Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells Expanded In Vitro for Treatment of Aplastic Anemia: A Multicenter Phase II Trial

Abstract

We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy‐four patients from seven centers received allogeneic BM‐MSCs at a dose of 1–2 × 106 cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions. All patients were evaluable. The overall response rate was 28.4% (95% confidence interval, 19%–40%), with 6.8% complete response and 21.6% partial response. The median times to response of leukocytic, erythrocytic, and megakaryocytic linages were 19 (range, 11–29), 17 (range, 12–25), and 31 (range, 26–84) days, respectively. After median follow‐up of 17 months, overall survival was 87.8%. Seven patients developed transitory and mild headache and fever, but no other adverse events were observed. Antithymocyte globulin used in previous treatment and no activated infection throughout treatment were predictors for response. Allogeneic BM‐MSCs infusion is a feasible and effective treatment option for refractory AA. The trial was registered at www.clinicaltrials.gov as NCT00195624. Stem Cells Translational Medicine 2017;6:1569–1575

Mesenchymal Stem Cell Benefits Observed in Bone Marrow Failure and Acquired Aplastic Anemia

“…Allogeneic transplant of MSCs can be a potential supplementary alternative to treat refractory SAA, since these cells are hypoimmunogenic, thus displaying low expression levels of human leukocyte antigen (HLA) class I, no expression of HLA class II [ 18 ]. Potentially, these cells may also be an addition to IS therapies because they possess broad immunomodulatory properties, secreting several biological molecules that influence both adaptive and innate immune responses [ 19 ].…”

Increased apoptosis and peripheral blood mononuclear cell suppression of bone marrow mesenchymal stem cells in severe aplastic anemia

“…In view of the association of SAA with immune‐mediated HSC destruction and BM microenvironmental insufficiency, MSCs offer new approaches for the treatment of this disorder. MSC infusions were applied as monotherapy in patients with refractory SAA and produced modest responses with complete or partial response rates ranging from 22% to 33% . By contrast, additive MSC infusions with HSCs were promising with better and faster engraftment in most patients receiving HSC transplantation .…”

Alternative Immune-Mediated-Based Methods in the Aplastic Anemia Treatment

“…The study development by Pang et al showed, six of 18 patients (33.3%) achieved a complete response or a partial response to MSCs treatment [107]. In six patients, two achieved a complete response including recovery of three hematopoietic cell lines after MSCs therapy.…”

“…One patient with RAEB-II died of disease progression, two patients died of intracranial hemorrhages, and six patients died of serious infection [107]. In other two studies were reported adverse events such as, fever, hypoxemia, mild dyspnea and diarrhea during MSCs administration or some hours after MSCs injection, this phenomenon occurs in 2 of 16 patients [107] and 7 of the 18 patients [108]. None major adverse effects were reported in all studies during months of follow-up of each respective study.…”