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1. PDGFRβ promotes oncogenic progression via STAT3/STAT5 hyperactivation in anaplastic large cell lymphoma

Author

Garces de los Fayos Alonso, I., Zujo, L., Wiest, I., Kodajova, P., Timelthaler, G., Edtmayer, S., Zrimšek, M., Kollmann, S., Giordano, C., Kothmayer, M., Neubauer, H. A., Dey, S., Schlederer, M., Schmalzbauer, B. S., Limberger, T., Probst, C., Pusch, O., Högler, S., Tangermann, S., Merkel, O., Schiefer, A. I., Kornauth, C., Prutsch, N., Zimmerman, M., Abraham, B., Anagnostopoulos, J., Quintanilla-Martinez, L., Mathas, S., Wolf, P., Stoiber, D., Staber, P. B., Egger, G., Klapper, W., Woessmann, W., Look, T. A., Gunning, P., Turner, S. D., Moriggl, R., Lagger, S., and Kenner, L.

Published
2022
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2. Leukämien und Lymphome

Author

Schrappe, M., Möricke, A., Attarbaschi, A., von Stackelberg, A., Creutzig, U., Reinhardt, D., Suttorp, M., Rensing-Ehl, A., Ehl, S., Burkhardt, B., Klapper, W., Wößmann, W., Körholz, D., Mauz-Körholz, C., Niemeyer, C., Niemeyer, Charlotte, editor, and Eggert, Angelika, editor

Published
2018
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3. Improving outcomes of childhood and young adult non-Hodgkin lymphoma (NHL); twenty-five years of research and collaboration within the framework of the European Intergroup for Childhood Non-Hodgkin Lymphoma (EICNHL)

Author

Beishuizen A, Mellgren K, Andrés M, Auperin A, Bacon CM, Bomken S, Burke GAA, Burkhardt B, Brugieres L, Chiang AKS, Damm-Welk C, dAmore E, Horibe K, Kabickova E, Khanam T, Kontny U, Klapper W, Lamant L, Le Deley MC, Loeffen J, Macintyre E, Mann G, Meyer-Wentrup F, Michgehl U, Minard-Colin V, Mussolin L, Oschlies I, Patte C, Pillon M, Reiter A, Rigaud C, Roncery L, Salaverria I, Simonitsch-Klupp I, Uyttebroeck A, Verdu Amoros J, Williams D, Woessmann W, Wotherspoon A, Wrobel G, Zimmermann M, Attarbaschi A, Turner SD

Published
2023
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5. VARIANT ALK-FUSION POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA (ALCL): A POPULATION-BASED COHORT OF THE NHL-BFM STUDY GROUP

Author

Damm-Welk, C., primary, Luedersen, J., additional, Stadt, U., additional, Richter, J., additional, Oschlies, I., additional, Klapper, W., additional, Rosenwald, A., additional, Kalinova, M., additional, Simonitsch-Klupp, I., additional, Siebert, R., additional, Zimmermann, M., additional, Alawi, M., additional, Nakel, J., additional, Scheinemann, K., additional, Knörr, F., additional, Attarbaschi, A., additional, Kabickova, E., additional, and Woessmann, W., additional

Published
2022
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6. PDGFRβ DRIVES PROGRESSION BY ONCOGENE TRANSCRIPTION THROUGH STAT3/STAT5 HYPERACTIVATION IN ALCL

Author

de los Fayos Alonso, I. Garces, primary, Zujo, L., additional, Krsmanovic, I., additional, Kodojova, P., additional, Schlederer, M., additional, Timelthaler, G., additional, Edtmayer, S., additional, Giordano, C., additional, Kothmayer, M., additional, Neubauer, H.A., additional, Dey, S., additional, Pusch, O., additional, Högler, S., additional, Tangermann, S., additional, Schiefer, A., additional, Kornauth, C., additional, Wolf, P., additional, Stoiber, D., additional, Staber, P., additional, Klapper, W., additional, Woessmann, W., additional, Gunning, P., additional, Turner, S., additional, Moriggl, R., additional, Lagger, S., additional, and Kenner, L., additional

Published
2022
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7. CHARACTERIZATION OF IG-MYC-BREAKPOINTS AND THEIR APPLICATION FOR QUANTITATIVE MINIMAL DISEASE MONITORING IN HIGH-RISK PEDIATRIC BURKITT-LYMPHOMA AND –LEUKEMIA

Author

Damm-Welk, C., primary, Möker, P., additional, Stadt, U., additional, Zimmermann, M., additional, Alawi, M., additional, Mueller, S., additional, Finger, J., additional, Knörr, F., additional, Riquelme, A., additional, Oschlies, I., additional, Klapper, W., additional, Bradtke, J., additional, Burkhardt, B., additional, and Woessmann, W., additional

Published
2022
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11. IL10RA modulates crizotinib sensitivity in NPM1-ALK+ anaplastic large cell lymphoma

