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  • br Results br Discussion This study assesses impacts

    2019-08-12


    Results
    Discussion This study assesses impacts of HLA-DPB1 and CMV reactivation on GVHD, relapse, and OS after allo-HSCT. Here we demonstrate that HLA-DPB1 and CMV reactivation both increase aGVHD risk independently. Consistent with reported data, we show that HLA-DPB1 mismatching is associated with increased risk of aGVHD and lower relapse resulting in no effects on OS. In contrast to recently published data [12,13], our study showed that CMV reactivation has no impact on relapse or OS after allo-HSCT. Stevanovi´c et al. had suggested that CMV reactivation induces HLA-DPB1 expression in GVHD targets as a result of inflammatory conditions created by immune response to CMV [4,6]. Our data suggest that increased risk of aGVHD in HLA-DPB1 mismatched allo-HCT cohorts is independent of CMV serostatus or CMV reactivation. One explanation for this discrepancy is that CMV infection is not the only factor that can provide an inflammatory milieu after allo-HCT. Inflammation post allo-HCT can be created by myeloablative conditioning, sepsis, and many types of viral infections [14]. It is well known that HLA-DPB1 mismatching is one but by far not the only potential target of alloreactivity causing GVHD. It is thus likely that up-regulation of these targets themselves, and/or of the relevant HLA restriction elements presenting them, could be at the basis of increased GVHD risk in the HLA-DPB1 matched setting. Additionally, Petersdorf et al recently reported that rs9277534G and rs9277534A Metoprolol Succinate are associated with high and low expression of HLA-DPB1 respectively [15]. One limitation of our study is that we did not assess the frequency of these alleles nor evaluate permissive versus non permissive status of HLA-DPB1 mismatching. The clinical association between HLA-DPB1 mismatches and transplant outcomes has been shown to be different in the T cell epitope group permissive vs non-permissive setting [[16], [17], [18], [19]]. Another limitation of our study is that we included both matched related and unrelated allo-allo-HCTs. There are significant immunogenetic differences other than HLA-DPB1 matching status between a genotypically HLA-identical sibling transplant and a phenotypically HLA-identical matched unrelated donor transplant. In our study, matched related donor allo-HCT comprised 79% and 4% of HLA-DPB1 matched and HLA-DPB1 mismatched groups. In the other word majority of HLA-DPB1 matched group were matched related allo-HCTs while majority of HLA-DPB1 mismatched groups were matched unrelated allo-HCTs. These two measures were highly correlated (Pearson correlation = 0.7), and as such, were not included together in the multivariable analysis. Surprisingly in our study patients with HLA-DP mismatch group had lower risk of chronic GVHD (Table 2). To our knowledge this has not been reported in previous studies [1,2,20]. There has been a notion of “CMV vs. leukemia effect” since the 1980s and recent studies by Elmaagacli et al and Green et al suggested a beneficial effect of CMV reactivation on leukemia relapse in patients with AML [12,13]. In our study, CMV reactivation had no effect on relapse after allo-HSCT. This is consistent with a recent CIBMTR study by Teira et al showing no CMV versus leukemia effect in a large multi-institutional study [21]. We assessed CMV reactivation by CMV pp65 antigen assay that is less sensitive and reproducible than CMV PCR assay [22] and may have resulted in underestimation of CMV reactivation in this study. CMV disease was rare in our study (3%) that is similar to other studies reporting CMV disease in patients receiving preemptive CMV treatment [23].
    Conflict of interest
    Authorship
    Acknowledgements A.G. was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2 TR002346 (principle investigator: Victoria J. Fraser).
    Introduction The clandestine manufacture of the illicit drug methamphetamine inadvertently leads to the chemical contamination of the “laboratory”, which in many cases can be a home or private dwelling. This is a growing concern in many countries around the world, and especially so in New Zealand, where the drug is popular [2], [3]. While the exact consequences of second- and third-hand methamphetamine exposure are not yet known, anecdotal accounts of ill-health have raised valid concerns for the safety of the inhabitants of these houses, especially infants, young children, pregnant women and the elderly [4], [5], [6]. Wipe sampling of surfaces within these sites, and subsequent analysis by gas or liquid chromatography-mass spectrometry, is the standard method for detection and quantitation of methamphetamine in former clan labs [7], [8]. However, the synthetic processes reportedly result in the release of airborne (particulate or vapour-phase) methamphetamine in the concentration range of 0.1–5000 μg m−3 [9], [10]. Additionally, smoking methamphetamine also results in indoor contamination [11]. A sensitive method to detect and quantitate airborne methamphetamine is necessary as a supplementary technique to wipe sampling analysis, to provide more comprehensive information regarding the extent of contamination.