1,641 results on '"Schrappe, M"'
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2. Patientensicherheit – aktuelle Probleme und Herausforderungen
- Author
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Schrappe, M., Müller, H., and Hecker, R.
- Published
- 2020
- Full Text
- View/download PDF
3. Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia
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Palmi, C, Bresolin, S, Junk, S, Fazio, G, Silvestri, D, Zaliova, M, Oikonomou, A, Scharov, K, Stanulla, M, Moericke, A, Zimmermann, M, Schrappe, M, Buldini, B, Bhatia, S, Borkhardt, A, Saitta, C, Galbiati, M, Bardini, M, Lo Nigro, L, Conter, V, Valsecchi, M, Biondi, A, Te Kronnie, G, Cario, G, Cazzaniga, G, Palmi C., Bresolin S., Junk S., Fazio G., Silvestri D., Zaliova M., Oikonomou A., Scharov K., Stanulla M., Moericke A., Zimmermann M., Schrappe M., Buldini B., Bhatia S., Borkhardt A., Saitta C., Galbiati M., Bardini M., Lo Nigro L., Conter V., Valsecchi M. G., Biondi A., Te Kronnie G., Cario G., Cazzaniga G., Palmi, C, Bresolin, S, Junk, S, Fazio, G, Silvestri, D, Zaliova, M, Oikonomou, A, Scharov, K, Stanulla, M, Moericke, A, Zimmermann, M, Schrappe, M, Buldini, B, Bhatia, S, Borkhardt, A, Saitta, C, Galbiati, M, Bardini, M, Lo Nigro, L, Conter, V, Valsecchi, M, Biondi, A, Te Kronnie, G, Cario, G, Cazzaniga, G, Palmi C., Bresolin S., Junk S., Fazio G., Silvestri D., Zaliova M., Oikonomou A., Scharov K., Stanulla M., Moericke A., Zimmermann M., Schrappe M., Buldini B., Bhatia S., Borkhardt A., Saitta C., Galbiati M., Bardini M., Lo Nigro L., Conter V., Valsecchi M. G., Biondi A., Te Kronnie G., Cario G., and Cazzaniga G.
- Abstract
Children with Down syndrome have an augmented risk for B-cell acute lymphoblastic leukemia (DS-ALL), which is associated with lower survival than in non-DS-ALL. It is known that cytogenetic abnormalities common in childhood ALL are less frequent in DS-ALL, while other genetic aberrancies (ie, CRLF2 overexpression and IKZF1 deletions) are increased. A possible cause for the lower survival of DS-ALL that we herewith evaluated for the first time was the incidence and prognostic value of the Philadelphia-like (Ph-like) profile and the IKZF1plus pattern. These features have been associated with poor outcome in non-DS ALL and therefore introduced in current therapeutic protocols. Forty-six out of 70 DS-ALL patients treated in Italy from 2000 to 2014 displayed Ph-like signature, mostly characterized by CRLF2 (n = 33) and IKZF1 (n = 16) alterations; only 2 cases were positive for ABL-class or PAX5-fusion genes. Moreover, in an Italian and German joint cohort of 134 DS-ALL patients, we observed 18% patients positive for IKZF1plus feature. Ph-like signature and IKZF1 deletion were associated with poor outcome (cumulative incidence of relapse: 27.7 ± 6.8% versus 13 ± 7%; P = 0.04 and 35.2 ± 8.6% versus 17 ± 3.9%; P = 0.007, respectively), which further worsens when IKZF1 deletion was co-occurring with P2RY8::CRLF2, qualifying for the IKZF1plus definition (13/15 patients had an event of relapse or treatment-related death). Notably, ex vivo drug screening revealed sensitivity of IKZF1plus blasts for drugs active against Ph-like ALL such as Birinapant and histone deacetylase inhibitors. We provided data in a large setting of a rare condition (DS-ALL) supporting that these patients, not associated with other high-risk features, need tailored therapeutic strategies.