Author

Prokoph, N, Probst, N, Lee, L, Monahan, J, Matthews, J, Liang, H, Bahnsen, K, Montes-Mojarro, I, Karaca-Atabay, E, Sharma, G, Malik, V, Larose, H, Forde, S, Ducray, S, Lobello, C, Wang, Q, Luan, S, Pospisilova, S, Gambacorti Passerini, C, Burke, G, Pervez, S, Attarbaschi, A, Janikova, A, Pacquement, H, Landman-Parker, J, Lambilliotte, A, Schleiermacher, G, Klapper, W, Jauch, R, Woessmann, W, Vassal, G, Kenner, L, Merkel, O, Mologni, L, Chiarle, R, Brugieres, L, Geoerger, B, Barbieri, I, Turner, S, Prokoph N., Probst N. A., Lee L. C., Monahan J. M., Matthews J. D., Liang H. -C., Bahnsen K., Montes-Mojarro I. A., Karaca-Atabay E., Sharma G. G., Malik V., Larose H., Forde S. D., Ducray S. P., Lobello C., Wang Q., Luan S. -L., Pospisilova S., Gambacorti Passerini C., Burke G. A. A., Pervez S., Attarbaschi A., Janikova A., Pacquement H., Landman-Parker J., Lambilliotte A., Schleiermacher G., Klapper W., Jauch R., Woessmann W., Vassal G., Kenner L., Merkel O., Mologni L., Chiarle R., Brugieres L., Geoerger B., Barbieri I., Turner S. D., Prokoph, N, Probst, N, Lee, L, Monahan, J, Matthews, J, Liang, H, Bahnsen, K, Montes-Mojarro, I, Karaca-Atabay, E, Sharma, G, Malik, V, Larose, H, Forde, S, Ducray, S, Lobello, C, Wang, Q, Luan, S, Pospisilova, S, Gambacorti Passerini, C, Burke, G, Pervez, S, Attarbaschi, A, Janikova, A, Pacquement, H, Landman-Parker, J, Lambilliotte, A, Schleiermacher, G, Klapper, W, Jauch, R, Woessmann, W, Vassal, G, Kenner, L, Merkel, O, Mologni, L, Chiarle, R, Brugieres, L, Geoerger, B, Barbieri, I, Turner, S, Prokoph N., Probst N. A., Lee L. C., Monahan J. M., Matthews J. D., Liang H. -C., Bahnsen K., Montes-Mojarro I. A., Karaca-Atabay E., Sharma G. G., Malik V., Larose H., Forde S. D., Ducray S. P., Lobello C., Wang Q., Luan S. -L., Pospisilova S., Gambacorti Passerini C., Burke G. A. A., Pervez S., Attarbaschi A., Janikova A., Pacquement H., Landman-Parker J., Lambilliotte A., Schleiermacher G., Klapper W., Jauch R., Woessmann W., Vassal G., Kenner L., Merkel O., Mologni L., Chiarle R., Brugieres L., Geoerger B., Barbieri I., and Turner S. D.

Abstract

Anaplastic large cell lymphoma (ALCL) is a T-cell malignancy predominantly driven by a hyperactive anaplastic lymphoma kinase (ALK) fusion protein. ALK inhibitors, such as crizotinib, provide alternatives to standard chemotherapy with reduced toxicity and side effects. Children with lymphomas driven by nucleophosmin 1 (NPM1)-ALK fusion proteins achieved an objective response rate to ALK inhibition therapy of 54% to 90% in clinical trials; however, a subset of patients progressed within the first 3 months of treatment. The mechanism for the development of ALK inhibitor resistance is unknown. Through genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation and knockout screens in ALCL cell lines, combined with RNA sequencing data derived from ALK inhibitor-relapsed patient tumors, we show that resistance to ALK inhibition by crizotinib in ALCL can be driven by aberrant upregulation of interleukin 10 receptor subunit alpha (IL10RA). Elevated IL10RA expression rewires the STAT3 signaling pathway, bypassing otherwise critical phosphorylation by NPM1-ALK. IL-10RA expression does not correlate with response to standard chemotherapy in pediatric patients, suggesting that a combination of crizotinib and chemotherapy could prevent ALK inhibitor resistance-specific relapse.

