might be a feasible and safe supplemental therapy for patients with severe LO-HC after allogeneic HSCT.

Placenta-Derived Decidua Stromal Cells for Hemorrhagic Cystitis after Stem Cell Transplantation

“…In one of the studies, macroscopic hematuria disappeared within a median period of 3 days in the responders, who were all treated early after the appearance of HC. Furthermore, in a study by Wang et al [21], 6 out of 7 patients received MSC infusions within 3 days of the start of HC. In that study, MSCs from Wharton jelly were used, which gave a median time to remission of 18 days (8-60) for HC of grade 3 or 4.…”

“…In GVHD, younger patients appear to have a better response to MSC therapy than older patients [42]. In the study by Wang et al [21], only 1 patient was over 30 years of age. In contrast, in the present study, only 2 patients were below 30 years of age.…”

“…Both BM-MSCs and Wharton jelly-derived MSCs have shown promising results [16,19,21,41]. There are several theoretical advantages to using DSCs over BM-MSCs for HC, such as smaller size, better coagulation capacity, less differentiation to cartilage and bone, and an increased expression of integrins that may facilitate migration to inflamed tissue [25,26,28].…”

“…We introduced MSCs as a treatment for severe steroid-refractory acute GVHD and HC [17,18,19]. Recently, the feasibility of MSCs as a treatment for HC was confirmed by others [20,21]. …”

Mesenchymal Stromal Cells: The Magic Band-Aid?

“…In their article ‘Mesenchymal stromal cells as an adjuvant treatment for severe late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation', published in this issue of Acta Haematologica , Dr. Wang and colleagues [1 ]report on their encouraging findings of response to the use of mesenchymal stromal cells (MSC) for transplant patients with severe hemorrhagic cystitis (HC). This was a retrospective study of 250 patients who received an allogeneic hematopoietic stem cell transplant, with 33 patients subsequently developing severe HC.…”