Translating in vitro prediction of cytotoxic T cell alloreactivity to hematopoietic stem cell transplantation outcome.
BACKGROUND
Previously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT).


METHODS
We selected patients transplanted with a 9/10 single HLA class I mismatched graft (n=171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor-recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis.


RESULTS
We observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest.


CONCLUSIONS
Further investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.
Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands. Electronic address: joris@europdonor.nl.
M M
MM
Jöris
Department of Pediatrics, LUMC, The Netherlands.
A C
AC
Lankester
Department of Hematology, LUMC, The Netherlands.
P A
PA
von dem Borne
Department of Hematology and Immunology, UMCU, The Netherlands.
J
J
Kuball
Wilhelmina Children's Hospital, UMCU, The Netherlands.
M
M
Bierings
Department of Hematology, Erasmus MC-Daniel den Hoed, The Netherlands.
J J
JJ
Cornelissen
HOVON Data Center, Erasmus MC-Daniel den Hoed, The Netherlands.
M E Groenendijk-
ME
Sijnke
HOVON Data Center, Erasmus MC-Daniel den Hoed, The Netherlands.
B
B
van der Holt
Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands.
J J
JJ
van Rood
Europdonor Foundation, The Netherlands; Department of Immunohematology and Blood transfusion, LUMC, The Netherlands.
M
M
Oudshoorn
Department of Immunohematology and Blood transfusion, LUMC, The Netherlands.
F H J
FH
Claas
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D064591:Allografts; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011237:Predictive Value of Tests; D057170:Translational Research, Biomedical; D061349:Unrelated Donors
D015395:Histocompatibility Antigens Class I
Acute GVHD; Amino acid; CTLp; Hematopoietic stem cell transplantation; Mismatch score