Published
2020

12. Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE

Author

Maria, O, Eva, B, Pamela R, K, Olga, K, Marko, O, Reineke A, S, Gilles, V, Achini, F, Balduzzi, A, Beck Popovic, M, Beishuizen, A, Bergamaschi, L, Biondi, A, Bourdeaut, F, Braicu, E, Brok, J, Brugières, L, Burke, A, Calaminus, G, Casanova, M, Choucair, M, Cleirec, M, Corbaciouglu, S, Genoveva Correa Llano, M, De Rojas, T, Domínguez Pinilla, N, Elmaraghi, C, Ferrari, A, Fossa, A, Gaspar, N, Herold, N, Karapiperi, K, Karu, M, Kjærsgaar, M, Knörr, F, Koenig, C, Kranjcec, I, Krawczyk, M, Lehmberg, K, Lehrnbecher, T, Lunesink, M, Massano, D, Matijasic, N, Merks, H, Metzler, M, Michalski, A, Minkov, M, Morland, B, Niktoreh, N, Oltenau, E, Orbach, D, Owens, C, Papachristidou, S, Pasqualini, C, Pavlovic, M, Perez Albert, P, Poyer, F, Radulovic, I, Reinhardt, D, Rebelo, J, Roser, E, Russo, I, Scheinemann, K, Schindera, C, Schrappe, M, Sehested, A, Sehouli, J, Spreafico, F, J Strauss, S, Stutterheim, J, Svojgr, K, Tzotzola, V, Van Ewijk, R, Verschuur, A, Vora, A, Woessmann, W, Zajac-Spychala, O, Zwaan, M, Otth, Maria, Brack, Eva, Kearns, Pamela R, Kozhaeva, Olga, Ocokoljic, Marko, Schoot, Reineke A, Vassal, Gilles, Federica Achini, Adriana Balduzzi, Maja Beck Popovic, Auke Beishuizen, Luca Bergamaschi, Andrea Biondi, Franck Bourdeaut, Elena Braicu, Jesper Brok, Laurence Brugières, Amos Burke, Gabriele Calaminus, Michela Casanova, Marie-Louise Choucair, Morgane Cleirec, Selim Corbaciouglu, Maria Genoveva Correa Llano, Teresa De Rojas, Nerea Domínguez Pinilla, Caroline Elmaraghi, Andrea Ferrari, Alexander Fossa, Nathalie Gaspar, Nikolas Herold, Kyriaki Karapiperi, Maarja Karu, Mimi Kjærsgaar, Fabian Knörr, Christa Koenig, Izabela Kranjcec, Malgorzata Krawczyk, Kai Lehmberg, Thomas Lehrnbecher, Maaike Lunesink, Davide Massano, Nuša Matijasic, Hans Merks, Markus Metzler, Anthony Michalski, Milen Minkov, Bruce Morland, Naghmeh Niktoreh, Elena Oltenau, Daniel Orbach, Cormac Owens, Smaragda Papachristidou, Claudia Pasqualini, Maja Pavlovic, Paula Perez Albert, Fiona Poyer, Ivana Radulovic, Dirk Reinhardt, Joana Rebelo, Eva Roser, Ida Russo, Katrin Scheinemann, Christina Schindera, Martin Schrappe, Astrid Sehested, Jalid Sehouli, Filippo Spreafico, Sandra J Strauss, Janine Stutterheim, Karel Svojgr, Vasiliki Tzotzola, Roelof Van Ewijk, Arnauld Verschuur, Ajay Vora, Willi Woessmann, Olga Zajac-Spychala, Michel Zwaan, Maria, O, Eva, B, Pamela R, K, Olga, K, Marko, O, Reineke A, S, Gilles, V, Achini, F, Balduzzi, A, Beck Popovic, M, Beishuizen, A, Bergamaschi, L, Biondi, A, Bourdeaut, F, Braicu, E, Brok, J, Brugières, L, Burke, A, Calaminus, G, Casanova, M, Choucair, M, Cleirec, M, Corbaciouglu, S, Genoveva Correa Llano, M, De Rojas, T, Domínguez Pinilla, N, Elmaraghi, C, Ferrari, A, Fossa, A, Gaspar, N, Herold, N, Karapiperi, K, Karu, M, Kjærsgaar, M, Knörr, F, Koenig, C, Kranjcec, I, Krawczyk, M, Lehmberg, K, Lehrnbecher, T, Lunesink, M, Massano, D, Matijasic, N, Merks, H, Metzler, M, Michalski, A, Minkov, M, Morland, B, Niktoreh, N, Oltenau, E, Orbach, D, Owens, C, Papachristidou, S, Pasqualini, C, Pavlovic, M, Perez Albert, P, Poyer, F, Radulovic, I, Reinhardt, D, Rebelo, J, Roser, E, Russo, I, Scheinemann, K, Schindera, C, Schrappe, M, Sehested, A, Sehouli, J, Spreafico, F, J Strauss, S, Stutterheim, J, Svojgr, K, Tzotzola, V, Van Ewijk, R, Verschuur, A, Vora, A, Woessmann, W, Zajac-Spychala, O, Zwaan, M, Otth, Maria, Brack, Eva, Kearns, Pamela R, Kozhaeva, Olga, Ocokoljic, Marko, Schoot, Reineke A, Vassal, Gilles, Federica Achini, Adriana Balduzzi, Maja Beck Popovic, Auke Beishuizen, Luca Bergamaschi, Andrea Biondi, Franck Bourdeaut, Elena Braicu, Jesper Brok, Laurence Brugières, Amos Burke, Gabriele Calaminus, Michela Casanova, Marie-Louise Choucair, Morgane Cleirec, Selim Corbaciouglu, Maria Genoveva Correa Llano, Teresa De Rojas, Nerea Domínguez Pinilla, Caroline Elmaraghi, Andrea Ferrari, Alexander Fossa, Nathalie Gaspar, Nikolas Herold, Kyriaki Karapiperi, Maarja Karu, Mimi Kjærsgaar, Fabian Knörr, Christa Koenig, Izabela Kranjcec, Malgorzata Krawczyk, Kai Lehmberg, Thomas Lehrnbecher, Maaike Lunesink, Davide Massano, Nuša Matijasic, Hans Merks, Markus Metzler, Anthony Michalski, Milen Minkov, Bruce Morland, Naghmeh Niktoreh, Elena Oltenau, Daniel Orbach, Cormac Owens, Smaragda Papachristidou, Claudia Pasqualini, Maja Pavlovic, Paula Perez Albert, Fiona Poyer, Ivana Radulovic, Dirk Reinhardt, Joana Rebelo, Eva Roser, Ida Russo, Katrin Scheinemann, Christina Schindera, Martin Schrappe, Astrid Sehested, Jalid Sehouli, Filippo Spreafico, Sandra J Strauss, Janine Stutterheim, Karel Svojgr, Vasiliki Tzotzola, Roelof Van Ewijk, Arnauld Verschuur, Ajay Vora, Willi Woessmann, Olga Zajac-Spychala, and Michel Zwaan

Abstract

Background: Shortages and unequal access to anticancer medicines for children and adolescents are a reality in Europe. The aim of the European Society for Paediatric Oncology (SIOPE) Essential Anticancer Medicines Project was to provide a list of anticancer medicines that are considered essential in the treatment of paediatric cancers to help ensure their continuous access to all children and adolescents with cancer across Europe. Methods: This pan-European project, done between Jan 20, 2020, and Feb 18, 2022, was designed to be a systematic collection and review of treatment protocols and strategies that are used to treat childhood cancer in Europe. We formed 16 working groups on the basis of paediatric cancer types, and which were based on the existing SIOPE Clinical Trial Groups. Workings groups consisted of representatives from the SIOPE Clinical Trial Groups, Young SIOPE members, and senior paediatric oncology experts. Each group collected existing treatment protocols that are used to treat the respective cancer types in Europe. Medicines from the standard group of each protocol were extracted. For medicines not on the WHO Essential Medicines List for children (EMLc) 2017, working groups did a literature search to determine whether the medicines should be defined as essential, promising, or neither essential nor promising. Each group provided an individual summary, and all medicines that were considered essential by at least one group were combined in a joint list. Findings: The working groups identified 73 treatment protocols used in Europe and defined 66 medicines as essential. For several newer medicines, such as kinase inhibitors or tisagenlecleucel, the supporting evidence was insufficient to consider them essential, so these medicines were defined as promising. 25 medicines were considered promising by at least one working group. 22 (33%) of the 66 essential and none of the promising medicines were included in the WHO EMLc 2017. The WHO EMLc 2021 included

Published
2022

13. No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

Author

Thiel, U., Wawer, A., Wolf, P., Badoglio, M., Santucci, A., Klingebiel, T., Basu, O., Borkhardt, A., Laws, H.-J., Kodera, Y., Yoshimi, A., Peters, C., Ladenstein, R., Pession, A., Prete, A., Urban, E.-C., Schwinger, W., Bordigoni, P., Salmon, A., Diaz, M.A., Afanasyev, B., Lisukov, I., Morozova, E., Toren, A., Bielorai, B., Korsakas, J., Fagioli, F., Caselli, D., Ehninger, G., Gruhn, B., Dirksen, U., Abdel-Rahman, F., Aglietta, M., Mastrodicasa, E., Torrent, M., Corradini, P., Demeocq, F., Dini, G., Dreger, P., Eyrich, M., Gozdzik, J., Guilhot, F., Holler, E., Koscielniak, E., Messina, C., Nachbaur, D., Sabbatini, R., Oldani, E., Ottinger, H., Ozsahin, H., Schots, R., Siena, S., Stein, J., Sufliarska, S., Unal, A., Ussowicz, M., Schneider, P., Woessmann, W., Jürgens, H., Bregni, M., and Burdach, S.

