Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation

Bochud, Pierre–Yves; Chien, Jason W.; Marr, Kieren A.; Leisenring, Wendy M.; Upton, Arlo; Janer, Marta; Rodrigues, Stéphanie; Li, Sarah; Hansen, John A.; Zhao, Lue Ping; Aderem, Alan; Boeckh, Michael

doi:10.1056/nejmoa0802629

Cited by 408 publications

(303 citation statements)

References 38 publications

(36 reference statements)

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“…32 Furthermore, CMV seropositivity is associated with increased risk of invasive aspergillosis after allo-SCT. 34 It is therefore possible that the lower NRM in CMV double seronegative transplants that we observed in this study is, at least in part, due to a lower rate of fatal infections. As data on CMV reactivation and infectious complications are not regularly reported to the registry, we cannot comment on whether this was relevant in the patients included in this study.…”

Section: Discussionmentioning

confidence: 71%

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

Auner

Szydlo

Biezen

et al. 2013

Bone Marrow Transplant

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Outcomes and prognostic factors of reduced intensity-conditioned allo-SCT (RIC allo-SCT) for multiple myeloma (MM) relapsing or progressing after prior autologous (auto)-SCT are not well defined. We performed an analysis of 413 MM patients who received a related or unrelated RIC allo-SCT for the treatment of relapse/progression after prior auto-SCT. Median age at RIC allo-SCT was 54.1 years, and 44.6% of patients had undergone two or more prior auto-SCTs. Median OS and PFS from the time of RIC allo-SCT for the entire population were 24.7 and 9.6 months, respectively. Cumulative non-relapse mortality (NRM) at 1 year was 21.5%. In multivariate analysis, CMV seronegativity of both patient and donor was associated with significantly better PFS, OS and NRM. Patient-donor gender mismatch was associated with better PFS, fewer than two prior auto-SCT was associated with better OS, and shorter time from the first auto-SCT to the RIC allo-SCT was associated with lower NRM. The results of this study identify patient and donor CMV seronegativity as the key prognostic factor for outcome after RIC allo-SCT for MM relapsing or progressing after prior auto-SCT.

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Section: Discussionmentioning

confidence: 71%

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

Auner

Szydlo

Biezen

et al. 2013

Bone Marrow Transplant

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“…Genetic variation affects susceptibility to fungal infection, 119 metabolism and drug interactions of antifungals and, it is now emerging, the development of resistance to the azoles in Aspergillus fumigatus. 120,121 Unsurprisingly, mutations of fungal CYP51, a prime target of the triazoles, seem to mediate the predominant resistance pathways.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…As scientists unravel the journey of antifungal drugs through the body and the many enzymes and transporters encountered en route, we will benefit from a better understanding of how genetic variation affects pharmacokinetics. An individual will have a unique profile of susceptibility to invasive fungal infection, 119 metabolic handling of and response to antifungal therapy. Meaningful analysis of this genomic profile is a tantalising prospect on the horizon, if not quite within our grasp.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Ashbee

Gilleece

2011

Bone Marrow Transplant

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“…[1][2][3][4] A link between polymorphic features of non-HLA cytokine-encoding genes and the incidence and severity of post transplant complications in allo-SCT recipients has been recognized, implying that donor-recipient genotyping, extended for immune response loci, may be of prognostic value for transplantation outcome. 5 Much effort has been devoted to the understanding of the role of T helper (Th) cell polarization in the manifestation of post transplant complications.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

Carvalho

Cunha

Ianni

et al. 2010

Bone Marrow Transplant

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T helper (Th) 17 cells have emerged as important mediators in infectious and inflammatory diseases and, recently, in transplant rejection. We analyzed the associations between five common genetic variants in the IL-23/ Th17 signaling pathway, namely in IL17A, IL17F and IL23R genes, and clinical outcome in T cell-depleted allogeneic SCT (allo-SCT). In the multivariate analysis, variants in IL23R and IL17A genes were the most important prognostic factors. Thus, patient GA genotype at rs11209026 in IL23R was associated with improved overall survival (hazard ratio (HR) ¼ 0.48; P ¼ 0.028) and, in donor, with decreased risk of fungal infections (P ¼ 0.05). In contrast, patient TC and CC genotypes at rs8193036 in IL17A gene were associated with increased risk of CMV infection (HR ¼ 3.68; P ¼ 0.011) and patient acute GVHD (HR ¼ 7.08; P ¼ 0.008), respectively. These results suggest that genetic variants in the IL-23/Th17 inflammatory pathway are important prognostic factors for the clinical outcome of allo-SCT. Although validation studies are ultimately required, our results would suggest the potential usefulness of IL-23/Th17 genotyping in donor selection and patient evaluation.

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Toll-like Receptor 4 Polymorphisms and Aspergillosis in Stem-Cell Transplantation

Abstract: BACKGROUND-Toll-like receptors (TLRs) are essential components of the immune response to fungal pathogens. We examined the role of TLR polymorphisms in conferring a risk of invasive aspergillosis among recipients of allogeneic hematopoietic-cell transplants.

Cited by 408 publications

References 38 publications

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

Reduced intensity-conditioned allogeneic stem cell transplantation for multiple myeloma relapsing or progressing after autologous transplantation: a study by the European Group for Blood and Marrow Transplantation

Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics

Prognostic significance of genetic variants in the IL-23/Th17 pathway for the outcome of T cell-depleted allogeneic stem cell transplantation

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