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2017 ; 5
(2
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
HLA-C KIR-Ligands Determine the Impact of Anti-Thymocyte Globulin (ATG) on Graft
versus Host and Graft versus Leukemia Effects Following Hematopoietic Stem Cell
Transplantation
#MMPMID28536356
Clausen J
; Böhm A
; Straßl I
; Stiefel O
; Buxhofer-Ausch V
; Machherndl-Spandl S
; König J
; Schmidt S
; Steitzer H
; Danzer M
; Kasparu H
; Weltermann A
; Nachbaur D
Biomedicines
2017[Mar]; 5
(2
): ä PMID28536356
show ga
Rabbit anti-thymocyte globulins (ATGs) are widely used for the prevention of
acute and chronic graft versus host disease (aGVHD, cGVHD) following allogeneic
hematopoietic stem cell transplantation (HSCT). However, most prospective and
retrospective studies did not reveal an overall survival (OS) benefit associated
with ATG. Homozygosity for human leukocyte antigen (HLA)-C group 1 killer-cell
immunoglobulin-like receptor ligands (KIR-L), i.e. C1/1 KIR-L status, was
recently shown to be a risk factor for severe aGVHD. Congruously, we have
previously reported favorable outcomes in C1/1 recipients after ATG-based
transplants in a monocentric analysis. Here, within an extended cohort, we test
the hypothesis that incorporation of ATG for GVHD prophylaxis may improve
survival particularly in HSCT recipients with at least one C1 KIR-ligand.
Retrospectively, 775 consecutive allogeneic (excluding haploidentical) HSCTs were
analyzed, including peripheral blood and bone marrow grafts for adults with
hematological diseases at two Austrian HSCT centers. ATG-Fresenius/Grafalon,
Thymoglobuline, and alemtuzumab were applied in 256, 87, and 7 transplants,
respectively (subsequently summarized as "ATG"), while 425 HSCT were performed
without ATG. Median follow-up of surviving patients is 48 months. Adjusted for
age, disease-risk, HLA-match, donor and graft type, sex match, cytomegalovirus
serostatus, conditioning intensity, and type of post-grafting GVHD prophylaxis,
Cox regression analysis of the entire cohort (n = 775) revealed a significant
association of ATG with decreased non-relapse mortality (NRM) (risk ratio (RR),
0.57; p = 0.001), and overall mortality (RR, 0.71; p = 0.014). Upon
stratification for HLA-C KIR-L, the greatest benefit for ATG emerged in C1/1
recipients (n = 291), by reduction of non-relapse (RR, 0.34; p = 0.0002) and
overall mortality (RR, 0.50; p = 0.003). Less pronounced, ATG decreased NRM (RR,
0.60; p = 0.036) in HLA-C group 1/2 recipients (n = 364), without significantly
influencing overall mortality (RR, 0.70; p = 0.065). After exclusion of
higher-dose ATG-based transplants, serotherapy significantly improved both NRM
(RR, 0.54; p = 0.019; n = 322) and overall mortality (RR, 0.60; p = 0.018) in
C1/2 recipients as well. In both, C1/1 (RR, 1.70; p = 0.10) and particularly in
C1/2 recipients (RR, 0.94; p = 0.81), there was no statistically significant
impact of ATG on relapse incidence. By contrast, in C2/2 recipients (n = 121),
ATG neither reduced NRM (RR, 1.10; p = 0.82) nor overall mortality (RR, 1.50; p =
0.17), but increased the risk for relapse (RR, 4.38; p = 0.02). These
retrospective findings suggest ATG may provide a survival benefit in recipients
with at least one C1 group KIR-L, by reducing NRM without significantly
increasing the relapse risk.