TY - JOUR A1 - Neuchel, Christine A1 - Fürst, Daniel A1 - Niederwieser, Dietger A1 - Bunjes, Donald A1 - Tsamadou, Chrysanthi A1 - Wulf, Gerald A1 - Pfreundschuh, Michael A1 - Wagner, Eva A1 - Stuhler, Gernot A1 - Einsele, Hermann A1 - Schrezenmeier, Hubert A1 - Mytilineos, Joannis T1 - Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - a retrospective study JF - PLOS One N2 - Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome. Our study, based on a cohort of 200 C1-negative patients, confirmed these findings for the endpoints: overall survival (OS: HR = 1.41, CI = 1.14–1.74, p = 0.0012), disease free survival (DFS: HR = 1.27, CI = 1.05–1.53, p = 0.015), treatment related mortality (TRM: HR = 1.41, CI = 1.01–1.96, p = 0.04), and relapse incidence (RI: HR = 1.33, CI = 1.01–1.75, p = 0.04) all being inferior when compared to C1-positive patients (n = 1246). Subsequent analysis showed that these findings applied for patients with myeloid malignancies but not for patients with lymphoproliferative diseases (OS: myeloid: HR = 1.51, CI = 1.15–1.99, p = 0.003; lymphoblastic: HR = 1.26, CI = 0.91–1.75, p = 0.16; DFS: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21; RI: myeloid: HR = 1.31, CI = 1.01–1.70, p = 0.04; lymphoblastic: HR = 1.21, CI = 0.90–1.61, p = 0.21). Interestingly, within the C1-negative patient group, transplantation with KIR2DS2 resulted in better OS (9/10 matched: HR = 0.24, CI = 0.08–0.67, p = 0.007) as well as DFS (9/10 matched: HR = 0,26, CI = 0.11–0.60, p = 0.002), and transplantation with KIR2DS1 positive donors was associated with a decreased RI (HR = 0.30, CI = 0.13–0.69, p = 0.005). TRM was increased when the donor was positive for KIR2DS1 (HR = 2.61, CI = 1.26–5.41, p = 0.001). Our findings suggest that inclusion of KIR2DS1/2/5 and KIR3DS1-genotyping in the unrelated donor search algorithm of C1-ligand negative patients with myeloid malignancies may prove to be of clinical relevance. KW - Hematopoietic stem cell transplantation KW - Cancer risk factors KW - Multivariate analysis KW - Stem cell transplantation KW - T-cells KW - Bone marrow transplantation KW - NK-cells KW - Immune receptor signaling KW - Killer cell immunoglobulin-like receptors KW - Acute myeloid leukemia KW - Acute lymphoblastic leukemia KW - Chronic lymphoblastic leukemia KW - Chronic myeloid leukemia Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180995 VL - 12 IS - 1 ER - TY - JOUR A1 - Tsamadou, Chrysanthi A1 - Fürst, Daniel A1 - Vucinic, Vladan A1 - Bunjes, Donald A1 - Neuchel, Christine A1 - Mytilineos, Daphne A1 - Gramatzki, Martin A1 - Arnold, Renate A1 - Wagner, Eva Maria A1 - Einsele, Hermann A1 - Müller, Carlheinz A1 - Schrezenmeier, Hubert A1 - Mytilineos, Joannis T1 - Human leukocyte antigen-E mismatch is associated with better hematopoietic stem cell transplantation outcome in acute leukemia patients JF - Haematologica N2 - The immunomodulatory role of human leukocyte antigen (HLA)-E in hematopoietic stem cell transplantation (HSCT) has not been extensively investigated. To this end, we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as a natural killer (NK)-alloreactivity mediator on HSCT outcome in an acute leukemia (AL) setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both univariate (53% vs. 38%, P=0.002, 5-year OS) and multivariate (hazard ratio (HR)=0.63, confidence interval (CI) 95%=0.48–0.83, P=0.001) analyses. Further subgroup analysis demonstrated that the positive effect of HLA-E mismatch was significant and pronounced in advanced disease patients (n=120) (5-year OS: 50% vs. 18%, P=0.005; HR=0.40, CI 95%=0.22–0.72, P=0.002; results from univariate and multivariate analyses, respectively). The study herein is the first to report an association between HLA-E incompatibility and improved post–transplant prognosis in AL patients who have undergone matched unrelated HSCT. Combined NK and T cell HLA-E-mediated mechanisms may account for the better outcomes observed. Notwithstanding the necessity for in vitro and confirmational studies, our findings highlight the clinical relevance of HLA-E matching and strongly support prospective HLA-E screening upon donor selection for matched AL unrelated HSCTs. KW - medicine KW - acute leukemia (AL) KW - hematopoietic stem cell transplantation (HSCT) KW - human leukocyte antigen-E (HLA-E) KW - HLA-E matching KW - HSTC outcome Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173325 VL - 102 IS - 11 ER - TY - JOUR A1 - Kleemann, Janina A1 - Zamora, Camilo A1 - Villacis-Chiluisa, Alexandra Belen A1 - Cuenca, Pablo A1 - Koo, Hongmi A1 - Noh, Jin Kyoung A1 - Fürst, Christine A1 - Thiel, Michael T1 - Deforestation in continental Ecuador with a focus on protected areas JF - Land N2 - Forest conservation is of particular concern in tropical regions where a large refuge of biodiversity is still existing. These areas are threatened by deforestation, forest degradation and fragmentation. Especially, pressures of anthropogenic activities adjacent to these areas significantly influence conservation effectiveness. Ecuador was chosen as study area since it is a globally relevant center of forest ecosystems and biodiversity. We identified hotspots of deforestation on the national level of continental Ecuador between 1990 and 2018, analyzed the most significant drivers of deforestation on national and biome level (the Coast, the Andes, The Amazon) as well as inside protected areas in Ecuador by using multiple regression analysis. We separated the national system of protected areas (SNAP) into higher and lower protection levels. Besides SNAP, we also considered Biosphere Reserves (BRs) and Ramsar sites. In addition, we investigated the rates and spatial patterns of deforestation in protected areas and buffer zones (5 km and 10 km outwards the protected area boundaries) using landscape metrics. Between 1990 and 2018, approximately 4% of the accumulated deforestation occurred within the boundaries of SNAP, and up to 25.5% in buffer zones. The highest rates of deforestation have been found in the 5 km buffer zone around the protected areas with the highest protection level. Protected areas and their buffer zones with higher protection status were identified as the most deforested areas among SNAP. BRs had the highest deforestation rates among all protected areas but most of these areas just became BRs after the year 2000. The most important driver of deforestation is agriculture. Other relevant drivers differ between the biomes. The results suggest that the SNAP is generally effective to prevent deforestation within their protection boundaries. However, deforestation around protected areas can undermine conservation strategies to sustain biodiversity. Actions to address such dynamics and patterns of deforestation and forest fragmentation, and developing conservation strategies of their landscape context are urgently needed especially in the buffer zones of areas with the highest protection status. KW - conservation KW - driving forces KW - forest KW - loss KW - human pressure KW - land use change KW - landscape metrics KW - protection status KW - spatial analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262078 SN - 2073-445X VL - 11 IS - 2 ER -