37 results on '"Finke, Jürgen"'
Search Results
2. Treosulfan compared with <scp>reduced‐intensity</scp> busulfan improves allogeneic hematopoietic cell transplantation outcomes of older acute myeloid leukemia and myelodysplastic syndrome patients: Final analysis of a prospective randomized trial
- Author
-
Beelen, Dietrich, Stelljes, Matthias, Reményi, Péter, Wagner‐Drouet, Eva‐Maria, Dreger, Peter, Bethge, Wolfgang, Ciceri, Fabio, Stölzel, Friedrich, Junghanß, Christian, Labussiere‐Wallet, Hélène, Schaefer‐Eckart, Kerstin, Grigoleit, Goetz U., Scheid, Christof, Patriarca, Francesca, Rambaldi, Alessandro, Niederwieser, Dietger, Hilgendorf, Inken, Russo, Domenico, Socié, Gérard, Holler, Ernst, Glass, Bertram, Casper, Jochen, Wulf, Gerald, Basara, Nadezda, Bieniaszewska, Maria, Stuhler, Gernot, Verbeek, Mareike, La Rocca, Ursula, Finke, Jürgen, Benedetti, Fabio, Pichlmeier, Uwe, Klein, Anja, Baumgart, Joachim, Markiewicz, Miroslaw, and Rocca, Ursula La
- Subjects
Leukemia, Myeloid, Acute ,Transplantation Conditioning ,Myelodysplastic Syndromes ,Medizin ,Hematopoietic Stem Cell Transplantation ,Graft vs Host Disease ,Humans ,Prospective Studies ,Hematology ,Middle Aged ,Busulfan ,Vidarabine ,Aged - Abstract
The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer-term follow-up are presented. Patients presenting HCT-specific comorbidity index >2 or aged >= 50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m(2) IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36-months-EFS rate 59.5% (95% CI, 52.2-66.1) vs. 49.7% (95% CI, 43.3-55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49-0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36-month-OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48-0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.
- Published
- 2022
3. Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
- Author
-
Dreger, Peter, Schweizerische Gesellschaft Für Hämatologie, Greinix, Hildegard, Schweizerische Gesellschaft Für Medizinische Onkologie, Luft, Thomas, Scheid, Christoph, Zeiser, Robert, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Finke, Jürgen, Mielke, Stephan, Holler, Ernst, Wolff, Daniel, Deutsche Arbeitsgemeinschaft Für Knochenmark- Und Blutstammzelltransplantation, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
- Subjects
Medizin und Gesundheit - Published
- 2022
- Full Text
- View/download PDF
4. Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
- Author
-
Dreger, Peter, Schweizerische Gesellschaft Für Hämatologie, Deutsche Arbeitsgemeinschaft Für Hämatopoetische Stammzelltransplantation Und Zelluläre Therapie, Greinix, Hildegard, Schweizerische Gesellschaft Für Medizinische Onkologie, Luft, Thomas, Scheid, Christoph, Zeiser, Robert, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Finke, Jürgen, Halter, Jörg, Mielke, Stephan, Holler, Ernst, Wolff, Daniel, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
- Subjects
Medizin und Gesundheit - Published
- 2022
- Full Text
- View/download PDF
5. Role of Age and Hematopoietic Cell Transplantation-Specific Comorbidity Index in Myelodysplastic Patients Undergoing an Allotransplant: A Retrospective Study from the Chronic Malignancies Working Party of the European Group for Blood and Marrow Transplantation
- Author
-
Carré, Martin, Porcher, Raphaël, Finke, Jürgen, Ehninger, Gerhard, Koster, Linda, Beelen, Dietrich, Ganser, Arnold, Volin, Liisa, Lozano, Sara, Friis, Lone, Michallet, Mauricette, Tischer, Johanna, Olavarria, Eduardo, Cascon, Maria Jesús Pascual, Iacobelli, Simona, Koc, Yener, Jindra, Pavel, Arat, Mutlu, de Witte, Theo, Yakoub Agha, Ibrahim, Kröger, Nicolaus, Robin, Marie, and Agha, Ibrahim Yakoub
- Subjects
Adult ,medicine.medical_specialty ,Transplantation Conditioning ,Multivariate analysis ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Myelodysplastic syndromes ,Medizin ,Comorbidity ,Hematopoietic stem cell transplantation ,Comorbidities ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Age ,0302 clinical medicine ,Bone Marrow ,Neoplasms ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Nonrelapse mortality ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Retrospective cohort study ,Hematology ,Settore MED/15 ,medicine.disease ,Settore MED/01 ,030220 oncology & carcinogenesis ,Stem cell ,business ,030215 immunology - Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative option for myelodysplastic syndromes (MDSs) but is severely limited by nonrelapse mortality (NRM), especially in this mostly older population. Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI). Moreover, the impact of age on NRM still remains a matter of debate. In recent years, the age at which transplants are made has been progressively increasing, and patients with comorbidities have become more common. Extricating the respective roles of age and comorbidities in toxic mortality is all the more important. This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014. Overall, 4-year NRM and overall survival were 32% and 47%, respectively. When considered as continuous predictors, HCT-CI score and age were associated with an increased hazard ratio (HR) for NRM. In multivariate analysis, age band (HR, 1.13; 95% CI, 1.02 to 1.25; P= .016), HCT-CI ≥3 (HR, 1.34; 95% CI, 1.04 to 1.73; P = .022), and Karnofsky Performance Status ≤80 (HR, 2.03; 95% CI, 1.52 to 2.73; P.0001) were significantly predictive of a worse NRM. In our large cohort, both comorbidities, evaluated by the original HCT-CI score, and chronological age significantly affected NRM. Thus, age should be part of the transplant decision-making process and should be integrated in future scoring systems predicting outcomes of HSCT in MDSs.
- Published
- 2020
6. Comparison of Dynamic International Prognostic Scoring System and MYelofibrosis SECondary to PV and ET Prognostic Model for Prediction of Outcome in Polycythemia Vera and Essential Thrombocythemia Myelofibrosis after Allogeneic Stem Cell Transplantation
- Author
-
Gagelmann, Nico, Eikema, Diderik-Jan, de Wreede, Liesbeth C, Koster, Linda, Wolschke, Christine, Arnold, Renate, Kanz, Lothar, McQuaker, Grant, Marchand, Tony, Socié, Gerard, Bourhis, Jean Henri, Mohty, Mohamad, Cornelissen, Jan J, Chevallier, Patrice, Bernasconi, Paolo, Stelljes, Matthias, Rohrlich, Pierre-Simon, Fanin, Renato, Finke, Jürgen, Maertens, Johan, Blaise, Didier, Itälä-Remes, Maija, Labussière-Wallet, Hélène, Robin, Marie, McLornan, Donal, Chalandon, Yves, Yakoub-Agha, Ibrahim, Kröger, Nicolaus, CMWP of the European Society for Blood and Marrow Transplantation, Hematology, and Medical Oncology
- Subjects
Adult ,medicine.medical_specialty ,Essential thrombocythemia ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Polycythemia vera ,Internal medicine ,Humans ,Transplantation, Homologous ,Medicine ,Allogeneic stem cell transplantation ,Secondary myelofibrosis ,Hematology ,Transplantation ,Myelofibrosis ,Polycythemia Vera ,Survival analysis ,Aged ,ddc:616 ,Framingham Risk Score ,business.industry ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,Prognosis ,medicine.disease ,Survival Analysis ,Treatment Outcome ,Primary Myelofibrosis ,International Prognostic Scoring System ,030220 oncology & carcinogenesis ,Cohort ,business ,Thrombocythemia, Essential ,030215 immunology - Abstract
We aimed to validate the MYelofibrosis SECondary to PV and ET prognostic model (MYSEC-PM) in 159 patients with myelofibrosis secondary to polycythemia vera (PV) and essential thrombocythemia (ET) from the European Society for Blood and Marrow Transplantation registry undergoing transplantation from matched siblings or unrelated donors. Furthermore, we aimed to test its prognostic performance in comparison with the Dynamic International Prognostic Scoring System (DIPSS). Score performance was analyzed using the concordance index (C): the probability that a patient who experienced an event had a higher risk score than a patient who did not (C > .5 suggesting predictive ability). Median follow-up of the total cohort was 41 months (range, 34 to 54), 45 months in post-PV and 38 months in post-ET myelofibrosis. Survival at 1, 2, and 4 years was 70% (95% CI, 63% to 77%), 61% (95% CI, 53% to 69%), and 52% (95% CI, 43% to 61%) for the total cohort; 70% (95% CI, 59% to 80%), 61% (95% CI, 49% to 73%), and 51% (95% CI, 38% to 64%) for post-PV; and 71% (95% CI, 61% to 81%), 61% (95% CI, 50% to 72%), and 54% (95% CI, 42% to 66%) for post-ET myelofibrosis (P = .78). Overall, the DIPSS was not significantly predictive of outcome (P = .28). With respect to the MYSEC-PM, overall survival at 4 years was 69% for the low-risk, 55% for the intermediate 1-risk, 47% for the intermediate 2-risk, and 22% (0% to 45%) for the high-risk groups. The prognostic model was predictive of survival overall (P = .05), whereas groups with intermediate 2 and high risk showed no significant difference (P = .44). Assessment of prognostic utility yielded a C-index of .575 (95% CI, .502 to .648) for the DIPSS, whereas assessment of the MYSEC-PM resulted in a C-statistics of .636 (95% CI, .563 to .708), indicating improvement in prediction of post-transplant survival using the new MYSEC-PM. In addition, transplantations from an unrelated donor in comparison with an HLA-identical sibling showed worse outcome (P = .04), and transplant recipients seropositive for cytomegalovirus in comparison with seronegative recipients (P = .01) showed worse survival. In conclusion, incorporating transplant-specific and clinical and mutational information together with the MYSEC-PM may enhance risk stratification. ispartof: Biol Blood Marrow Transplant vol:25 issue:6 pages:e204-e208 ispartof: location:United States status: published
