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48 results on '"Moericke, Anja"'

1. CD371-positive pediatric B-cell acute lymphoblastic leukemia: propensity to lineage switch and slow early response to treatment

Author

Buldini, Barbara, Varotto, Elena, Maurer-Granofszky, Margarita, Gaipa, Giuseppe, Schumich, Angela, Brüggemann, Monika, Mejstrikova, Ester, Cazzaniga, Giovanni, Hrusak, Ondrej, Szczepanowski, Monika, Scarparo, Pamela, Zimmermann, Martin, Strehl, Sabine, Schinnerl, Dagmar, Zaliova, Marketa, Karawajew, Leonid, Bourquin, Jean-Pierre, Feuerstein, Tamar, Cario, Gunnar, Alten, Julia, Möricke, Anja, Biffi, Alessandra, Parasole, Rosanna, Fagioli, Franca, Valsecchi, Maria Grazia, Biondi, Andrea, Locatelli, Franco, Attarbaschi, Andishe, Schrappe, Martin, Conter, Valentino, Basso, Giuseppe, and Dworzak, Michael N.

Published
2024
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2. Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia

Author

Attarbaschi, Andishe, Adams, Madeline R, Andres-Jensen, Liv, Bardi, Edit, Barzilai-Birenboim, Shlomit, Baust, Katja, Bhojwani, Deepa, Boesten, Tineke, Calaminus, Gabriele, Conyers, Rachel, Darlington, Anne-Sophie, de Ville, Maëlle, Escherich, Gabriele, Hagleitner, Melanie, Halsey, Christina, Harila-Saari, Arja, Hou, Jen-Yin, Huang, Ting-Huan, Hudson, Melissa, Jeha, Sima, Jenney, Meriel, Kato, Motohiro, Krawczuk-Rybak, Maryna, Kremer, Leontine, Lautem, Melchior, Liu, Hse-Che, Lopez Lopez, Elixabet, Mateos, Marion, Mlynarski, Wojciech, Möricke, Anja, Muszynska-Roslan, Katarzyna, Niinimaki, Riitta, Pieters, Rob, Piette, Caroline, Raetz, Elizabeth, Ronceray, Leila, Schmiegelow, Kjeld, Toro, Claudia, Trahair, Toby, Valsecchi, Maria Grazia, van der Sluis, Inge, van Litsenburg, Raphaële, Vrooman, Lynda, Weinreb, Sigal, Wiener, Andreas, Winick, Naomi, Yano, Michihiro, Yeh, Ting-Chi, Zapotocka, Ester, Andrés-Jensen, Liv, Hagleitner, Melanie M, van Litsenburg, Raphaele R L, Hudson, Melissa M, Kremer, Leontien, Grazia Valsecchi, Maria, and Vrooman, Lynda M

Published
2021
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4. Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets

Author

Hoell, Jessica I., Ginzel, Sebastian, Kuhlen, Michaela, Kloetgen, Andreas, Gombert, Michael, Fischer, Ute, Hein, Daniel, Demir, Salih, Stanulla, Martin, Schrappe, Martin, zur Stadt, Udo, Bader, Peter, Babor, Florian, Schuster, Friedhelm, Strahm, Brigitte, Alten, Julia, Moericke, Anja, Escherich, Gabriele, von Stackelberg, Arend, Thiele, Ralf, McHardy, Alice C., Peters, Christina, Bornhauser, Beat, Bourquin, Jean-Pierre, Krause, Stefan, Enczmann, Juergen, Meyer, Lüder Hinrich, Eckert, Cornelia, Borkhardt, Arndt, and Meisel, Roland

Published
2019
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5. International cooperative study identifies treatment strategy in childhood ambiguous lineage leukemia

Author

Hrusak, Ondrej, de Haas, Valerie, Stancikova, Jitka, Vakrmanova, Barbora, Janotova, Iveta, Mejstrikova, Ester, Capek, Vaclav, Trka, Jan, Zaliova, Marketa, Luks, Ales, Bleckmann, Kirsten, Möricke, Anja, Irving, Julie, Konatkowska, Benigna, Alexander, Thomas B., Inaba, Hiroto, Schmiegelow, Kjeld, Stokley, Simone, Zemanova, Zuzana, Moorman, Anthony V., Rossi, Jorge Gabriel, Felice, Maria Sara, Dalla-Pozza, Luciano, Morales, Jessa, Dworzak, Michael, Buldini, Barbara, Basso, Giuseppe, Campbell, Myriam, Cabrera, Maria Elena, Marinov, Neda, Elitzur, Sarah, Izraeli, Shai, Luria, Drorit, Feuerstein, Tamar, Kolenova, Alexandra, Svec, Peter, Kreminska, Olena, Rabin, Karen R., Polychronopoulou, Sophia, da Costa, Elaine, Marquart, Hanne Vibeke, Kattamis, Antonis, Ratei, Richard, Reinhardt, Dirk, Choi, John K., Schrappe, Martin, and Stary, Jan

Published
2018
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6. Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia

Author

Palmi, Chiara, primary, Bresolin, Silvia, additional, Junk, Stefanie, additional, Fazio, Grazia, additional, Silvestri, Daniela, additional, Zaliova, Marketa, additional, Oikonomou, Athanasios, additional, Scharov, Katerina, additional, Stanulla, Martin, additional, Moericke, Anja, additional, Zimmermann, Martin, additional, Schrappe, Martin, additional, Buldini, Barbara, additional, Bhatia, Sanil, additional, Borkhardt, Arndt, additional, Saitta, Claudia, additional, Galbiati, Marta, additional, Bardini, Michela, additional, Lo Nigro, Luca, additional, Conter, Valentino, additional, Valsecchi, Maria Grazia, additional, Biondi, Andrea, additional, te Kronnie, Geertruy, additional, Cario, Gunnar, additional, and Cazzaniga, Giovanni, additional

Published
2023
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7. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus

Author

Schmiegelow, Kjeld, Attarbaschi, Andishe, Barzilai, Shlomit, Escherich, Gabriele, Frandsen, Thomas Leth, Halsey, Christina, Hough, Rachael, Jeha, Sima, Kato, Motohiro, Liang, Der-Cherng, Mikkelsen, Torben Stamm, Möricke, Anja, Niinimäki, Riitta, Piette, Caroline, Putti, Maria Caterina, Raetz, Elizabeth, Silverman, Lewis B, Skinner, Roderick, Tuckuviene, Ruta, van der Sluis, Inge, and Zapotocka, Ester

