Oncotarget

Research Papers:

Infusion of bone marrow derived multipotent mesenchymal stromal cells for the treatment of steroid-refractory acute graft-versus-host disease: a multicenter prospective study

Sophie Servais _, Frédéric Baron, Chantal Lechanteur, Laurence Seidel, Dominik Selleslag, Johan Maertens, Etienne Baudoux, Pierre Zachee, Michel Van Gelder, Lucien Noens, Tessa Kerre, Philippe Lewalle, Wilfried Schroyens, Aurélie Ory and Yves Beguin

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Oncotarget. 2018; 9:20590-20604. https://doi.org/10.18632/oncotarget.25020

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Abstract

Sophie Servais1,2, Frédéric Baron1,2, Chantal Lechanteur1,2, Laurence Seidel3, Dominik Selleslag4, Johan Maertens5, Etienne Baudoux1,2, Pierre Zachee6, Michel Van Gelder7, Lucien Noens8, Tessa Kerre8, Philippe Lewalle9, Wilfried Schroyens10, Aurélie Ory11 and Yves Beguin1,2

1Department of Hematology, CHU of Liège, 4000 Liège, Belgium

2Laboratory of Cell and Gene Therapy, CHU of Liège, 4000 Liège, Belgium;

3Department of biostatistics, SIMÉ, CHU of Liège, 4000 Liège, Belgium

4Department of Hematology, AZ Sint-Jan, 8000 Brugge, Belgium

5Department of Hematology, AZ Gasthuisberg, 3000 Leuven, Belgium

6Department of Hematology, ZNA Stuivenberg, 2060 Antwerp, Belgium

7Department of Internal Medicine, Hematology Division, Maastricht University Medical Center, 6202 AZ Maastricht, The Nertherlands

8Department of Hematology, UZ Gent, 9000 Ghent, Belgium

9Department of Hematology, Institut Jules-Bordet, 1000 Brussels, Belgium

10Department of Hematology, Antwerp University Hospital, 2650 Edegem and University of Antwerp, 2610 Antwerp, Belgium

11Clinical Research Associate of the Belgian Hematology Society, CHU Sart-Tilman, 4000 Liège, Belgium

Correspondence to:

Sophie Servais, email: s.servais@chu.ulg.ac.be

Keywords: allogeneic hematopoietic cell transplantation; corticosteroid-refractory acute graft-versus-host disease; multipotent mesenchymal stromal cells

Received: November 13, 2017     Accepted: March 17, 2018     Published: April 17, 2018

ABSTRACT

The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) remains poor and better treatments are urgently needed. Multipotent mesenchymal stromal cell (MSC)-based therapy emerged as a promising approach but response rates were highly variable across studies. We conducted a multicenter prospective study assessing the efficacy of 1–2 infusion(s) of cryopreserved, third-party donor bone marrow-derived MSCs for treating grade II-IV steroid-refractory or -dependent aGVHD in a series of 33 patients. MSCs were produced centrally and distributed to 8 hospitals throughout Belgium to be infused in 2 consecutive cohorts of patients receiving 1–2 or 3–4 × 106 MSCs/kg per dose, respectively. All patients received MSCs as the first rescue therapy after corticosteroids, with the exception for one patient who received prior treatment with mycophenolate mofetil (that was still ongoing by the time of MSC therapy). In these conditions, MSC therapy resulted in at least a partial response in 13 patients (40.6%) at day 30 and in 15 patients (46%) within 90 days after first MSC infusion. The corresponding complete response rates were 21.6% (7 patients) and 30% (10 patients), respectively. Only 5 patients achieved a sustained complete response, lasting for at least 1 month. The 1-year overall survival was 18.2% (95% CI: 8.82–37.5%). Higher response and survival rates were observed among patients receiving 3–4 × 106 MSCs/kg for first infusion, as compared with patients receiving 1–2 × 106 MSCs/ kg. Response and survival with MSC therapy for SR/SD-aGVHD remains to be optimized.


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