- Published
- 2019
7. The impact of cytogenetic risk on the outcomes of allogeneic hematopoietic cell transplantation in patients with relapsed/refractory acute myeloid leukemia : On behalf of the acute leukemia working party (ALWP) of the European group for blood and marrow transplantation (EBMT)
- Author
-
Poiani, Monica, Labopin, Myriam, Battipaglia, Giorgia, Beelen, Dietrich, Tischer, Johanna, Finke, Jürgen, Brecht, Arne, Forcade, Edouard, Ganser, Arnold, Passweg, Jakob R., Labussiere-Wallet, Helene, Yakoub-Agha, Ibrahim, Schäfer-Eckart, Kerstin, Kroeger, Nicolaus, Guffroy, Blandine, Ruggeri, Annalisa, Esteve, Jordi, Nagler, Arnon, and Mohty, Mohamad
- Subjects
Medizin - Published
- 2021
8. Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
- Author
-
Dreger, Peter, Schweizerische Gesellschaft Für Hämatologie, Deutsche Arbeitsgemeinschaft Für Hämatopoetische Stammzelltransplantation Und Zelluläre Therapie, Greinix, Hildegard, Schweizerische Gesellschaft Für Medizinische Onkologie, Luft, Thomas, Scheid, Christoph, Zeiser, Robert, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Finke, Jürgen, Halter, Jörg, Holler, Ernst, Wolff, Daniel, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
- Subjects
Medizin und Gesundheit - Published
- 2021
- Full Text
- View/download PDF
9. Association of serum ferritin levels before start of conditioning with mortality after alloSCT: A prospective, non-interventional study of the EBMT transplant complications working party
- Author
-
Penack, Olaf, Peczynski, Christophe, Werf, Steffie, van der, Finke, Jürgen, Ganser, Arnold, Schoemans, Helene, Pavlu, Jiri, Niittyvuopio, Riitta, Schroyens, Wilfried, Kaynar, Leylagül, Blau, Igor W., Velden, Walter J. F. M., van der, Sierra, Jorge, Cortelezzi, Agostino, Wulf, Gerald, Turlure, Pascal, Rovira, Montserrat, Ozkurt, Zubeydenur, Pascual-Cascon, Maria J., Moreira, Maria C., Clausen, Johannes, Greinix, Hildegard, Duarte, Rafael F., Basak, Grzegorz W., UAM. Departamento de Medicina, HUS Comprehensive Cancer Center, Hematologian yksikkö, Clinicum, and Department of Oncology
- Subjects
Adult ,Male ,lcsh:Immunologic diseases. Allergy ,Transplantation Conditioning ,Adolescent ,IMPACT ,Medicina ,3122 Cancers ,Graft vs Host Disease ,ACUTE MYELOID-LEUKEMIA ,ALBUMIN ,DIAGNOSIS ,DISEASE RISK INDEX ,immunology ,Young Adult ,Postoperative Complications ,INFECTION ,Biomarkers, Tumor ,IRON OVERLOAD ,Humans ,Transplantation, Homologous ,Immunology and Allergy ,iron metabolism ,Prospective Studies ,Original Research ,Aged ,Peripheral Blood Stem Cell Transplantation ,Science & Technology ,CELL TRANSPLANTATION ,ferritin ,Middle Aged ,stem cell ,Hematologic Neoplasms ,Ferritins ,1182 Biochemistry, cell and molecular biology ,biomarker ,Female ,3111 Biomedicine ,Human medicine ,lcsh:RC581-607 ,Life Sciences & Biomedicine ,transplantation - Abstract
Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 μg/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5–4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6–3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2–3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5–6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6–9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT., JP acknowledges the support of the Imperial NIHR-BCR. OP acknowledges the support of José Carreras Leukämie-Stiftung (11R2016 and 3R2019), Deutsche Krebshilfe (70113519), and Deutsche Forschungsgemeinschaft (PE 1450/7-1)
- Published
- 2020
10. Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
- Author
-
Dreger, Peter, Strahm, Brigitte, Bornhäuser, Martin, Platzbecker, Uwe, Bader, Peter, Schmid, Christoph, Burchert, Andreas, Zeiser, Robert, Finke, Jürgen, Meisel, Roland, Bethge, Wolfgang Andreas, Christopeit, Maximilian Erich Joachim, Kobbe, Guido, Müller, Antonia Maria Susanne, Müller, Lutz Peter, Deutsche Arbeitsgemeinschaft Für Knochenmark- Und Blutstammzelltransplantation, Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie, Beelen, Dietrich W., Sauer, Martin Günther, Einsele, Hermann, Kröger, Nicolaus, and Stelljes, Matthias
- Subjects
Medizin und Gesundheit - Published
- 2020
- Full Text
- View/download PDF
11. Ibrutinib in patients with relapsed/refractory central nervous system lymphoma: A retrospective single-centre analysis
- Author
-
Lauer, Eliza M., Waterhouse, Miguel, Braig, Moritz, Mutter, Jurik, Bleul, Sabine, Duque-Afonso, Jesús, Duyster, Justus, Marks, Reinhard, Reinacher, Peter Christoph, Prinz, Marco, Illerhaus, Gerald, Finke, Jürgen, Schorb, Elisabeth, Scherer, Florian, and Publica
- Subjects
real-world analysis ,relapsed / refractory disease ,Ibrutinib ,BTK inhibition ,central nervous system lymphoma - Published
- 2020
12. Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis
- Author
-
Robin, Marie, De Wreede, Liesbeth C., Wolschke, Christine, Schetelig, Johannes, Eikema, Diderik-Jan, Van Lint, Maria Teresa, Knelange, Nina Simone, Beelen, Dietrich, Brecht, Arne, Niederwieser, Dietger, Vitek, Antonin, Bethge, Wolfgang, Arnold, Renate, Finke, Jürgen, Volin, Liisa, Yakoub-Agha, Ibrahim, Nagler, Arnon, Poiré, Xavier, Einsele, Hermann, Chevallier, Patrice, Holler, Ernst, Ljungman, Per, Robinson, Stephen, Radujkovic, Alekxandar, McLornan, Donal, Chalandon, Yves, Kröger, Nicolaus, Eikema, Dirk-Jan, Radujkovic, Aleksandar, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (SLuc) Service d'hématologie, HUS Comprehensive Cancer Center, Hematologian yksikkö, and Department of Oncology
- Subjects
Male ,Ruxolitinib ,BLOOD ,Multivariate analysis ,Survival ,medicine.medical_treatment ,Medizin ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Disease ,PROGNOSTIC SCORING SYSTEM ,GRUPPO-ITALIANO ,MIDOLLO-OSSEO ,0302 clinical medicine ,Risk Factors ,Midollo-Osseo ,RUXOLITINIB ,Registries ,SOCIETE FRANCAISE ,Cause of death ,ddc:616 ,education.field_of_study ,Remission Induction ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,3. Good health ,Blood ,Treatment Outcome ,SURVIVAL ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,LATE MORTALITY ,Population ,Article ,Disease-Free Survival ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,ddc:610 ,education ,Myelofibrosis ,Aged ,EUROPEAN GROUP ,business.industry ,medicine.disease ,Transplantation ,LATE DEATHS ,Primary Myelofibrosis ,3121 General medicine, internal medicine and other clinical medicine ,Multivariate Analysis ,Myeloproliferative Neoplasms ,Neoplasm Recurrence, Local ,business ,030215 immunology - 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 = 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.
- Published
- 2019
13. Leitlinie : Empfehlungen der Fachgesellschaft zur Diagnostik und Therapie hämatologischer und onkologischer Erkrankungen
- Author
-
Zeiser, Robert, Dreger, Peter, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Schweizerische Gesellschaft Für Hämatologie, Greinix, Hildegard, Finke, Jürgen, Holler, Ernst, Schweizerische Gesellschaft Für Medizinische Onkologie, Luft, Thomas, Wolff, Daniel, Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie, and Scheid, Christof
- Subjects
Medizin und Gesundheit - Published
- 2019
- Full Text
- View/download PDF
14. Comparable Long-Term Outcome after Allogeneic Stem-Cell Transplantation from Sibling and Matched Unrelated Donors in AML Patients Older than 50 years : A Report on Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation
- Author
-
Shimoni, Avichai, Labopin, Myriam, Savani, B., Byrne, Michael, Volin, L., Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, J.J., Mohty, Mohamad, Nagler, A., and Cornelissen, Jan J.
- Subjects
Medizin - Published
- 2019
15. Erratum : Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
- Author
-
Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thomas, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert
- Abstract
This corrects the article DOI: 10.1038/nm.4484.