Published
2011
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16. Molecular features of non-anaplastic peripheral T-cell lymphoma in children and adolescents

Author

Au-Yeung, R.K.H., Richter, J., Iaccarino, I., Abramov, D., Bacon, C.M., Balagué, O., d'Amore, E.S., Simonitsch-Klupp, I., Hebeda, K.M., Nakazawa, A., Oschlies, I., Kontny, U., Woessmann, W., Burkhardt, B., Klapper, W., Au-Yeung, R.K.H., Richter, J., Iaccarino, I., Abramov, D., Bacon, C.M., Balagué, O., d'Amore, E.S., Simonitsch-Klupp, I., Hebeda, K.M., Nakazawa, A., Oschlies, I., Kontny, U., Woessmann, W., Burkhardt, B., and Klapper, W.

Abstract

Item does not contain fulltext, Non-anaplasticperipheral T-cell lymphomas (PTCL) are rare tumors in children, adolescents, and young adults (CAYA) with poor prognosis and scarce genetic data. We analyzed lymphoma tissue from 36 patients up to 18 years old with PTCL, not otherwise specified (PTCL-NOS), hepatosplenic T-cell lymphoma, Epstein-Barr virus (EBV)-positive T-lymphoproliferative diseases, subcutaneous panniculitis-like T-cell lymphoma, and other PTCL types. Twenty-three patients (64%) had at least one genetic variant detectable, including TET2, KMT2C, PIK3D, and DMNT3A. TP53 and RHOA variants, commonly found in adults, were not identified. Eight of 20 (40%) CAYA PTCL-NOS had no detectable mutations. The genetic findings suggest that CAYA PTCL differ from adult cases.

Published
2021

17. Treatment and Outcome Analysis of 639 Relapsed Non-Hodgkin Lymphomas in Children and Adolescents and Resulting Treatment Recommendations

Author

Burkhardt, B, Taj, M, Garnier, N, Minard-Colin, V, Hazar, V, Mellgren, K, Osumi, T, Fedorova, A, Myakova, N, Verdu-Amoros, J, Andres, M, Kabickova, E, Attarbaschi, A, Chiang, A, Bubanska, E, Donska, S, Hjalgrim, L, Wachowiak, J, Pieczonka, A, Uyttebroeck, A, Lazic, J, Loeffen, J, Buechner, J, Niggli, F, Csoka, M, Krivan, G, Palma, J, Burke, G, Beishuizen, A, Koeppen, K, Mueller, S, Herbrueggen, H, Woessmann, W, Zimmermann, M, Balduzzi, A, Pillon, M, Burkhardt, Birgit, Taj, Mary, Garnier, Nathalie, Minard-Colin, Veronique, Hazar, Volkan, Mellgren, Karin, Osumi, Tomoo, Fedorova, Alina, Myakova, Natalia, Verdu-Amoros, Jaime, Andres, Mara, Kabickova, Edita, Attarbaschi, Andishe, Chiang, Alan Kwok Shing, Bubanska, Eva, Donska, Svetlana, Hjalgrim, Lisa Lyngsie, Wachowiak, Jacek, Pieczonka, Anna, Uyttebroeck, Anne, Lazic, Jelena, Loeffen, Jan, Buechner, Jochen, Niggli, Felix, Csoka, Monika, Krivan, Gergely, Palma, Julia, Burke, G A Amos, Beishuizen, Auke, Koeppen, Kristin, Mueller, Stephanie, Herbrueggen, Heidi, Woessmann, Wilhelm, Zimmermann, Martin, Balduzzi, Adriana, Pillon, Marta, Burkhardt, B, Taj, M, Garnier, N, Minard-Colin, V, Hazar, V, Mellgren, K, Osumi, T, Fedorova, A, Myakova, N, Verdu-Amoros, J, Andres, M, Kabickova, E, Attarbaschi, A, Chiang, A, Bubanska, E, Donska, S, Hjalgrim, L, Wachowiak, J, Pieczonka, A, Uyttebroeck, A, Lazic, J, Loeffen, J, Buechner, J, Niggli, F, Csoka, M, Krivan, G, Palma, J, Burke, G, Beishuizen, A, Koeppen, K, Mueller, S, Herbrueggen, H, Woessmann, W, Zimmermann, M, Balduzzi, A, Pillon, M, Burkhardt, Birgit, Taj, Mary, Garnier, Nathalie, Minard-Colin, Veronique, Hazar, Volkan, Mellgren, Karin, Osumi, Tomoo, Fedorova, Alina, Myakova, Natalia, Verdu-Amoros, Jaime, Andres, Mara, Kabickova, Edita, Attarbaschi, Andishe, Chiang, Alan Kwok Shing, Bubanska, Eva, Donska, Svetlana, Hjalgrim, Lisa Lyngsie, Wachowiak, Jacek, Pieczonka, Anna, Uyttebroeck, Anne, Lazic, Jelena, Loeffen, Jan, Buechner, Jochen, Niggli, Felix, Csoka, Monika, Krivan, Gergely, Palma, Julia, Burke, G A Amos, Beishuizen, Auke, Koeppen, Kristin, Mueller, Stephanie, Herbrueggen, Heidi, Woessmann, Wilhelm, Zimmermann, Martin, Balduzzi, Adriana, and Pillon, Marta

