Multipotent Mesenchymal Stromal Cells for Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation:a Multicenter Prospective Study
Authors: Servais Sophie , Baron Frédéric , Lechanteur Chantal , Baudoux Etienne , Briquet Alexandra , Selleslag Dominik , Maertens Johan A. , Poire Xavier , Schroyens Wilfried , Graux Carlos , Schots Rik , Zachée Pierre , Ory Aurelie , Herman Julie , Kerre Tessa , Beguin Yves 
Published: February 2020

Poor graft function (PGF) is a rare but serious complication of hematopoietic cell transplantation (HCT). Boost of CD34+stem cells could be a therapeutic option but is not always feasible nor successfull. Due to their hematopoietic support properties and immune regulatory effects, multipotent mesenchymal stromal cells (MSC) could be considered a good candidate to help restore bone marrow (BM) niches homeostasis and facilitate hematopoiesis after HCT. Here, we conducted a multicenter prospective study to evaluate the efficacy of MSC perfusion to improve PGF after HCT.
Thirty patients (median age 51y, range 11 to 70y) received a single IV administration of third-party donor BM-derived MSC (1-2 x 10 exp6/kg body weight) for PGF after allogeneic HCT (median 151 days after HCT, range 62- 430). PGF was defined as (1) at least one cytopenia (Hb &lt; 80 g/L, absolute neutrophil count [ANC] &lt;0.5 x 10exp9/L, platelet count &lt;20 x 10exp9/L) and/or (2) transfusion dependence. Overall, 3 patients were treated for tri-, 17 for bi- (mainly platelets and red blood cells [RBC]) and 10 for mono- (mainly RBC) lineage cytopenia(s). Only 5/30 patients had isolated or combined severe neutropenia. All patients were screened for full-donor chimerism, absence of disease relapse and absence of any other identifiable cause of cytopenia at inclusion.
The primary endpoint was response at day +90 after MSC administration. A significant decrease in RBC and platelet transfusion requirements was observed at day + 90 after MSC (median monthly frequencies of 0 and 0 vs. 5 and 4 before MSC, respectively, p ≤0.001). An increase in ANC was also noted (median 2.500 at day 90 vs. 1.767 x 10exp9/L before MSC, p= 0.04), with 2/5 patients with severe neutropenia having recovered an ANC &gt; 0.5 x 10exp9/L. At day 90 post-MSC, 51.8% (95% CI, 33 - 70.7%) of patients resolved at least one of their cytopenias (overall response, OR) and 40.7% (95% CI, 22.2 - 59.3%) achieved a complete haematological recovery (CR: ANC &gt;0.5 x 10exp9/L and transfusion independence). Corresponding response rates increased at day 180, with 69.2% (95% CI, 51.5 - 86.9%) OR and 61.5% (95% CI, 42.8 - 80.2%) CR, respectively. Overall survival at 1 year post-MSC was 70% (95% CI, 53.6 - 86.3%), with all but one of the d90-responders being alive (1 death to relapse of hematological malignancy). No severe adverse event related to MSC administration was reported during the 1-year follow-up.
In conclusion , perfusion of BM-derived MSC from a third party donor appeared to be safe and to improve PGF after allogeneic HCT, although spontaneous amelioration cannot be excluded. Further (ideally comparative) studies are warranted to confirme our results.

Disclosures
Selleslag: Celyad: Other: Clinical trial research (no honoraria recieved); Novartis: Consultancy, Honoraria, Speakers Bureau.