Rapid natural killer cell recovery determines outcome after T-cell-depleted HLA-identical stem cell transplantation in patients with myeloid leukemias but not with acute lymphoblastic leukemia.
Natural killer (NK) cells are the first lymphocytes to recover after allogeneic stem cell transplantation (SCT) and can exert powerful graft-versus-leukemia (GVL) effects determining transplant outcome. Conditions governing NK cell alloreactivity and the role of NK recovery in sibling SCT are not well defined. NK cells on day 30 post-transplant (NK30) were measured in 54 SCT recipients with leukemia and donor and recipient killer immunoglobulin-like receptor (KIR) genotype determined. In univariate analysis, donor KIR genes 2DL5A, 2DS1, 3DS1 (positive in 46%) and higher numbers of inhibitory donor KIR correlated with higher NK30 counts and were associated with improved transplant outcome. NK30 counts also correlated directly with the transplant CD34 cell dose and inversely with the CD3+ cell dose. In multivariate analysis, the NK30 emerged as the single independent determinant of transplant outcome. Patients with NK30 >150/microl had less relapse (HR 18.3, P=0.039), acute graft-versus-host disease (HR 3.2, P=0.03), non-relapse mortality (HR 10.7, P=0.028) and improved survival (HR 11.4, P=0.03). Results suggest that T cell-depleted SCT might be improved and the GVL effect enhanced by selecting donors with favorable KIR genotype, and by optimizing CD34 and CD3 doses.
Stem Cell Transplantation Section, Hematology Branch, National Institutes of Health, Bethesda, MD 20892-1202, USA.
B N
BN
Savani
S
S
Mielke
S
S
Adams
M
M
Uribe
K
K
Rezvani
A S M
AS
Yong
J
J
Zeilah
R
R
Kurlander
R
R
Srinivasan
R
R
Childs
N
N
Hensel
A J
AJ
Barrett
D000293:Adolescent; D000328:Adult; D018952:Antigens, CD34 / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D002648:Child; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D020544:Graft vs Leukemia Effect; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology* / Q000378:metabolism; D007951:Leukemia, Myeloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods*; D013601:T-Lymphocytes / Q000378:metabolism*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D017252:CD3 Complex; D006680:HLA Antigens; C490245:GEM protein, human; D020559:Monomeric GTP-Binding Proteins