Abstract

Despite poor survival, controversies remain in the treatment for refractory or relapsed pediatric non-Hodgkin lymphoma (r/r NHL). The current project aimed to collect international experience on the re-induction treatment of r/r NHL, hematopoietic stem cell transplantation (HSCT), risk factors associated with outcome, and to suggest treatment recommendations. Inclusion criteria were (i) refractory disease, disease progression or relapse of any NHL subtype except anaplastic large cell lymphoma, (ii) age < 18 years at initial diagnosis, (iii) diagnosis in/after January 2000. Data from 639 eligible patients were evaluable. The eight-year probability of overall survival was 34 ± 2% with highly significant differences according to NHL subtypes: 28 ± 3% for 254 Burkitt lymphoma/leukemia, 50 ± 6% for 98 diffuse large B-cell lymphomas, 57 ± 8% for 41 primary mediastinal large B-cell lymphomas, 27 ± 3% for 177 T-lymphoblastic lymphomas, 52 ± 10% for 34 precursor-B-cell lymphoblastic lymphomas and 30 ± 9% for 35 patients with rare NHL subtypes. Subtype-specific factors associated with survival and treatment recommendations are suggested. There were no survivors without HSCT, except in few very small subgroups. Conclusions: There is an urgent need to further improve survival in r/r NHL. The current study provides the largest real-world series, which underlines the role of HSCT and suggests treatment recommendations.

Published
2021

19. CLINICAL IMPACT OF POST-TRANSPLANT CHIMERISM MONITORING IN CD33/34 BONE MARROW SUBPOPULATIONS AND WHOLE PERIPHERAL BLOOD IN PEDIATRIC AML: PROSPECTIVE COMPARISON OF HIGHLY SENSITIVE REAL TIME SEQUENCE POLYMORPHISM PCR VERSUS GOLD-STANDARD STR-PCR: PH-O097

Author

Willasch, Manfred A., Rettinger, E., Zabel, M., Kreyenberg, H., Meyer, V., Merker, M., Borkhardt, A., Metzler, M., Kremens, B., Strahm, B., Woessmann, W., Mauz-Koerholz, C., Gruhn, B., Burdach, S., Albert, M., Schlegel, P.-G., Klingebiel, T., and Bader, P.

Published
2014

20. Second malignant neoplasms after treatment of non-Hodgkin's lymphoma-a retrospective multinational study of 189 children and adolescents

Author

Attarbaschi A, Carraro E, Ronceray L, Andrés M, Barzilai-Birenboim S, Bomken S, Brugières L, Burkhardt B, Ceppi F, Chiang AKS, Csoka M, Fedorova A, Jazbec J, Kabickova E, Loeffen J, Mellgren K, Miakova N, Moser O, Osumi T, Pourtsidis A, Rigaud C, Uyttebroeck A, Woessmann W, Pillon M, and European Intergroup for Childhood Non-Hodgkin’s Lymphoma (EICNHL) and the Intern

Subjects
hemic and lymphatic diseases
Abstract

Data on the spectrum of second malignant neoplasms (SMNs) after primary childhood non-Hodgkin's lymphoma (NHL) are scarce. One-hundred-and-eighty-nine NHL patients diagnosed in a 30 years period of 1980-2010 developing an SMN were retrieved from 19 members of the European Intergroup for Childhood NHL and/or the international Berlin-Frankfurt-Münster Study Group. Five subgroups of SMNs were identified: (1) myeloid neoplasms (n = 43; 23%), (2) lymphoid neoplasms (n = 51; 27%), (3) carcinomas (n = 48; 25%), (4) central nervous system (CNS) tumors (n = 19; 10%), and (5) "other" SMNs (n = 28; 15%). In 37 patients (20%) preexisting disorders were reported with 90% having any kind of cancer predisposition syndrome (CPS). For the 189 primary NHL patients, 5-year overall survival (OS) after diagnosis of an SMN was 56 ± 4%, being worst for patients with preexisting disorders at 28 ± 8%. Five-year OS rates were 38 ± 8%, 59 ± 7%, 79 ± 8%, 34 ± 12%, and 62 ± 11%, respectively, for patients with myeloid and lymphoid neoplasms, carcinomas, CNS tumors, and "other" SMNs (p < 0.0001). Patients with SMNs after childhood NHL having a reported CPS, mostly mismatch repair disorders, carried a very poor prognosis. Moreover, although outcome was favorable in some subtypes of SMNs after childhood NHL (carcinomas, lymphoid neoplasms), other SMNs such as myeloid neoplasms and CNS tumors had a dismal prognosis.

Published
2020

31. Hematopoietic Stem Cell Transplantation as Treatment for Patients with DOCK8 Deficiency

Author

Aydin, S.E., Freeman, A.F., Al-Herz, W., Al-Mousa, H.A., Arnaout, R.K., Aydin, R.C., Barlogis, V., Belohradsky, B.H., Bonfim, C., Bredius, R.G., Chu, J.I., Ciocarlie, O.C., Dogu, F., Gaspar, H.B., Geha, R.S., Gennery, A.R., Hauck, F., Hawwari, A., Hickstein, D.D., Hoenig, M., Ikinciogullari, A., Klein, C., Kumar, A., Ifversen, M.R.S., Matthes, S., Metin, A., Neven, B., Pai, S.Y., Parikh, S.H., Picard, C., Renner, E.D., Sanal, O., Schulz, A.S., Schuster, F., Shah, N.N., Shereck, E.B., Slatter, M.A., Su, H.C., Montfrans, J. van, Woessmann, W., Ziegler, J.B., Albert, M.H., Inborn Errors Working Party Europe, and European Soc Primary Immunodefici

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, DOCK8 deficiency, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Kaplan-Meier Estimate, Treosulfan, Article, Young Adult, Internal medicine, medicine, Journal Article, Immunology and Allergy, Guanine Nucleotide Exchange Factors, Humans, Child, Immunodeficiency, business.industry, Hematopoietic Stem Cell Transplantation, Immunologic Deficiency Syndromes, Infant, Retrospective cohort study, medicine.disease, Combined immunodeficiency, Regimen, Graft-versus-host disease, surgical procedures, operative, Child, Preschool, Failure to thrive, HSCT, Female, medicine.symptom, business, Busulfan, medicine.drug
Abstract