- Published
- 2023
4. Hypersensitivity Reactions to Native E. coli L-asparaginase in Children with Acute Lymphoblastic Leukemia Treated in Trial ALL-BFM 2000: Impact of Treatment Schedule and Type of Glucocorticoid in Induction
- Author
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Moricke, A, Rizzari, C, Alten, J, Attarbaschi, A, Beier, R, Biondi, A, Burkhardt, B, Bodmer, N, Boos, J, Cario, G, Conter, V, Flotho, C, Kulozik, A, Lanvers-Kaminsky, C, Mann, G, Niggli, F, Silvestri, D, Von Stackelberg, A, Stanulla, M, Valsecchi, M, Schrappe, M, Zimmermann, M, Moricke A., Rizzari C., Alten J., Attarbaschi A., Beier R., Biondi A., Burkhardt B., Bodmer N., Boos J., Cario G., Conter V., Flotho C., Kulozik A., Lanvers-Kaminsky C., Mann G., Niggli F., Silvestri D., Von Stackelberg A., Stanulla M., Valsecchi MG., Schrappe M., Zimmermann M., Moricke, A, Rizzari, C, Alten, J, Attarbaschi, A, Beier, R, Biondi, A, Burkhardt, B, Bodmer, N, Boos, J, Cario, G, Conter, V, Flotho, C, Kulozik, A, Lanvers-Kaminsky, C, Mann, G, Niggli, F, Silvestri, D, Von Stackelberg, A, Stanulla, M, Valsecchi, M, Schrappe, M, Zimmermann, M, Moricke A., Rizzari C., Alten J., Attarbaschi A., Beier R., Biondi A., Burkhardt B., Bodmer N., Boos J., Cario G., Conter V., Flotho C., Kulozik A., Lanvers-Kaminsky C., Mann G., Niggli F., Silvestri D., Von Stackelberg A., Stanulla M., Valsecchi MG., Schrappe M., and Zimmermann M.
- Published
- 2023
5. Incidence and Characteristics of Hypersensitivity Reactions to PEG-asparaginase Observed in 6136 Children with Acute Lymphoblastic Leukemia Enrolled in the AIEOP-BFM ALL 2009 Study Protocol
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Rizzari, C, Möricke, A, Valsecchi, M, Conter, V, Zimmermann, M, Silvestri, D, Attarbaschi, A, Niggli, F, Barbaric, D, Stary, J, Elitzur, S, Cario, G, Vinti, L, Boos, J, Zucchetti, M, Lanvers-Kaminsky, C, Von Stackelberg, A, Biondi, A, Schrappe, M, Rizzari C., Möricke A., Valsecchi M. G., Conter V., Zimmermann M., Silvestri D., Attarbaschi A., Niggli F., Barbaric D., Stary J., Elitzur S., Cario G., Vinti L., Boos J., Zucchetti M., Lanvers-Kaminsky C., Von Stackelberg A., Biondi A., Schrappe M., Rizzari, C, Möricke, A, Valsecchi, M, Conter, V, Zimmermann, M, Silvestri, D, Attarbaschi, A, Niggli, F, Barbaric, D, Stary, J, Elitzur, S, Cario, G, Vinti, L, Boos, J, Zucchetti, M, Lanvers-Kaminsky, C, Von Stackelberg, A, Biondi, A, Schrappe, M, Rizzari C., Möricke A., Valsecchi M. G., Conter V., Zimmermann M., Silvestri D., Attarbaschi A., Niggli F., Barbaric D., Stary J., Elitzur S., Cario G., Vinti L., Boos J., Zucchetti M., Lanvers-Kaminsky C., Von Stackelberg A., Biondi A., and Schrappe M.
- Abstract
The incidence of hypersensitivity reactions (HSRs) to PEG-asparaginase (PEG-ASNase) was evaluated in 6136 children with ALL enrolled in the AIEOP-BFM ALL 2009 study. Patients with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) were stratified as standard-risk/medium-risk (MR)/high-risk (HR) and those with T-ALL as non-High/HR. PEG-ASNase was administered intravenously at 2500 IU/sqm/dose. All patients received 2 PEG-ASNase doses in induction; thereafter non-HR versus HR patients received 1 versus 6 PEG-ASNase doses, respectively. After the single regular dose of PEG-ASNase at the beginning of delayed intensification, BCP-ALL-MR patients were randomized to receive 9 additional PEG-ASNase doses every 2 weeks (experimental arm [EA]) versus none (standard arm [SA]); HR patients were randomized to receive, in consolidation, 4 weekly PEG-ASNase doses (EA) versus none (SA). The HSR cumulative incidence (CI) was estimated adjusting for competing risks. An HSR occurred in 472 of 6136 (7.7%) patients. T-non- HR/BCP-Standard-Risk, BCP-MR-SA, BCP-MR-EA, HR-SA and HR-EA patients had 1-year-CI-HSR (±SE) rates of 5.2% (0.5), 5.2% (0.5), 4.0% (0.8), 20.2% (1.2), and 6.4% (1.3), respectively. The randomized intensification of PEG-ASNase did not significantly impact on HSR incidence in BCP-MR patients (1-y-CI-HSR 3.8% [0.8] versus 3.2% [0.6] in MR-EA versus MR-SA; P = 0.55), while impacted significantly in HR patients (1-y-CI-HSR 6.4% [1.3] versus 17.9% [1.8] in HR-EA and HR-SA, respectively; P < 0.001). The CI-HSR was comparable among non-HR groups and was not increased by a substantial intensification of PEG-ASNase in the BCP-MR-EA group whilst it was markedly higher in HR-SA than in HR-EA patients, suggesting that, in such a chemotherapy context, a continuous exposure to PEG-ASNase reduces the risk of developing an HSR.
