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4. Long-Term Results of Allogeneic Stem Cell Transplantation in Adult Ph- Negative High-Risk Acute Lymphoblastic Leukemia

Author

Beelen, Dietrich W., Arnold, Renate, Stelljes, Matthias, Alakel, Nael, Brecht, Arne, Bug, Gesine, Bunjes, Donald, Faul, Christoph, Finke, Jürgen, Franke, Georg-Nikolaus, Holler, Ernst, Kobbe, Guido, Kröger, Nicolaus, Rösler, Wolf, Scheid, Christof, Schönland, Stefan, Stadler, Michael, Tischer, Johanna, Wagner-Drouet, Eva, Wendelin, Knut, Brüggemann, Monika, Reiser, Lena, Hoelzer, Dieter, and Gökbuget, Nicola

Published
2022
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5. Role of allogeneic transplantation in chronic myelomonocytic leukemia: an international collaborative analysis

Author

Robin, Marie, de Wreede, Liesbeth C., Padron, Eric, Bakunina, Katerina, Fenaux, Pierre, Koster, Linda, Nazha, Aziz, Beelen, Dietrich W., Rampal, Raajit K., Sockel, Katja, Komrokji, Rami S., Gagelmann, Nico, Eikema, Dirk-Jan, Radujkovic, Aleksandar, Finke, Jürgen, Potter, Victoria, Killick, Sally B., Legrand, Faezeh, Solary, Eric, Broom, Angus, Garcia-Manero, Guillermo, Rizzoli, Vittorio, Hayden, Patrick, Patnaik, Mrinal M., Onida, Francesco, Yakoub-Agha, Ibrahim, and Itzykson, Raphael

Published
2022
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6. GLA/DRST real-world outcome analysis of CAR T-cell therapies for large B-cell lymphoma in Germany

Author

Bethge, Wolfgang A., Martus, Peter, Schmitt, Michael, Holtick, Udo, Subklewe, Marion, von Tresckow, Bastian, Ayuk, Francis, Wagner-Drouet, Eva Marie, Wulf, Gerald G., Marks, Reinhard, Penack, Olaf, Schnetzke, Ulf, Koenecke, Christian, von Bonin, Malte, Stelljes, Matthias, Glass, Bertram, Baldus, Claudia D., Vucinic, Vladan, Mougiakakos, Dimitrios, Topp, Max, Fante, Matthias A., Schroers, Roland, Bayir, Lale, Borchmann, Peter, Buecklein, Veit, Hasenkamp, Justin, Hanoun, Christine, Thomas, Simone, Beelen, Dietrich W., Lengerke, Claudia, Kroeger, Nicolaus, and Dreger, Peter

Published
2022
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9. A prognostic score including mutation profile and clinical features for patients with CMML undergoing stem cell transplantation

Author

Gagelmann, Nico, Badbaran, Anita, Beelen, Dietrich W., Salit, Rachel B., Stölzel, Friedrich, Rautenberg, Christina, Becker, Heiko, Radujkovic, Aleksandar, Panagiota, Victoria, Bogdanov, Rashit, Christopeit, Maximilian, Park, Yong, Nibourel, Olivier, Luft, Thomas, Koldehoff, Michael, Corsten, Maarten, Heuser, Michael, Finke, Jürgen, Kobbe, Guido, Platzbecker, Uwe, Robin, Marie, Scott, Bart L., and Kröger, Nicolaus

Published
2021
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10. Permissive HLA-DPB1 mismatches in HCT depend on immunopeptidome divergence and editing by HLA-DM

Author

Meurer, Thuja, Crivello, Pietro, Metzing, Maximilian, Kester, Michel, Megger, Dominik A., Chen, Weiqiang, van Veelen, Peter A., van Balen, Peter, Westendorf, Astrid M., Homa, Georg, Layer, Sophia E., Turki, Amin T., Griffioen, Marieke, Horn, Peter A., Sitek, Barbara, Beelen, Dietrich W., Falkenburg, J. H. Frederik, Arrieta-Bolaños, Esteban, and Fleischhauer, Katharina

Published
2021
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11. 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, and Robin, Marie

Published
2020
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13. A dynamic time‐to‐event model for prediction of acute graft‐versus‐host disease in patients after allogeneic hematopoietic stem cell transplantation

Author

Och, Katharina, primary, Turki, Amin T., additional, Götz, Katharina M., additional, Selzer, Dominik, additional, Brossette, Christian, additional, Theobald, Stefan, additional, Braun, Yvonne, additional, Graf, Norbert, additional, Rauch, Jochen, additional, Rohm, Kerstin, additional, Weiler, Gabriele, additional, Kiefer, Stephan, additional, Schwarz, Ulf, additional, Eisenberg, Lisa, additional, Pfeifer, Nico, additional, Ihle, Matthias, additional, Grandjean, Andrea, additional, Fix, Sonja, additional, Riede, Claudia, additional, Rissland, Jürgen, additional, Smola, Sigrun, additional, Beelen, Dietrich W., additional, Kaddu‐Mulindwa, Dominic, additional, Bittenbring, Jörg, additional, and Lehr, Thorsten, additional