BACKGROUND: Biallelic variations in the dedicator of cytokinesis 8 (DOCK8) gene cause a combined immunodeficiency with eczema, recurrent bacterial and viral infections, and malignancy. Natural disease outcome is dismal, but allogeneic hematopoietic stem cell transplantation (HSCT) can cure the disease.OBJECTIVE: To determine outcome of HSCT for DOCK8 deficiency and define possible outcome variables.METHODS: We performed a retrospective study of the results of HSCT in a large international cohort of DOCK8-deficient patients.RESULTS: We identified 81 patients from 22 centers transplanted at a median age of 9.7 years (range, 0.7-27.2 years) between 1995 and 2015. After median follow-up of 26 months (range, 3-135 months), 68 (84%) patients are alive. Severe acute (III-IV) or chronic graft versus host disease occurred in 11% and 10%, respectively. Causes of death were infections (n = 5), graft versus host disease (5), multiorgan failure (2), and preexistent lymphoma (1). Survival after matched related (n = 40) or unrelated (35) HSCT was 89% and 81%, respectively. Reduced-toxicity conditioning based on either treosulfan or reduced-dose busulfan resulted in superior survival compared with fully myeloablative busulfan-based regimens (97% vs 78%; P = .049). Ninety-six percent of patients younger than 8 years at HSCT survived, compared with 78% of those 8 years and older (P = .06). Of the 73 patients with chimerism data available, 65 (89%) had more than 90% donor T-cell chimerism at last follow-up. Not all disease manifestations responded equally well to HSCT: eczema, infections, and mollusca resolved quicker than food allergies or failure to thrive.CONCLUSIONS: HSCT is curative in most DOCK8-deficient patients, confirming this approach as the treatment of choice. HSCT using a reduced-toxicity regimen may offer the best chance for survival. (C) 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology

Published
2019

32. Primary central nervous system lymphoma: initial features, outcome, and late effects in 75 children and adolescents

Author

Attarbaschi A, Abla O, Ronceray L, Bansil S, Bomken S, Burkhardt B, Ceppi F, Chiang A, Dave H, Fedorova A, Henry M, Jazbec J, Kabickova E, Kotecha R, Lazic J, Loeffen J, Miakova N, Osumi T, Pillon M, Pourtsidis A, Rigaud C, Tamamyan G, Tandon S, Uyttebroeck A, Verdu-Amoros J, Woessmann W, Wrobel G, Giulino-Roth L, European Intergrp Childhood Non-Ho, Int Berlin-Frankfurt-Munster Study, and Selected North Amer Ctr Pediat Hem

Published
2019

35. 115 - PDGFRβ DRIVES PROGRESSION BY ONCOGENE TRANSCRIPTION THROUGH STAT3/STAT5 HYPERACTIVATION IN ALCL

Author

de los Fayos Alonso, I. Garces, Zujo, L., Krsmanovic, I., Kodojova, P., Schlederer, M., Timelthaler, G., Edtmayer, S., Giordano, C., Kothmayer, M., Neubauer, H.A., Dey, S., Pusch, O., Högler, S., Tangermann, S., Schiefer, A., Kornauth, C., Wolf, P., Stoiber, D., Staber, P., Klapper, W., Woessmann, W., Gunning, P., Turner, S., Moriggl, R., Lagger, S., and Kenner, L.

Published
2022
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43. Large B-cell lymphomas with ALK-rearrangement display a different genetic and epigenetic profile than diffuse large B-cell lymphoma

Author

Wagener, R., Schnaudt, C., Kleinheinz, K., Ammerpohl, O., Altmueller, J., Thiele, H., Kolarova, J., Agirre, X., Nurnberg, P., Brousset, P., Klapper, W., Laurent, C., Martin-Subero, I., Propser, F., Woessmann, W., Xerri, L., Schlesner, M., Siebert, R., Wagener, R., Schnaudt, C., Kleinheinz, K., Ammerpohl, O., Altmueller, J., Thiele, H., Kolarova, J., Agirre, X., Nurnberg, P., Brousset, P., Klapper, W., Laurent, C., Martin-Subero, I., Propser, F., Woessmann, W., Xerri, L., Schlesner, M., and Siebert, R.

Published
2018

44. Clinical and Genetic Risk Factors Define Two Risk Groups of Extracranial Rhabdoid Tumors: A Plea for High Risk Tailored Therapies

Author

Nemes, K., Kachanov, D., Simon, T., Hauser, P., Tippelt, S., Woessmann, W., Flotho, C., Grigulls, L., Hernaiz-Driever, P., Schlegel, P. G., Abbink, F., Gi-da-Costa, M. J., Lowis, S., Hernandes Marquez, C., Graf, N., Nysom, K., Bens, S., Kroencke, T., Furtwaengler, R., Fruehwald, M., Nemes, K., Kachanov, D., Simon, T., Hauser, P., Tippelt, S., Woessmann, W., Flotho, C., Grigulls, L., Hernaiz-Driever, P., Schlegel, P. G., Abbink, F., Gi-da-Costa, M. J., Lowis, S., Hernandes Marquez, C., Graf, N., Nysom, K., Bens, S., Kroencke, T., Furtwaengler, R., and Fruehwald, M.

Published
2018

45. ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH REDUCED‐TOXICITY CONDITIONING FOR PEDIATRIC RELAPSED OR REFRACTORY ALK‐POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA.

Author

Knörr, F., Zimmermann, M., Müller, I., Bader, P., Lang, P., Basu, O., Burkhardt, B., Beier, R., and Woessmann, W.

Subjects
ANAPLASTIC large-cell lymphoma, HEMATOPOIETIC stem cell transplantation, SEVERE combined immunodeficiency, ANAPLASTIC thyroid cancer
Abstract

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION WITH REDUCED-TOXICITY CONDITIONING FOR PEDIATRIC RELAPSED OR REFRACTORY ALK-POSITIVE ANAPLASTIC LARGE CELL LYMPHOMA B Introduction: b For children and adolescents with refractory or relapsed ( I r i / I r i ) anaplastic large cell lymphoma (ALCL), consolidation by allogeneic hematopoietic stem cell transplantation (SCT) after re-induction chemotherapy offers long-time cure. To describe the efficacy of the different conditioning regimens, we performed a population-based analysis of pediatric patients with I r i / I r i ALCL consolidated by allogeneic SCT in Germany between 2013 and 2021. [Extracted from the article]

Published
2023
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46. MINIMAL DISSEMINATED AND MINIMAL RESIDUAL DISEASE IN CHILDHOOD AND ADOLESCENT NON‐HODGKIN LYMPHOMA.