Published
2016
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8. Dexamethasone vs prednisone in induction treatment of pediatric ALL: results of the randomized trial AIEOP-BFM ALL 2000

Author

Möricke, Anja, Zimmermann, Martin, Valsecchi, Maria Grazia, Stanulla, Martin, Biondi, Andrea, Mann, Georg, Locatelli, Franco, Cazzaniga, Giovanni, Niggli, Felix, Aricò, Maurizio, Bartram, Claus R., Attarbaschi, Andishe, Silvestri, Daniela, Beier, Rita, Basso, Giuseppe, Ratei, Richard, Kulozik, Andreas E., Lo Nigro, Luca, Kremens, Bernhard, Greiner, Jeanette, Parasole, Rosanna, Harbott, Jochen, Caruso, Roberta, von Stackelberg, Arend, Barisone, Elena, Rössig, Claudia, Conter, Valentino, and Schrappe, Martin

Published
2016
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11. Ph-like and IKZF1plus Features in Children with Down Syndrome and B Cell Precursor Acute Lymphoblastic Leukemia

Author

Palmi, Chiara, primary, Bresolin, Silvia, additional, Junk, Stefanie V., additional, Fazio, Grazia, additional, Silvestri, Daniela, additional, Zaliova, Marketa, additional, Oikonomou, Athanasios, additional, Scharov, Katerina, additional, Stanulla, Martin, additional, Moericke, Anja, additional, Zimmermann, Martin, additional, Schrappe, Martin, additional, Buldini, Barbara, additional, Saitta, Claudia, additional, Galbiati, Marta, additional, Bardini, Michela, additional, Bhatia, Sanil, additional, Borkhardt, Arndt, additional, Lo Nigro, Luca, additional, Conter, Valentino, additional, Valsecchi, Maria Grazia, additional, Biondi, Andrea, additional, Te Kronnie, Geertruij, additional, Cario, Gunnar, additional, and Cazzaniga, Giovanni, additional

Published
2022
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12. Impact of Additional Intensive L-Asparaginase Therapy during Consolidation Phase for High-Risk Acute Lymphoblastic Leukemia: Results of a Randomized Controlled Trial in the AIEOP-BFM ALL 2009 Protocol

Author

Conter, Valentino, primary, Valsecchi, Maria Grazia, additional, Cario, Gunnar, additional, Zimmermann, Martin, additional, Attarbaschi, Andishe, additional, Stary, Jan, additional, Niggli, Felix, additional, Dalla Pozza, Luciano, additional, Elitzur, Sarah, additional, Silvestri, Daniela, additional, Locatelli, Franco, additional, Moericke, Anja, additional, Engstler, Gernot, additional, Smisek, Petr, additional, Bodmer, Nicole, additional, Barbaric, Draga, additional, Izraeli, Shai, additional, Rizzari, Carmelo, additional, Boos, Joachim, additional, Buldini, Barbara, additional, Lanvers-Kaminsky, Claudia, additional, Cazzaniga, Giovanni, additional, Gruhn, Bernd, additional, Biondi, Andrea, additional, and Schrappe, Martin, additional

Published
2022
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13. Invasive Fungal Diseases Impact On Outcome of Childhood ALL – An Analysis of the International Trial AIEOP-BFM ALL 2009

Author

Lehrnbecher, Thomas, primary, Groll, Andreas, additional, Cesaro, Simone, additional, Alten, Julia, additional, Attarbaschi, Andishe, additional, Barbaric, Draga, additional, Bodmer, Nicole, additional, Conter, Valentino, additional, Izraeli, Shai, additional, Mann, Georg, additional, Moericke, Anja, additional, Niggli, Felix, additional, Schrappe, Martin, additional, Stary, Jan, additional, Zapotocka, Ester, additional, Zimmermann, Martin, additional, and Elitzur, Sarah, additional

Published
2022
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14. Hypersensitivity Reactions to Native E. coli L-Asparaginase in Children with Acute Lymphoblastic Leukemia May Vary By Treatment Schedule and Type of Glucocorticoid in Induction: Results of Trial ALL-BFM 2000

Author

Möricke, Anja, Schrappe, Martin, Rizzari, Carmelo, Alten, Julia, Attarbaschi, Andishe, Beier, Rita, Biondi, Andrea, Burkhardt, Birgit, Bodmer, Nicole, Boos, Joachim, Cario, Gunnar, Conter, Valentino, Flotho, Christian, Kulozik, Andreas E., Lanvers-Kaminsky, Claudia, Mann, Georg, Niggli, Felix, Silvestri, Daniela, von Stackelberg, Arend, Stanulla, Martin, Valsecchi, Maria Grazia, and Zimmermann, Martin

Published
2022
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15. 3159 – PH-LIKE AND IKZF1PLUS FEATURES IN CHILDREN WITH DOWN SYNDROME ACUTE LYMPHOBLASTIC LEUKAEMIA

Author

Palmi, Chiara, primary, Bresolin, Silvia, additional, Junk, Stefanie, additional, Fazio, Grazia, additional, Silvestri, Daniela, additional, Zaliova, Marketa, additional, Stanulla, Martin, additional, Moericke, Anja, additional, Zimmermann, Martin, additional, Schrappe, Martin, additional, Buldini, Barbara, additional, Saitta, Claudia, additional, Galbiati, Marta, additional, Bardini, Michela, additional, Nigro, Luca Lo, additional, Conter, Valentino, additional, Valsecchi, Maria Grazia, additional, Biondi, Andrea, additional, Kronnie, Geertruy Te, additional, Cario, Gunnar, additional, and Cazzaniga, Giovanni, additional

Published
2022
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16. Superior Overall Survival with Blinatumomab Versus Chemotherapy As Pre-Transplant Consolidation Treatment in Children with High-Risk First-Relapse B-Cell Precursor Acute Lymphoblastic Leukemia (B-ALL): Longer Follow-up (FU) of a Phase 3 Randomized Controlled Trial (RCT)

Author

Locatelli, Franco, primary, Zugmaier, Gerhard, additional, Rizzari, Carmelo, additional, Morris, Joan D, additional, Gruhn, Bernd, additional, Klingebiel, Thomas, additional, Parasole, Rosanna, additional, Linderkamp, Christin, additional, Flotho, Christian, additional, Petit, Arnaud, additional, Micalizzi, Concetta, additional, Zeng, Yi, additional, Pilankar, Deepali Dilip, additional, Kormany, William N, additional, Eckert, Cornelia, additional, Moericke, Anja, additional, Sartor, Mary, additional, Hrusak, Ondrej, additional, Peters, Christina, additional, Saha, Vaskar, additional, Vinti, Luciana, additional, and von Stackelberg, Arend, additional

