@article{NeuchelFuerstNiederwieseretal.2017,
  author    = {Neuchel, Christine and F{\"u}rst, Daniel and Niederwieser, Dietger and Bunjes, Donald and Tsamadou, Chrysanthi and Wulf, Gerald and Pfreundschuh, Michael and Wagner, Eva and Stuhler, Gernot and Einsele, Hermann and Schrezenmeier, Hubert and Mytilineos, Joannis},
  title     = {Impact of donor activating KIR genes on HSCT outcome in C1-ligand negative myeloid disease patients transplanted with unrelated donors - a retrospective study},
  series = {PLOS One},
  volume    = {12},
  journal   = {PLOS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0169512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180995},
  pages     = {39},
  year      = {2017},
  abstract  = {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.},
  language  = {en}
}
@article{SantoroLabopinGiannottietal.2018,
  author    = {Santoro, Nicole and Labopin, Myriam and Giannotti, Federica and Ehninger, Gerard and Niederwieser, Dietger and Brecht, Arne and Stelljes, Matthias and Kr{\"o}ger, Nicolaus and Einsele, Herman and Eder, Matthias and Hallek, Michael and Glass, Bertram and Finke, J{\"u}rgen and Ciceri, Fabio and Mohty, Mohamad and Ruggeri, Annalisa and Nagler, Arnon},
  title     = {Unmanipulated haploidentical in comparison with matched unrelated donor stem cell transplantation in patients 60 years and older with acute myeloid leukemia: a comparative study on behalf of the ALWP of the EBMT},
  series = {Journal of Hematology \& Oncology},
  volume    = {11},
  journal   = {Journal of Hematology \& Oncology},
  doi       = {10.1186/s13045-018-0598-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227315},
  pages     = {55, 1-10},
  year      = {2018},
  abstract  = {Background: Acute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need. Methods: We retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients >= 60 years. Results: Median follow-up was 23 months. Disease status at transplant differs significantly between the two groups (p < 10(-4)). Reduced intensity conditioning (RIC) was administrated to 73 and 77\% of Haplo and MUD, respectively (p = 0.23). Stem cell source was the bone marrow (BM) in 52\% of the Haplo and 6\% of MUD (p < 10(-4)). Anti-thymocyte globulin (ATG) was most frequently used in MUD (p < 10(-4)) while post-Tx cyclophosphamide (PT-Cy) was given in 62\% of Haplo. Engraftment was achieved in 90\% of the Haplo vs 97\% of MUD (p < 10(-4)). In multivariate analysis, no significant difference was found between Haplo and MUD for acute (a) graft versus host disease (GVHD) grade II-IV, relapse incidence (RI), non-relapse mortality (NRM), leukemia free survival (LFS), graft-versus-host-free-relapse free survival (GRFS), and overall survival (OS). Extensive chronic (c) GVHD was significantly higher for MUD as compared to Haplo (HR 2, p = 0.01, 95\% CI 1.17-3.47). A propensity score analysis confirmed the higher risk of extensive cGVHD for MUD without differences for other outcomes. Conclusions: Allo-SCT from both Haplo and MUD are valid option for AML patients >= 60 years of age with similar results. Transplantation from MUD was associated with higher extensive cGVHD. Our findings suggest that Haplo is a suitable and attractive graft source for patients >= 60 with AML in need of allo-SCT.},
  language  = {en}
}
@article{RobindeWreedeWolschkeetal.2019,
  author    = {Robin, Marie and de Wreede, Liesbeth C. and Wolschke, Christine and Schetelig, Johannes and Eikema, Diderik-Jan and Van Lint, Maria Teresa and Knelange, Nina Simone and Beelen, Dietrich and Brecht, Arne and Niederwieser, Dietger and Vitek, Antonin and Bethge, Wolfgang and Arnold, Renate and Finke, J{\"u}rgen and Volin, Liisa and Yakoub-Agha, Ibrahim and Nagler, Arnon and Poir{\´e}, Xavier and Einsele, Hermann and Chevallier, Patrice and Holler, Ernst and Ljungman, Per and Robinson, Stephen and Radujkovic, Alekxandar and McLornan, Donal and Chalandon, Yves and Kr{\"o}ger, Nicolaus},
  title     = {Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis},
  series = {Haematologica},
  volume    = {104},
  journal   = {Haematologica},
  number    = {9},
  doi       = {10.3324/haematol.2018.205211},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226386},
  pages     = {1782-1788},
  year      = {2019},
  abstract  = {Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64\% (60-68\%) and overall survival was 74\% (71-78\%) at ten years; results were better in younger individuals and in women. Excess mortality was 14\% (8-21\%) in patients aged <45 years and 33\% (13-53\%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.},
  subject      = {Midollo-Osseo},
  language  = {en}
}
@article{SaraceniLabopinBrechtetal.2019,
  author    = {Saraceni, Francesco and Labopin, Myriam and Brecht, Arne and Kr{\"o}ger, Nicolaus and Eder, Matthias and Tischer, Johanna and Labussiere-Wallet, Helene and Einsele, Hermann and Beelen, Dietrich and Bunjes, Donald and Niederwieser, Dietger and Bochtler, Tilman and Savani, Bipin N. and Mohty, Mohamad and Nagler, Arnon},
  title     = {Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)},
  series = {Journal of Hematology \& Oncology},
  volume    = {12},
  journal   = {Journal of Hematology \& Oncology},
  number    = {44},
  doi       = {10.1186/s13045-019-0727-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227345},
  pages     = {1-10},
  year      = {2019},
  abstract  = {Background Limited data is available to guide the choice of the conditioning regimen for patients with acute myeloid leukemia (AML) undergoing transplant with persistent disease. Methods We retrospectively compared outcome of fludarabine-treosulfan (FT), thiotepa-busulfan-fludarabine (TBF), and sequential fludarabine, intermediate dose Ara-C, amsacrine, total body irradiation/busulfan, cyclophosphamide (FLAMSA) conditioning in patients with refractory or relapsed AML. Results Complete remission rates at day 100 were 92\%, 80\%, and 88\% for FT, TBF, and FLAMSA, respectively (p=0.13). Non-relapse mortality, incidence of relapse, acute (a) and chronic (c) graft-versus-host disease (GVHD) rates did not differ between the three groups. Overall survival at 2years was 37\% for FT, 24\% for TBF, and 34\% for FLAMSA (p=0.10). Independent prognostic factors for survival were Karnofsky performance score and patient CMV serology (p=0.01; p=0.02), while survival was not affected by age at transplant. The use of anti-thymocyte globulin (ATG) was associated with reduced risk of grade III-IV aGVHD (p=0.02) and cGVHD (p=0.006), with no influence on relapse. Conclusions In conclusion, FT, TBF, and FLAMSA regimens provided similar outcome in patients undergoing transplant with active AML. Survival was determined by patient characteristics as Karnofsky performance score and CMV serology, however was not affected by age at transplant. ATG appears able to reduce the incidence of acute and chronic GVHD without influencing relapse risk.},
  language  = {en}
}