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Impact of genomic risk factors on survival after haematopoietic stem cell transplantation for patients with acute leukaemia
- Source :
- International journal of immunogenetics. 43(6)
- Publication Year :
- 2016
-
Abstract
- Summary The EBMT risk score is an established tool successfully used in the prognosis of survival post-HSCT and is applicable for a range of haematological disorders. One of its main advantages is that score generation involves summation of clinical parameters that are available pretransplant. However, the EBMT risk score is recognized as not being optimal. Previous analyses, involving patients with various diagnoses, have shown that non-HLA gene polymorphisms influence outcome after allogeneic HSCT. This study is novel as it focuses only on patients having acute leukaemia (N = 458) and attempts to demonstrate how non-HLA gene polymorphisms can be added to the EBMT risk score in a Cox regression model to improve prognostic ability for overall survival. The results of the study found that three genetic factors improved EBMT risk score. The presence of MAL (rs8177374) allele T in the patient, absence of glucocorticoid receptor haplotype (consisting of rs6198, rs33389 and rs33388) ACT in the patient and absence of heat-shock protein 70-hom (+2437) (rs2227956) allele C in the patient were associated with decreased survival time. When compared to the EBMT risk score, the scores combining EBMT risk score with the genetic factors had an improved correlation with clinical outcome and better separation of risk groups. A bootstrapping technique, involving repeated testing of a model using multiple validation sets, also revealed that the newly proposed model had improved predictive value when compared to the EBMT risk score alone. Results support the view that non-HLA polymorphisms could be useful for pretransplant clinical assessment and provide evidence that polymorphisms in the recipient genotype may influence incoming donor cells, suppressing the initiation of the graft versus leukaemia effect and reducing survival.
- Subjects :
- 0301 basic medicine
Oncology
Gerontology
Adult
Male
medicine.medical_specialty
Genotype
Immunology
Separation (statistics)
Graft vs Host Disease
03 medical and health sciences
0302 clinical medicine
Risk Factors
Internal medicine
Genetics
medicine
Humans
Transplantation, Homologous
HSP70 Heat-Shock Proteins
Allele
Molecular Biology
Genetics (clinical)
Framingham Risk Score
Leukemia
Proportional hazards model
business.industry
Histocompatibility Testing
Haplotype
Hematopoietic Stem Cell Transplantation
General Medicine
Genomics
Middle Aged
Prognosis
3. Good health
Transplantation
Haematopoiesis
030104 developmental biology
Haplotypes
Female
business
030215 immunology
Subjects
Details
- ISSN :
- 1744313X
- Volume :
- 43
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- International journal of immunogenetics
- Accession number :
- edsair.doi.dedup.....c37ec37c287607f54429e86817a98e24