The present project aims at evaluating the capacity of MSC to improve one-year overall survival of patients transplanted with HLA-mismatched PBSC from related or unrelated donors after non-myeloablative conditioning. Co-infusion of MSC has been shown to facilitate engraftment of hematopoietic stem cell (HSC) in an immunodeficient mouse model. In addition, it has been shown that infusion of third party MSC in HSC transplantation could be successfully used as treatment for grade II-IV steroid-refractory acute graft versus host disease. One hundred and twenty patients with HLA-mismatched donors will be included over 6 years at multiple centers across Belgium through the transplant committee of the Belgian Hematological Society. The conditioning regimen will consist of fludarabine and 2 Gy TBI, followed by the infusion of donor HSC. Patients will be randomized 1/1 in double-blind fashion to receive or not MSC (1.5-.3.0 x106/kg) from third-party (either haploidentical family members or unrelated volunteer) donors on day 0. Postgrafting immunosuppression will combine tacrolimus and MMF. Except for the collection, expansion and infusion of MSC, the clinical management of the patient will not differ from that of routine NM-HCT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
39
Mesenchymal stem cell injection
Isotonic solution injection
UZA
Edegem, Antwerpen, Belgium
St-Luc UCL
Brussels, Brabant, Belgium
AZ Gasthuisberg Leuven
Leuven, Flamish Brabant, Belgium
UZ Gent
Ghent, Flanders Ost, Belgium
AZ St-Jan
Bruges, Flanders West, Belgium
Cliniques Universitaires Mont-Godinne
Yvoir, Namur, Belgium
Hôpital Stuyvenberg
Antwerp, Belgium
Bordet Institute
Brussels, Belgium
Vrije Universiteit Brussel
Brussels, Belgium
CHU-ULg
Liège, Belgium
One-year overall survival in the 2 arms.
Time frame: One year
Incidence of grade II-IV and grade III-IV acute GVDH
Time frame: 100 days
Number of absolute donor T cells after HCT in each arm
Time frame: 28
Cumulative incidence of non-relapse mortality
Time frame: 100, 365 and 730 days
Incidence of extensive chronic GVHD in each arm
Time frame: 365 days
Incidence of graft rejection in each arm.
Time frame: 365 days
Quality and timing of immunologic reconstitution in each arm.
Time frame: 100, 365 and 730 days
Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC
Time frame: 40 days
Proportion of patients with measurable disease at HCT who achieve a complete response in each arm.
Time frame: 100, 365 and 730 days
Cumulative incidence of relapse
Time frame: 365 and 730 days
Incidence of progression-free survival
Time frame: 365 and 730 days
Incidence of infections
Time frame: 100 days
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