Published
2023
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14. Myeloablative and Reduced-Intensity Conditioned Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: A Retrospective Study by the Chronic Malignancies Working Party of the European Society for Blood and Marrow Transplantation

Author

McLornan, Donal, Szydlo, Richard, Koster, Linda, Chalandon, Yves, Robin, Marie, Wolschke, Christine, Beelen, Dietrich, Socié, Gerard, Bornhäuser, Martin, Angelucci, Emanuele, Niederwieser, Dietger, Gerbitz, Arnim, Finke, Jürgen, Vitek, Antonin, Itälä-Remes, Maija, Radujkovic, Aleksandar, Kanz, Lothar, Potter, Victoria, Chevallier, Patrice, Stelljes, Matthias, Petersen, Eefke, Robinson, Stephen, Poiré, Xavier, Klyuchnikov, Evgeny, Hernández-Boluda, Juan Carlos, Czerw, Tomasz, Hayden, Patrick, Kröger, Nicolaus, and Yakoub-Agha, Ibrahim

Published
2019
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15. Comparable Long-Term Outcome after Allogeneic Stem Cell Transplantation from Sibling and Matched Unrelated Donors in Patients with Acute Myeloid Leukemia 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, Bipin, Byrne, Michael, Volin, Liisa, Finke, Jürgen, Niederwieser, Dietger, Ehninger, Gerhard, Blaise, Didier, Beelen, Dietrich, Tabrizi, Reza, Sengeloev, Henrik, Ganser, Arnold, Cornelissen, Jan J., Mohty, Mohamad, and Nagler, Arnon

Published
2019
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16. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Patients Age >69 Years with Acute Myelogenous Leukemia: On Behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Ringdén, Olle, Boumendil, Ariane, Labopin, Myriam, Canaani, Jonathan, Beelen, Dietrich, Ehninger, Gerhard, Niederwieser, Dietger, Finke, Jurgen, Stelljes, Matthias, Gerbitz, Armin, Ganser, Arnold, Kröger, Nicolaus, Kantz, Lothar, Brecht, Arne, Savani, Bipin, Sadeghi, Behnam, Mohty, Mohamad, and Nagler, Arnon

Published
2019
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18. P352: PROPHYLACTIC AND PREEMPTIVE USE OF DLI COMPARE FAVOURABLY TO THEIR THERAPEUTIC USE IN ADULT ACUTE LYMPHOBLASTIC LEUKEMIA (ALL) – RESULTS OF A MULTICENTRE RETROSPECTIVE STUDY

Author

Haupt, Maik, primary, Jäkel, Nadja, additional, Wachsmuth, Maria, additional, Stadler, Michael, additional, Beelen, Dietrich, additional, Finke, Juergen, additional, Alakel, Nael, additional, Hemmati, Philipp, additional, Schönland, Stefan, additional, Bethge, Wolfgang, additional, Wulf, Gerald, additional, Wolff, Daniel, additional, Maria Tischer, Johanna, additional, Wagner-Drouet, Eva, additional, Brandt, Anna, additional, Kröger, Nicolaus, additional, Vucinic, Vladan, additional, Bärmann, Ben-Niklas, additional, Brüggemann, Monika, additional, Gromann, Cora, additional, Müller-Tidow, Carsten, additional, Gökbuget, Nicola, additional, and Mueller, Lutz, additional

Published
2023
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20. Transplant Outcomes for Secondary Acute Myeloid Leukemia: Acute Leukemia Working Party of the European Society for Blood and Bone Marrow Transplantation Study

Author

Sengsayadeth, Salyka, Labopin, Myriam, Boumendil, Ariane, Finke, Jürgen, Ganser, Arnold, Stelljes, Matthias, 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., and Nagler, Arnon

Published
2018
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21. Intravenous Busulfan Compared with Treosulfan-Based Conditioning for Allogeneic Stem Cell Transplantation in Acute Myeloid Leukemia: A Study on Behalf of the Acute Leukemia Working Party of European Society for Blood and Marrow Transplantation

Author

Shimoni, Avichai, Labopin, Myriam, Savani, Bipin, Hamladji, Rose-Marie, Beelen, Dietrich, Mufti, Ghulam, Socié, Gerard, Delage, Jeremy, Blaise, Didier, Chevallier, Patrice, Forcade, Edouard, Deconinck, Eric, Mohty, Mohamad, and Nagler, Arnon

Published
2018
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22. Allogeneic Stem Cell Transplantation for Myelodysplastic Syndrome Patients with a 5q Deletion

Author

Garderet, Laurent, Ziagkos, Dimitris, van Biezen, Anja, Iacobelli, Simona, Finke, Jürgen, Maertens, Johan, Volin, Liisa, Ljungman, Per, Chevallier, Patrice, Passweg, Jakob, Schaap, Nicolaas, Beelen, Dietrich, Nagler, Arnon, Blaise, Didier, Poiré, Xavier, Yakoub-Agha, Ibrahim, Lenhoff, Stig, Craddock, Charles, Schots, Rik, Rambaldi, Alessandro, Sanz, Jaime, Jindra, Pavel, Mufti, Ghulam J., Robin, Marie, and Kröger, Nicolaus

