# Prognostic value of CPSS cytogenetic risk classification in patients with CMML after allogeneic hematopoietic cell transplantation: a retrospective multicenter study of the Chronic Malignancies Working Party of the EBMT.

C. Koenecke, D. J. Eikema, S. Hazelaar, T. Schroeder, V. Potter, N. Kröger, M. Bornhäuser, J. Finke, U. Platzbecker, A. Radujkovic, et al.

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## To cite this version:

C. Koenecke, D. J. Eikema, S. Hazelaar, T. Schroeder, V. Potter, et al., Prognostic value of CPSS cytogenetic risk classification in patients with CMML after allogeneic hematopoietic cell transplantation: a retrospective multicenter study of the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplantation, 2022, Bone Marrow Transplantation, 57, pp.1607-1611. 10.1038/s41409-022-01759-7. hal-04509067

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# Prognostic value of CPSS cytogenetic risk classification in patients with CMML after allogeneic hematopoietic cell transplantation: a retrospective multicenter study of the Chronic Malignancies Working Party of the EBMT

© The Author(s) 2022

*Bone Marrow Transplantation* (2022) 57:1607–1611; https://doi.org/10.1038/s41409-022-01759-7

**TO THE EDITOR:**

The only curative treatment approach for patients with chronic myelomonocytic leukemia (CMML) is allogeneic hematopoietic cell transplantation (allo-HCT), but disease relapse after transplantation is a major concern [1]. Predictors for disease outcome after transplant are limited. However, beside other risk factors (ASXL1 mutations, monocytosis, cytopenias and circulating immature myeloid cells), cytogenetic abnormalities have been shown to serve as predictors for outcome in CMML patients [2–5]. Cytogenetic abnormalities are frequently seen in 20–30% of patients [6, 7]. According to the CMML-specific prognostic scoring system (CPSS) patients can be categorized into three risk groups (high risk: trisomy 8, chromosome 7 abnormalities, or complex karyotype; low risk: normal karyotype and -Y; intermediate risk: all other chromosomal abnormalities) [8]. There is evidence, that adverse cytogenetics are also a risk factor for worse outcome after allo-HCT [9]. However, cytogenetic information according to CPSS was not evaluated in the setting of allo-HCT to date. Therefore, the aim of this large multicentric, international study was to retrospectively determine the impact of CPSS-cytogenetic on outcome after allo-HSCT.

Adult patients (age $\ge$ 18years) who had received a first allo-HCT for the treatment of CMML between 2000 and 2015 were selected from the European Society of Bone and Marrow Transplantation (EBMT) database. 233 centers participated into this study. In total, 1347 patients were included. Impact of CPSS-cytogenetic classification was analysed regarding overall survival (OS), progression free survival (PFS) and cumulative incidence of relapse and non-relapse mortality (NRM) after transplant. OS and PFS were estimated using the Kaplan-Meier product limit estimation method, and differences in subgroups were assessed by the Log-Rank test. Median follow-up was determined using the reverse Kaplan-Meier method. The cumulative incidence of relapse (RI) and NRM were analysed together in a competing risks framework. Subgroup differences in cumulative incidences were assessed using Gray's test. Multivariable Cox regression was applied to investigate the simultaneous impact of multiple covariates on OS and PFS. Included covariates were: CPSS (intermediate, high versus low), stage at transplant (no CR, untreated versus CR), disease (transformed to AML versus other),

age at transplant (in decades) and year of allo-HCT. Continuous variables are presented in the text as median and interquartile range (IQR) or range and categorical variables as percentages. All survival estimates and hazard ratios are reported with corresponding 95% confidence intervals in parentheses. All *p*-values are two-sided and *p* < 0.05 is considered significant. Statistical analyses were performed in R version 3.6.0 (R Development Core Team, Vienna, Austria), using packages 'survival', 'prodlim' and 'cmprsk'.

