Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning.
Recent studies have suggested that coinfusion of mesenchymal stem cells (MSCs) the day of hematopoietic cell transplantation (HCT) might promote engraftment and prevent graft-versus-host disease (GVHD) after myeloablative allogeneic HCT. This prompted us to investigate in a pilot study whether MSC infusion before HCT could allow nonmyeloablative (NMA) HCT (a transplant strategy based nearly exclusively on graft-versus-tumor effects for tumor eradication) from HLA-mismatched donors to be performed safely. Twenty patients with hematologic malignancies were given MSCs from third party unrelated donors 30-120 minutes before peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors, after conditioning with 2 Gy total body irradiation (TBI) and fludarabine. The primary endpoint was safety, defined as a 100-day incidence of nonrelapse mortality (NRM) <35%. One patient had primary graft rejection, whereas the remaining 19 patients had sustained engraftment. The 100-day cumulative incidence of grade II-IV acute GVHD (aGVHD) was 35%, whereas 65% of the patients experienced moderate/severe chronic GVHD (cGVHD). One-year NRM (10%), relapse (30%), overall survival (OS) (80%) and progression-free survival (PFS) (60%), and 1-year incidence of death from GVHD or infection with GVHD (10%) were encouraging. These figures compare favorably with those observed in a historic group of 16 patients given HLA-mismatched PBSCs (but no MSCs) after NMA conditioning, which had a 1-year incidence of NRM of 37% (P = .02), a 1-year incidence of relapse of 25% (NS), a 1-year OS and PFS of 44% (P = .02), and 38% (P = .1), respectively, and a 1-year rate of death from GVHD or infection with GVHD of 31% (P = .04). In conclusion, our data suggest that HLA-mismatched NMA HCT with MSC coinfusion appeared to be safe.
Baron
Frédéric
F
Department of Medicine, Division of Hematology, CHU of Liège, Liège, Belgium. F.Baron@ulg.ac.be
Lechanteur
Chantal
C
Willems
Evelyne
E
Bruck
France
F
Baudoux
Etienne
E
Seidel
Laurence
L
Vanbellinghen
Jean-François
JF
Hafraoui
Kaoutar
K
Lejeune
Marie
M
Gothot
André
A
Fillet
Georges
G
Beguin
Yves
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006084:Graft Rejection; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000517:prevention & control*; D020350:Graft vs Tumor Effect; D006680:HLA Antigens / Q000276:immunology*; D019337:Hematologic Neoplasms / Q000601:surgery; D006648:Histocompatibility / Q000276:immunology*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D010865:Pilot Projects; D016019:Survival Analysis; D018183:Transplantation Chimera / Q000097:blood; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
D006680:HLA Antigens