- Published
- 2023
6. Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial
- Author
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Hunger, S, Tran, T, Saha, V, Devidas, M, Valsecchi, M, Gastier-Foster, J, Cazzaniga, G, Reshmi, S, Borowitz, M, Moorman, A, Heerema, N, Carroll, A, Martin-Regueira, P, Loh, M, Raetz, E, Schultz, K, Slayton, W, Cario, G, Schrappe, M, Silverman, L, Biondi, A, Hunger S. P., Tran T. H., Saha V., Devidas M., Valsecchi M. G., Gastier-Foster J. M., Cazzaniga G., Reshmi S. C., Borowitz M. J., Moorman A. V., Heerema N. A., Carroll A. J., Martin-Regueira P., Loh M. L., Raetz E. A., Schultz K. R., Slayton W. B., Cario G., Schrappe M., Silverman L. B., Biondi A., Hunger, S, Tran, T, Saha, V, Devidas, M, Valsecchi, M, Gastier-Foster, J, Cazzaniga, G, Reshmi, S, Borowitz, M, Moorman, A, Heerema, N, Carroll, A, Martin-Regueira, P, Loh, M, Raetz, E, Schultz, K, Slayton, W, Cario, G, Schrappe, M, Silverman, L, Biondi, A, Hunger S. P., Tran T. H., Saha V., Devidas M., Valsecchi M. G., Gastier-Foster J. M., Cazzaniga G., Reshmi S. C., Borowitz M. J., Moorman A. V., Heerema N. A., Carroll A. J., Martin-Regueira P., Loh M. L., Raetz E. A., Schultz K. R., Slayton W. B., Cario G., Schrappe M., Silverman L. B., and Biondi A.
- Abstract
Background: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia. Methods: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study. Eligible patients (aged >1 year to <18 years) with newly diagnosed Ph-positive acute lymphoblastic leukaemia and performance status of at least 60% received EsPhALL chemotherapy plus dasatinib 60 mg/m2 orally once daily from day 15 of induction. Patients with minimal residual disease of at least 0·05% after induction 1B or who were positive for minimal residual disease after the three consolidation blocks were classified as high risk and allocated to receive haematopoietic stem-cell transplantation (HSCT) in first complete remission. The remaining patients were considered standard risk and received chemotherapy plus dasatinib for 2 years. The primary endpoint was the 3-year event-free survival of dasatinib plus chemotherapy compared with external historical controls. The trial was considered positive if one of the following conditions was met: superiority over chemotherapy alone in the AIEOP-BFM 2000 high-risk group; or non-inferiority (with a margin of –5%) or superiority to imatinib plus chemotherapy in the EsPhALL 2010 cohort. All participants who received at least one dose of dasatinib were included in the safety and efficacy analyses. This trial was registered with ClinicalTrials.gov, NCT01460160, and recruitment is closed. Findings: Between March 13, 2012, and May 27, 2014, 109 patients were enrolled at 69 sites (including 51 COG sites in t
- Published
- 2023
7. Leukämien und Lymphome
- Author
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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
- Full Text
- View/download PDF
8. Versorgungsforschung: Definition, Gegenstand, Methodik und Perspektiven
- Author
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Neugebauer, E. A. M., Schrappe, M., Pfaff, H., and Glaeske, G.