Author

Woessmann, W.

Subjects
NON-Hodgkin's lymphoma, JUVENILE diseases, ANAPLASTIC large-cell lymphoma, TEENAGERS
Abstract

Next-generation sequencing based methods and the use of circulating cell-free tumour DNA as medium may provide new options and applications for minimal disease evaluation in childhood lymphomas. In Burkitt-lymphoma and -leukemia, I MYC-Ig- i fusion sequences or I Ig i -rearrangements enable minimal disease detection. B Introduction: b Minimal disease determination might serve for risk stratification, response evaluation and follow-up disease monitoring in childhood Non-Hodgkin lymphomas. [Extracted from the article]

Published
2023
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47. Results and conclusions of the European intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma

Author

Landmann, E. (Eva), Burkhardt, B. (Birgit), Zimmermann, M. (Martin), Meyer, U. (Ulrike), Woessmann, W. (Wilhelm), Klapper, W. (Wolfram), Wrobel, G. (Grazyna), Rosolen, A. (Angelo), Pillon, M. (Marta), Escherich, G. (Gabriele), Attarbaschi, A. (Andishe), Beishuizen, A. (Auke), Mellgren, K. (Karin), Wynn, R.F. (Robert F.), Ratei, R. (Richard), Plesa, A. (Adriana), Schrappe, M. (Martin), Reiter, A. (Alfred), Bergeron, C. (Christophe), Patte, C. (Catherine), Bertrand, Y. (Yves), Landmann, E. (Eva), Burkhardt, B. (Birgit), Zimmermann, M. (Martin), Meyer, U. (Ulrike), Woessmann, W. (Wilhelm), Klapper, W. (Wolfram), Wrobel, G. (Grazyna), Rosolen, A. (Angelo), Pillon, M. (Marta), Escherich, G. (Gabriele), Attarbaschi, A. (Andishe), Beishuizen, A. (Auke), Mellgren, K. (Karin), Wynn, R.F. (Robert F.), Ratei, R. (Richard), Plesa, A. (Adriana), Schrappe, M. (Martin), Reiter, A. (Alfred), Bergeron, C. (Christophe), Patte, C. (Catherine), and Bertrand, Y. (Yves)

Abstract

In the European Intergroup EURO-LB02 trial, children and adolescents with lymphoblastic lymphoma underwent the non-Hodgkin lymphoma Berlin-Frankfurt-Münster protocol without prophylactic cranial radiotherapy. The primary aims of this trial were to test whether replacing prednisone with dexamethasone during induction increases event-free survival in the subgroups with T-cell lymphoblastic lymphoma and whether therapy duration could be reduced from 24 to 18 months (factorial design, randomizations). These questions could not be answered due to premature closure of the trial. Here we report on the secondary aims of the trial: whether the results of the NHL-BFM90 study could be reproduced and evaluation of disease features and prognostic factors. Three hundred and nineteen patients (66 with precursor B-cell lymphoblastic lymphoma, 233 with T-cell lymphoblastic lymphoma, 12 with mixed phenotype, 8 not classifiable) were enrolled. In induction, 215 patients received prednisone and 104 patients received dexamethasone. The median follow-up was 6.8 years (range, 3.0-10.3). The 5-year event-free

Published
2017
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48. Results and conclusions of the European Intergroup EURO-LB02 trial in children and adolescents with lymphoblastic lymphoma

Author

Landmann, E, Burkhardt, B, Zimmermann, M, Meyer, U, Woessmann, W, Klapper, W, Wrobel, G, Rosolen, A, Pillon, M, Escherich, G, Attarbaschi, A, Beishuizen, Auke, Mellgren, K, Wynn, R, Ratei, R, Plesa, A, Schrappe, M, Reiter, A, Bergeron, C, Patte, C, Bertrand, Y, Landmann, E, Burkhardt, B, Zimmermann, M, Meyer, U, Woessmann, W, Klapper, W, Wrobel, G, Rosolen, A, Pillon, M, Escherich, G, Attarbaschi, A, Beishuizen, Auke, Mellgren, K, Wynn, R, Ratei, R, Plesa, A, Schrappe, M, Reiter, A, Bergeron, C, Patte, C, and Bertrand, Y

Published
2017

49. No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor patients

Author

Thiel, U., Wawer, A., Wolf, P., Badoglio, M., Santucci, A., Klingebiel, T., Basu, O., Borkhardt, A., Laws, H.-J, Kodera, Y., Yoshimi, A., Peters, C., Ladenstein, R., Pession, A., Prete, A., Urban, E.-C, Schwinger, W., Bordigoni, P., Salmon, A., Diaz, M. A., Afanasyev, B., Lisukov, I., Morozova, E., Toren, A., Bielorai, B., Korsakas, J., Fagioli, F., Caselli, D., Ehninger, G., Gruhn, B., Dirksen, U., Abdel-Rahman, F., Aglietta, M., Mastrodicasa, E., Torrent, M., Corradini, P., Demeocq, F., Dini, G., Dreger, P., Eyrich, M., Gozdzik, J., Guilhot, F., Holler, E., Koscielniak, E., Messina, C., Nachbaur, D., Sabbatini, R., Oldani, E., Ottinger, H., Ozsahin, H., Schots, R., Siena, S., Stein, J., Sufliarska, S., Unal, A., Ussowicz, M., Schneider, P., Woessmann, W., Jürgens, H., Bregni, M., Burdach, S., Thiel, U., Wawer, A., Wolf, P., Badoglio, M., Santucci, A., Klingebiel, T., Basu, O., Borkhardt, A., Laws, H.-J, Kodera, Y., Yoshimi, A., Peters, C., Ladenstein, R., Pession, A., Prete, A., Urban, E.-C, Schwinger, W., Bordigoni, P., Salmon, A., Diaz, M. A., Afanasyev, B., Lisukov, I., Morozova, E., Toren, A., Bielorai, B., Korsakas, J., Fagioli, F., Caselli, D., Ehninger, G., Gruhn, B., Dirksen, U., Abdel-Rahman, F., Aglietta, M., Mastrodicasa, E., Torrent, M., Corradini, P., Demeocq, F., Dini, G., Dreger, P., Eyrich, M., Gozdzik, J., Guilhot, F., Holler, E., Koscielniak, E., Messina, C., Nachbaur, D., Sabbatini, R., Oldani, E., Ottinger, H., Ozsahin, H., Schots, R., Siena, S., Stein, J., Sufliarska, S., Unal, A., Ussowicz, M., Schneider, P., Woessmann, W., Jürgens, H., Bregni, M., and Burdach, S.