Published
2018
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23. Late treatment-related mortality versus competing causes of death after allogeneic transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia

Author

Schetelig, Johannes, de Wreede, Liesbeth C., van Gelder, Michel, Koster, Linda, Finke, Jürgen, Niederwieser, Dietger, Beelen, Dietrich, Mufti, G. J., Platzbecker, Uwe, Ganser, Arnold, Heidenreich, Silke, Maertens, Johan, Socié, Gerard, Brecht, Arne, Stelljes, Matthias, Kobbe, Guido, Volin, Liisa, Nagler, Arnon, Vitek, Antonin, Luft, Thomas, Ljungman, Per, Yakoub-Agha, Ibrahim, Robin, Marie, and Kröger, Nicolaus

Published
2019
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25. Allogeneic Stem Cell Transplantation for Patients Age ≥ 70 Years with Myelodysplastic Syndrome: A Retrospective Study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT

Author

Heidenreich, Silke, Ziagkos, Dimitris, de Wreede, Liesbeth C., van Biezen, Anja, Finke, Jürgen, Platzbecker, Uwe, Niederwieser, Dietger, Einsele, Hermann, Bethge, Wolfgang, Schleuning, Michael, Beelen, Dietrich W., Tischer, Johanna, Nagler, Arnon, Glass, Bertram, Maertens, Johan, Yáñez, Lucrecia, Beguin, Yves, Sill, Heinz, Scheid, Christof, Stelljes, Matthias, Ganser, Arnold, Zachée, Pierre, Selleslag, Dominik, de Witte, Theo, Robin, Marie, and Kröger, Nicolaus

Published
2017
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26. Inferior outcome of allogeneic stem cell transplantation for secondary acute myeloid leukemia in first complete remission as compared to de novo acute myeloid leukemia

Author

Schmaelter, Ann-Kristin, Labopin, Myriam, Socié, Gerard, Itälä-Remes, Maija, Blaise, Didier, Yakoub-Agha, Ibrahim, Forcade, Edouard, Cornelissen, Jan, Ganser, Arnold, Beelen, Dietrich, Labussière-Wallet, Hélène, Passweg, Jakob, Savani, Bipin N., Schmid, Christoph, Nagler, Arnon, and Mohty, Mohamad

Published
2020
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27. Measurable residual disease at myeloablative allogeneic transplantation in adults with acute lymphoblastic leukemia: a retrospective registry study on 2780 patients from the acute leukemia working party of the EBMT

Author

Pavlů, Jiří, Labopin, Myriam, Niittyvuopio, Riitta, Socié, Gerard, Yakoub-Agha, Ibrahim, Wu, Depei, Remenyi, Peter, Passweg, Jakob, Beelen, Dietrich W., Aljurf, Mahmoud, Kröger, Nicolaus, Labussière-Wallet, Hélène, Perić, Zinaida, Giebel, Sebastian, Nagler, Arnon, and Mohty, Mohamad

Published
2019
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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, 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, 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
Interleukin-15 -- Health aspects, Gene mutation -- Health aspects, Sorafenib -- Patient outcomes, Gene expression -- Health aspects, Acute myelocytic leukemia -- Genetic aspects -- Development and progression -- Drug therapy, Biological sciences, 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[sup.+] leukemia cells. This synergized with the allogeneic CD8[sup.+] T cell response, leading to long-term survival in six mouse models of FLT3-ITD[sup.+] AML. Sorafenib-related IL-15 production caused an increase in CD8[sup.+]CD107a[sup.+]IFN-[gamma][sup.+] 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[sup.+] 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[sup.+] 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., Author(s): Nimitha R Mathew [1, 2]; Francis Baumgartner [1]; Lukas Braun [1]; David O'Sullivan [3]; Simone Thomas [4]; Miguel Waterhouse [1]; Tony A Müller [1]; Kathrin Hanke [1, 2]; Sanaz [...]

Published
2018
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29. 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

30. Time series clustering of T cell subsets dissects heterogeneity in immune reconstitution and clinical outcomes among MUD-HCT patients receiving ATG or PTCy

Author

Leserer, Saskia, primary, Graf, Theresa, additional, Franke, Martina, additional, Bogdanov, Rashit, additional, Arrieta-Bolaños, Esteban, additional, Buttkereit, Ulrike, additional, Leimkühler, Nils, additional, Fleischhauer, Katharina, additional, Reinhardt, Hans Christian, additional, Beelen, Dietrich W., additional, and Turki, Amin T., additional

Published
2023
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32. Allogeneic Hematopoietic Cell Transplantation vs Standard Consolidation Chemotherapy in Patients with Intermediate-Risk Acute Myeloid Leukemia : A Randomized Clinical Trial