Published
2021
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17. Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia

Author

Zuna, Jan, Moericke, Anja, Arens, Mari, Koehler, Rolf, Panzer-Grümayer, Renate, Bartram, Claus R., Fischer, Susanna, Fronkova, Eva, Zaliova, Marketa, Schrauder, André, Stanulla, Martin, Zimmermann, Martin, Trka, Jan, Stary, Jan, Attarbaschi, Andishe, Mann, Georg, Schrappe, Martin, and Cario, Gunnar

Published
2016
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18. Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols

Author

Cario, G, Leoni, V, Conter, V, Attarbaschi, A, Zaliova, M, Sramkova, L, Cazzaniga, G, Fazio, G, Sutton, R, Elitzur, S, Izraeli, S, Lauten, M, Locatelli, F, Basso, G, Buldini, B, Bergmann, A, Lentes, J, Steinemann, D, Göhring, G, Schlegelberger, B, Haas, O, Schewe, D, Buchmann, S, Moericke, A, White, D, Revesz, T, Stanulla, M, Mann, G, Bodmer, N, Arad-Cohen, N, Zuna, J, Valsecchi, M, Zimmermann, M, Schrappe, M, Biondi, A, Cario, Gunnar, Leoni, Veronica, Conter, Valentino, Attarbaschi, Andishe, Zaliova, Marketa, Sramkova, Lucie, Cazzaniga, Giovanni, Fazio, Grazia, Sutton, Rosemary, Elitzur, Sarah, Izraeli, Shai, Lauten, Melchior, Locatelli, Franco, Basso, Giuseppe, Buldini, Barbara, Bergmann, Anke K, Lentes, Jana, Steinemann, Doris, Göhring, Gudrun, Schlegelberger, Brigitte, Haas, Oskar A, Schewe, Denis, Buchmann, Swantje, Moericke, Anja, White, Deborah, Revesz, Tamas, Stanulla, Martin, Mann, Georg, Bodmer, Nicole, Arad-Cohen, Nira, Zuna, Jan, Valsecchi, Maria Grazia, Zimmermann, Martin, Schrappe, Martin, Biondi, Andrea, Cario, G, Leoni, V, Conter, V, Attarbaschi, A, Zaliova, M, Sramkova, L, Cazzaniga, G, Fazio, G, Sutton, R, Elitzur, S, Izraeli, S, Lauten, M, Locatelli, F, Basso, G, Buldini, B, Bergmann, A, Lentes, J, Steinemann, D, Göhring, G, Schlegelberger, B, Haas, O, Schewe, D, Buchmann, S, Moericke, A, White, D, Revesz, T, Stanulla, M, Mann, G, Bodmer, N, Arad-Cohen, N, Zuna, J, Valsecchi, M, Zimmermann, M, Schrappe, M, Biondi, A, Cario, Gunnar, Leoni, Veronica, Conter, Valentino, Attarbaschi, Andishe, Zaliova, Marketa, Sramkova, Lucie, Cazzaniga, Giovanni, Fazio, Grazia, Sutton, Rosemary, Elitzur, Sarah, Izraeli, Shai, Lauten, Melchior, Locatelli, Franco, Basso, Giuseppe, Buldini, Barbara, Bergmann, Anke K, Lentes, Jana, Steinemann, Doris, Göhring, Gudrun, Schlegelberger, Brigitte, Haas, Oskar A, Schewe, Denis, Buchmann, Swantje, Moericke, Anja, White, Deborah, Revesz, Tamas, Stanulla, Martin, Mann, Georg, Bodmer, Nicole, Arad-Cohen, Nira, Zuna, Jan, Valsecchi, Maria Grazia, Zimmermann, Martin, Schrappe, Martin, and Biondi, Andrea

Abstract

ABL-class fusions other than BCR-ABL1 characterize about 2-3% of precursor B-cell acute lymphoblastic leukemia. Case series indicated that patients suffering from these subtypes have a dismal outcome and may benefit from the introduction of tyrosine kinase inhibitors. We analyzed clinical characteristics and outcome of 46 ABL-class fusion positive cases other than BCR-ABL1 treated according to AIEOP-BFM ALL 2000 and 2009 protocols; 13 of them received a tyrosine kinase inhibitor during different phases of treatment. ABL-class fusion positive cases had a poor early treatment response: minimal residual disease levels of >5x10-4 were observed in 71.4% of patients after induction treatment and in 51.2% after consolidation phase. For the entire cohort of 46 cases the 5-year probability of event-free survival was 49.1+8.9% and that of overall survival 69.6+7.8%; the cumulative incidence of relapse was 25.6+8.2% and treatment-related mortality 20.8+6.8%. One out of 13 cases with tyrosine kinase inhibitor added to chemotherapy relapsed while eight of 33 cases without tyrosine kinase inhibitor treatment suffered from relapse, including six in 17 patients who had not received hematopoietic stem cell transplantation. Stem cell transplantation seems to be effective in preventing relapses (only three relapses in 25 patients), but was associated with a very high treatment-related mortality (6 patients). These data indicate a major need for an early identification of ABL-class fusion positive acute lymphoblastic leukemia cases and to establish a properly designed, controlled study aimed at investigating the use of tyrosine kinase inhibitors, the appropriate chemotherapy backbone and the role of hematopoietic stem cell transplantation. (ClinicalTrials.gov identifier: NTC00430118, NCT00613457, NCT01117441).