436 female (32.4%) and 909 male (67.6%) patients were included into the study. Median age at HSCT was 58.1 years (range 20–75.4). At time of HCT, 383 (68.6%) patients were diagnosed with CMML-I, 175 (31.4%) with CMML-II, 412 (74.9%) with dysplastic and 138 (25.1%) with proliferative CMML. Only 392 (30.6%) patients were in complete remission, whereas 668 (52.2%) had not reached CR and 220 (17.2%) had not received chemotherapy before allo-HCT. 212 (35.0%) patients received conventional chemotherapy and 119 (19.6%) hypomethylating agents before transplantation. Matched related donor allo-HCT was performed in 35.6% of the patients, matched unrelated donor in 7.4%, unrelated donor (complete HLA unavailable) in 51.6%, mismatched related in 2.8% and mismatched unrelated in 2.6%. Bone marrow (10.2%), peripheral blood (87.3%), or both (0.2%) served as the stem cell graft. Cord blood was used in 2.3%. Myeloablative conditioning regimens were used in 187 patients (13.9%), and less intensive regimens were given to 1156 patients (86.1%). Median follow-up of patients was 51.4 (47.8–56.8) months.

Two-year and five-year PFS were 39% (36–42%) and 29% (26–32%), respectively. Two- and 5-year relapse incidence were 35% (33–38%) and 41% (38–44%) respectively, with a relapse observed in 474 patients at any time during follow-up. The median time to relapse in the patients who relapsed was 4.9 months (IQR 2.7–11.7). Two- and 5-year NRM were 26% (23–28%) and 30% (27–33%), respectively. Two- and 5-year OS were 46% (43–49%) and 33% (30–36%).

570 patients had sufficient cytogenetic information according to CPSS (777 missing). 132 (23.2%) patients could be categorized into CPSS-high, 76 (13.3%) into intermediate and 362 (63.5%) into low-risk cytogenetics, respectively. In univariate analysis CPSS cytogenetic information was found to be strongly associated with OS (*p* < 0.001; low 35% (29–41%), intermediate 39% (27–51%), high 24% (15–32%)) at 5 years. A higher cumulative incidence of relapse (*p* = 0.015; low 42% (37–48%), intermediate 43% (30–56%), high 51% (42–60%)) was detected. In line, cytogenetic status was associated with PFS (*p* < 0.001; low 30% (25–36%), intermediate 30% (18–42%), high 21% (13–28%). However, NRM
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**Fig. 1** CPSS cytogenetic information predict outcome after allogeneic transplantation in CMML patients. **a–d** Probability of overall survival (OS), progression free survival (PFS), relapse incidence and non relapse mortality (NRM) of CMML patients with low, intermediate or high risk cytogenic. **e–g** Forest plots on overall survival (OS), progression free survival (PFS) and relapse incidence.
(p = 0.87; low 27% (22–33%), intermediate 27% (16–38%), high 29% (20–37%)) at 60 months was not affected by cytogenetic status at time of transplantation (Fig. 1).

In multivariable analysis (MVA), including only patients with available data on included covariates, CPSS-high risk cytogenetics was associated with shorter overall survival after allogeneic transplantation compared to intermediate and low risk cytogenetics (hazard ratio (HR), 1.57 (1.17–2.1)). This finding was also present in MVA for PFS (HR 1.44 (1.09–1.91)) and RI (HR 1.6 (1.12–2.27)). Patients' age, year of transplant, and status of the disease at transplant were not associated with a reduced OS, PFS and RI (Table 1). In another study by this working group, status of the disease before transplantation was associated with survival [10].

Our results show that CPSS cytogenetics is a strong predictor of relapse and overall survival after allo-HCT. Adverse cytogenetic alterations lead to a disease biology which is more likely to be resistant to an allograft. This observation has been made in a variety of myeloid malignant diseases, such as MDS and AML [11]. Currently, molecular diagnostics are becoming more and more standard in patients with CMML. We were not able to include such information into this retrospective study. It might be that even more distinct risk-groups can be identified using that diagnostic tool [5].

In this international, multicentric analysis we show that CMML patients with high-risk cytogenetics had significantly worse overall and progression-free survival after allo-HCT than patients with intermediate or low risk cytogenetics according to CPSS. New therapeutic strategies to prevent relapse after allo-HCT in CMML patients with high-risk cytogenetics are needed.

