Alloreactivity: the Janus-face of hematopoietic stem cell transplantation
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Alloreactivity: the Janus-face of hematopoietic stem cell transplantation. / Gratwohl, A; Sureda, A; Cornelissen, J; Apperley, J; Dreger, P; Duarte, R; Greinix, H T; Mc Grath, E; Kroeger, N; Lanza, F; Nagler, A; Snowden, J A; Niederwieser, D; Brand, R.
In: LEUKEMIA, Vol. 31, No. 8, 08.2017, p. 1752-1759.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Alloreactivity: the Janus-face of hematopoietic stem cell transplantation
AU - Gratwohl, A
AU - Sureda, A
AU - Cornelissen, J
AU - Apperley, J
AU - Dreger, P
AU - Duarte, R
AU - Greinix, H T
AU - Mc Grath, E
AU - Kroeger, N
AU - Lanza, F
AU - Nagler, A
AU - Snowden, J A
AU - Niederwieser, D
AU - Brand, R
PY - 2017/8
Y1 - 2017/8
N2 - Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.
AB - Differences in major and minor histocompatibility antigens between donor and recipient trigger powerful graft-versus-host reactions after allogeneic hematopoietic stem cell transplantation (HSCT). The clinical effects of alloreactivity present a Janus-face: detrimental graft-versus-host disease increases non-relapse mortality, beneficial graft-versus-malignancy may cure the recipient. The ultimate consequences on long-term outcome remain a matter of debate. We hypothesized that increasing donor-recipient antigen matching would decrease the negative effects, while preserving antitumor alloreactivity. We analyzed retrospectively a predefined cohort of 32 838 such patients and compared it to 59 692 patients with autologous HSCT as reference group. We found a significant and systematic decrease in non-relapse mortality with decreasing phenotypic and genotypic antigen disparity, paralleled by a stepwise increase in overall and relapse-free survival (Spearman correlation coefficients of cumulative excess event rates at 5 years 0.964; P<0.00; respectively 0.976; P<0.00). We observed this systematic stepwise effect in all main disease and disease-stage categories. The results suggest that detrimental effects of alloreactivity are additive with each step of mismatching; the beneficial effects remain preserved. Hence, if there is a choice, the best match should be donor of choice. The data support an intensified search for predictive genomic and environmental factors of 'no-graft-versus-host disease'.
KW - Journal Article
U2 - 10.1038/leu.2017.79
DO - 10.1038/leu.2017.79
M3 - SCORING: Journal article
C2 - 28270691
VL - 31
SP - 1752
EP - 1759
JO - LEUKEMIA
JF - LEUKEMIA
SN - 0887-6924
IS - 8
ER -