- Published
- 2018
- Full Text
- View/download PDF
9. Incidence and Characteristics of Hypersensitivity Reactions to PEG-asparaginase Observed in 6136 Children with Acute Lymphoblastic Leukemia Enrolled in the AIEOP-BFM ALL 2009 Study Protocol
- Author
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Rizzari C., Möricke A., Valsecchi M. G., Conter V., Zimmermann M., Silvestri D., Attarbaschi A., Niggli F., Barbaric D., Stary J., Elitzur S., Cario G., Vinti L., Boos J., Zucchetti M., Lanvers-Kaminsky C., Von Stackelberg A., Biondi A., Schrappe M., Rizzari, C, Möricke, A, Valsecchi, M, Conter, V, Zimmermann, M, Silvestri, D, Attarbaschi, A, Niggli, F, Barbaric, D, Stary, J, Elitzur, S, Cario, G, Vinti, L, Boos, J, Zucchetti, M, Lanvers-Kaminsky, C, Von Stackelberg, A, Biondi, A, and Schrappe, M
- Subjects
MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,acute lymphoblastic leukemia, childhood, chemoterapy, asparaginase - Abstract
The incidence of hypersensitivity reactions (HSRs) to PEG-asparaginase (PEG-ASNase) was evaluated in 6136 children with ALL enrolled in the AIEOP-BFM ALL 2009 study. Patients with B-cell precursor-acute lymphoblastic leukemia (BCP-ALL) were stratified as standard-risk/medium-risk (MR)/high-risk (HR) and those with T-ALL as non-High/HR. PEG-ASNase was administered intravenously at 2500 IU/sqm/dose. All patients received 2 PEG-ASNase doses in induction; thereafter non-HR versus HR patients received 1 versus 6 PEG-ASNase doses, respectively. After the single regular dose of PEG-ASNase at the beginning of delayed intensification, BCP-ALL-MR patients were randomized to receive 9 additional PEG-ASNase doses every 2 weeks (experimental arm [EA]) versus none (standard arm [SA]); HR patients were randomized to receive, in consolidation, 4 weekly PEG-ASNase doses (EA) versus none (SA). The HSR cumulative incidence (CI) was estimated adjusting for competing risks. An HSR occurred in 472 of 6136 (7.7%) patients. T-non- HR/BCP-Standard-Risk, BCP-MR-SA, BCP-MR-EA, HR-SA and HR-EA patients had 1-year-CI-HSR (±SE) rates of 5.2% (0.5), 5.2% (0.5), 4.0% (0.8), 20.2% (1.2), and 6.4% (1.3), respectively. The randomized intensification of PEG-ASNase did not significantly impact on HSR incidence in BCP-MR patients (1-y-CI-HSR 3.8% [0.8] versus 3.2% [0.6] in MR-EA versus MR-SA; P = 0.55), while impacted significantly in HR patients (1-y-CI-HSR 6.4% [1.3] versus 17.9% [1.8] in HR-EA and HR-SA, respectively; P < 0.001). The CI-HSR was comparable among non-HR groups and was not increased by a substantial intensification of PEG-ASNase in the BCP-MR-EA group whilst it was markedly higher in HR-SA than in HR-EA patients, suggesting that, in such a chemotherapy context, a continuous exposure to PEG-ASNase reduces the risk of developing an HSR.