Christian Koenecke¹✉, Dirk-Jan Eikema², Sheree Hazelaar³, Thomas Schroeder⁴, Victoria Potter⁵, Nicolaus Kröger⁶, Martin Bornhäuser⁷, Jürgen Finke⁸, Uwe Platzbecker⁹, Aleksandar Radujkovic¹⁰, Arnold Ganser¹, Urpu Salmenniem¹¹, Didier Blaise¹², Guido Kobbe¹³, Ellen Meijer¹⁴, Lone Friis¹⁵, Johan Maertens¹⁶, Dolores Caballero¹⁷, Jan J. Cornelissen¹⁸, Attilio Olivieri¹⁹, Ozet Gulsum²⁰, Patrick J. Hayden²¹, Francesco Onida²², Marie Robin²³ and Ibrahim Yakoub-Agha²⁴

¹Hannover Medical School, Hannover, Germany. ²EBMT statistical Unit, Leiden, The Netherlands. ³EBMT data office Leiden, Leiden, The Netherlands. ⁴Universitätsklinikum Essen, Essen, Germany. ⁵GKT School of Medicine, London, UK. ⁶University Hospital Eppendorf, Hamburg, Germany. ⁷University Hospital TU Dresden, Dresden, Germany. ⁸University of Freiburg, Freiburg, Germany. ⁹University Hospital Leipzig, Leipzig, Germany. ¹⁰University of Heidelberg, Heidelberg, Germany. ¹¹HUCH Comprehensive Cancer Center, Helsinki, Finland. ¹²Institut Paoli-Calmettes, Marseille, France. ¹³Heinrich Heine Universitaet, Duesseldorf, Germany. ¹⁴Vrije Universiteit Medical center, Amsterdam, The Netherlands.

¹⁵Rigshospitalet, Copenhagen, Denmark. ¹⁶University Hospital Gasthuisberg, Leuven, Belgium. ¹⁷Hospital Clinico, Salamanca, Spain. ¹⁸Erasmus MC Cancer Institute, Rotterdam, The Netherlands.

¹⁹Azienda Ospedali Riuniti di Ancona, Ancona, Italy. ²⁰Ankara Sehir Hastanesi, Ankara, Turkey. ²¹Trinity College Dublin, St. James's Hospital, Dublin, Ireland. ²²Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico-University of Milan, Milan, Italy. ²³Hopital St. Louis, Paris, France. ²⁴CHU de Lille, INSERM U1286, Infinite, Université de Lille, 59000 Lille, France.

✉email: koenecke.christian@mh-hannover.de

DATA AVAILABILITY

CK, DJE, and IYA had full access to all study data (available upon data-specific request).

<table><caption>**Table 1.** Multivariate analysis overall (OS), progression free survival (PFS) and relapse incidence (RI).</caption><thead><tr><th rowspan="2"></th><th colspan="2">OS</th><th colspan="2">PFS</th><th colspan="2">RI</th></tr><tr><th>N</th><th>HR (95% CI)</th><th>p</th><th>HR (95% CI)</th><th>p</th><th>HR (95% CI)</th><th>p</th></tr></thead><tbody><tr><td>Total</td><td>433</td><td></td><td></td><td>421</td><td></td><td>421</td><td></td></tr><tr><td>CPSS</td><td>279</td><td></td><td></td><td>270</td><td></td><td>270</td><td></td></tr><tr><td>Low</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Intermediate</td><td>54</td><td>0.95 (0.64–1.42)</td><td>0.8</td><td>0.95 (0.65–1.37)</td><td>0.8</td><td>1.01 (0.63–1.62)</td><td>&gt;0.99</td></tr><tr><td>High</td><td>100</td><td>1.57 (1.17–2.1)</td><td>0.002</td><td>1.44 (1.09–1.91)</td><td>0.01</td><td>1.6 (1.12–2.27)</td><td>0.009</td></tr><tr><td>Stage at transplant</td><td>110</td><td></td><td></td><td>108</td><td></td><td>108</td><td></td></tr><tr><td>CR</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>no CR</td><td>241</td><td>1.16 (0.86–1.58)</td><td>0.3</td><td>1.01 (0.76–1.34)</td><td>0.9</td><td>0.93 (0.65–1.33)</td><td>0.7</td></tr><tr><td>Untreated</td><td>82</td><td>0.85 (0.57–1.28)</td><td>0.4</td><td>0.92 (0.63–1.34)</td><td>0.7</td><td>0.78 (0.48–1.25)</td><td>0.3</td></tr><tr><td>Disease</td><td>341</td><td></td><td></td><td>330</td><td></td><td>330</td><td></td></tr><tr><td>tAML</td><td>92</td><td>1.11 (0.82–1.5)</td><td>0.5</td><td>1.06 (0.79–1.43)</td><td>0.7</td><td>1.05 (0.72–1.52)</td><td>0.8</td></tr><tr><td>Age (decades)</td><td>433</td><td>1.08 (0.94–1.24)</td><td>0.3</td><td>1.03 (0.9–1.17)</td><td>0.7</td><td>0.96 (0.82–1.13)</td><td>0.6</td></tr><tr><td>Tx year</td><td>433</td><td>0.97 (0.94–1.01)</td><td>0.16</td><td>0.97 (0.93–1.01)</td><td>0.09</td><td>0.96 (0.92–1)</td><td>0.08</td></tr></tbody></table>
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AUTHOR CONTRIBUTIONS

