In vitro and in vivo T-cell depletion with myeloablative or reduced-intensity conditioning in pediatric hematopoietic stem cell transplantation.
OBJECTIVE
Anti-thymocyte globulin (ATG) is given in various conditioning regimens for children and young adults undergoing hematopoietic stem cell transplantation (HSCT) from HLA non-identical donors in order to reduce the risks of graft-versus-host disease (GvHD) and rejection after the transplant. The aim of this study was to define the effect of in vitro T-cell depletion in addition to ATG on the reconstitution of T-cell-mediated immunity.


METHODS
We retrospectively analyzed the engraftment kinetics and clinical performance of 134 patients (median age 5.80 years) who received ATG during myeloablative or reduced intensity conditioning, and either in vitro T-cell-depleted or unmanipulated grafts.


RESULTS
T-cell reconstitution was significantly delayed after T-cell-depleted grafts, irrespectively of the conditioning intensity (p<0.001). The incidence of fatal viral and fungal infections was higher in recipients of T-cell-depleted grafts than in those receiving unmanipulated grafts (26.6-29% versus <or=13%). The rejection rate was likewise higher in recipients of T-cell-depleted grafts whether following myeloablative or reduced intensity conditioning (37% and 18%, associated with recipient chimerism or non-engraftment, respectively) versus <or=4% without graft T-cell depletion. Grades 3 and 4 acute GvHD (CI+/-SE <or=0.11+/-0.03) and severe Epstein-Barr virus lymphoproliferative disease (1.49% fatal) were rare.


CONCLUSIONS
A combination of ex vivo and in vivo T-cell depletion, although inhibiting GvHD, prolongs the interval of T cell deficiency after HSCT and favors rejection and infections, implying that the requirement for this type of extensive T-cell depletion should be carefully re-evaluated.
Seidel
Markus G
MG
St. Anna Children's Hospital and Children's Cancer Research Institute (CCRI) Kinderspitalgasse 6, A-1090 Wien, Austria.
Fritsch
Gerhard
G
Matthes-Martin
Susanne
S
Lawitschka
Anita
A
Lion
Thomas
T
Pötschger
Ulrike
U
Rosenmayr
Agathe
A
Fischer
Gottfried
G
Gadner
Helmut
H
Peters
Christina
C
D000293:Adolescent; D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion; D008297:Male; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D019172:Transplantation Conditioning / Q000009:adverse effects* / Q000379:methods
D000961:Antilymphocyte Serum