- Published
- 2018
16. Graft-versus-Host Erkrankung, akut
- Author
-
Dreger, Peter, Schweizerische Gesellschaft Für Hämatologie, Greinix, Hildegard, Schweizerische Gesellschaft Für Medizinische Onkologie, Luft, Thomas, Scheid, Christoph, Zeiser, Robert, Österreichische Gesellschaft Für Hämatologie & Medizinische Onkologie, Finke, Jürgen, Holler, Ernst, Wolff, Daniel, Deutsche Arbeitsgemeinschaft Für Knochenmark- Und Blutstammzelltransplantation, and Deutsche Gesellschaft Für Hämatologie Und Medizinische Onkologie
- Subjects
Medizin und Gesundheit - Published
- 2018
- Full Text
- View/download PDF
17. Treosulfan conditioning for allogenic hematopoietic stem cell transplantation in multiple myeloma, advantages for non-relapse mortality and survival, but with high incidence of relapse
- Author
-
Gran, Charlotte, Wang, Junfeng, Nahi, Hareth, Koster, Linda, Einsele, Herman, Itälä-Remes, Maija, Holler, Ernst, Beelen, Dietrich, Ciceri, Fabio, Ehninger, Gerhard, Finke, Jürgen, de Wreede, Liesbeth, Ljungman, Per, Tischer, Johanna, Verbeek, Mareike, Klyuchnikov, Evgeny, Hilgendorf, Inken, Schäfer-Eckart, Kerstin, Scheid, Christof, Bunjes, Donald, Basara, Nadezda, Haenel, Mathias, Müller, Lutz Peter, Biersack, Harald, Gahrton, Gösta, Garderet, Laurent, and Kröger, Nicolaus
- Subjects
Medizin - Published
- 2018
18. Comparison of the outcomes of allogeneic hematopoietic stem cell transplantation from HLA-identical siblings versus unmanipulated haploidentical donors in relapsed or refractory acute myeloid leukemia
- Author
-
Battipaglia, Giorgia, Boumendil, Ariane, Labopin, Myriam, Ruggeri, Annalisa, Ciceri, Fabio, Tischer, Johanna, Steljes, Matthias, Ehninger, Gerhard, Beelen, Dietrich, Finke, Jürgen, Van Lint, Maria Teresa, Ganser, Arnold, Afanasyev, Boris, Fanin, Renato, Mohty, Mohamad, and Nagler, Arnon
- Subjects
Medizin - Published
- 2018
19. Centre characteristics and procedure-related factors have an impact on outcomes of allogeneic transplantation for patients with CLL: a retrospective analysis from the European Society for Blood and Marrow Transplantation (EBMT)
- Author
-
Schetelig, Johannes, de Wreede, Liesbeth C., Andersen, Niels S., Moreno, Carol, van Gelder, Michel, Vitek, Antonin, Karas, Michal, Michallet, Mauricette, Machaczka, Maciej, Gramatzki, Martin, Beelen, Dietrich, Finke, Jürgen, Delgado, Julio, Volin, Liisa, Passweg, Jakob, Dreger, Peter, Schaap, Nicolaas, Wagner, Eva, Henseler, Anja, van Biezen, Anja, Bornhäuser, Martin, Iacobelli, Simona, Putter, Hein, Schönland, Stefan O., Kröger, Nicolaus, Esteve, Jordi, Ljungman, Per, de Witte, Theo, Stelljes, Matthias, Sierra, Jorge, Socié, Gerard, Ganser, Arnold, Wulf, Gerhard G., Deconinck, Eric, Faber, Edgar, Feguex, Nathalie, Gedde-Dahl, Tobias, Kolbe, Karin, Chalandon, Yves, Krüger, William, Huynh, Anne, Bourhis, Jean Henri, Schouten, Harry, Ribera Santasusana, Josep M., Interne Geneeskunde, MUMC+: MA Hematologie (9), RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, and Chalandon, Yves
- Subjects
Oncology ,Male ,Transplantation Conditioning ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,Chronic lymphocytic leukemia ,Medizin ,QUALITY MANAGEMENT-SYSTEM ,Kaplan-Meier Estimate ,risk factor analysis ,GUIDELINES ,Biochemistry ,allogeneic stem cell transplantation ,centre effects ,chronic lymphocytic leukaemia ,frailties ,Transplantation Conditioning / methods ,0302 clinical medicine ,Recurrence ,Risk Factors ,Leukemia, Lymphocytic, Chronic, B-Cell / mortality ,Registries ,Delivery of Health Care / statistics & numerical data ,IBRUTINIB ,ddc:616 ,0303 health sciences ,ALEMTUZUMAB ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Professional Practice ,Hematology ,Middle Aged ,3. Good health ,Europe ,030220 oncology & carcinogenesis ,ABT-199 ,Cohort ,SURVIVAL ,Alemtuzumab ,Female ,Europe / epidemiology ,medicine.drug ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Immunology ,Lower risk ,DIAGNOSIS ,Settore MED/01 - Statistica Medica ,03 medical and health sciences ,Leukemia, Lymphocytic, Chronic, B-Cell / therapy ,Hematopoietic Stem Cell Transplantation / methods ,Internal medicine ,medicine ,Humans ,Karnofsky Performance Status ,030304 developmental biology ,Aged ,Retrospective Studies ,business.industry ,Proportional hazards model ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Retrospective cohort study ,STEM-CELL TRANSPLANTATION ,Cell Biology ,medicine.disease ,Leukemia, Lymphocytic, Chronic, B-Cell ,Confidence interval ,Surgery ,Professional Practice / statistics & numerical data ,Transplantation ,business ,Delivery of Health Care ,030215 immunology ,RESPONSES - Abstract
Introduction:Even in the era of novel targeted therapies for the treatment of Chronic Lymphocytic Leukemia (CLL) patients, such as BTK, PI3K and BCL2 inhibitors, allogeneic hematopoietic stem cell transplantations (alloHCT) will remain an important treatment option for a subset of patients with very high risk CLL. The current study focused on the impact of center and procedure-related factors on outcomes after alloHCT, taking into account the impact of patient- and disease-related risk factors. Patients and Methods:Data of 684 CLL patients who received a first alloHCT between 2000 and 2011 were analyzed. Their data were collected as part of the EBMT CLL Data Quality Initiative. Outcomes of interest were Event-Free Survival (EFS) up to 5 years after transplantation and mortality in the first 100 days after alloHCT. Outcomes were analyzed by means of the Kaplan-Meier method and Cox proportional hazards models with a frailty (random effects) component to take into account unexplained center heterogeneity. The following factors describing center characteristics or the transplant procedure were analyzed: experience in alloHCT in general and, for CLL specifically, accreditation by the Joint Accreditation Committee-ISCT & EBMT (JACIE), Gross National Income (GNI)/capita based on purchasing power parity (PPP) (GNI/cap), donor type, donor-patient sex-match, type of conditioning, stem cell source and T-cell depletion (TCD). Results:Five-year EFS of the whole cohort was 37% (95% Confidence Interval, 33%-42%), Day-100 survival was 90% (88%-92%). Experience of the transplant center was measured by the number of all alloHCTs, and alloHCTs for patients with CLL respectively. The median total number of alloHCTs per center per year was 45 (range 0-169) and the median number of CLL alloHCTs was only 2 per center per year (range 0-19). Greater experience with transplantation of patients with CLL (Hazard Ratio (HR) 0.96 per additional transplant, p=0.002), JACIE accreditation (HR 0.7, p=0.045) and a higher GNI/cap (HR 0.4, 95% CI 0.2-0.96, p=0.04) showed a protective impact on 5-year EFS in the Cox model. In vivo TCD with alemtuzumab (HR 1.5 compared to no TCD, p=0.03) and a female donor for a male patient (HR 1.4 compared to a male donor for a male patient, p=0.02) were the only procedure-related factors significantly associated with EFS. Event-Free Survival after in vivo TCD with Anti-Thymocyte-Globulin or after ex vivo TCD was comparable to EFS without TCD (HR 0.9, 0.7-1.3, p=0.6; HR 0.9, 0.5-1.6, p=0.8). Non-myeloablative conditioning did not have a negative impact on 5-year EFS, and exposed patients to a lower risk of non-relapse mortality. Measured and unmeasured center characteristics did not have a significant impact on 100-day mortality. Even when correcting for patient-, procedure- and center-related characteristics, there was still significant variation in center outcome, expressed by center-specific HRs derived from the frailty models, ranging from 0.6 to 1.2. Their impact is illustrated in a model-based plot for EFS (see Figure) which shows outcomes for three reference patients with the same characteristics who would be transplanted in three centers with the same measured characteristics but with the highest, average and lowest HRs in the dataset. These unexplained center effects likely represent a mixture of differences which could apply to the location of the transplant center, unmeasured characteristics of the patient population transplanted at this center, selection criteria which were not reported and factors determining the success of the transplant procedure which might differ between centers. Conclusion: We have confirmed that both center- and procedure-related factors have a significant impact on the EFS of patients with CLL undergoing alloHCT. Our results may help to interpret outcomes of single or multicenter studies better. Since non-myeloablative conditioning did not have a negative impact on EFS and exposed patients to a lower risk of non-relapse mortality, this approach should be favored for future alloHCT for CLL. Probability of Event-Free Survival up to Five Years Post-HCT for three Reference Patients Contribution: J.S. designed the research and wrote the paper. L.C.d.W conducted the statistical analysis and produced the figure. Figure Figure. Disclosures Schetelig: Sanofi: Honoraria. Gramatzki:Janssen: Other: Travel/Accommodation/Expenses, Research Funding. Dreger:Gilead: Consultancy; Gilead: Speakers Bureau; Janssen: Consultancy; Novartis: Speakers Bureau; Novartis: Consultancy; Roche: Consultancy.
