During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.353.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
- MeSH
- dospělí MeSH
- genomika MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- homologní transplantace škodlivé účinky MeSH
- leukemie genetika imunologie patologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoc štěpu proti hostiteli imunologie MeSH
- prognóza MeSH
- proteiny tepelného šoku HSP70 genetika MeSH
- rizikové faktory MeSH
- testování histokompatibility MeSH
- transplantace hematopoetických kmenových buněk škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- proteiny tepelného šoku HSP70 MeSH
Previous studies of non-histocompatibility leukocyte antigen (HLA) gene single-nucleotide polymorphisms (SNPs) on subgroups of patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT) revealed an association with transplant outcome. This study further evaluated the association of non-HLA polymorphisms with overall survival in a cohort of 762 HSCT patients using data on 26 polymorphisms in 16 non-HLA genes. When viewed in addition to an already established clinical risk score (EBMT-score), three polymorphisms: rs8177374 in the gene for MyD88-adapter-like (MAL; P=0.026), rs9340799 in the oestrogen receptor gene (ESR; P=0.003) and rs1800795 in interleukin-6 (IL-6; P=0.007) were found to be associated with reduced overall survival, whereas the haplo-genotype (ACC/ACC) in IL-10 was protective (P=0.02). The addition of these non-HLA polymorphisms in a Cox regression model alongside the EBMT-score improved discrimination between risk groups and increased the level of prediction compared with the EBMT-score alone (gain in prediction capability for EBMT-genetic-score 10.8%). Results also demonstrated how changes in clinical practice through time have altered the effects of non-HLA analysis. The study illustrates the significance of non-HLA genotyping prior to HSCT and the importance of further investigation into non-HLA gene polymorphisms in risk prediction.
- MeSH
- alfa receptor estrogenů genetika MeSH
- alografty MeSH
- dítě MeSH
- dospělí MeSH
- genotyp MeSH
- haplotypy MeSH
- hematologické nádory mortalita terapie MeSH
- histokompatibilita MeSH
- hodnocení rizik metody MeSH
- infekce mortalita MeSH
- interleukin-10 genetika MeSH
- interleukin-6 genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- Kaplanův-Meierův odhad MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny genetika MeSH
- mladiství MeSH
- multiorgánové selhání mortalita MeSH
- následné studie MeSH
- nemoc štěpu proti hostiteli mortalita MeSH
- příčina smrti MeSH
- příprava pacienta k transplantaci škodlivé účinky MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- receptory interleukinu-1 genetika MeSH
- senioři MeSH
- transplantace hematopoetických kmenových buněk mortalita MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa receptor estrogenů MeSH
- ESR1 protein, human MeSH Prohlížeč
- IL10 protein, human MeSH Prohlížeč
- IL6 protein, human MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-6 MeSH
- membránové glykoproteiny MeSH
- receptory interleukinu-1 MeSH
- TIRAP protein, human MeSH Prohlížeč