Published
2020

19. Incidence of Hypersensitivity Reactions (HSR) Reactions (HSR) to Peg-Asparaginase (PEG-ASP) in 6136 Patients Treated in the AIEOP-BFM ALL 2009 Study Protocol

Author

Rizzari, Carmelo, primary, Moericke, Anja, additional, Conter, Valentino, additional, Valsecchi, Maria Grazia, additional, Zimmermann, Martin, additional, Silvestri, Daniela, additional, Mann, Georg, additional, Niggli, Felix, additional, Dalla-Pozza, Luciano, additional, Stary, Jan, additional, Elitzur, Sarah, additional, Cario, Gunnar, additional, Locatelli, Franco, additional, Boos, Joachim, additional, Zucchetti, Massimo, additional, Biondi, Andrea, additional, and Schrappe, Martin, additional

Published
2019
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20. Poor Prognosis in Children with ABL-Class Fusion Positive B-Cell Acute Lymphoblastic Leukemia Treated According to AIEOP-BFM Protocols

Author

Cario, Gunnar, primary, Leoni, Veronica, additional, Conter, Valentino, additional, Attarbaschi, Andishe, additional, Zaliova, Marketa, additional, Sramkova, Lucie, additional, Cazzaniga, Giovanni, additional, Fazio, Grazia, additional, Sutton, Rosemary, additional, Elitzur, Sarah, additional, Izraeli, Shai, additional, Lauten, Melchior, additional, Locatelli, Franco, additional, Basso, Giuseppe, additional, Buldini, Barbara, additional, Bergmann, Anke K, additional, Lentes, Jana, additional, Steinemann, Doris, additional, Gohring, Gudrun, additional, Schlegelberger, Brigitte, additional, Haas, Oskar A, additional, Schewe, Denis Martin, additional, Buchmann, Swantje, additional, Moericke, Anja, additional, White, Deborah L., additional, Revesz, Tamas, additional, Stanulla, Martin, additional, Mann, Georg, additional, Bodmer, Nicole, additional, Arad-Cohen, Nira, additional, Zuna, Jan, additional, Valsecchi, Maria Grazia, additional, Zimmermann, Martin, additional, Schrappe, Martin, additional, and Biondi, Andrea, additional

Published
2019
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21. THROMBOTECT - a randomized study comparing low molecular weight heparin, antithrombin and unfractionated heparin for thromboprophylaxis during induction therapy of acute lymphoblastic leukemia in children and adolescents

Author

Greiner, Jeanette, Schrappe, Martin, Claviez, Alexander, Zimmermann, Martin, Niemeyer, Charlotte, Kolb, Reinhard, Eberl, Wolfgang, Berthold, Frank, Bergstrasser, Eva, Gnekow, Astrid, Lassay, Elisabeth, Vorwerk, Peter, Lauten, Melchior, Sauerbrey, Axel, Rischewski, Johannes, Beilken, Andreas, Henze, Guenter, Korte, Wolfgang, Moericke, Anja, Greiner, Jeanette, Schrappe, Martin, Claviez, Alexander, Zimmermann, Martin, Niemeyer, Charlotte, Kolb, Reinhard, Eberl, Wolfgang, Berthold, Frank, Bergstrasser, Eva, Gnekow, Astrid, Lassay, Elisabeth, Vorwerk, Peter, Lauten, Melchior, Sauerbrey, Axel, Rischewski, Johannes, Beilken, Andreas, Henze, Guenter, Korte, Wolfgang, and Moericke, Anja

Abstract

Thromboembolism is a serious complication of induction therapy for childhood acute lymphoblastic leukemia. We prospectively compared the efficacy and safety of antithrombotic interventions in the consecutive leukemia trials ALL-BFM 2000 and AIEOP-BFM ALL 2009. Patients with newly diagnosed acute lymphoblastic leukemia (n=949, age 1 to 18 years) were randomized to receive low-dose unfractionated heparin, prophylactic low molecular weight heparin (enoxaparin) or activity-adapted antithrombin throughout induction therapy. The primary objective of the study was to determine whether enoxaparin or antithrombin reduces the incidence of thromboembolism as compared to unfractionated heparin. The principal safety outcome was hemorrhage; leukemia outcome was a secondary endpoint. Thromboembolism occurred in 42 patients (4.4%). Patients assigned to unfractionated heparin had a higher risk of throm-boembolism (8.0%) compared with those randomized to enoxaparin (3.5%; P=0.011) or antithrombin (1.9%; P<0.001). The proportion of patients who refused antithrombotic treatment as allocated was 3% in the unfractionated heparin or antithrombin arms, and 33% in the enoxaparin arm. Major hemorrhage occurred in eight patients (no differences between the groups). The 5-year event-free survival was 80.9 +/- 2.2% among patients assigned to antithrombin compared to 85.9 +/- 2.0% in the unfractionated heparin group (P=0.06), and 86.2 +/- 2.0% in the enoxaparin group (P=0.10). In conclusion, prophylactic use of antithrombin or enoxaparin significantly reduced thromboembolism. Despite the considerable number of patients rejecting the assigned treatment with subcutaneous injections, the result remains unambiguous. Thromboprophylaxis - for the present time primarily with enoxaparin - can be recommended for children and adolescents with acute lymphoblastic leukemia during induction therapy. Whether and how antithrombin may affect leukemia outcome remains to be determined.

Published
2019

22. Pediatric ALL relapses after allo-SCT show high individuality, clonal dynamics, selective pressure, and druggable targets

Author

Hoell, Jessica I, Ginzel, Sebastian, Kuhlen, Michaela, Kloetgen, Andreas, Gombert, Michael, Fischer, Ute, Hein, Daniel, Demir, Salih, Stanulla, Martin, Schrappe, Martin, Zur Stadt, Udo, Bader, Peter, Babor, Florian, Schuster, Friedhelm, Strahm, Brigitte, Alten, Julia, Moericke, Anja, Escherich, Gabriele, von Stackelberg, Arend, Thiele, Ralf, McHardy, Alice C, Peters, Christina, Bornhauser, Beat, Bourquin, Jean-Pierre, Krause, Stefan, Enczmann, Juergen, Meyer, Lüder Hinrich, Eckert, Cornelia, Borkhardt, Arndt, Meisel, Roland, Hoell, Jessica I, Ginzel, Sebastian, Kuhlen, Michaela, Kloetgen, Andreas, Gombert, Michael, Fischer, Ute, Hein, Daniel, Demir, Salih, Stanulla, Martin, Schrappe, Martin, Zur Stadt, Udo, Bader, Peter, Babor, Florian, Schuster, Friedhelm, Strahm, Brigitte, Alten, Julia, Moericke, Anja, Escherich, Gabriele, von Stackelberg, Arend, Thiele, Ralf, McHardy, Alice C, Peters, Christina, Bornhauser, Beat, Bourquin, Jean-Pierre, Krause, Stefan, Enczmann, Juergen, Meyer, Lüder Hinrich, Eckert, Cornelia, Borkhardt, Arndt, and Meisel, Roland