- Published
- 2017
20. Additional file 1 Table 1S: of Comparison of matched sibling donors versus unrelated donors in allogeneic stem cell transplantation for primary refractory acute myeloid leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT
- Author
-
Eolia Brissot, Labopin, Myriam, Stelljes, Matthias, Ehninger, Gerhard, Schwerdtfeger, Rainer, Finke, Jürgen, Hans-Jochem Kolb, Ganser, Arnold, Schäfer-Eckart, Kerstin, Zander, Axel, Bunjes, Donald, Mielke, Stephan, Bethge, Wolfgang, Milpied, Noël, Kalhs, Peter, Igor-Woflgang Blau, Kröger, Nicolaus, Vitek, Antonin, Gramatzki, Martin, Holler, Ernst, Schmid, Christoph, Esteve, Jordi, Mohty, Mohamad, and Nagler, Arnon
- Abstract
Conditioning regimens: univariate analysis for RI, NRM, LFS, OS, cGVHD. (DOCX 20 kb)
- Published
- 2017
- Full Text
- View/download PDF
21. Additional file 1: Table S1. of The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
- Author
-
Rubio, Marie, Bipin Savani, Labopin, Myriam, Polge, Emmanuelle, Niederwieser, Dietger, Ganser, Arnold, Schwerdtfeger, Rainer, Ehninger, Gerhard, Finke, Jürgen, Renate, Arnold, Craddock, Charles, Kröger, Nicolaus, Hallek, Michael, Jindra, Pavel, Mohty, Mohamad, and Nagler, Arnon
- Abstract
List of institutions reporting patients’ data for the study. (DOCX 29 kb)
- Published
- 2016
- Full Text
- View/download PDF
22. Particular Treatment Procedures
- Author
-
Deschler, Barbara, Waller, Cornelius, Engelhardt, Monika, Müller, Antonia, Luebbert, Michael, Finke, Jürgen, Bertz, Hartmut, Illerhaus, Gerald, Kaskel, Anna-Katharina, Mackensen, A., Veelken, Hendrik, Rosenthal, F. M., Müller, Claudia I., Scheele, Jürgen, and Martens, Uwe
- Subjects
Umbilical Cord Blood ,Stem Cell ,Graft Versus Host Disease ,Total Body Irradiation ,Hematopoietic Cell Transplantation ,Article - Published
- 2008
23. Hematology and Hemostasis
- Author
-
Finke, Jürgen, Bertz, Hartmut, Kaskel, Anna-Katharina, Heinz, Jürgen, Thomas, A.K., Berger, Dietmar P., Engelhardt, Rupert, and Schmah, Oliver
- Subjects
Folic Acid ,Disseminate Intravascular Coagulation ,Fresh Freeze Plasma ,Hemolytic Anemia ,Aplastic Anemia ,Article - Published
- 2008
24. Bone marrow or peripheral blood stem cell transplantation from unrelated donors in adult patients with acute myeloid leukaemia, an Acute Leukaemia Working Party analysis in 2262 patients
- Author
-
Ringdén, Olle, Labopin, Myriam, Beelen, Dietrich, Volin, Liisa, Ehninger, Gerhard E., Finke, Jürgen D., Greinix, Hildegard T., Kyrcz-Krzemien, Sławomira, Bunjes, Donald W., Brinch, Lorentz J.C., Niederwieser, Dietger W., Arnold, Renate, Mohty, Mohamad, and Rocha, Vanderson G.
- Subjects
Medizin - Published
- 2012
25. Correspondence (reply): In Reply
- Author
-
Zander, Axel R., Bacher, Ulrike, and Finke, Jürgen
- Subjects
Correspondence - Published
- 2009
26. Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: Establishment of Indications on the Basis of Individual Risk Stratification
- Author
-
Zander, Axel Rolf, Bacher, Ulrike, and Finke, Jürgen
- Subjects
Review Article - Abstract
Acute myeloid leukemia (AML) is a heterogeneous disorder with subtypes that differ considerably in morphology and in their underlying chromosomal and molecular aberrations, which, in turn, determine their prognosis. The establishment of the indications for allogeneic stem cell transplantation (SCT) therefore requires individualized risk stratification based on a combination of multiple diagnostic methods, including cytogenetic and molecular genetic studies, and immunophenotyping, as well as the sensitivity of the disease to chemotherapy.This article surveys the current strategies for establishing the indications for SCT in AML on the basis of a selective review of the relevant literature in the Medline database.In patients with a high risk constellation-e.g., chromosome 7 anomalies, complex aberrations, or FLT3-length mutations-there is an indication for SCT in first remission. The balanced translocations t(15;17) and t(8;21), and the inversion inv(16) are prognostically favorable and are thus not considered an indication for SCT in first remission. The establishment of indications for stem cell transplantation also depends on the residual leukemic cell burden (minimal residual disease, MRD) as determined by the quantitative polymerase chain reaction or by flow cytometry, as well as an insufficient response to induction chemotherapy. Reduced-dose conditioning, a new technique that lessens acute toxicity, has been found to be associated with a 30% to over 50% two-year survival rate when used in the treatment of chemotherapeutically unresponsive or relapsing AML.The indications for allogeneic SCT in AML should be further refined by more investigation in large studies.
- Published
- 2008
27. Prognostic Factors Affecting Outcome after Allogeneic Transplantation for Hematological Malignancies from Unrelated Donors: Results from a Randomized Trial
- Author
-
Finke, Jürgen, Schmoor, Claudia, Bethge, Wolfgang A., Ottinger, Hellmut, Stelljes, Matthias, Zander, Axel R., Volin, Liisa, Heim, Dominik A., Schwerdtfeger, Rainer, Kolbe, Karin, Mayer, Jiri, Maertens, Johan A., Linkesch, Werner, Holler, Ernst, Koza, Vladimir, Bornhäuser, Martin, Einsele, Hermann, Bertz, Hartmut, Grishina, Olga, Socié, Gérard, and for the ATG-Fresenius Trial Group
- Subjects
Male ,Oncology ,Transplantation Conditioning ,medicine.medical_treatment ,Medizin ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Severity of Illness Index ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,HLA Antigens ,law ,immune system diseases ,hemic and lymphatic diseases ,Allogeneic hematopoietic stem-cell transplantation ,Medicine ,Prospective Studies ,Prospective cohort study ,Hematology ,Histocompatibility Testing ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Middle Aged ,3. Good health ,Survival Rate ,surgical procedures, operative ,030220 oncology & carcinogenesis ,Acute Disease ,Female ,Unrelated Donors ,Adult ,medicine.medical_specialty ,Allogeneic transplantation ,Adolescent ,Graft-versus-host-disease prophylaxis ,03 medical and health sciences ,Internal medicine ,Humans ,Transplantation, Homologous ,HLA-matching ,Survival rate ,Antilymphocyte Serum ,Transplantation ,business.industry ,Myeloablative Agonists ,Chronic Disease ,Immunology ,business ,030215 immunology - Abstract
Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD. © 2012 American Society for Blood and Marrow Transplantation.
- Full Text
- View/download PDF
28. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
- Author
-
Mathew, Nimitha R, Baumgartner, Francis, Braun, Lukas, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Markus, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst Müller, Thomas Niklaus, Schroeder, Thomas, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandros, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-De-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yves, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolaus, Ayuk, Francis, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, Van Der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andreas, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, McLornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Shah, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andreas, Neubauer, Andreas, Beelen, Dietrich, Mackensen, Andreas, Von Bubnoff, Nikolas, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justus, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert
- Subjects
hemic and lymphatic diseases ,610 Medicine & health ,neoplasms ,3. Good health - Abstract
Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD leukemia cells. This synergized with the allogeneic CD8 T cell response, leading to long-term survival in six mouse models of FLT3-ITD AML. Sorafenib-related IL-15 production caused an increase in CD8CD107aIFN-γ T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8 T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.
29. Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT – A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party
- Author
-
Penack, Olaf, Peczynski, Christophe, Werf, Steffie, Van Der, Finke, Jürgen, Ganser, Arnold, Schoemans, Helene, Pavlu, Jiri, Niittyvuopio, Riitta, Schroyens, Wilfried, Kaynar, Leylagül, Blau, Igor W., Velden, Walter J. F. M., Van Der, Sierra, Jorge, Cortelezzi, Agostino, Wulf, Gerald, Turlure, Pascal, Rovira, Montserrat, Ozkurt, Zubeydenur, Pascual-Cascon, Maria J., Moreira, Maria C., Clausen, Johannes, Greinix, Hildegard, Duarte, Rafael F., and Basak, Grzegorz W.
- Subjects
stem cell ,immunology ,ferritin ,biomarker ,iron metabolism ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit ,3. Good health ,transplantation - Abstract
Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 mu g/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, p < 0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.
