Alloreactivity: the Janus-face of hematopoietic stem cell transplantation
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 incr...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
08 March 2017
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| In: |
Leukemia
Year: 2017, Volume: 31, Issue: 8, Pages: 1752-1759 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2017.79 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/leu.2017.79 Verlag, Volltext: https://www.nature.com/articles/leu201779 
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| Author Notes: | A. Gratwohl, A. Sureda, J. Cornelissen, J. Apperley, P. Dreger, R. Duarte, H. T. Greinix, E. Mc Grath, N. Kroeger, F. Lanza, A. Nagler, J. A. Snowden, D. Niederwieser, R. Brand |
| Summary: | 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’. |
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| Item Description: | Gesehen am 03.05.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/leu.2017.79 |