CK assembled and analyzed data and wrote the paper. CK, MR, FO, and IYA designed the study, supervised research and analyzed data. DJE and SH assembled the data, performed statistical analysis, and commented on the paper. All other co-authors collected data, recruited patients, and helped with writing the paper. All authors approved submission of the paper for publication. Alymen Bushra Ahmed, Haukeland University Hospital, Bergen, Norway; Carmen Albo López Álvaro Cunqueiro —Complejo Hospitalario Universitario de Vigo, Vigo, Spain; Adrián Alegre Amor, Hospital de la Princesa, Madrid, Spain; Mahmoud Aljurf, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia; Achilles Adestopoulos, George Papanicolaou General Hospital, Thessaloniki, Greece; Emanuele Angelucci, Ospedale San Martino, Genova, Italy; Jane Apperley, Imperial College, London, UK; William Arcese, "Tor Vergata" University of Rome, Rome, Italy; Grzegorz Basak, Central Clinical Hospital, Warsaw, Poland; Jacques-Olivier Bay, CHU ESTAING, Clermont_Ferr, France; Yves Beguin, University of Liege, Liege, Belgium; Fabio Benedetti, Policlinico G.B. Rossi, Verona, Italy; Arancha Bermúdez Rodríguez, Hospital U. Marqués de Valdecilla, Santander, Spain; Wolfgang Bethge, Universitaet Tuebingen, Tuebingen, Germany; Igor Wolfgang Blau, Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Berlin, Germany; Adrian Bloor, Christie NHS Trust Hospital, Manchester, UK; Francesca Bonifazi, Bologna University, S.Orsola-Malpighi Hospital, Bologna, Italy; Jean Henri Bourhis, Gustave Roussy Cancer Campus, Villejuif, France; Peter Brossart, Universitaet Bonn, Bonn, Germany; Gesine Bug, Goethe-Universitaet, Frankfurt_Main, Germany; Claude Eric Bulabois, CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France; Alessandro Busca, S.S.C.V.D Trapianto di Cellule Staminali, Torino, Italy; Jenny Byrne, Nottingham University, Nottingham, UK; Jörg Cammenga, University Hospital, Linkoeping, Sweden; Antonio Campos, Inst. Português de Oncologia do Porto, Porto, Portugal; Angelo Michele Carella, IRCCS, Casa Sollievo della Sofferenza, SGiovanni_Rot, Italy; Kristina Carlson, University Hospital, Uppsala, Sweden; Ben Carpenter, University College London Hospital, London, UK; Marco Casini, Hospital San Maurizio, Bolzano, Italy; Jochen Casper, Klinikum Oldenburg, Oldenburg, Germany; Luca Castagna, U.O.D Trapianti di midollo osseo, Palermo, Italy; Yves Chalandon, Département d'Oncologie, Service