30. Acute GVHD prophylaxis plus ATLG after myeloablative allogeneic haemopoietic peripheral blood stem-cell transplantation from HLA-identical siblings in patients with acute myeloid leukaemia in remission : final results of quality of life and long-term outcome analysis of a phase 3 randomised study
- Author
-
Francesca, Bonifazi, Carlos, Solano, Christine, Wolschke, Mariarosaria, Sessa, Francesca, Patriarca, Francesco, Zallio, Arnon, Nagler, Carmine, Selleri, Antonio Maria, Risitano, Giuseppe, Messina, Wolfgang, Bethge, Pilar, Herrera, Anna, Sureda, Angelo Michele, Carella, Michele, Cimminiello, Stefano, Guidi, Jürgen, Finke, Roberto, Sorasio, Christelle, Ferra, Jorge, Sierra, Domenico, Russo, Edoardo, Benedetti, Giuseppe, Milone, Fabio, Benedetti, Marion, Heinzelmann, Domenico, Pastore, Manuel, Jurado, Elisabetta, Terruzzi, Franco, Narni, Andreas, Völp, Francis, Ayuk, Tapani, Ruutu, Nicolaus, Kröger, Department of Medicine, Clinicum, HUS Comprehensive Cancer Center, Bonifazi, Francesca, Solano, Carlo, Wolschke, Christine, Sessa, Mariarosaria, Patriarca, Francesca, Zallio, Francesco, Nagler, Arnon, Selleri, Carmine, Risitano, Antonio Maria, Messina, Giuseppe, Bethge, Wolfgang, Herrera, Pilar, Sureda, Anna, Carella, Angelo Michele, Cimminiello, Michele, Guidi, Stefano, Finke, Jürgen, Sorasio, Roberto, Ferra, Christelle, Sierra, Jorge, Russo, Domenico, Benedetti, Edoardo, Milone, Giuseppe, Benedetti, Fabio, Heinzelmann, Marion, Pastore, Domenico, Jurado, Manuel, Terruzzi, Elisabetta, Narni, Franco, Völp, Andrea, Ayuk, Franci, Ruutu, Tapani, and Kröger, Nicolaus
- Subjects
Adult ,Male ,Sibling ,allogeneic transplant, GVHD ,Adolescent ,MATCHED UNRELATED DONORS ,GVHD ,MULTICENTER ,Graft vs Host Disease ,END-POINT ,HEMATOLOGICAL MALIGNANCIES ,Disease-Free Survival ,Young Adult ,HLA Antigens ,T-LYMPHOCYTE GLOBULIN ,VERSUS-HOST-DISEASE ,Humans ,HLA Antigen ,Aged ,Antilymphocyte Serum ,Siblings ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,allogeneic transplant ,RELAPSE-FREE SURVIVAL ,OPEN-LABEL ,ANTI-THYMOCYTE GLOBULIN ,Leukemia, Myeloid, Acute ,MARROW ,3121 General medicine, internal medicine and other clinical medicine ,Quality of Life ,Female ,Human - Abstract
We previously showed that human anti-T-lymphocyte globulin (ATLG) plus ciclosporin and methotrexate given to patients with acute leukaemia in remission, having allogeneic haemopoietic stem-cell transplantation with peripheral blood stem cells from an HLA-identical sibling donor after myeloablative conditioning, significantly reduced 2-year chronic graft-versus-host disease (cGVHD) incidence and severity, without increasing disease relapse and infections, and improves cGVHD-free and relapse-free survival (cGRFS). The aim of an extended follow-up study was the assessment of long-term outcomes, which are, in this context, scarcely reported in the literature. We report unpublished data on quality of life (QoL) from the original study and the results of a follow-up extension.In the original open-label study, patients with acute myeloid and lymphoblastic leukaemia in first or subsequent remission, having sibling HLA-identical allogeneic peripheral blood stem-cell transplantation, were randomly assigned (1:1) to receive ATLG plus standard GVHD prophylaxis with ciclosporin and short-term methotrexate (ATLG group) or standard GVHD prophylaxis without ATLG (non-ATLG group). Conditioning regimens were cyclophosphamide 120 mg/kg with either total body irradiation (12 Gy) or busulfan (12·8 mg/kg intravenously or 16 mg/kg orally), with or without etoposide (30-60 mg/kg). Randomisation was stratified according to centre and disease risk. The primary endpoint was cumulative incidence of cGVHD at 2 years. The primary and secondary endpoints, excluding QoL, have been published. QoL, assessed using European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-HDC29 questionnaires, was an unpublished secondary endpoint, which we now report here. A follow-up extension was then done, with the primary endpoint cumulative incidence of cGVHD. Enrolment has been completed for both studies. The original trial (number, NCT00678275) and follow-up extension (number, NCT03042676) are registered at ClinicalTrials.gov.In the original study, from Dec 14, 2006, to Feb 2, 2012, 161 patients were enrolled and 155 were randomly assigned to either the ATLG group (n=83) or to the non-ATLG group (n=72). In the follow-up study, which started on Feb 7, 2017, and was completed on June 30, 2017, 61 patients were included in the ATLG group and 53 were included in the non-ATLG group. Global health status showed a more favourable time course in the ATLG group compared with the non-ATLG group (p=0·02; treatment by visit interaction). ATLG was descriptively superior to non-ATLG at 24 months for physical function (points estimate -14·8 [95% CI -26·4 to -3·1]; p=0·014) and social function (-19·1 [-38·0 to -0·2]; p=0·047), gastrointestinal side-effects (8·8 [2·5-15·1]; p=0·008) and effect on family (13·5 [1·2-25·8]; p=0·032). Extended follow-up (median 5·9 years [IQR 1·7-7·9]) confirmed a lower 5-year cGVHD incidence (30·0% [95% CI 21·4-41·9] vs 69·1% [59·1-80·1]; analysis for entire follow-up, p0·001), no increase in relapses (35·4% [26·4-47·5] vs 22·5% [14·6-34·7]; p=0·09), improved cGRFS (34·3% [24·2-44·5] vs 13·9% [7·1-22·9]; p=0·005), and fewer patients still in immunosuppression (9·6% vs 28·3%; p=0·017) in the ATLG group compared with the non-ATLG group. 5-year overall survival, relapse-free survival, and non-relapse mortality did not differ significantly between groups.The addition of ATLG to standard GVHD prophylaxis improves the probability of surviving without disease relapse and cGVHD after myeloablative peripheral blood stem-cell transplantation from an HLA-identical sibling donor for patients with acute leukaemia in remission. Further additional benefits are better QoL and shorter immunosuppressive treatment compared with standard GVHD prophylaxis without ATLG. Therefore, in this setting, ATLG plus standard GVHD prophylaxis should be preferred over the standard GVHD prophylaxis alone.Neovii Biotech.
- Published
- 2019
31. Expanding transplant options to patients over 50 years. Improved outcome after reduced intensity conditioning mismatched-unrelated donor transplantation for patients with acute myeloid leukemia: a report from the Acute Leukemia Working Party of the EBMT
- Author
-
Jordi Esteve, Gérard Socié, Fabio Ciceri, Jürgen Finke, Donald Bunjes, Myriam Labopin, Gerhard Ehninger, Norbert Claude Gorin, Bertram Glass, Nicolaus Kröger, Per Ljungman, Rainer Schwerdtfeger, Mohamad Mohty, Charles Craddock, Frédéric Baron, Sebastian Giebel, Bipin N. Savani, Arnon Nagler, Dietger Niederwieser, Christoph Schmid, Savani, Bipin N., Labopin, Myriam, Kröger, Nicolau, Finke, Jürgen, Ehninger, Gerhard, Niederwieser, Dietger, Schwerdtfeger, Rainer, Bunjes, Donald, Glass, Bertram, Socié, Gerard, Ljungman, Per, Craddock, Charle, Baron, Frédéric, Ciceri, Fabio, Gorin, Norbert Claude, Esteve, Jordi, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon
- Subjects
Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Survival analysis ,Aged ,Retrospective Studies ,Aged, 80 and over ,Acute leukemia ,business.industry ,Graft Survival ,Age Factors ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,Retrospective cohort study ,Hematology ,Middle Aged ,Survival Analysis ,Surgery ,Transplantation ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Cohort ,Female ,Unrelated Donors ,business ,030215 immunology - Abstract
The outcome of patients undergoing HLA-matched unrelated donor allogeneic hematopoietic cell transplantation following reduced-intensity conditioning or myeloablative regimens is reported to be equivalent; however, it is not known if the intensity of the conditioning impacts outcomes after mismatched unrelated donor transplantation for acute myeloid leukemia. Eight hundred and eighty three patients receiving reduced-intensity conditioning were compared with 1041 myeloablative conditioning regimen recipients in the setting of mismatched unrelated donor transplantation. The donor graft was HLA-matched at 9/10 in 872 (83.8%) and at 8/10 in 169 (16.2%) myeloablative conditioning recipients, while in the reduced-intensity conditioning cohort, 754 (85.4%) and 129 (14.6%) were matched at 9/10 and 8/10 loci, respectively. Myeloablative conditioning regimen recipients were younger, 70% being
- Published
- 2016
32. Oncogenic JAK2 V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms
- Author
-
Khalid Shoumariyeh, Robert Zeiser, Sivahari P. Gorantla, Sebastian Halbach, Frederike A. Hartl, Alica J. Emhardt, Julius Wehrle, Jonas S. Jutzi, Sebastian Fuchs, Ioanna Triviai, Sandra Duquesne, Michael Hettich, Annette Schmitt-Graeff, Eliana Ruggiero, Susana Minguet, Wolfgang Melchinger, Jürgen Finke, Chiara Bonini, Nicolaus Kröger, Pia Veratti, Anna Lena Illert, Bruce R. Blazar, Melanie Boerries, Mark Bartholomä, Teresa Poggio, Geoffrey R. Hill, Steven W. Lane, Gabriele Niedermann, Petya Apostolova, Slavica Vuckovic, Nikolas von Bubnoff, Konrad Aumann, Hauke Busch, Stephan Ehl, Florian H. Heidel, Sandra Pennisi, Dietmar Pfeifer, Justus Duyster, Cornelius Miething, David O’Sullivan, Marie Follo, Lukas Braun, Christine Dierks, Heiko Becker, Heike L. Pahl, Jan Rohr, Tilman Brummer, Alessandro Prestipino, Erika L. Pearce, Prestipino, Alessandro, Emhardt, Alica J, Aumann, Konrad, O'Sullivan, David, Gorantla, Sivahari P, Duquesne, Sandra, Melchinger, Wolfgang, Braun, Luka, Vuckovic, Slavica, Boerries, Melanie, Busch, Hauke, Halbach, Sebastian, Pennisi, Sandra, Poggio, Teresa, Apostolova, Petya, Veratti, Pia, Hettich, Michael, Niedermann, Gabriele, Bartholomä, Mark, Shoumariyeh, Khalid, Jutzi, Jonas S, Wehrle, Juliu, Dierks, Christine, Becker, Heiko, Schmitt-Graeff, Annette, Follo, Marie, Pfeifer, Dietmar, Rohr, Jan, Fuchs, Sebastian, Ehl, Stephan, Hartl, Frederike A, Minguet, Susana, Miething, Corneliu, Heidel, Florian H, Kröger, Nicolau, Triviai, Ioanna, Brummer, Tilman, Finke, Jürgen, Illert, Anna L, Ruggiero, Eliana, Bonini, Chiara, Duyster, Justu, Pahl, Heike L, Lane, Steven W, Hill, Geoffrey R, Blazar, Bruce R, von Bubnoff, Nikola, Pearce, Erika L, and Zeiser, Robert
- Subjects
0301 basic medicine ,Janus kinase 2 ,Myeloid ,biology ,T cell ,food and beverages ,General Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,hemic and lymphatic diseases ,030220 oncology & carcinogenesis ,biology.protein ,medicine ,STAT protein ,Cancer research ,Receptor ,STAT3 ,STAT5 ,K562 cells - Abstract
Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2V617F–myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition. JAK2V617F mutational burden, pSTAT3, and PD-L1 expression were highest in primary MPN patient–derived monocytes, megakaryocytes, and platelets. PD-1 (programmed death receptor 1) inhibition prolonged survival in human MPN xenograft and primary murine MPN models. This effect was dependent on T cells. Mechanistically, PD-L1 surface expression in JAK2V617F-mutant cells affected metabolism and cell cycle progression of T cells. In summary, we report that in MPN, constitutive JAK2/STAT3/STAT5 activation, mainly in monocytes, megakaryocytes, and platelets, caused PD-L1–mediated immune escape by reducing T cell activation, metabolic activity, and cell cycle progression. The susceptibility of JAK2V617F-mutant MPN to PD-1 targeting paves the way for immunomodulatory approaches relying on PD-1 inhibition.