Abstract

Survival of patients with pediatric acute lymphoblastic leukemia (ALL) after allogeneic hematopoietic stem cell transplantation (allo-SCT) is mainly compromised by leukemia relapse, carrying dismal prognosis. As novel individualized therapeutic approaches are urgently needed, we performed whole-exome sequencing of leukemic blasts of 10 children with post-allo-SCT relapses with the aim of thoroughly characterizing the mutational landscape and identifying druggable mutations. We found that post-allo-SCT ALL relapses display highly diverse and mostly patient-individual genetic lesions. Moreover, mutational cluster analysis showed substantial clonal dynamics during leukemia progression from initial diagnosis to relapse after allo-SCT. Only very few alterations stayed constant over time. This dynamic clonality was exemplified by the detection of thiopurine resistance-mediating mutations in the nucleotidase NT5C2 in 3 patients' first relapses, which disappeared in the post-allo-SCT relapses on relief of selective pressure of maintenance chemotherapy. Moreover, we identified TP53 mutations in 4 of 10 patients after allo-SCT, reflecting acquired chemoresistance associated with selective pressure of prior antineoplastic treatment. Finally, in 9 of 10 children's post-allo-SCT relapse, we found alterations in genes for which targeted therapies with novel agents are readily available. We could show efficient targeting of leukemic blasts by APR-246 in 2 patients carrying TP53 mutations. Our findings shed light on the genetic basis of post-allo-SCT relapse and may pave the way for unraveling novel therapeutic strategies in this challenging situation.

Published
2019

23. Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL

Author

Locatelli, Franco, Valsecchi, Maria Grazia, Möricke, Anja, Zimmermann, Martin, Gruhn, Bernd, Biondi, Andrea, Kulozik, Andreas E., Silvestri, Daniela, Bodmer, Nicole, Putti, Maria Caterina, Burdach, Stefan, Micalizzi, Concetta, Teigler-Schlegel, Andrea, Ritter, Jörg, Pession, Andrea, Cario, Gunnar, Bielack, Stefan, Basso, Giuseppe, Klingebiel, Thomas, Vinti, Luciana, Rizzari, Carmelo, Attarbaschi, Andishe, Santoro, Nicola, Parasole, Rosanna, Mann, Georg, Karawajew, Leonid, Haas, Oskar A., Conter, Valentino, and Schrappe, Martin

Published
2017
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24. Treatment and outcome of IG-MYC+ neoplasms with precursor B-cell phenotype in childhood and adolescence

Author

Herbrueggen, Heidi, primary, Mueller, Stephanie, additional, Rohde, Jonas, additional, Arias Padilla, Laura, additional, Moericke, Anja, additional, Attarbaschi, Andishe, additional, Zimmermann, Martin, additional, Ratei, Richard, additional, Brueggemann, Monika, additional, Siebert, Reiner, additional, Goehring, Gudrun, additional, Schlegelberger, Brigitte, additional, Bradtke, Jutta, additional, Klapper, Wolfram, additional, Woessmann, Willi, additional, and Burkhardt, Birgit, additional

Published
2019
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25. Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols

Author

Cario, Gunnar, primary, Leoni, Veronica, additional, Conter, Valentino, additional, Attarbaschi, Andishe, additional, Zaliova, Marketa, additional, Sramkova, Lucie, additional, Cazzaniga, Gianni, additional, Fazio, Grazia, additional, Sutton, Rosemary, additional, Elitzur, Sarah, additional, Izraeli, Shai, additional, Lauten, Melchior, additional, Locatelli, Franco, additional, Basso, Giuseppe, additional, Buldini, Barbara, additional, Bergmann, Anke K., additional, Lentes, Jana, additional, Steinemann, Doris, additional, Göhring, Gudrun, additional, Schlegelberger, Brigitte, additional, Haas, Oskar A., additional, Schewe, Denis, additional, Buchmann, Swantje, additional, Moericke, Anja, additional, White, Deborah, additional, Revesz, Tamas, additional, Stanulla, Martin, additional, Mann, Georg, additional, Bodmer, Nicole, additional, Arad-Cohen, Nira, additional, Zuna, Jan, additional, Valsecchi, Maria Grazia, additional, Zimmermann, Martin, additional, Schrappe, Martin, additional, and Biondi, Andrea, additional

Published
2019
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26. Asparagine levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia treated with pegylated-asparaginase in the induction phase of the AIEOP-BFM ALL 2009 study

Author

Rizzari, Carmelo, primary, Lanvers-Kaminsky, Claudia, additional, Valsecchi, Maria Grazia, additional, Ballerini, Andrea, additional, Matteo, Cristina, additional, Gerss, Joachim, additional, Wuerthwein, Gudrun, additional, Silvestri, Daniela, additional, Colombini, Antonella, additional, Conter, Valentino, additional, Biondi, Andrea, additional, Schrappe, Martin, additional, Moericke, Anja, additional, Zimmermann, Martin, additional, von Stackelberg, Arend, additional, Linderkamp, Christin, additional, Frühwald, Michael C., additional, Legien, Sabine, additional, Attarbaschi, Andishe, additional, Reismüller, Bettina, additional, Kasper, David, additional, Smisek, Petr, additional, Stary, Jan, additional, Vinti, Luciana, additional, Barisone, Elena, additional, Parasole, Rosanna, additional, Micalizzi, Concetta, additional, Zucchetti, Massimo, additional, and Boos, Joachim, additional

Published
2019
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27. Surgical Implications for Diagnosis and Treatment of Intestinal Aspergillosis in Pediatric Patients with ALL

Author

Fischer, Janina, Simon, Thorsten, Hamprecht, Axel, Hos, Nina, Moericke, Anja, Cernaianu, Grigore, Tharun, Lars, Gruhn, Bernd, Plum, Georg, Duebbers, Martin, Fischer, Janina, Simon, Thorsten, Hamprecht, Axel, Hos, Nina, Moericke, Anja, Cernaianu, Grigore, Tharun, Lars, Gruhn, Bernd, Plum, Georg, and Duebbers, Martin