Author

Bornhäuser, Martin, Schliemann, Christoph, Schetelig, Johannes, Röllig, Christoph, Kramer, Michael, Glass, Bertram, Platzbecker, Uwe, Burchert, Andreas, Hänel, Mathias, Müller, Lutz P., Klein, Stefan, Bug, Gesine, Beelen, Dietrich, Rösler, Wolf, Schäfer-Eckart, Kerstin, Schmid, Christoph, Jost, Edgar, Lenz, Georg, Tischer, Johanna, Spiekermann, Karsten, Pfirrmann, Markus, Serve, Hubert, Stölzel, Friedrich, Alakel, Nael, Middeke, Jan Moritz, Thiede, Christian, Ehninger, Gerhard, Berdel, Wolfgang E., and Stelljes, Matthias

Subjects
Cancer Research, Oncology, Medizin
Abstract

ImportanceThe ideal postremission strategy in intermediate-risk acute myeloid leukemia (AML) in first complete remission (CR) has been a matter of debate.ObjectiveTo explore the optimal therapy for patients with intermediate-risk AML after first complete remission.Design, Settings, and ParticipantsThis investigator-initiated, open-label, 2-armed, phase 3 randomized clinical trial assessed patients at 16 hospitals in Germany from February 2, 2011, until July 1, 2018. Key eligibility criteria included cytogenetically defined intermediate-risk AML according to Medical Research Council classification, first CR or CR with incomplete blood cell count recovery after conventional induction therapy, age of 18 to 60 years, and availability of a human leukocyte antigen (HLA)–matched sibling or unrelated donor. A detailed statistical analysis plan was written and finalized on July 7, 2020. Data were exported for analysis on April 13, 2021.InterventionsPatients were randomized 1:1 to receive allogeneic hematopoietic cell transplantation (HCT) or high-dose cytarabine for consolidation and salvage HCT only in case of relapse. Strata for randomization included age (18-40 vs 41-60 years), NPM1 and CEBPA variation status, and donor type (unrelated vs related).Main Outcomes and MeasuresEnd points included overall-survival as the primary outcome and disease-free survival, cumulative incidence of relapse, treatment-related mortality, and quality of life measured according to the Medical Outcomes Study 36-Item Short-Form Health Survey as secondary outcomes.ResultsA total of 143 patients (mean [SD] age, 48.2 [9.8] years; 81 [57%] male) with AML who fulfilled the eligibility criteria were randomized. In the intention-to-treat analysis, the probability of survival at 2 years was 74% (95% CI, 62%-83%) after primary allogeneic HCT and 84% (95% CI, 73%-92%) after consolidation chemotherapy (P = .22). Disease-free survival after HCT at 2 years was 69% (95% CI, 57%-80%) compared with 40% (95% CI, 28%-53%) after consolidation chemotherapy (P = .001). Allogeneic HCT during the first CR was associated with a cumulative incidence of relapse at 2 years of 20% (95% CI, 13%-31%) compared with 58% (95% CI, 47%-71%; P P = .005). Similar outcomes were observed when analyses were confined to the 96 patients at intermediate risk according to the European Leukemia Network classification. Most importantly, all 41 patients relapsing after consolidation chemotherapy (36 hematologic, 4 molecular, and 1 extramedullary) proceeded to allogeneic HCT. No significant differences in health-related quality of life measures were observed between groups.Conclusions and RelevancePrimary allogeneic HCT during first CR was not associated with superior overall survival compared with consolidation chemotherapy in patients 60 years or younger with intermediate-risk AML during the first CR and an available donor.Trial RegistrationClinicalTrials.gov Identifier: NCT01246752

Published
2023

33. Patient-reported patterns of follow-up care in the ‘Aftercare in Blood Cancer Survivors’ (ABC) study

Author

Baum, Julia, Lax, Hildegard, Lehmann, Nils, Merkel-Jens, Anja, Beelen, Dietrich W., Jöckel, Karl-Heinz, and Dührsen, Ulrich

Subjects
Medizin
Abstract

Background: Follow-up care provides long-term support for cancer survivors. Little is known about follow-up care in hematologic malignancies. Methods: Our questionnaire-based study included blood cancer survivors diagnosed at the University Hospital of Essen before 2010, with a ≥ 3-year interval since the last intense treatment. The primary goal of the retrospective study was the identification and characterization of follow-up institutions. Results: Of 2386 survivors meeting the inclusion criteria, 1551 (65.0%) consented to participate, with a follow-up duration > 10 years in 731. The university hospital provided care for 1045 participants (67.4%), non-university oncologists for 231 (14.9%), and non-oncological internists or general practitioners for 203 (13.1%). Seventy-two participants (4.6%) abstained from follow-up care. The disease spectrum differed among follow-up institutions (p < 0.0001). While allogeneic transplant recipients clustered at the university hospital, survivors with monoclonal gammopathy, multiple myeloma, myeloproliferative disorders, or indolent lymphomas were often seen by non-university oncologists, and survivors with a history of aggressive lymphoma or acute leukemia by non-oncological internists or general practitioners. Follow-up intervals mirrored published recommendations. Follow-up visits were dominated by conversations, physical examination, and blood tests. Imaging was more often performed outside than inside the university hospital. Satisfaction with follow-up care was high, and quality of life was similar in all follow-up institutions. A need for improvement was reported in psychosocial support and information about late effects. Conclusions: The naturally evolved patterns identified in the study resemble published care models: Follow-up clinics for complex needs, specialist-led care for unstable disease states, and general practitioner-led care for stable conditions. in press