- Published
- 2018
33. HLA mismatched donors in patients with myelodysplastic syndrome: an EBMT registry analysis
- Author
-
Patrice Chevallier, Nicolaus Kröger, Christine Wolschke, Maria Jesús Pascual Cascon, Raphaël Porcher, Yener Koc, Emanuele Angelucci, Arnon Nagler, Rohini Radia, Hélène Labussière-Wallet, Eliane Gluckman, Nathalie Fegueux, Friedrich Stölzel, Didier Blaise, Theo de Witte, Linda Koster, Fabio Ciceri, Jürgen Finke, Mareike Verbeek, Victoria T Potter, Ibrahim Yakoub-Agha, Jan J. Cornelissen, Annalisa Ruggeri, Marie Robin, Alessandro Rambaldi, Robin, Marie, Porcher, Raphaël, Ruggeri, Annalisa, Blaise, Didier, Wolschke, Christine, Koster, Linda, Angelucci, Emanuele, Stölzel, Friedrich, Potter, Victoria, Yakoub-Agha, Ibrahim, Koc, Yener, Ciceri, Fabio, Finke, Jürgen, Labussière-Wallet, Hélène, Cascon, Maria Jesús Pascual, Verbeek, Mareike, Rambaldi, Alessandro, Cornelissen, Jan J, Chevallier, Patrice, Radia, Rohini, Nagler, Arnon, Fegueux, Nathalie, Gluckman, Eliane, de Witte, Theo, Kröger, Nicolaus, and Hematology
- Subjects
Male ,Oncology ,medicine.medical_specialty ,Prognostic variable ,Cyclophosphamide ,HLA mismatched donor ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Graft vs Host Disease ,Human leukocyte antigen ,Hematopoietic stem cell transplantation ,Lower risk ,Disease-Free Survival ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,HLA Antigens ,Risk Factors ,Internal medicine ,HLA-mismatched donor ,medicine ,MDS ,Humans ,haplo-identical transplant ,Registries ,Prospective cohort study ,Aged ,Retrospective Studies ,Transplantation ,Haploidentical transplant ,business.industry ,Histocompatibility Testing ,Confounding ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Survival Rate ,Myelodysplastic Syndromes ,030220 oncology & carcinogenesis ,Cord blood ,Female ,Unrelated Donors ,business ,Myelodysplastic syndrome ,Follow-Up Studies ,030215 immunology ,medicine.drug - Abstract
Recently, haploidentical transplantation (haplo) using post-transplant cyclophosphamide (PTCy) has been reported to give very encouraging results in patients with hematological malignancies. Patients who have no HLA-matched donor currently have the choice between a mismatched unrelated donor, an unrelated cord blood (CB) donor, and a haploidentical related donor. The aim of our study is to compare the outcome of patients with myelodysplastic syndrome (MDS) who have been transplanted from a haploidentical donor using PTCy, an HLA-mismatched unrelated donor (marrow or peripheral blood stem cells), or an unrelated mismatched CB donor. A total of 833 MDS patients from the European Group for Blood and Marrow Transplantation (EBMT) registry, transplanted between 2011 and 2016, were identified. The potential benefit of haplo was compared with mismatched unrelated and CB donors in an adjusted and weighted model taking into account potential confounders and other prognostic variables. Haplo was at lower risk of acute graft-versus-host disease (GVHD) than mismatched unrelated donor (P = .010) but at similar risk than CB. Progression-free survival was better after haplo (versus mismatched unrelated, P = .056; versus CB, P = .003) and overall survival tended to be superior after haplo (versus mismatched unrelated, P = .082; versus CB, P = .002). Nonrelapse mortality was not significantly different between haplo and mismatched unrelated donors. Relapse risk was not influenced by the type of donor. In conclusion, patients with MDS from the EBMT registry receiving hematopoietic stem cell transplantation from a haplo donor have significantly better outcome than those receiving hematopoietic stem cell transplantation from a CB donor and at least similar or better outcome than with a mismatched unrelated donor. Prospective studies comparing the type of donors will be needed to confirm this assumption.
- Published
- 2018
34. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study
- Author
-
Katie S. Gatwood, Jordi Esteve, Patrice Chevallier, Peter Dreger, Matthias Stelljes, Myriam Labopin, Bipin N. Savani, Norbert Claude Gorin, Arnold Ganser, Audrey Mailhol, Juergen Finke, Dietrich W. Beelen, Sebastian Giebel, Ghulam J. Mufti, Gerhard Ehninger, Arnon Nagler, Christoph Schmid, Frédéric Baron, Didier Blaise, Ariane Boumendil, Dietger Niederwieser, Mohamad Mohty, Fabio Ciceri, Salyka Sengsayadeth, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Réanimation Médicale [CHU Saint-Antoine], Hannover Medical School [Hannover] (MHH), Westfälische Wilhelms-Universität Münster (WWU), University of Münster, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Dept. of Bone Marrow Transplantation, University Hospital, Essen, University Hospital Essen, Division Hematology, Oncology and Hemostasiology [Leipzig, Germany], University Hospital in Leipzig [Germany], Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Department of Medicine V, Universität Heidelberg [Heidelberg], King's College Hospital (KCH), Département d'Hématologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (DRPH/SRBE/LTCRA), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), IRCCS Ospedale San Raffaele [Milan, Italy], Université de Liège, Ludwig Maximilian University [Munich] (LMU), Cancer Center Gliwice, Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gatwood, Katie S., Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N., Nagler, Arnon, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg] = Heidelberg University, Laboratoire de Thérapie Cellulaire et de Radioprotection Accidentelle (IRSN/DRPH/SRBE/LTCRA), Service de RadioBiologie et d'Epidémiologie (IRSN/DRPH/SRBE), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN)
- Subjects
Adult ,Male ,medicine.medical_specialty ,Secondary ,Transplantation Conditioning ,Adolescent ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Secondary Acute Myeloid Leukemia ,Cumulative incidence ,ddc:610 ,Aged ,Bone Marrow Transplantation ,Aged, 80 and over ,Acute leukemia ,Univariate analysis ,Transplantation ,Acute myeloid leukemia ,Toxicity ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,Confidence interval ,3. Good health ,Allogeneic stem cell transplantation ,Europe ,Antileukemic effect ,Leukemia, Myeloid, Acute ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,business ,030215 immunology ,Conditioning - Abstract
International audience; Secondary acute myeloid leukemia (sAML) has been associated with inferior outcomes compared with de novo AML. Little is known about patient risk factors and outcomes in sAML after allogeneic hematopoietic stem cell transplantation (HCT); thus, this large systemic analysis of the European Society for Blood and Bone Marrow Transplantation registry was performed. This study included 4997 patients with sAML who received HCT from 2000 to 2016. In univariate analysis the 2-year cumulative incidence of chronic graft-versus-host disease (GVHD), relapse, and nonrelapse mortality (NRM) were 33.5% (95% confidence interval [Cl], 32% to 34.9%), 33.7% (95% CI, 32.3% to 35.1%), and 27.5% (95% CI, 26.1% to 28.7%), respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free survival (GRFS) at 2 years were 44.5% (95% CI, 43% to 46%), 38.8% (95% CI, 37.4% to 40.3%), and 27.2% (95% Cl, 25.9% to 28.6%), respectively. In multivariate analysis, patients receiving myeloablative regimens had decreased relapse (hazard ratio, .859; 95% CI, .761 to .97; P = .01), higher NRM (hazard ratio, 1.175; 95% CI, 1.03 to 1341; P = .02), and no differences in OS, LFS, and GRFS compared with patients receiving reduced-intensity conditioning regimens. Active disease, adverse cytogenetics, older age, Karnofsky performance status (
