Alloreactivity: the Janus-face of hematopoietic stem cell transplantation.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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'.
Date Issued
2017-04-07
Date Acceptance
2017-02-22
Citation
Leukemia, 2017, 31, pp.1752-1759
ISSN
0887-6924
Publisher
Nature Publishing Group
Start Page
1752
End Page
1759
Journal / Book Title
Leukemia
Volume
31
Copyright Statement
© 2017 The Author(s). This work is licensed under a Creative Commons AttributionNonCommercial-NoDerivs
4.0 International License. The images or
other third party material in this article are included in the article’s Creative Commons
license, unless indicated otherwise in the credit line; if the material is not included under
the Creative Commons license, users will need to obtain permission from the license
holder to reproduce the material. To view a copy of this license, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/
4.0 International License. The images or
other third party material in this article are included in the article’s Creative Commons
license, unless indicated otherwise in the credit line; if the material is not included under
the Creative Commons license, users will need to obtain permission from the license
holder to reproduce the material. To view a copy of this license, visit http://
creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
National Institute for Health Research
Identifier
PII: leu201779
Grant Number
NF-SI-0611-10275
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Hematology
VERSUS-HOST-DISEASE
BONE-MARROW-TRANSPLANTATION
ALTERNATIVE DONORS
BLOOD
MORTALITY
HUMANS
EUROPE
SCT
AML
1103 Clinical Sciences
1112 Oncology And Carcinogenesis
Immunology
Publication Status
Published