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  • Cremers, Eline M. P.; de Witte, Theo; de Wreede, Liesbeth; Eikema, Diderik-Jan; Koster, Linda; van Biezen, Anja; Finke, Jurgen; Socie, Gerard; Beelen, Dietrich; Maertens, Johan; Nagler, Arnon; Kobbe, Guido; Ziagkos, Dimitris; Itälä-Remes, Maija; Gedde-Dahl, Tobias; Sierra, Jorge; Niederwieser, Dietger; Ljungman, Per; Beguin, Yves; Ozkurt, Zubeyde Nur; Anagnostopoulos, Achilles; Jindra, Pavel; Robin, Marie; Kröger, Nicolaus (2019)
    Most myelodysplastic syndromes (MDS)-patients receive multiple red blood cell transfusions (RBCT). Transfusions may cause iron-related toxicity and mortality, influencing outcome after allogeneic HSCT. This prospective non-interventional study evaluated 222 MDS and CMML patients undergoing HSCT. Overall survival (OS), relapse-free survival (RFS), non-relapse mortality (NRM), and relapse incidence (RI) at 36 months were 52%, 44%, 25%, and 31%, respectively. Age, percentage of marrow blasts and severe comorbidities impacted OS. RFS was significantly associated with RBCT burden prior to HSCT (HR: 1.7; p = .02). High ferritin levels had a significant negative impact on OS and RI, but no impact on NRM. Administration of iron chelation therapy prior to HSCT did not influence the outcome, but early iron reduction after HSCT (started before 6 months) improved RFS significantly after transplantation (56% in the control group vs. 90% in the treated group, respectively; p = .04). This study illustrates the impact of RBCT and related parameters on HSCT-outcome. Patients with an expected prolonged survival after transplantation may benefit from early iron reduction therapy after transplantation.
  • Garderet, Laurent; Ziagkos, Dimitris; Van Biezen, Anja; Iacobelli, Simona; Finke, Juergen; Maertens, Johan; Volin, Liisa; Ljungman, Per; Chevallier, Patrice; Passweg, Jakob; Schaap, Nicolaas; Beelen, Dietrich; Nagler, Arnon; Blaise, Didier; Poire, Xavier; Yakoub-Agha, Ibrahim; Lenhoff, Stig; Craddock, Charles; Schots, Rik; Rambaldi, Alessandro; Sanz, Jaime; Jindra, Pavel; Mufti, Ghulam J.; Robin, Marie; Kroeger, Nicolaus (2018)
    The deletion (5q) karyotype (del [5q]) in patients with myelodysplastic syndrome (MDS) is the most common karyotypic abnormality in de novo MDS. An increased number of blasts and additional karyotypic abnormalities (del [al]+) are associated with a poor outcome. We analyzed the outcome of allogeneic hematopoietic cell transplants (HCT) in patients suffering from MDS with only del (5q) or del (5q)+. A total of 162 patients, of median age 54 years (range, 9 to 73), having MDS and del (5q) abnormalities received HCT from identical siblings (n = 87) or unrelated donors (n = 75). The cumulative incidence of nonrelapse mortality and relapse incidence at 4 years was 29% (95% CI, 22 to 36) and 46% (95% CI, 38 to 54), whereas the estimated 4 year survival, relapse-free and overall, was 25% (95% CI, 18 to 33) and 30% (95% CI, 23 to 38), respectively. In a multivariate analysis patients with del (5q) and a blast excess displayed poorer survival (hazard ratio, 2.38; 95% CI, 1.44 to 3.93; P
  • Robin, Marie; Chevret, Sylvie; Koster, Linda; Wolschke, Christine; Yakoub-Agha, Ibrahim; Bourhis, Jean Henri; Chevallier, Patrice; Cornelissen, Jan J.; Remenyi, Peter; Maertens, Johan; Poire, Xavier; Craddock, Charles; Socie, Gerard; Itälä-Remes, Maija; Schouten, Harry C.; Marchand, Tony; Passweg, Jakob; Blaise, Didier; Damaj, Gandhi; Ozkurt, Zubeyde Nur; Zuckerman, Tsila; Cluzeau, Thomas; Labussiere-Wallet, Helene; Cammenga, Jörg; McLornan, Donal; Chalandon, Yves; Kroger, Nicolaus (2019)
    The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n= 287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P= 0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versushost disease without increasing the risk of relapse.
  • Robin, Marie; de Wreede, Liesbeth C.; Wolschke, Christine; Schetelig, Johannes; Eikema, Dirk-Jan; Van Lint, Maria Teresa; Knelange, Nina Simone; Beelen, Dietrich; Brecht, Arne; Niederwieser, Dietger; Vitek, Antonin; Bethge, Wolfgang; Arnold, Renate; Finke, Juergen; Volin, Liisa; Yakoub-Agha, Ibrahim; Nagler, Arnon; Poire, Xavier; Einsele, Hermann; Chevallier, Patrice; Holler, Ernst; Ljungman, Per; Robinson, Stephen; Radujkovic, Aleksandar; McLornan, Donal; Chalandon, Yves; Kroeger, Nicolaus (2019)
    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 = 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.
  • Scheid, C.; de Wreede, L.; van Biezen, A.; Koenecke, C.; Gohring, G.; Volin, L.; Maertens, J.; Finke, J.; Passweg, J.; Beelen, D.; Cornelissen, J. J.; Itälä-Remes, M.; Chevallier, P.; Russell, N.; Petersen, E.; Milpied, N.; Espiga, C. Richard; Peniket, A.; Sierra, J.; Mufti, G.; Crawley, C.; Veelken, J. H.; Ljungman, P.; Cahn, J. Y.; Alessandrino, E. P.; de Witte, T.; Robin, M.; Kroeger, N. (2017)
    The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assessed before transplant rather than at diagnosis we performed a retrospective analysis of the EBMT database. A total of 579 patients had sufficient information available to calculate IPSS-R at transplant. Median overall survival (OS) from transplant was significantly different according to IPSS-R: very low 23.6 months, low 55.0 months, intermediate 19.7 months, high 13.5 months, very high 7.8 months (P <0.001). In a multivariate Cox model the following parameters were significant risk factors for OS: IPSS-R, graft source, age and prior treatment. Median relapse free survival also showed significant differences according to IPSS-R: very low: 23.6 months, low: 24.8 months, intermediate 10.6 months, high 7.9 months, very high 5.5 months (P <0.001). Multivariate risk factors for relapse-free survival (RFS) were: IPSS-R, reduced intensity conditioning, graft source and prior treatment. A trend for an increased relapse incidence was noted for very high risk IPSS-R. We conclude that the IPSS-R at transplant is a useful prognostic score for predicting OS and RFS after transplantation, capturing both disease evolution and response to prior treatment before transplant.