- Published
- 2018
35. Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells
- Author
-
Donald Bunjes, Sebastian Halbach, Dietmar Pfeifer, Philipp Hemmati, Robert S. Negrin, Fabio Ciceri, Jean-Yves Cahn, Markus Ditschkowski, Pavan Reddy, Kathrin Hanke, Daniela Dörfel, Susan Klaeger, Jürgen Finke, Zehan Hu, Gabriele Ihorst, Gérard Socié, Sanaz Taromi, Andreas Hochhaus, Glen A Kennedy, Omid Shah, Andreas Neubauer, Robert Thimme, Michael Schultheiss, Sabine Spath, Dietrich W. Beelen, Sandra Duquesne, Arnim Weber, Geoffrey R. Hill, Ronjon Chakraverty, Jürgen Kuball, Guido Kobbe, Nikolas von Bubnoff, Andrea S. Henden, Betul Oran, Burkhard Becher, Bernhard Kuster, Christoph Rummelt, Lena Osswald, Hartmut Bertz, Wolfgang Bethge, Eva-Maria Wagner, Arnon Nagler, Eliana Ruggiero, Saar Gill, Miguel Waterhouse, Andreas Mackensen, Dominik Bettinger, Francis Baumgartner, Florian Kuchenbauer, Anita Sarma, Takanori Teshima, Erika L. Pearce, Antonia M.S. Müller, Kathleen Stabla, John M. Magenau, Evelyn Ullrich, Nicolaus Kröger, Georg Häcker, Simone Thomas, Myriam Labopin, Ghulam J. Mufti, Jan E. Ehlert, Lutz P. Müller, Marie Follo, Dominik Wolf, Tony Andreas Müller, Michael Lübbert, Jacqueline Schnell, Christof Scheid, Takeshi Kondo, Donal P. McLornan, Thomas Pabst, Konrad Wilhelm, Chiara Bonini, Wolf Rösler, Simon Richardson, Cordula A. Jilg, Andrea Schmidts, Luca Vago, Joseph H. Antin, Annette Schmitt-Graeff, Yakup Tanriver, Michael A. Caligiuri, Wolfgang Herr, Kai-Li Yan, Lukas Braun, Daniel J. Weisdorf, Katayoun Rezvani, Giang Lam Vuong, Tilman Brummer, Stephan Meckel, Ralph Wäsch, Geoffroy Andrieux, Soroush Doostkam, Hauke Busch, Dennis Dong Hwan Kim, Sabine Gerull, Bruce R. Blazar, Robert Zeiser, Merav Bar, Flore Sicre-de-Fontbrune, Daniel Feger, Melanie Börries, Wolfgang Melchinger, Petya Apostolova, C. Leiber, Udo Holtick, Walter J.F.M. van der Velden, Renate Arnold, Rainer Claus, Justus Duyster, Nimitha R. Mathew, David O’Sullivan, Alexandros Spyridonidis, S K Metzelder, Thomas Schroeder, Jörg Halter, Johanna Haag, Friedrich Stölzel, Christoph Schmid, Anna Lena Illert, Claudia Lengerke, Björn Hackanson, Joern Dengjel, Francis Ayuk, Rainer Ordemann, Sonia Tugues, Marco Prinz, Inken Hilgendorf, Andreas Burchert, Mathew, Nimitha R, Baumgartner, Franci, Braun, Luka, O'Sullivan, David, Thomas, Simone, Waterhouse, Miguel, Müller, Tony A, Hanke, Kathrin, Taromi, Sanaz, Apostolova, Petya, Illert, Anna L, Melchinger, Wolfgang, Duquesne, Sandra, Schmitt-Graeff, Annette, Osswald, Lena, Yan, Kai-Li, Weber, Arnim, Tugues, Sonia, Spath, Sabine, Pfeifer, Dietmar, Follo, Marie, Claus, Rainer, Lübbert, Michael, Rummelt, Christoph, Bertz, Hartmut, Wäsch, Ralph, Haag, Johanna, Schmidts, Andrea, Schultheiss, Michael, Bettinger, Dominik, Thimme, Robert, Ullrich, Evelyn, Tanriver, Yakup, Vuong, Giang Lam, Arnold, Renate, Hemmati, Philipp, Wolf, Dominik, Ditschkowski, Marku, Jilg, Cordula, Wilhelm, Konrad, Leiber, Christian, Gerull, Sabine, Halter, Jörg, Lengerke, Claudia, Pabst, Thoma, Schroeder, Thoma, Kobbe, Guido, Rösler, Wolf, Doostkam, Soroush, Meckel, Stephan, Stabla, Kathleen, Metzelder, Stephan K, Halbach, Sebastian, Brummer, Tilman, Hu, Zehan, Dengjel, Joern, Hackanson, Björn, Schmid, Christoph, Holtick, Udo, Scheid, Christof, Spyridonidis, Alexandro, Stölzel, Friedrich, Ordemann, Rainer, Müller, Lutz P, Sicre-de-Fontbrune, Flore, Ihorst, Gabriele, Kuball, Jürgen, Ehlert, Jan E, Feger, Daniel, Wagner, Eva-Maria, Cahn, Jean-Yve, Schnell, Jacqueline, Kuchenbauer, Florian, Bunjes, Donald, Chakraverty, Ronjon, Richardson, Simon, Gill, Saar, Kröger, Nicolau, Ayuk, Franci, Vago, Luca, Ciceri, Fabio, Müller, Antonia M, Kondo, Takeshi, Teshima, Takanori, Klaeger, Susan, Kuster, Bernhard, Kim, Dennis Dong Hwan, Weisdorf, Daniel, van der Velden, Walter, Dörfel, Daniela, Bethge, Wolfgang, Hilgendorf, Inken, Hochhaus, Andrea, Andrieux, Geoffroy, Börries, Melanie, Busch, Hauke, Magenau, John, Reddy, Pavan, Labopin, Myriam, Antin, Joseph H, Henden, Andrea S, Hill, Geoffrey R, Kennedy, Glen A, Bar, Merav, Sarma, Anita, Mclornan, Donal, Mufti, Ghulam, Oran, Betul, Rezvani, Katayoun, Sha, Omid, Negrin, Robert S, Nagler, Arnon, Prinz, Marco, Burchert, Andrea, Neubauer, Andrea, Beelen, Dietrich, Mackensen, Andrea, von Bubnoff, Nikola, Herr, Wolfgang, Becher, Burkhard, Socié, Gerard, Caligiuri, Michael A, Ruggiero, Eliana, Bonini, Chiara, Häcker, Georg, Duyster, Justu, Finke, Jürgen, Pearce, Erika, Blazar, Bruce R, and Zeiser, Robert
- Subjects
0301 basic medicine ,Sorafenib ,medicine.drug_class ,Interferon Regulatory Factor-7 ,Medizin ,Graft vs Host Disease ,CD8-Positive T-Lymphocytes ,Article ,General Biochemistry, Genetics and Molecular Biology ,Tyrosine-kinase inhibitor ,Mice ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Animals ,Humans ,Transplantation, Homologous ,Medicine ,ddc:610 ,neoplasms ,Interleukin-15 ,business.industry ,Hematopoietic Stem Cell Transplantation ,Myeloid leukemia ,General Medicine ,Cellular Reprogramming ,medicine.disease ,Activating Transcription Factor 4 ,3. Good health ,Gene Expression Regulation, Neoplastic ,Transplantation ,Leukemia, Myeloid, Acute ,Leukemia ,030104 developmental biology ,fms-Like Tyrosine Kinase 3 ,Tandem Repeat Sequences ,Interleukin 15 ,030220 oncology & carcinogenesis ,Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5] ,Cancer research ,IRF7 ,business ,CD8 ,medicine.drug - Abstract
Contains fulltext : 190745.pdf (Publisher’s version ) (Closed access) Individuals with acute myeloid leukemia (AML) harboring an internal tandem duplication (ITD) in the gene encoding Fms-related tyrosine kinase 3 (FLT3) who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) have a 1-year survival rate below 20%. We observed that sorafenib, a multitargeted tyrosine kinase inhibitor, increased IL-15 production by FLT3-ITD(+) leukemia cells. This synergized with the allogeneic CD8(+) T cell response, leading to long-term survival in six mouse models of FLT3-ITD(+) AML. Sorafenib-related IL-15 production caused an increase in CD8(+)CD107a(+)IFN-gamma(+) T cells with features of longevity (high levels of Bcl-2 and reduced PD-1 levels), which eradicated leukemia in secondary recipients. Mechanistically, sorafenib reduced expression of the transcription factor ATF4, thereby blocking negative regulation of interferon regulatory factor 7 (IRF7) activation, which enhanced IL-15 transcription. Both IRF7 knockdown and ATF4 overexpression in leukemia cells antagonized sorafenib-induced IL-15 production in vitro. Human FLT3-ITD(+) AML cells obtained from sorafenib responders following sorafenib therapy showed increased levels of IL-15, phosphorylated IRF7, and a transcriptionally active IRF7 chromatin state. The mitochondrial spare respiratory capacity and glycolytic capacity of CD8(+) T cells increased upon sorafenib treatment in sorafenib responders but not in nonresponders. Our findings indicate that the synergism of T cells and sorafenib is mediated via reduced ATF4 expression, causing activation of the IRF7-IL-15 axis in leukemia cells and thereby leading to metabolic reprogramming of leukemia-reactive T cells in humans. Therefore, sorafenib treatment has the potential to contribute to an immune-mediated cure of FLT3-ITD-mutant AML relapse, an otherwise fatal complication after allo-HCT.