Published
2023

34. Leukemia relapse following unmanipulated haploidentical transplantation: a risk factor analysis on behalf of the ALWP of the EBMT

Author

Piemontese, Simona, Boumendil, Ariane, Labopin, Myriam, Schmid, Christoph, Ciceri, Fabio, Arcese, William, Koc, Yener, Gulbas, Zafar, Tischer, Johanna, Bruno, Benedetto, Wu, Depei, Blaise, Didier, Beelen, Dietrich, Irrera, Giuseppe, Ruggeri, Annalisa, Houhou, Mohamed, Mohty, Mohamad, Nagler, Arnon, and on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Published
2019
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35. Fludarabine-treosulfan compared to thiotepa-busulfan-fludarabine or FLAMSA as conditioning regimen for patients with primary refractory or relapsed acute myeloid leukemia: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Author

Saraceni, Francesco, Labopin, Myriam, Brecht, Arne, Kröger, Nicolaus, Eder, Matthias, Tischer, Johanna, Labussière-Wallet, Hélène, Einsele, Hermann, Beelen, Dietrich, Bunjes, Donald, Niederwieser, Dietger, Bochtler, Tilmann, Savani, Bipin N., Mohty, Mohamad, and Nagler, Arnon

Published
2019
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36. Treatment of Acute Myeloid Leukemia or Myelodysplastic Syndrome Relapse after Allogeneic Stem Cell Transplantation with Azacitidine and Donor Lymphocyte Infusions—A Retrospective Multicenter Analysis from the German Cooperative Transplant Study Group

Author

Schroeder, Thomas, Rachlis, Elena, Bug, Gesine, Stelljes, Matthias, Klein, Stefan, Steckel, Nina Kristin, Wolf, Dominik, Ringhoffer, Mark, Czibere, Akos, Nachtkamp, Kathrin, Dienst, Ariane, Kondakci, Mustafa, Stadler, Michael, Platzbecker, Uwe, Uharek, Lutz, Luft, Thomas, Fenk, Roland, Germing, Ulrich, Bornhäuser, Martin, Kröger, Nicolaus, Beelen, Dietrich W., Haas, Rainer, and Kobbe, Guido

Published
2015
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37. Thiotepa‐based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic leukemia: A matched‐pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Author

Eder, Sandra, Canaani, Jonathan, Beohou, Eric, Labopin, Myriam, Sanz, Jaime, Arcese, William, Or, Reuven, Finke, Juergen, Cortelezzi, Agostino, Beelen, Dietrich, Passweg, Jakob, Socié, Gerard, Gurman, Gunhan, Aljurf, Mahmoud, Stelljes, Matthias, Giebel, Sebastian, Mohty, Mohamad, and Nagler, Arnon

Published
2017
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38. CMV serostatus still has an important prognostic impact in de novo acute leukemia patients after allogeneic stem cell transplantation: a report from the Acute Leukemia Working Party of EBMT

Author

Schmidt-Hieber, Martin, Labopin, Myriam, Beelen, Dietrich, Volin, Liisa, Ehninger, Gerhard, Finke, Jürgen, Socié, Gerard, Schwerdtfeger, Rainer, Kröger, Nicolaus, Ganser, Arnold, Niederwieser, Dietger, Polge, Emmanuelle, Blau, Igor W., and Mohty, Mohamad

Published
2013
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39. Total body irradiation + fludarabine compared to busulfan + fludarabine as 'reduced-toxicity conditioning' for patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation in first complete remission: a study by the Acute Leukemia Working Party of the EBMT

Author

Giebel, Sebastian, Labopin, Myriam, Sobczyk-Kruszelnicka, Malgorzata, Stelljes, Matthias, Byrne, Jenny, Fegueux, Nathalie, Beelen, Dietrich, Rovira, Montserrat, Spyridonidis, Alexandros, Blaise, Didier, Bornhäuser, Martin, Karadogan, Ihsan, Savani, Bipin, Nagler, Arnon, Mohty, Mohamad, Martin, Sonja, Chevallier, Patrice, Neubauer, Andreas, Damaj, Gandhi, Koc, Yener, Ganser, Arnold, Collin, Matthew, Yakoub-Agha, Ibrahim, Ozdogu, Hakan, Araujo, Mercedes Colorado, Itäla-Remes, Maija, Orchard, Kim, Isaksson, Cecilia, Bethge, Wolfgang, Martin, Hans, Aljurf, Mahmoud, Faber, Edgar, Caballero, Dolores, Zák, Pavel, Leleu, Xavier, Bay, Jacques-Olivier, Rohrlich, Pierre-Simon, Kröger, Nicolaus, Huynh, Anne, Schäfer-Eckart, Kerstin, Milpied, Noel, Lenhoff, Stig, Ho, Aloysius, López, Jose Luis Bello, Mordini, Nicola, Lioure, Bruno, Halaburda, Kazimierz, Olivieri, Attilio, Gedde-Dahl, Tobias, Protheroe, Rachel, Tischer, Johanna, Klammer, Matthias, Clausen, Johannes, Potter, Victoria, Ladetto, Marco, Tilly, Herve, Deconinck, Eric, Brecht, Arne, Müller, Lutz Peter, Heinicke, Thomas, Carrete, Juan Pio Torres, Bazarbachi, Ali, Reményi, Péter, Rubio, Marie Thérèse, Fanin, Renato, Pérez-Simón, Jose Antonio, Niels, Murawski, Diez-Martin, J., Arat, Mutlu, Hermine, Olivier, Socié, Gerard, Cornelissen, Jan, Santarone, Stella, Guyotat, Denis, Bulabois, Claude Eric, Bernasconi, Paolo, Johansson, Jan-Erik, Vrhovac, Radovan, Greinix, Hildegard, Lorenzo, José Luis López, Apte, Shashikant, Craddock, Charles, Kobbe, Guido, Zahrani, Mohsen Al, Dreger, Peter, Lange, Andrzej, Tbakhi, Abdelghani, Meijer, Ellen, Llamas, Carlos Vallejo, Santasusana, Josep Maria Ribera, Corradini, Paolo, Benedetti, Fabio, Rambaldi, Alessandro, Gandemer, Virginie, Malfuson, Jean-Valère, Kaare, Ain, Risitano, Antonio, Petrini, Mario, Selleri, Carmine, Wu, Depei, Hematology, CCA - Cancer Treatment and quality of life, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, and 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)