Abstract

Background The incidence of invasive aspergillosis (IA) in children with hematooncological malignancies is increasing as a result of intensive treatment, immunosuppression, and extended use of broad-spectrum antibiotics. Infection of the GI tract by Aspergillus spp. is a rare and fatal complication, which often requires surgical diagnostic and therapeutic exploration. Objective The aim of this study was to determine the characteristics of symptomatic intestinal aspergillosis, diagnosis, treatment, and outcome of pediatric patientswith an underlying hemato-oncologic disease. Patients andMethods We analyzed 2,307 German patients with acute lymphoblastic leukemia (ALL) from age 1 to 17 years registered in the AIEOP-BFM ALL 2000 study from 2000 to 2006. All reported adverse events were assessed for symptoms of IA and retrospectively reviewed for any sign or proof of intestinal involvement of IA. Results In this cohort, IA was reported in 30 of 2,307 patients while intestinal involvement was documented in five patients. Four of these patients had intestinal symptoms and three patients underwent explorative laparotomy. Among clinical cases with IA, gastrointestinal manifestation of IA mostly occurred in adolescent patients (10-16 years). Symptoms varied from abdominal tenderness and pain to constipation. Intestinal aspergillosis was proven by microbiological and histopathological examination and fungal infection was observed macroscopically in the jejunal lumen during surgery. Despite the extended surgery and antifungal therapy, outcome of disseminated IA with intestinal involvement remains poor. Conclusion Surgeons should be aware of surgical complications of intestinal aspergillosis in children with hematooncological diseases requiring exploration and resection. IA is a rare event and still difficult to diagnose due to unspecific abdominal symptoms. Thus, biopsy sampling is of utmost importance to ensure diagnosis, and resection of necrotic or perforated tissue should b

Published
2018

28. Osteonecrosis in children with acute lymphoblastic leukemia at initial diagnosis and prior to any chemotherapy

Author

Krull, Kathinka, primary, Kunstreich, Marina, additional, Bronsema, Annika, additional, Bleckmann, Kirsten, additional, Classen, Carl-Friedrich, additional, Erdlenbruch, Bernhard, additional, Jorch, Norbert, additional, Kolb, Reinhard, additional, Leipold, Alfred, additional, Moser, Olga, additional, Prokop, Aram, additional, Scheurlen, Wolfram, additional, Steinbach, Daniel, additional, Klasen-Sansone, Janina, additional, Klee, Dirk, additional, Escherich, Gabriele, additional, Moericke, Anja, additional, Schrappe, Martin, additional, Borkhardt, Arndt, additional, and Kuhlen, Michaela, additional

Published
2018
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29. NUTM1-Rearranged Infant and Pediatric B Cell Precursor Acute Lymphoblastic Leukemia: A Good Prognostic Subtype Identified in a Collaborative International Study

Author

Boer, Judith M., Valsecchi, Maria Grazia, Hormann, Femke M., Antic, Zeljko, Zaliova, Marketa, Schwab, Claire, Cazzaniga, Giovanni, Arfeuille, Chloé, Cavé, Hélène, Attarbaschi, Andishe, Strehl, Sabine, Escherich, Gabriele, Imamura, Toshihiko, Ohki, Kentaro, Gruber, Tanja A., Sutton, Rosemary, Pastorczak, Agata, Lammens, Tim, Lambert, Frederic, Li, Chi Kong, Carrillo de Santa Pau, Enrique, Hoffmann, Steve, Möricke, Anja, Harrison, Christine J., Den Boer, Monique L., De Lorenzo, Paola, Stam, Ronald W., Bergmann, Anke K., and Pieters, Rob

Published
2020
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30. Population Pharmacokinetics to Model the Time-Varying Clearance of the PEGylated Asparaginase Oncaspar® in Children with Acute Lymphoblastic Leukemia

Author

Wuerthwein, Gudrun, Lanvers-Kaminsky, Claudia, Hempel, Georg, Gastine, Silke, Moericke, Anja, Schrappe, Martin, Karlsson, Mats O, Boos, Joachim, Wuerthwein, Gudrun, Lanvers-Kaminsky, Claudia, Hempel, Georg, Gastine, Silke, Moericke, Anja, Schrappe, Martin, Karlsson, Mats O, and Boos, Joachim

Abstract

The pharmacokinetics of the polyethylene glycol (PEG)-conjugated asparaginase Oncaspar® are characterized by an increase in elimination over time. The focus of our analysis is the better understanding of this time-dependency. In paediatric acute lymphoblastic leukemia therapy (AIEOP-BFM ALL 2009), two administrations of Oncaspar® (2500 U/m(2) intravenously) in induction phase (14-day interval) and one single administration in reinduction were followed by weekly monitoring of asparaginase activity. Non-linear mixed-effects modeling techniques (NONMEM) were used. Samples indicating immunological inactivation were excluded to describe the pharmacokinetics under standard conditions. Models with time-constant or time-varying clearance (CL) as well as transit compartment models with an increase in CL over a chain of compartments were investigated. Models with time-constant elimination could not adequately describe 6107 asparaginase activities from 1342 patients. Implementing a time-varying CL improved the fit. Modeling an increase of CL over time after dose (E-max- and Weibull-functions) were superior to models with an increase of CL over time after the first administration. However, a transit compartment model came out to be the best structural model. The increase in elimination of PEGylated asparaginase appears to be driven by physicochemical processes that are drug-related. The observed hydrolytically in vitro instability of the drug leads to the hypothesis that this increase in CL might be due to an in vivo hydrolysis of the instable ester bond between PEG and the enzyme combined with an increased elimination of the partly de-PEGylated enzyme (Trial registered at www.clinicaltrials.gov, NCT0111744).

Published
2017
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31. Molecular characterization of acute lymphoblastic leukemia with highCRLF2gene expression in childhood

Author

Schmäh, Juliane, primary, Fedders, Birthe, additional, Panzer-Grümayer, Renate, additional, Fischer, Susanna, additional, Zimmermann, Martin, additional, Dagdan, Elif, additional, Bens, Susanne, additional, Schewe, Denis, additional, Moericke, Anja, additional, Alten, Julia, additional, Bleckmann, Kirsten, additional, Siebert, Reiner, additional, Schrappe, Martin, additional, Stanulla, Martin, additional, and Cario, Gunnar, additional

Published
2017
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32. Osteonecrosis develops independently from radiological leukemic infiltration of bone in adolescents with acute lymphoblastic leukemia – first findings of the OPAL trial

Author

Krull, Kathinka, primary, Kunstreich, Marina, additional, Klasen-Sansone, Janina, additional, Kloetgen, Andreas, additional, Gruener, Franziska, additional, Escherich, Gabriele, additional, Bleckmann, Kirsten, additional, Moericke, Anja, additional, Schrappe, Martin, additional, Jorch, Norbert, additional, Steinbach, Daniel, additional, Classen, Carl-Friedrich, additional, Guggemos, Andreas, additional, Kolb, Reinhard, additional, Klee, Dirk, additional, Borkhardt, Arndt, additional, and Kuhlen, Michaela, additional

Published
2017
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33. Mutational Landscape of Pediatric Acute Lymphoblastic Leukemia Relapsing after Allogeneic Stem Cell Transplantation

Author

Hoell, Jessica I, primary, Ginzel, Sebastian, additional, Eckert, Cornelia, additional, Gombert, Michael, additional, Fischer, Ute, additional, Stanulla, Martin, additional, Schrappe, Martin, additional, zur Stadt, Udo, additional, Bader, Peter, additional, Strahm, Brigitte, additional, Alten, Julia, additional, Moericke, Anja, additional, Escherich, Gabriele, additional, Stackelberg, Arend, additional, Peters, Christina, additional, Borkhardt, Arndt, additional, and Meisel, Roland, additional

Published
2016
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35. Osteonecrosis in children with acute lymphoblastic leukemia at initial diagnosis and prior to any chemotherapy.

