Safety and Side Effects of Using Placenta-Derived Decidual Stromal Cells for Graft-versus-Host Disease and Hemorrhagic Cystitis

Abstract

Mesenchymal stromal cells (MSCs) are increasingly used in regenerate medicine. Placenta-derived decidual stromal cells (DSCs) are a novel therapy for acute graft-versus-host-disease (GVHD) and hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT). DSCs are more immunosuppressive than MSCs. We assessed adverse events and safety using DSCs among 44 treated patients and 40 controls. The median dose of infused cells was 1.5 (range 0.9–2.9) × 106 DSCs/kg. The patients were given 2 (1–5) doses, with a total of 82 infusions. Monitoring ended 3 months after the last DSC infusion. Three patients had transient reactions during DSC infusion. Laboratory values, hemorrhages, and transfusions were similar in the two groups. The frequency of leukemic relapse (2/2, DSC/controls) and invasive fungal infections (6/6) were the same in the two groups. Causes of death were those seen in HSCT patients: infections (5/3), respiratory failure (1/1), circulatory failure (3/1), thromboembolism (1/0), multiorgan failure (0/1), and GVHD and others (2/7). One-year survival for the DSC patients with GVHD was 67%, which was significantly better than achieved previously at our center. One-year survival was 90% in the DSC-treated HC group. DSC infusions appear safe. Randomized studies are required to prove efficacy.

Placenta-Derived Decidua Stromal Cells for Treatment of Severe Acute Graft-Versus-Host Disease

“…Based on the findings in this study and the safety report, it appears that treatment with DSCs is safe . The causes of SAEs and deaths were infections, relapse, and other common complications seen among patients undergoing HSCT, especially those with severe acute GVHD.…”

“…We also saw a high frequency of invasive fungal infection in the controls and in patients treated with MSCs . In a safety study, we found that the side effects and causes of death were similar in patients with GVHD and hemorrhagic cystitis who were treated with DSCs and in controls treated with other therapies . Because the patients treated with DSCs have survived longer than expected, they have had more time to experience severe adverse events after HSCT complicated by acute GVHD and heavy immunosuppressive treatment.…”

“…Severe adverse events in the DSC patients ( n = 38) and in the control group ( n = 32) included the following: relapse (8/10), pneumonia (5/9), proven or probable invasive fungal infection (6/5), bacterial infection (2/6), graft failure (3/3), multiple organ failure (1/5), viral infection (2/3), central nervous system complication (2/3), septicemia (2/2), skin squamous cell carcinoma (2/0), interstitial pneumonitis (0/1), acute pancreatitis (1/0), and cardiac failure (0/1). Adverse events in DSC patients and laboratory values are reported in detail in a separate article .…”

Clinical Cellular Therapeutics Accelerate Clot Formation

“…Heparin has been shown as an effective method of preventing the CCT procoagulant effect in in vitro human studies and in vivo animal studies . In an in vivo human study, Baygan et al demonstrated a successful anticoagulation protocol using heparin for the delivery of decidual stromal cells for hemorrhagic cystitis and graft versus host disease after allogenic hematopoietic stem cell transplantation. We demonstrate that simple dilution of CCT treatments will decrease the procoagulant effect regardless of tissue type.…”

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

“…The patients treated with DSCs for HC have a more favorable TRM than those treated conservatively [8]. Regarding toxicity using DSCs, we performed a detailed study including 44 patients treated for acute GVHD or HC and compared them to historical controls [44]. It was a detailed study of safety and side-effects using a novel clinical therapy: DSCs for acute GVHD in 34 patients, and HC in 10 patients.…”