Subjects
medicine.medical_specialty, Transplantation Conditioning, MESH: Busulfan, Medizin, MESH: Graft vs Host Disease, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Busulfan, MESH: Hematopoietic Stem Cell Transplantation, MESH: Transplantation Conditioning, Retrospective Studies, Transplantation, Acute leukemia, MESH: Humans, MESH: Middle Aged, business.industry, Hazard ratio, Hematopoietic Stem Cell Transplantation, Myeloid leukemia, MESH: Retrospective Studies, Retrospective cohort study, Hematology, Middle Aged, Total body irradiation, Fludarabine, Leukemia, Myeloid, Acute, Regimen, 030220 oncology & carcinogenesis, MESH: Vidarabine, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Leukemia, Myeloid, Acute, business, MESH: Whole-Body Irradiation, Vidarabine, Whole-Body Irradiation, 030215 immunology, medicine.drug
Abstract

International audience; The optimal conditioning for patients with acute myeloid leukemia in first complete remission treated with allogeneic hematopoietic cell transplantation (allo-HCT) has not been defined so far. In this retrospective study, we compared two "reduced-toxicity" regimens: intravenous busulfan at a total dose of 9.6 mg/kg (3 days) + fludarabine (Bu3/Flu) and total body irradiation at a dose of 8 Gy + fludarabine (TBI8Gy/Flu). In the entire study cohort (n = 518), the probabilities of overall survival (OS), leukemia-free survival (LFS), relapse and non-relapse mortality (NRM) at 2 years for Bu3/Flu and TBI8Gy/Flu were 62% vs. 72.5% (p = 0.051), 59.5% vs. 65% (p = 0.15), 30% vs. 20% (p = 0.01), and 10% vs. 14% (p = 0.18), respectively. In multivariate model for patients

Published
2021

40. Treosulfan compared with reduced‐intensity 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 W., primary, Stelljes, Matthias, additional, Reményi, Péter, additional, Wagner‐Drouet, Eva‐Maria, additional, Dreger, Peter, additional, Bethge, Wolfgang, additional, Ciceri, Fabio, additional, Stölzel, Friedrich, additional, Junghanß, Christian, additional, Labussiere‐Wallet, Hélène, additional, Schaefer‐Eckart, Kerstin, additional, Grigoleit, Goetz U., additional, Scheid, Christof, additional, Patriarca, Francesca, additional, Rambaldi, Alessandro, additional, Niederwieser, Dietger, additional, Hilgendorf, Inken, additional, Russo, Domenico, additional, Socié, Gérard, additional, Holler, Ernst, additional, Glass, Bertram, additional, Casper, Jochen, additional, Wulf, Gerald, additional, Basara, Nadezda, additional, Bieniaszewska, Maria, additional, Stuhler, Gernot, additional, Verbeek, Mareike, additional, La Rocca, Ursula, additional, Finke, Jürgen, additional, Benedetti, Fabio, additional, Pichlmeier, Uwe, additional, Klein, Anja, additional, Baumgart, Joachim, additional, and Markiewicz, Miroslaw, additional

Published
2022
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41. Stem cell transplantation can provide durable disease control in blastic plasmacytoid dendritic cell neoplasm: a retrospective study from the European Group for Blood and Marrow Transplantation

Author

Roos-Weil, Damien, Dietrich, Sascha, Boumendil, Ariane, Polge, Emmanuelle, Bron, Dominique, Carreras, Enric, Iriondo Atienza, Arturo, Arcese, William, Beelen, Dietrich W., Cornelissen, Jan J., Kröger, Nicolaus, Milone, Giuseppe, Rossi, Giuseppe, Jardin, Fabrice, Peters, Christina, Rocha, Vanderson, Sureda, Anna, Mohty, Mohamad, and Dreger, Peter