Author

Krull, Kathinka, Kunstreich, Marina, Bronsema, Annika, Bleckmann, Kirsten, Classen, Carl-Friedrich, Erdlenbruch, Bernhard, Jorch, Norbert, Kolb, Reinhard, Leipold, Alfred, Moser, Olga, Prokop, Aram, Scheurlen, Wolfram, Steinbach, Daniel, Klasen-Sansone, Janina, Klee, Dirk, Escherich, Gabriele, Moericke, Anja, Schrappe, Martin, Borkhardt, Arndt, and Kuhlen, Michaela

Subjects
LYMPHOBLASTIC leukemia, ACUTE leukemia
Abstract

Osteonecrosis (ON) is a common and debilitating side effect of anti-leukemic treatment in children with acute lymphoblastic leukemia (ALL). However, the impact of leukemia itself on ON development remains elusive. We analyzed 76 children enrolled in the ongoing OPAL trial, who had magnetic resonance imaging (MRI) studies at diagnosis. MRI screening revealed 14 osteonecrotic lesions (5 × hips, 9 × knees) of any grade (I-III) in 7 (9.2%) patients. Six months on, the number of ON per patient increased (1 patient), remained constant (2), and decreased (2). The severity increased from grade I to II in two patients, remained constant (1), completely resolved (2), and decreased from grade III to osteoedema (1). No differences between adolescents initially presenting with/without ON were observed concerning age, pubertal stage, body mass index, leukemia characteristics, and clinical presentation. In MRI screening, a remarkable number of adolescents with ALL present with ON at diagnosis. The course of these ON remains highly unpredictable. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy

Author

Vora, Ajay, primary, Andreano, Anita, additional, Pui, Ching-Hon, additional, Hunger, Stephen P., additional, Schrappe, Martin, additional, Moericke, Anja, additional, Biondi, Andrea, additional, Escherich, Gabriele, additional, Silverman, Lewis B., additional, Goulden, Nicholas, additional, Taskinen, Mervi, additional, Pieters, Rob, additional, Horibe, Keizo, additional, Devidas, Meenakshi, additional, Locatelli, Franco, additional, and Valsecchi, Maria Grazia, additional

Published
2016
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37. Constitutive Activation of FLT3 Is a Positive Prognostic Factor in Infants with MLL-Rearranged Acute Lymphoblastic Leukemia

Author

Fedders, Henning, primary, Schewe, Denis Martin, additional, Zimmermann, Martin, additional, Alsadeq, Ameera, additional, Moericke, Anja, additional, zur Stadt, Udo, additional, Horstmann, Martin A., additional, Pieters, Rob, additional, Schrappe, Martin, additional, Cario, Gunnar, additional, and Stanulla, Martin, additional

Published
2015
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40. Clinical Implication of BCR/ABL Fusion Transcript Monitoring in Addition to Ig/TCR Gene Rearrangement-Based Minimal Residual Disease in Philadelphia Chromosome-Positive Childhood Acute Lymphoblastic Leukemia

Author

Bleckmann, Kirsten, primary, Alten, Julia, additional, Moericke, Anja, additional, Attarbashi, Andishe, additional, Teigler-Schlegel, Andrea, additional, Damm-Welk, Christine, additional, Koehler, Rolf, additional, and Schrappe, Martin, additional

Published
2014
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41. Ph-likeand IKZF1plusFeatures in Children with Down Syndrome and B Cell Precursor Acute Lymphoblastic Leukemia

Author

Palmi, Chiara, Bresolin, Silvia, Junk, Stefanie V., Fazio, Grazia, Silvestri, Daniela, Zaliova, Marketa, Oikonomou, Athanasios, Scharov, Katerina, Stanulla, Martin, Moericke, Anja, Zimmermann, Martin, Schrappe, Martin, Buldini, Barbara, Saitta, Claudia, Galbiati, Marta, Bardini, Michela, Bhatia, Sanil, Borkhardt, Arndt, Lo Nigro, Luca, Conter, Valentino, Valsecchi, Maria Grazia, Biondi, Andrea, Te Kronnie, Geertruij, Cario, Gunnar, and Cazzaniga, Giovanni

Published
2022
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43. Analyses of a Pair of Concordant Twins with Infant ALL and Discordant Clinical Outcome Reveals Immunoescape As a Mechanism of Disease Persistence in MLL-Rearranged Leukemia

Author

Fedders, Henning, Alsadeq, Ameera, Petersen, Britt-Sabina, Kellner, Christian, Peipp, Matthias, Valerius, Thomas, Haesler, Robert, Alten, Julia, Möricke, Anja, Strube, Susanne, Wiesel, Thomas, Cario, Gunnar, Schrappe, Martin, Franke, Andre, Stanulla, Martin, and Schewe, Denis Martin

Published
2014
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47. Durable remissions in TCF3-HLF positive acute lymphoblastic leukemia with blinatumomab and stem cell transplantation