d'Hématologie, Geneva, Switzerland; Amandine Charbonnick, University of Amiens: CHU Amiens, Amiens, France; Patrice Chevallier, CHU Nantes, Nantes, France; Fabio Ciceri, Ospedale San Raffaele s.r.l., Milano, Italy; Andrew Clark, Bone Marrow Transplant Unit, Glasgow, UK; Johannes Clausen, Elisabethwenin-Hospital, Linz, Austria; Thomas Cluzeau, CHU Nice - Hôpital de l'ARCHET I, Nice, France; Matthew Collin, Adult HSCT unit, Newcastle_Tyne, UK; Paolo Corradini, University of Milano, Milano, Italy; Charles Craddock, University Hospital Birmingham NHSTrust, Birmingham, UK; Charles Crawley, Addenbrooke's Hospital, Cambridge, UK; Eric Deconinck, Hopital Jean Minjoz, Besancon, France; Dries Deeren, AZ Delta, Roeselare, Belgium; J.L. Diez-Martin, Hospital Gregorio Marañón, Madrid, Spain; Rafael Duarte, Clínica Puerta de Hierro, Madrid, Spain; Jaroslaw Dybko, DCTK, Wroclaw, Poland; Matthias Edinger, University Regensburg, Regensburg, Germany; Hermann Einsele, Universitaetsklinikum Wuerzburg, Wuerzburg, Germany; Ahmet Elmaagaci, Asklepios Klinik St. Georg, Hamburg, Germany; Edgar Faber, NADACE HAIMOM, Olomouc, Czech Rep; Franca Fagioli, Onco-Ematologia Pediatrica, Torino, Italy; Nathalie Fegueux, CHU Lapeyronne, Montpellier, France; Damian Finnegan, Belfast City Hospital, Belfast, UK; Catherine Flynn, Hope Directorate, Dublin, Ireland; Edouard Forcade, CHU Bordeaux, Pessac, France; Virginie Gandemer, Centre Hospitalier Universitaire de Rennes, Rennes, France; Tobias Gedde-Dahl, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Lidia Gil, Poznan University of Medical Sciences, Poznan, Poland; Soledad González Muñiz, Hospital Universitario Central de Asturias, Oviedo, Spain; Sonia Gonzalez Pérez, Hospital Clínico Universitario, S_de_Compostela, Spain; Richard Greil, Gemeinnützige Salzburger, Salzburg, Austria; Hildegard Greinix, LKH - University Hospital Graz, Graz, Austria; John Gribben, St. Bartholomew's and The Royal London NHS Trust, London, UK; Laimonas Griskevicius, Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania; Zafer Gülbas, Anadolu Medical Center Hospital, Kocaeli, Turkey; Gunhan Gurman, Ankara University Faculty of Medicine, Ankara, Turkey; Denis Guyotat, Institut de Cancerologie Lucien Neuwirth, Saint Etienne, France; Kazimierz Halaburda, Institute of Hematology and Transfusion Medicine, Warsaw, Poland; Rose-Marie Hamladiji, Centre Pierre et Marie Curie, Alger, Algeria; Thomas Heinicke, Universitaetsklinikum Magdeburg, Magdeburg, Germany; Grzegorz Helbig, Silesian Medical Academy, Katowice, Poland; Inmaculada Heras, Hospital Morales Meseguer, Murcia, Spain; Olivier Hermine, Hôpital Necker, Paris, France; Bernd Hertenstein, Klinikum Bremen-Mitte, Bremen, Germany; Inken Hilgendorf, Universitaetsklinikum Jena, Jena, Germany; Mathilde Hunault-Berger, CHRU, Angers, France; Anne Huynh, CHU - Institut Universitaire du Cancer Toulouse, Toulouse, France; Cecilia Isaksson, Umea University Hospital, Umea, Sweden; Maija Itäla-Remes, Turku University Hospital, Turku, Finland; Pavel Jindra, Charles University Hospital, Pilsen, Czech Rep; Jan-Erik Johansson, Sahlgrenska University Hospital, Goeteborg, Sweden; Peter R.E. Johnson, Western General Hospital, Edinburgh, UK; Manuel Jurado Chacón, Hospital Univ. Virgen de las Nieves, Granada, Spain; Wu Ka Lung, ZNA, Antwerp, Belgium; Ain Kaare, Tartu University Hospital, Tartu, Estonia; Dimitrios Karakasis, Evangelismos Hospital, Athens, Greece; Martin Kaufmann, Robert_Bosch_Krankenhaus, Stuttgart, Germany; Tessa Kerre, Ghent University Hospital, Gent, Belgium; Anjum Khan, Yorkshire Blood & Marrow Transplant Programme, Leeds, UK; Michael Kiehl, Klinikum Frankfurt (Oder) GmbH, Frankfurt_Oder, Germany; Matthias Kammer, St. George's Hospital, London, UK; Stefan Klein, Universitaetsmedizin Mannheim, Mannheim, Germany; Yener Koc, Medicana International Hospital Istanbul, Istanbul, Turkey; William Krüger, Klinik fuer Innere Medizin C, Greifswald, Germany; Jürgen Kuball, University Medical Centre, Utrecht, Netherlands; Aleksandr Kulagin, First State Pavlov Medical University of St. Petersburg, St_Petersburg, Russia; Giorgio La Nasa, Centro Trapianti Unico Di CSE Adulti e Pediatrico A. O Brotzu, Cagliari, Italy; Hélène Labussière-Wallet, Centre Hospitalier Lyon Sud, Lyon, France; Marco Ladetto, H SS. Antonio e Biagio, Alessandria, Italy; Véronique Leblond, Université Paris IV, Hopital la Pitié-Salpetrière, Paris, France; Xavier Leleu, Hopital La Miletrie, Poitiers, France; Stig Lenhoff, Skanes University Hospital, Lund, Sweden; Philippe Lewalle, Institut Jules Bordet, Brussels, Belgium; Bruno Lioure, Techniciens d'Etude Clinique suivi de patients greffes, Strasbourg, France; José Luis López Lorenzo, Fundación Jiménez Díaz, Madrid, Spain; Javier López-Jiménez, Hospital Ramón y Cajal, Madrid, Spain; David Marks, Bristol Royal Hospital for Children, Bristol, UK; Massimo Martino, Grande Ospedale Metropolitanino Bianchi Melacrin Morelli - Centro Unico Trapianti A. Neri, Reggio_Calabria, Italy; Sebastien Maury, Hôpital