Results of a pilot study on the use of third-party donor mesenchymal stromal cells in cord blood transplantation in adults.
OBJECTIVE
Cord blood (CB) transplants with co-infusion of third-party donor (TPD) mobilized hematopoietic stem cells (MHSC) have been shown to result in 'bridge' engraftment with prompt neutrophil recovery and high final rates of CB engraftment and full chimerism. This strategy overcomes the limitation posed by low cellularity of CB units for unrelated transplants in adults. Enhancement of adaptive immunity reconstitution without increasing risks of graft-versus-host disease (GvHD) is required to optimize results further. Our objectives were to evaluate co-infusion of mesenchymal stromal cells (MSC) from the same TPD regarding tolerance, CB engraftment and effects on acute (a)GvHD, both preventive and therapeutic.


METHODS
Ex vivo-expanded bone marrow MSC were infused at the time of the transplant or the in case of refractory aGvHD.


RESULTS
Nine patients received 1.04 - 2.15 x 10(6)/kg (median 1.20) MSC immediately after CB and TPD MHSC. Neither immediate adverse side-effects nor significant differences regarding CB engraftment or aGvHD development were observed. Four patients developed grade II aGvHD, refractory to steroids in two. These reached complete remission after therapeutic infusions of MSC.


CONCLUSIONS
In recipients of 'dual CB/TPD MHSC transplants', MSC infusions were therapeutically effective for severe aGvHD but no significant differences in CB engraftment and incidence of severe aGvHD were observed following their prophylactic use. Although results of this study alone cannot conclusively determine the application of MSC in CB transplantation, we believe that, in this setting, the best use of MSC could be as pre-emptive treatment for aGvHD.
Gonzalo-Daganzo
Rosa
R
Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Madrid, Spain.
Regidor
Carmen
C
Martín-Donaire
Trinidad
T
Rico
Miguel Angel
MA
Bautista
Guiomar
G
Krsnik
Isabel
I
Forés
Rafael
R
Ojeda
Emilio
E
Sanjuán
Isabel
I
García-Marco
Jose A
JA
Navarro
Belen
B
Gil
Santiago
S
Sánchez
Rocio
R
Panadero
Nuria
N
Gutiérrez
Yolanda
Y
García-Berciano
Miguel
M
Pérez
Nuria
N
Millán
Isabel
I
Cabrera
Rafael
R
Fernández
Manuel N
MN
D000208:Acute Disease; D000328:Adult; D001853:Bone Marrow / Q000378:metabolism; D002452:Cell Count; D046528:Chimerism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D010865:Pilot Projects; D012074:Remission Induction; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D014019:Tissue Donors; D014184:Transplantation, Homologous