Author

Volkan Hazar, Sema Anak, Brice Mouttet, Sarah Elitzur, Jean-Pierre Bourquin, Martin Schrappe, Benoit Brethon, Luciana Vinti, Jerry Stein, Martin Stanulla, Philip Ancliff, Yöntem Yaman, Ajay Vora, Anja Möricke, Joachim B. Kunz, Christiane Chen-Santel, Nicole Bodmer, Gunnar Cario, Franco Locatelli, Arend von Stackelberg, André Baruche, Mouttet, Brice, Bodmer, Nicole, Bourquin, Jean-Pierre Univ Childrens Hosp Zurich, Pediat Oncol, Zurich, Switzerland, Vinti, Luciana, Locatelli, Franco Sapienza Univ Rome, IRCCS Osped Bambino Gesu, Dept Pediat Haematooncol, Rome, Italy, Ancliff, Philip, Vora, Ajay Great Ormond St Hosp Sick Children, Haematol & Oncol Dept, London, England, Brethon, Benoit, Baruchel, Andre Hop Robert Debre, AP HP, Dept Pediat Hematol, Paris, France, Cario, Gunnar, Moericke, Anja, Schrappe, Martin Christian Albrechts Univ Kiel, ALL BFM Study Grp, Dept Pediat 1, Kiel, Germany, Schrappe, Martin Univ Med Ctr Schleswig Holstein, Kiel, Germany, Chen-Santel, Christiane, von Stackelberg, Arend Charite, Dept Pediat Oncol Hematol, Berlin, Germany, Elitzur, Sarah Tel Aviv Univ, Sackler Fac Med, Schneider Childrens Med Ctr, Pediat Hematol Oncol, Tel Aviv, Israel, Hazar, Volkan, Yaman, Yontem, Anak, Sema Medipol Univ Hosp, Dept Pediat Hematol, Istanbul, Turkey, Kunz, Joachim Heidelberg Univ, Pediat Oncol Hematol & Immunol, Heidelberg, Germany, Stein, Jerry Tel Aviv Univ, Sackler Fac Med, Schneider Childrens Med Ctr, Bone Marrow Transplant Unit, Tel Aviv, Israel, Schrappe, Martin Christian Albrechts Univ Kiel, Univ Med Ctr, Pediat, Kiel, Germany, Stanulla, Martin Hannover Med Sch, Pediat Hematol & Oncol, Hannover, Germany, University of Zurich, and Bourquin, Jean-Pierre

Subjects
Oncogene Proteins, Fusion, Oncogene Proteins, 2720 Hematology, 610 Medicine & health, EDDY, Antineoplastic Agents, Immunological, Text mining, immune system diseases, hemic and lymphatic diseases, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Antibodies, Bispecific, medicine, Homologous chromosome, Humans, Transplantation, Homologous, Combined Modality Therapy, Online Only Articles, Mandibular Molar, business.industry, Hematopoietic Stem Cell Transplantation, Consolidation Chemotherapy, Hematology, Transplantation, Treatment Outcome, 10036 Medical Clinic, Smear Layer, Cancer research, Blinatumomab, Debris, Stem cell, business, Root Canal Preparation, medicine.drug
Abstract

WOS: 000469839300005 PubMed ID: 30765470 TCF3-HLF-positive leukemia represents a rare subtypeof childhood acute lymphoblastic leukemia (ALL), characterized by a high rate of treatment failure despite treatment intensification and allogeneic stem cell transplantation (SCT). Given the high and homogeneous expressionof CD19 on blast cells of this leukemia subtype, thesepatients may benefit from CD19-directed immunotherapy. Here, we report the experience on nineTCF3-HLF-positive ALL patients, most of whom weretreated early in first consolidation with blinatumomab asa bridge to SCT between 2015 and 2018. Treatment withblinatumomab was generally well tolerated; reversibleneurotoxicity was observed in two patients. All ninepatients achieved molecular remission after blinatumomab treatment; seven underwent SCT and for onepatient SCT is planned. Median follow up after start ofblinatumomab treatment was 342 days, and four patientsremain in molecular remission after a follow up of 1317,1292, 1245, and 342 days, respectively. Three patientsdied because of infectious complications not directlyrelated to blinatumomab, because they occurred eitherafter SCT or after emergence of a CD19-negativeleukemia clone. In the light of these encouraging observations, CD19-directed immunotherapy should be considered early after induction chemotherapy inTCF3-HLF-positive ALL children and patients’ outcomemonitored systematically by study groups.

Published
2019

48. Relapses and treatment-related events contributed equally to poor prognosis in children with ABL-class fusion positive B-cell acute lymphoblastic leukemia treated according to AIEOP-BFM protocols.

Author

Cario G, Leoni V, Conter V, Attarbaschi A, Zaliova M, Sramkova L, Cazzaniga G, Fazio G, Sutton R, Elitzur S, Izraeli S, Lauten M, Locatelli F, Basso G, Buldini B, Bergmann AK, Lentes J, Steinemann D, Göhring G, Schlegelberger B, Haas OA, Schewe D, Buchmann S, Moericke A, White D, Revesz T, Stanulla M, Mann G, Bodmer N, Arad-Cohen N, Zuna J, Valsecchi MG, Zimmermann M, Schrappe M, and Biondi A

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, B-Lymphocytes, Child, Humans, Neoplasm, Residual, Prognosis, Recurrence, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma diagnosis, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
Abstract

ABL-class fusions other than BCR-ABL1 characterize around 2-3% of precursor B-cell acute lymphoblastic leukemia. Case series indicated that patients suffering from these subtypes have a dismal outcome and may benefit from the introduction of tyrosine kinase inhibitors. We analyzed clinical characteristics and outcome of 46 ABL-class fusion positive cases other than BCR-ABL1 treated according to AIEOP-BFM (Associazione Italiana di Ematologia-Oncologia Pediatrica-Berlin-Frankfurt-Münster) ALL 2000 and 2009 protocols; 13 of them received a tyrosine kinase inhibitor (TKI) during different phases of treatment. ABL-class fusion positive cases had a poor early treatment response: minimal residual disease levels of ≥5×10 -4 were observed in 71.4% of patients after induction treatment and in 51.2% after consolidation phase. For the entire cohort of 46 cases, the 5-year probability of event-free survival was 49.1+8.9% and that of overall survival 69.6+7.8%; the cumulative incidence of relapse was 25.6+8.2% and treatment-related mortality (TRM) 20.8+6.8%. One out of 13 cases with TKI added to chemotherapy relapsed while eight of 33 cases without TKI treatment suffered from relapse, including six in 17 patients who had not received hematopoietic stem cell transplantation. Stem cell transplantation seems to be effective in preventing relapses (only three relapses in 25 patients), but was associated with a very high TRM (6 patients). These data indicate a major need for an early identification of ABL-class fusion positive acute lymphoblastic leukemia cases and to establish a properly designed, controlled study aimed at investigating the use of TKI, the appropriate chemotherapy backbone and the role of hematopoietic stem cell transplantation. (Registered at: clinicaltrials.gov identifier: NTC00430118, NCT00613457, NCT01117441) ., (Copyright© 2020 Ferrata Storti Foundation.)

Published
2020
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