Henri Mondor, Creteil, France; Patrizio Mazza, Ospedale Nord, Taranto, Italy; Patrick Medd, University Hospitals Plymouth NHS Trust, Plymouth, UK; Stephan Mielke, Karolinska University Hospital, Stockholm, Sweden; Nuno Miranda, Inst. Portugues Oncologia, Lisboa, Portugal; Mohamad Mohty, Hopital Saint Antoine, Paris, France; José Mª Moraleda, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain; Ashrafsadat Mousavi, Shariati Hospital, Teheran, Iran; Lutz Peter Müller, Martin-Luther-Universitaet Halle-Wittenberg, Halle, Germany; Alberto Mussetti, ICO—Hospital Duran i Reynals, Barcelona, Spain; Maurizio Musso, Ospedale La Maddalena—Dpt. Oncologico, Palermo, Italy; Arnon Nagler, Chaim Sheba Medical Center, Tel_Hasher, Israel; Andreas Neubauer, Philippa Universitaet Marburg, Marburg, Germany; Emma Nicholson, Royal Marsden Hospital, London, UK; Bendt Nielsen, University Department of Hematology, Aarhus, Denmark; Yana Novis, Hospital Sirio-Libanes, Sao_Paulo, Brazil; Kim Orchard, Southampton General Hospital, Southampton, UK; Zubeyde Nur Ozkurt, Gazi
University Faculty of Medicine, Ankara, Turkey; Shankara Paneesha, Birmingham
Heartlands Hospital, Birmingham, UK; Maria Jesús Pascual Cascon, Hospital Regional
de Málaga, Malaga, Spain; Jakob Passweg, University Hospital, Basel, Switzerland;
Andy Peniket, Department of Haematology, Oxford, UK; "Maria del Mar Perera
Alvarez, Hospital de Gran Canaria 'Dr Negrin', Las_Palmas, Spain;" Jose Antonio Pérez-
Simón, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Mario Petrini, Azienda
Ospedaliero Universitaria Pisana, Pisa, Italy; Pietro Piottelli, Ospedale San Gerardo,
Monza, Italy; Xavier Poiré, Cliniques Universitaires St. Luc, Brussels, Belgium; Mike
Potter, The Trustee of London Clinic, London, UK; Werner Rabitsch, Medizinische
Universitaet Wien, Vienna, Austria; Ron Ram, Tel Aviv Sourasky Medical Center,
Tel_Aviv, Israel; Alessandro Rambaldi, ASST Papa Giovanni XXIII, Bergamo, Italy; Péter
Reményi, Dél-pesti Centrumkórház—, Budapest, Hungary; Josep Maria Ribera
Santasusana, ICO-Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Mark
Ringhoffer, Klinikum Karlsruhe gGmbH, Karlsruhe, Germany; Wolf Rösler, University
Hospital Erlangen, Erlangen, Germany; Montserrat Rovira, Hospital Clinic, Barcelona,
Spain; Marie Thérèse Rubio, CHRU Brabois, Vandœuvre-lès-Nancy, France; Piotr
Rzepecki, Military Institute of Health Services BMT Unit, Warsaw, Poland; Riccardo
Saccardi, Azienda Ospedaliera Universitaria Careggi, Firenze, Italy; Elisa Sala, Klinik
fuer Innere Medzin III, Ulm, Germany; Antònia Sampol, Fundació Institut d'Investi-
gació Sanitària Illes Balears—IdISBa, Palma_Mallorca, Spain; Stella Santarone,
Ospedale Civile, Pescara, Italy; Jaime Sanz, University Hospital La Fe, Valencia, Spain;
Valery Savchenko, National Research Center for Hematology, Moscow, Russia;
Nicolaas Schaap, Nijmegen Medical Centre, Nijmegen, Netherlands; Kerstin Schäfer-
Eckart, Klinikum Nuernberg, Nuernberg, Germany; Urs Schanz, University Hospital,
Zurich, Switzerland; Christof Scheid, University of Cologne, Cologne, Germany;
Christoph Schmid, Klinikum Augsburg, Augsburg, Germany; Roland Schroers, ZIS
Universitaetsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Germany;
Wilfried Schroyens, Antwerp University Hospital (UZA), Antwerp_Edegem, Belgium;
Dominik Selleslag, A.Z. Sint-Jan, Brugge, Belgium; Matjaz Sever, University Med.
Center, Ljubljana, Slovenia; Jorge Sierra, Hospital Santa Creu i Sant Pau, Barcelona,
Spain; Aleksander B. Skotnicki, Jagiellonian University, Krakow, Poland; John
Snowden, Sheffield Teaching Hospitals NHS Trust, Sheffield, UK; Gerard Socié,
Hopital St. Louis, Paris, France; Alexandros Spyridonidis, Research Committee -
University of Patras, Patras, Greece; Dragana Stamatovic, Clinic of Hematology,
Belgrade, Serbia; Matthias Stelljes, University of Muenster, Muenster, Germany; Polina
Stepensky, Hadassah University Hospital, Jerusalem, Israel; "Eleni Tholouli, Manche-
ster Royal Infirmary, Manchester, UK;" Lorenz Thurner, University of Saarland,
Homburg, Germany; Herve Tilly, Centre Henri Becquerel, Rouen, France; Johanna
Tischer, Klinikum Grosshadern, Munich, Germany; Amos Toren, Edmond & Lily Safra
Children's Hospital, Tel_Hashomer, Israel; Juan Pio Torres Carrete, Complejo
Hospitalario de A Coruña, La_Coruna, Spain; Pascal Turlure, CHRU Limoges, Limoges,
France; Ali Unal, Erciyes Medical School, Kayseri, Turkey; David Valcárcel, Hospital Vall
d'Hebron, Barcelona, Spain; Thomas Valerius, University Medical Center Schleswig-
Holstein, Campus Kiel, Kiel, Germany; Carlos Vallejo Llamas, Hospital Universitario
Donostia, San_Sebastian, Spain; Gwendolyn Van Gorkom, University Hospital
Maastricht, Maastricht, Netherlands; David Veale, Royal Devon and Exeter Hospital,
Exeter, UK; Joan Hendrik Veelken, Leiden University Hospital, Leiden, Netherlands;
Mareike Verbeek, Klinikum Rechts der Isar, Munich, Germany; Giuseppe Visani,
AORMN Hospital, Pesaro, Italy; Nikolas von Bubnoff, University Medical Center

