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
For adults with acute leukemia, it is important to know whether the therapeutic schemes initially planned were actually implemented. The European Group for Blood and Marrow transplantation Acute Leukemia Working Party prospectively followed 695 consecutive patients who were registered at the time of HLA typing. Of 304 patients with an available matched sibling donor (MSD), SCT was planned in 264, chemotherapy in 33 and autografting in 7. For the rest, an unrelated donor (UD) search was initiated in 198. Among these, 117 were transplanted, 114 received chemotherapy and 77 underwent autografting. Probabilities of receiving a planned treatment were 60 and 65% at 1 and 2 years, respectively. Patients scheduled to receive MSD SCT had an 82% probability, whereas those scheduled to undergo UD SCT had a 57% probability, of receiving their transplant at 1 year. The only factor associated with a lower probability of MSD SCT in first remission was delayed HLA typing (HR=0.82; P=0.03). One year after enrollment, 40% of patients did not follow their initial treatment plan. Because OS was 50% only at 3 years and only 57% of the patients without a MSD underwent SCT, this suggests room for improvement in outcomes for adults with acute leukemia.
- MeSH
- akutní lymfatická leukemie terapie MeSH
- akutní myeloidní leukemie terapie MeSH
- dospělí MeSH
- HLA antigeny chemie MeSH
- indukce remise MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- pravděpodobnost MeSH
- přežití po terapii bez příznaků nemoci MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- registrace MeSH
- senioři MeSH
- sourozenci MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
The impact of in vivo T-cell depletion on transplantation outcomes in patients transplanted with reduced-intensity conditioning (RIC) remains controversial. This study assessed the outcome of 1250 adult patients with de novo AML in first CR (CR1) given PBSC from HLA-identical siblings after chemotherapy-based RIC. A total of 554 patients did not receive any form of in vivo T-cell depletion (control group), whereas antithymocyte globulin (ATG) and alemtuzumab were given in 444 and 252 patients, respectively. The incidences of grade II-IV acute GVHD were 21.4, 17.6 and 10.2% in control, ATG and alemtuzumab patients, respectively (P<0.001). In multivariate analysis, the use of ATG and the use of alemtuzumab were each associated with a lower risk of chronic GVHD (P<0.001 each), but a similar risk of relapse, and of nonrelapse mortality, and similar leukemia-free survival and OS. Further, among patients given BU-based RIC, the use of <6 mg/kg ATG did not increase the risk of relapse (hazard ratio, HR=1.1), whereas there was a suggestion for higher relapse risk in patients given 6 mg/kg ATG (HR=1.4, P=0.08). In summary, these data suggest that a certain amount of in vivo T-cell depletion can be safely used in the conditioning of AML patients in CR1 given PBSC after chemotherapy-based RIC.
- MeSH
- akutní myeloidní leukemie krev terapie MeSH
- antilymfocytární sérum metabolismus MeSH
- dárci tkání MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- homologní transplantace MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- incidence MeSH
- indukce remise MeSH
- kmenové buňky cytologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- melfalan terapeutické užití MeSH
- mladý dospělý MeSH
- multivariační analýza MeSH
- nemoc štěpu proti hostiteli MeSH
- přežití po terapii bez příznaků nemoci MeSH
- příprava pacienta k transplantaci metody MeSH
- proporcionální rizikové modely MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- senioři MeSH
- sourozenci MeSH
- T-lymfocyty cytologie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
