Allogeneic mesenchymal stem cell therapy for refractory cytopenias after hematopoietic stem cell transplantation

Abstract

BACKGROUND: Posttransplant cytopenias are a severe complication after allogeneic stem cell transplantation (allo‐SCT) and their origin is often multifactorial or unknown. They are frequently refractory to standard therapy, which may include steroids and/or immunoglobulins. Mesenchymal stem cells (MSCs) are an attractive therapeutic tool in the allo‐SCT setting for the ability to enhance engraftment as well as acting as immunosuppressants for graft‐versus‐host disease. There is no prior experience in the literature of the use of MSCs to treat cytopenias after allo‐SCT. CASE REPORTS: In this work we report for the first time four cases of refractory posttransplant cytopenias (three patients with thrombocytopenia and one with neutropenia) that were treated with MSCs from a third‐party donor. MSCs were expanded from 100 mL of marrow obtained under standard good manufacturing practice conditions. Most patients received more than one cell dose, and median dose of MSCs administered was 1 × 106/kg. RESULTS: All patients recovered normal blood counts, with a mean follow‐up of 12.5 months. There were no adverse events related to MSC administration. CONCLUSION: MSC therapy may contribute to the recovery of refractory posttransplant peripheral cytopenias in patients undergoing allo‐SCT.

In vitro anti‐myeloma activity of TRAIL‐expressing adipose‐derived mesenchymal stem cells

“…In a number of in vivo studies, indeed, either systemically or locally injected allogeneic MSCs were demonstrated to induce neither graft‐versus‐host disease, nor abnormalities in liver and renal functions of treated animals (Liu et al , , ), suggesting that allogeneic transplantations of MSCs are apparently feasible and safe. Safety of similar procedures, moreover, has been also reported in humans (Dandan et al , ; Sánchez‐Guijo et al , ), while several clinical trials using MSCs for cancer therapy are ongoing to definitely validate these observations (http://www.clinicaltrials.gov).…”

Sequential Third-Party Mesenchymal Stromal Cell Therapy for Refractory Acute Graft-versus-Host Disease

“…Infliximab, an anti-TNF alpha molecule, is associated with response rates in the range of 50% to 60% but also with a high mortality rate because of infectious complications [33,34]. It can be hypothesized that 1 of the reasons for the lower rate of infections is the absence of hematological toxicity after MSC therapy, which is also being explored to treat cytopenias after allo-SCT [35]. The ultimate consequence of the low toxicity is that those patients achieving a CR after MSC therapy have a high rate of survival, in our series, as shown in Figure 1.…”

Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials

“…Among completed trials with published reports are two large-scale multicenter Phase 2 studies for treatment of steroid-resistant, severe acute GVHD, both of which showed striking efficacy [56, 57]. Smaller trials on other related complications have also been published: refractory cytopenias [58] and attenuated dry eye in patients with chronic GVHD [59, 60]. Currently, there are 46 registered trials of MSCs for GVHD and related complications.…”