Schleswig-Holstein, Luebeck, Germany; Radovan Vrhovac, University Hospital Center
Rebro, Zagreb, Croatia; Jan Vydra, Institute of Hematology and Blood Transfusion,
Prague, Czech Rep; Eva Maria Wagner-Drouet, University Medical Center Mainz,
Mainz, Germany; Keith M. O. Wilson, Department of Haematology, Cardiff, UK;
Dominik Wolf, University Hospital Innsbruck, Innsbruck, Austria; Depei Wu, First
Affiliated Hospital of Soochow University, Suzhou, China; Gerald. G. Wulf,
Universitaetsklinikum Goettingen, Goettingen, Germany; Ipek Yonal-Hindilerden,
Ystanbul Tip Fakultesi, Istanbul, Turkey; Pavel Zák, Charles University Hospital,
Hradec_Kralove, Czech Rep; Jan Zaucha, Medical University of Gdansk, Gdansk,
Poland; Marco Zecca, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Tsila
Zuckerman, Rambam Medical Center, Haifa, Israel; Teresa Zudaire, Unidad de Ensayos
Clinicos de Hematologia Pabellón A, bajo., Pamplona, Spain.

FUNDING

Open Access funding enabled and organized by Projekt DEAL.

COMPETING INTERESTS

The authors declare no competing interests.

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