Published
2013
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43. Allogeneic Hematopoietic Cell Transplantation in Patients Age 60-70 Years with De Novo High-Risk Myelodysplastic Syndrome or Secondary Acute Myelogenous Leukemia: Comparison with Patients Lacking Donors Who Received Azacitidine

Author

Platzbecker, Uwe, Schetelig, Johannes, Finke, Jürgen, Trenschel, Rudolf, Scott, Bart L., Kobbe, Guido, Schaefer-Eckart, Kerstin, Bornhäuser, Martin, Itzykson, Raphael, Germing, Ulrich, Beelen, Dietrich, Ehninger, Gerhard, Fenaux, Pierre, Deeg, H. Joachim, and Adès, Lionel

Published
2012
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44. Favourable Outcome after Treosulfan Based Conditioning of Patients Receiving an Allogeneic Hematopoietic Cell Transplantation (AlloHCT) for the Treatment of a Myelodysplastic Syndrome (MDS)

Author

Stelljes, Matthias, primary, Trenschel, Rudolf, additional, Beelen, Dietrich Wilhelm, additional, Markiewicz, Miroslaw, additional, Wagner, Eva Maria, additional, Bethge, Wolfgang, additional, Remenyi, Peter, additional, Niederwieser, Dietger, additional, Grigoleit, Goetz, additional, Schaefer-Eckart, Kerstin, additional, Stölzel, Friedrich, additional, Ciceri, Fabio, additional, Dreger, Peter, additional, Junghanß, Christian, additional, Holler, Ernst, additional, Rambaldi, Alessandro, additional, Russo, Domenico, additional, Verbeek, Mareike, additional, Casper, Jochen, additional, Patriarca, Francesca, additional, Bieniaszewska, Maria, additional, Glass, Bertram, additional, Scheid, Christoph, additional, Basara, Nadezda, additional, Finke, Jürgen, additional, Hilgendorf, Inken, additional, Labussière-Wallet, Hélène, additional, Stuhler, Gernot, additional, and Schroeder, Thomas, additional

Published
2022
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45. Favourable Outcome after Treosulfan Based Conditioning in Patients Undergoing an Allogeneic Hematopoietic Cell Transplantation (alloHCT) for the Treatment of Acute Myleloid Leukaemia (AML): A Subgroup Analysis of the Randomized Phase III MC-Fludt.14/L Trial

Author

Stölzel, Friedrich, primary, Stelljes, Matthias, additional, Beelen, Dietrich Wilhelm, additional, Markiewicz, Miroslaw, additional, Remenyi, Peter, additional, Dreger, Peter, additional, Ciceri, Fabio, additional, Wagner-Drouet, Eva-Maria, additional, Junghanss, Christian, additional, Scheid, Christoph, additional, Patriarca, Francesca, additional, Socié, Gerard, additional, Hilgendorf, Inken, additional, Rambaldi, Alessandro, additional, Schaefer-Eckart, Kerstin, additional, Russo, Domenico, additional, Grigoleit, Goetz, additional, Wulf, Gerald, additional, Basara, Nadezda, additional, Glass, Bertram, additional, Stuhler, Gernot, additional, Bieniaszewska, Maria, additional, Casper, Jochen, additional, Holler, Ernst, additional, Benedetti, Fabio, additional, Iori, Anna Paola, additional, Trenschel, Rudolf, additional, and Bethge, Wolfgang, additional

Published
2022
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47. Measurable residual disease, FLT3‐ITD mutation, and disease status have independent prognostic influence on outcome of allogeneic stem cell transplantation in NPM1‐mutated acute myeloid leukemia

Author

Al Hamed, Rama, primary, Labopin, Myriam, additional, Daguindau, Etienne, additional, Niittyvuopio, Riitta, additional, Huynh, Anne, additional, Socié, Gerard, additional, Srour, Micha, additional, Henri Bourhis, Jean, additional, Kröger, Nicolaus, additional, Tholouli, Eleni, additional, Choi, Goda, additional, Poiré, Xavier, additional, Martin, Hans, additional, Rubio, Marie‐Thérèse, additional, Jindra, Pavel, additional, Blaise, Didier, additional, Beelen, Dietrich, additional, Labussière‐Wallet, Hélène, additional, Nagler, Arnon, additional, Bazarbachi, Ali, additional, and Mohty, Mohamad, additional

Published
2022
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48. Allogeneic stem cell transplantation in AML with t(6;9)(p23;q34);DEK-NUP214 shows a favourable outcome when performed in first complete remission

Author

Marina Díaz-Beyá, Harry C. Schouten, Mauricette Michallet, Mohamad Mohty, Jordi Esteve, Jorge Sierra, Arnon Nagler, Gérard Socié, Myriam Labopin, Mahmoud Alijurf, Jakob Passweg, Nicolaas Schaap, Rainer Schwerdtfeger, Beelen Dietrich, Emmanuelle Polge, Johan Maertens, Liisa Volin, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Hematologie (9), and Interne Geneeskunde