- Published
- 2018
- Full Text
- View/download PDF
36. Conditioning intensity in secondary AML with prior myelodysplastic syndrome/myeloproliferative disorders: an EBMT ALWP study
- Author
-
Sebastian Giebel, Arnold Ganser, Myriam Labopin, Audrey Mailhol, Peter Dreger, Gerhard Ehninger, Dietger Niederwieser, Ariane Boumendil, Dietrich W. Beelen, Norbert Claude Gorin, Salyka Sengsayadeth, Katie S. Gatwood, Fabio Ciceri, Jürgen Finke, Mohamad Mohty, Arnon Nagler, Matthias Stelljes, Patrice Chevallier, Ghulam J. Mufti, Frédéric Baron, Bipin N. Savani, Christoph Schmid, Didier Blaise, Maria H. Gilleece, Jordi Esteve, Service d’Hématologie [Institut Paoli Calmettes, Marseille], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sengsayadeth, Salyka, Gatwood, Katie S, Boumendil, Ariane, Labopin, Myriam, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthia, Ehninger, Gerhard, Beelen, Dietrich, Niederwieser, Dietger, Blaise, Didier, Dreger, Peter, Mufti, Ghulam, Chevallier, Patrice, Mailhol, Audrey, Gilleece, Maria H, Gorin, Norbert, Esteve, Jordi, Ciceri, Fabio, Baron, Frederic, Schmid, Christoph, Giebel, Sebastian, Mohty, Mohamad, Savani, Bipin N, and Nagler, Arnon
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Transplantation Conditioning ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Medizin ,Hematopoietic stem cell transplantation ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,hemic and lymphatic diseases ,medicine ,Humans ,Cumulative incidence ,Registries ,Survival rate ,Aged ,Retrospective Studies ,Acute leukemia ,Univariate analysis ,Transplantation ,business.industry ,Hazard ratio ,Hematopoietic Stem Cell Transplantation ,food and beverages ,Retrospective cohort study ,Neoplasms, Second Primary ,Hematology ,Middle Aged ,Allografts ,3. Good health ,Survival Rate ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Hematologic Neoplasms ,Myelodysplastic Syndromes ,Female ,business ,030215 immunology - Abstract
Patients with secondary AML (sAML) with antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs) tend to have high-risk disease based on the older age of patients, high-risk cytogenetics, and higher number of prior treatments. Allogeneic hematopoietic cell transplant (HCT) is the only potentially curative therapy available. Eight hundred and two adults with sAML and prior MDS/MPN who received a first HCT between 2000 and 2016 were included in the European Society for Blood and Marrow Transplant (EBMT) Acute Leukemia Working Party (ALWP) study. Median age of the cohort was 59.6 years (range, 18.6-78.6 years). Myeloablative conditioning (MAC) was given to 40% of patients, and 60% received reduced-intensity conditioning (RIC). Overall, the 2-year cumulative incidence of relapse (RI) was 37%, leukemia-free survival (LFS) was 40%, overall survival (OS) was 46%, nonrelapse mortality (NRM) was 23%, and chronic graft-versus-host disease (cGVHD) was 39%. In univariate analysis, a statistical difference between conditioning regimens 6 months after HCT in favor of the MAC group was noted with regard to RI (hazard ratio [HR], 1.47; P = .03), LFS (HR, 1.43; P = .01), and OS (HR, 1.55; P < .05). There was no difference in the cumulative incidence of NRM (HR, 1.38; P = .15). This effect was similarly seen in multivariate analysis (MVA): cumulative incidence of relapse (HR, 1.79; P < .05), LFS (HR, 1.43; P = .02), and OS (HR, 1.53; P = .005) with no difference in NRM (HR, 1; P = .98). This EBMT ALWP analysis suggests that long-term survival can be achieved in patients with sAML with antecedent MDS/MPN and that MAC is a suitable conditioning regimen in patients with sAML.
- Published
- 2018
37. Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease
- Author
-
Fabio Benedetti, Angelo Michele Carella, Michele Cimminiello, Elisabetta Terruzzi, Jaime Pérez De Oteiza, Kröger N, Francesca Bonifazi, Nicola Mordini, Rafael F. Duarte, Jorge Sierra, Jürgen Finke, Francesca Patriarca, Christine Wolschke, Carlos Solano, Franco Narni, Antonio M. Risitano, Domenico Pastore, Wolfgang Bethge, Francis Ayuk, Mario Petrini, Carmine Selleri, Tapani Ruutu, Giuseppe Messina, Arnon Nagler, Andreas Völp, Christelle Ferra, Marion Heinzelmann, Massimo Pini, Giuseppe Bandini, Manuel Jurado, Giuseppe Milone, Domenico Russo, Stefano Guidi, [Kröge,N, Wolschke ,C, Heinzelmann,M, Ayuk,F ] University Medical Center Hamburg-Eppendorf,Hamburg, Germany. [Finke,J] University Hospital Freiburg, Freiburg ,Germany. [Bethge,W] University Hospital Tübingen, Tübingen, Germany. [Völp,A] Psy Consult, Frankfurt, Germany. [Solano,C] Hospital Clinico Universitario, Valencia, Spain. [Pérez de Oteiza,J] Hospital Ramon y Cajal, Madrid, Spain. [Duarte,R] Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. [Ferra,C] Servicio de Hematología, Institut Català d’Oncologia, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. [Sierra,J] Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. [Jurado,M] Hospital Virgen de las Nieves, Granada, Spain. [Bandini,G, Bonifaz,F] Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy. [Patriarca,F] Hematology, DISM, University Udine, Udine. Azienda Ospedaliera SS Antonio e Biagio e C. Arrigo, Alessandria, Italy. [Pini,M] Università Federico II di Napoli, Naples, Italy. [Selleri,C, Risitano,A) A.O. Bianchi-Melacrino-Morelli, Reggio Calabria, Italy. [Messina,G] Ospedale Casa Sollievo della Sofferenza IRCCCS, San Giovanni Rotondo, Italy. [Carella,AM] Azienda Ospedaliera San Carlo, Potenza, Italy. [Cimminiello,M] Azienda Ospedaliera Careggi, Florence, Italy. [Guido,E] Ospedale Santa Croce, e Carle, Cuneo, Italy. [Mordini,N] University of Brescia, Department of Clinical and Experimental Sciences, Brescia, Italy. [Russo,D] University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy. [Petrini,M] Programma di Trapianto Emopoietico Metropolitano, Azienda Policlinico-Vittorio Emanuele, Catania, Italy. [Milone,R] Policlinico G.B. Rossi, Verona, Italy. [Benedetti,F] Azienda Ospedaliera, Universitaria Ospedale, Bari, Italy. [Pastore,D] Ospedale San Gerardo, Monza, Italy. [Terruzzi,E] Policlinico Modena, Modena, Italy. [Narni,F] Università di Salerno, Salerno, Italy. [Nagler,A] Chaim Sheba Medical Center, Tel Hashomer, Ramat-Gan, Israel. [Tapani,R] Helsinki University Hospital, Helsinki., Supported by a research grant from Neovii Biotech and by the European Society for Blood and Marrow Transplantation (EBMT) as an EBMT-labeled-study of the Chronic Malignancies Working Party., Kröger, Nicolau, Solano, Carlo, Wolschke, Christine, Bandini, Giuseppe, Patriarca, Francesca, Pini, Massimo, Nagler, Arnon, Selleri, Carmine, Risitano, ANTONIO MARIA, Messina, Giuseppe, Bethge, Wolfgang, De Oteiza, Jaime Pérez, Duarte, Rafael, Carella, Angelo Michele, Cimminiello, Michele, Guidi, Stefano, Finke, Jürgen, Mordini, Nicola, Ferra, Christelle, Sierra, Jorge, Russo, Domenico, Petrini, Mario, Milone, Giuseppe, Benedetti, Fabio, Heinzelmann, Marion, Pastore, Domenico, Jurado, Manuel, Terruzzi, Elisabetta, Narni, Franco, Völp, Andrea, Ayuk, Franci, Ruutu, Tapani, and Bonifazi, Francesca
- Subjects
Male ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Models, Statistical::Proportional Hazards Models [Medical Subject Headings] ,T-Lymphocytes ,Phases of clinical research ,Graft vs Host Disease ,Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,Linfocitos t ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Immunosuppressive Agent ,0302 clinical medicine ,Trasplante homólogo ,Estudios prospectivos ,Medicine ,Cumulative incidence ,Prospective Studies ,Prospective cohort study ,Child ,Transplantation, Homologou ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Immune Sera::Antilymphocyte Serum [Medical Subject Headings] ,Acute leukemia ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Chronic Disease [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Child::Child, Preschool [Medical Subject Headings] ,Medicine (all) ,Incidence ,Suero antilinfocítico ,General Medicine ,Middle Aged ,Modelos de riesgos proporcionales ,3. Good health ,Humanos ,Survival Rate ,030220 oncology & carcinogenesis ,Named Groups::Persons::Age Groups::Adolescent [Medical Subject Headings] ,Child, Preschool ,Female ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic Factors::Immunosuppressive Agents [Medical Subject Headings] ,Immunosuppressive Agents ,Human ,Homologous ,Adult ,medicine.medical_specialty ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings] ,Adolescent ,Enfermedad injerto contra huésped ,Disease-Free Survival ,03 medical and health sciences ,Young Adult ,Internal medicine ,Named Groups::Persons::Age Groups::Adult [Medical Subject Headings] ,Humans ,Transplantation, Homologous ,Supervivencia sin enfermedad ,Preschool ,Survival rate ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Disease-Free Survival [Medical Subject Headings] ,Named Groups::Persons::Age Groups::Child [Medical Subject Headings] ,Antilymphocyte Serum ,Proportional Hazards Models ,Transplantation ,business.industry ,Enfermedad crónica ,medicine.disease ,Inmunosupresores ,Anti-thymocyte globulin ,Surgery ,Diseases::Immune System Diseases::Graft vs Host Disease [Medical Subject Headings] ,Prospective Studie ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Transplantation, Homologous [Medical Subject Headings] ,Graft-versus-host disease ,T-Lymphocyte ,Check Tags::Female [Medical Subject Headings] ,Chronic Disease ,Proportional Hazards Model ,business ,030215 immunology - Abstract
Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; BACKGROUND Chronic graft-versus-host disease (GVHD) is the leading cause of later illness and death after allogeneic hematopoietic stem-cell transplantation. We hypothesized that the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia would result in a significant reduction in chronic GVHD 2 years after allogeneic peripheral-blood stem-cell transplantation from an HLA-identical sibling. METHODS We conducted a prospective, multicenter, open-label, randomized phase 3 study of ATG as part of a conditioning regimen. A total of 168 patients were enrolled at 27 centers. Patients were randomly assigned in a 1:1 ratio to receive ATG or not receive ATG, with stratification according to center and risk of disease. RESULTS After a median follow-up of 24 months, the cumulative incidence of chronic GVHD was 32.2% (95% confidence interval [CI], 22.1 to 46.7) in the ATG group and 68.7% (95% CI, 58.4 to 80.7) in the non-ATG group (P
- Published
- 2016
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.