Abstract

Background: Outcomes of Ewing tumor (ET) patients treated with allogeneic stem cell transplantation (allo-SCT) were compared regarding the use of reduced-intensity conditioning (RIC) and high-intensity conditioning (HIC) regimens as well as human leukocyte antigen (HLA)-matched and HLA-mismatched grafts. Patients and methods: We retrospectively analyzed data of 87 ET patients from the European Group for Blood and Marrow Transplantation, Pediatric Registry for Stem Cell Transplantations, Asia Pacific Blood and Marrow Transplantation and MetaEICESS registries treated with allo-SCT. Fifty patients received RIC (group A) and 37 patients received HIC (group B). Twenty-four patients received HLA-mismatched grafts and 63 received HLA-matched grafts. Results: Median overall survival was 7.9 months [±1.24, 95% confidence interval (CI) 5.44-10.31] for group A and 4.4 months (±1.06, 95% CI 2.29-6.43) for group B patients (P = 1.3). Death of complications (DOC) occurred in 4 of 50 (0.08) and death of disease (DOD) in 33 of 50 (0.66) group A and in 16 of 37 (0.43) and 17 of 37 (0.46) group B patients, respectively. DOC incidence was decreased (P < 0.01) and DOD/relapse increased (P < 0.01) in group A compared with group B. HLA mismatch was not generally associated with graft-versus-Ewing tumor effect (GvETE). Conclusions: There was no improvement of survival with RIC compared with HIC due to increased DOD/relapse incidence after RIC despite less DOC incidence. This implicates general absence of a clinically relevant GvETE with current protocols

Published
2017

50. Non-Hodgkin lymphoma and pre-existing conditions: Spectrum, clinical characteristics and outcome in 213 children and adolescents

Author

Attarbaschi, A. (Andishe), Carraro, E. (Elisa), Abla, O. (Oussama), Barzilai-Birenboim, S. (Shlomit), Bomken, S. (Simon), Brugières, L. (Laurence), Bubanska, E. (Eva), Burkhardt, B. (Birgit), Chiang, A.K.S. (Alan K. S.), Csoka, M. (Monika), Fedorova, A. (Alina), Jazbec, J., Kabickova, E. (Edita), Krenova, Z. (Zdenka), Lazic, J. (Jelena), Loeffen, J. (Jan), Mann, G. (Georg), Niggli, F. (Felix), Miakova, N. (Natalia), Osumi, T. (Tomoo), Ronceray, L. (Leila), Uyttebroeck, A. (Anne), Williams, D., Woessmann, W. (Wilhelm), Wrobel, G. (Grazyna), Pillon, M. (Marta), Attarbaschi, A. (Andishe), Carraro, E. (Elisa), Abla, O. (Oussama), Barzilai-Birenboim, S. (Shlomit), Bomken, S. (Simon), Brugières, L. (Laurence), Bubanska, E. (Eva), Burkhardt, B. (Birgit), Chiang, A.K.S. (Alan K. S.), Csoka, M. (Monika), Fedorova, A. (Alina), Jazbec, J., Kabickova, E. (Edita), Krenova, Z. (Zdenka), Lazic, J. (Jelena), Loeffen, J. (Jan), Mann, G. (Georg), Niggli, F. (Felix), Miakova, N. (Natalia), Osumi, T. (Tomoo), Ronceray, L. (Leila), Uyttebroeck, A. (Anne), Williams, D., Woessmann, W. (Wilhelm), Wrobel, G. (Grazyna), and Pillon, M. (Marta)

Abstract

Children and adolescents with pre-existing conditions such as DNA repair defects or other primary immunodeficiencies have an increased risk of non-Hodgkin lymphoma. However, largescale data on patients with non-Hodgkin lymphoma and their entire spectrum of pre-existing conditions are scarce. A retrospective multinational study was conducted by means of questionnaires sent out to the national study groups or centers, by the two largest consortia in childhood non-Hodgkin lymphoma, the European Intergroup for Childhood non-Hodgkin Lymphoma, and the international Berlin-Frankfurt-Münster Study Group. The study identified 213 patients with non-Hodgkin lymphoma and a pre-existing condition. Four subcategories were established: a) cancer predisposition syndromes (n=124, 58%); b) primary immunodeficiencies not further specified (n=27, 13%); c) genetic diseases with no increased cancer risk (n=40, 19%); and d) non-classifiable conditions (n=22, 10%). Seventy-nine of 124 (64%) cancer predispositions were reported in groups with more than 20 patients: ataxia telangiectasia (n=32), Nijmegen breakage syndrome (n=26), constitutional mismatch repair deficiency (n=21). For the 151 patients with a known cancer risk, 5-year event-free survival and overall survival rates were 40%±4% and 51%±4%, respectively. Five-year cumulative incidences of progression/relapse and treatment-related death as a first event were 22%±4% and 24%±4%, respectively. Ten-year incidence of second malignancy was 24%±5% and 7-year overall survival of the 21 patients with a second malignancy was 41%±11%. Patients with non-Hodgkin lymphoma and pre-existing conditions have an inferior survival rate with a large proportion of therapy-related deaths compared to patients with non-Hodgkin lymphoma and no pre-existing conditions. They may require special vigilance when receiving standard or modified/reduced-intensity chemotherapy or when undergoing allogeneic stem cell transplantation.

Published
2016
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