Subjects
Oncology, Male, Disease status, PROGNOSIS, BLOOD, Oncogene Proteins, Fusion, Chromosomal Proteins, Non-Histone, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Medizin, Graft vs Host Disease, Internal tandem duplication, Kaplan-Meier Estimate, Translocation, Genetic, 0302 clinical medicine, hemic and lymphatic diseases, Gene Duplication, Medicine, Poly-ADP-Ribose Binding Proteins, Oncogene Proteins, Marrow transplantation, Incidence (epidemiology), Remission Induction, Hematology, Middle Aged, Allografts, EUROPEAN-SOCIETY, 3. Good health, Leukemia, Myeloid, Acute, surgical procedures, operative, Treatment Outcome, aml, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 6, Female, Cord Blood Stem Cell Transplantation, Stem cell, Chromosomes, Human, Pair 9, Adult, medicine.medical_specialty, internal tandem duplication, dek-nup214, ACUTE MYELOID-LEUKEMIA, Disease-Free Survival, CLASSIFICATION, allo-SCT, working party, 03 medical and health sciences, 9) aml, Internal medicine, Humans, In patient, Proportional Hazards Models, Peripheral Blood Stem Cell Transplantation, business.industry, Complete remission, Transplantation, Nuclear Pore Complex Proteins, fms-Like Tyrosine Kinase 3, business, t(6, 030215 immunology
Abstract

Contains fulltext : 220562.pdf (Publisher’s version ) (Closed access) Acute myeloid leukaemia (AML) with t(6;9)(p23;q34) is a poor-risk entity, commonly associated with FLT3-ITD (internal tandem duplication). Allogeneic stem-cell tranplantation (allo-SCT) is recommended, although studies analysing the outcome of allo-SCT in this setting are lacking. We selected 195 patients with t(6;9) AML, who received a first allo-SCT between 2000 and 2016 from the EBMT (European Society for Blood and Marrow Transplantation) registry. Disease status at time of allo-SCT was the strongest independent prognostic factor, with a two-year leukaemia-free survival and relapse incidence of 57% and 19% in patients in CR1 (first complete remission), 34% and 33% in CR2 (second complete remission), and 24% and 49% in patients not in remission, respectively (P < 0.001). This study, which represents the largest one available in t(6;9) AML, supports the recommendation to submit these patients to allo-SCT in CR1.

Published
2020

50. Combined Analysis of Early CD4+ T Cell Counts and CMV Serostatus May Improve CMV Risk Assessment after Allogeneic Hematopoietic Cell Transplantation

Author

Leserer, Saskia, Arrieta-Bolaños, Esteban, Buttkereit, Ulrike, Beelen, Dietrich W., and Turki, Amin T.

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, CMV risk assessment, Adolescent, QH301-705.5, Cytomegalovirus, unsupervised learning, Risk Assessment, clustering -- unsupervised learning -- CMV risk assessment -- CMV reactivation -- CMV serostatus -- CD4+ T helper cells -- immune reconstitution -- T cell reconstitution -- R+ serostatus, Article, Young Adult, CMV serostatus, CD4+ T helper cells, Humans, Transplantation, Homologous, Lymphocyte Count, ddc:610, Biology (General), Aged, CMV reactivation, Incidence, T cell reconstitution, Hematopoietic Stem Cell Transplantation, immune reconstitution, Middle Aged, Medizinische Fakultät » Universitätsklinikum Essen » Institut für Zelltherapeutische Forschung, Prognosis, Medizinische Fakultät » Universitätsklinikum Essen » Klinik für Hämatologie und Stammzelltransplantation, Cytomegalovirus Infections, R+ serostatus, Female, clustering
Abstract

The incidence and severity of viral complications after cellular therapy are highly variable. Recent publications describe relevant interactions between the human Cytomegalovirus (CMV) and host immunity in recipients of allogeneic hematopoietic cell transplantation (HCT). Although immune monitoring is routinely performed in HCT patients, validated cut-off levels correlating with transplant outcomes such as survival or CMV reactivation are mostly limited to day +100, which is later than the median time for CMV reactivation in the absence of medical prophylaxis. To address this gap in early risk assessment, we applied an unsupervised machine learning technique based on clustering of day +30 CD4+ helper T cell count data, and identified relevant cut-off levels within the diverse spectrum of early CD4+ reconstitution. These clusters were stratified for CMV recipient serostatus to identify early risk groups that predict clinical HCT outcome. Indeed, the new risk groups predicted subsequent clinical events such as NRM, OS, and high CMV peak titers better than the most established predictor, i.e., the positive CMV recipient serostatus (R+). More specifically, patients from the R+/low CD4+ subgroup strongly associated with high CMV peak titers and increased 3-year NRM (subdistribution hazard ratio (SHR) 10.1, 95% CI 1.38–73.8, p = 0.023), while patients from the R-/very high CD4+ subgroup showed comparable NRM risks (SHR 9.57, 95% CI 1.12–81.9, p = 0.039) without such an association. In short, our study established novel cut-off levels for early CD4+ T cells via unsupervised learning and supports the integration of host cellular immunity into clinical risk-assessment after HCT in the context of CMV reactivation.

Published
2021

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