Multipotent mesenchymal stromal cells as treatment for poor graft function after allogeneic hematopoietic cell transplantation: A multicenter prospective analysis

Abstract

IntroductionPoor graft function (PGF) is a rare but serious complication of allogeneic hematopoietic cell transplantation (alloHCT). Due to their hematopoietic supporting properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help to restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after alloHCT.MethodsWe prospectively assessed the efficacy and safety of ex-vivo expanded BM-derived MSC from third-party donor in a series of 30 patients with prolonged severe cytopenia and PGF after alloHCT. This multicenter trial was registered at www.clinicaltrials.gov (#NTC00603330).ResultsWithin 90 days post-MSC infusion, 53% (95% CI, 35 – 71%) of patients improved at least one cytopenia (overall response, OR) and 37% (95% CI, 19 - 54%) achieved a complete hematological response (CR: absolute neutrophil count, ANC >0.5 x 109/L, Hb > 80g/L and platelet count > 20 x 109/L with transfusion independence). Corresponding response rates increased to 67% (95% CI, 50 - 84%) OR and 53% (95% CI, 35 - 71%) CR within 180 days after MSC infusion. A significant decrease in red blood cells and platelets transfusion requirement was observed after MSC (median of 30-days transfusion requirement of 0.5 and 0 from d90-120 post-MSC versus 5 and 6.5 before MSC, respectively, p ≤0.001). An increase in ANC was also noted by day +90 and +180, with 3/5 patients with severe neutropenia having recovered an ANC > 1 x 109/L within the 90-120 days after MSC infusion. Overall survival at 1 year post-MSC was 70% (95% CI, 55.4 – 88.5), with all but one of the patients who achieved CR being alive. A single infusion of third-party MSC appeared to be safe, with the exception of one deep vein thrombotic event possibly related to the intervention.DiscussionIn conclusion, a single i.v. infusion of BM-derived MSC from third party donor seemed to improve hematological function after alloHCT, although spontaneous amelioration cannot be excluded. Comparative studies are warranted to confirm these encouraging results.

Mesenchymal stromal cells in the treatment of pediatric hematopoietic cell transplantation-related complications (graft vs. host disease, hemorrhagic cystitis, graft failure and poor graft function): a single center experience

“…In a meta-analysis by Li et al ( 18 ), studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone where analyzed (19 clinical trials), showing that MSC co-infusion generally improved engraftment without increasing mortality or relapse. In another study by Servais et al, ( 20 ). MSC were administered as a single i.v.…”

“…Regarding survival analysis, and according to literature, OS rates varies between 50 and 80%, depending on MSCs indication and time-point of analysis, among others ( 18 , 20 , 22 , 46 , 47 ). In our study, OS was 90% at 3 months (95% CI: 79–100) and 79% at one year (95% CI: 65–95).…”

“…For GF, CR was achieved when ANC ≥0.5 × 10 9 /L was recovered. PGF CR was defined as ANC >1 × 10 9 /L, platelet count >30 × 10 9 /L, Hb >10 g/dl ( 20 ). Response in at least 1 hematopoietic cell lineage was considered as PR.…”

Post‐transplant de novo anti‐HLA donor specific antibodies may contribute to poor graft function after haploidentical haematopoietic stem cell transplantation

“…This therapy has been proved safe and efficient, and has been used in desensitisation of DSAs before HSCT 22 . Besides, MSC infusion was used to maintain and regulate the patient's haematopoiesis, which has also been proved beneficial for PGF treatment 23 . Trombopoietin and Eltrombopag were also used to improve platelet count.…”