- Published
- 2023
10. Hypersensitivity Reactions to Native E. coli L-asparaginase in Children with Acute Lymphoblastic Leukemia Treated in Trial ALL-BFM 2000: Impact of Treatment Schedule and Type of Glucocorticoid in Induction
- Author
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Moricke A., Rizzari C., Alten J., Attarbaschi A., Beier R., Biondi A., Burkhardt B., Bodmer N., Boos J., Cario G., Conter V., Flotho C., Kulozik A., Lanvers-Kaminsky C., Mann G., Niggli F., Silvestri D., Von Stackelberg A., Stanulla M., Valsecchi MG., Schrappe M., Zimmermann M., Moricke, A, Rizzari, C, Alten, J, Attarbaschi, A, Beier, R, Biondi, A, Burkhardt, B, Bodmer, N, Boos, J, Cario, G, Conter, V, Flotho, C, Kulozik, A, Lanvers-Kaminsky, C, Mann, G, Niggli, F, Silvestri, D, Von Stackelberg, A, Stanulla, M, Valsecchi, M, Schrappe, M, and Zimmermann, M
- Subjects
acute lymphoblastic leukemia ,immunotherapy ,MED/38 - PEDIATRIA GENERALE E SPECIALISTICA ,chemotherapy ,childhood - Published
- 2023
11. Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol
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Stutterheim, J, de Lorenzo, P, van der Sluin, I, Alten, J, Ancliffe, P, Attarbaschi, A, Aversa, L, Boer, J, Biondi, A, Brethon, B, Diaz, P, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Leung, A, Locatelli, F, Silverman, L, Stary, J, Szczepanski, T, van der Velden, V, Vora, A, Zuna, J, Schrappe, M, Valsecchi, M, Pieters, R, Stutterheim J., de Lorenzo P., van der Sluin I. M., Alten J., Ancliffe P., Attarbaschi A., Aversa L., Boer J. M., Biondi A., Brethon B., Diaz P., Cazzaniga G., Escherich G., Ferster A., Kotecha R. S., Lausen B., Leung A. W., Locatelli F., Silverman L., Stary J., Szczepanski T., van der Velden V. H. J., Vora A., Zuna J., Schrappe M., Valsecchi M. G., Pieters R., Stutterheim, J, de Lorenzo, P, van der Sluin, I, Alten, J, Ancliffe, P, Attarbaschi, A, Aversa, L, Boer, J, Biondi, A, Brethon, B, Diaz, P, Cazzaniga, G, Escherich, G, Ferster, A, Kotecha, R, Lausen, B, Leung, A, Locatelli, F, Silverman, L, Stary, J, Szczepanski, T, van der Velden, V, Vora, A, Zuna, J, Schrappe, M, Valsecchi, M, Pieters, R, Stutterheim J., de Lorenzo P., van der Sluin I. M., Alten J., Ancliffe P., Attarbaschi A., Aversa L., Boer J. M., Biondi A., Brethon B., Diaz P., Cazzaniga G., Escherich G., Ferster A., Kotecha R. S., Lausen B., Leung A. W., Locatelli F., Silverman L., Stary J., Szczepanski T., van der Velden V. H. J., Vora A., Zuna J., Schrappe M., Valsecchi M. G., and Pieters R.
- Abstract
Background: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. Methods: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10−4), and high (≥5∗10−4). Results: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10−4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10−4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). Conclusion: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.
- Published
- 2022
12. Pre-existing antibodies against polyethylene glycol reduce asparaginase activities on first administration of pegylated E. coli asparaginase in children with acute lymphocytic leukemia
- Author
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Khalil, A, Wurthwein, G, Golitsch, J, Hempel, G, Fobker, M, Gerss, J, Moricke, A, Zimmermann, M, Smisek, P, Zucchetti, M, Nath, C, Attarbaschi, A, Von Stackelberg, A, Gokbuget, N, Rizzari, C, Conter, V, Schrappe, M, Boos, J, Lanvers-Kaminsky, C, Khalil A., Wurthwein G., Golitsch J., Hempel G., Fobker M., Gerss J., Moricke A., Zimmermann M., Smisek P., Zucchetti M., Nath C., Attarbaschi A., Von Stackelberg A., Gokbuget N., Rizzari C., Conter V., Schrappe M., Boos J., Lanvers-Kaminsky C., Khalil, A, Wurthwein, G, Golitsch, J, Hempel, G, Fobker, M, Gerss, J, Moricke, A, Zimmermann, M, Smisek, P, Zucchetti, M, Nath, C, Attarbaschi, A, Von Stackelberg, A, Gokbuget, N, Rizzari, C, Conter, V, Schrappe, M, Boos, J, Lanvers-Kaminsky, C, Khalil A., Wurthwein G., Golitsch J., Hempel G., Fobker M., Gerss J., Moricke A., Zimmermann M., Smisek P., Zucchetti M., Nath C., Attarbaschi A., Von Stackelberg A., Gokbuget N., Rizzari C., Conter V., Schrappe M., Boos J., and Lanvers-Kaminsky C.
- Abstract
Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples of 701 children, 673 with primary ALL, 28 with relapsed ALL, and 188 adults with primary ALL were analyzed for anti-PEG IgG and IgM. Measurements in 58 healthy infants served as reference to define cut-points for antibody-positive and -negative samples. Anti-PEG antibodies were detected in ALL patients prior the first PEG-ASNase with a prevalence of 13.9% (anti-PEG IgG) and 29.1% (anti-PEG IgM). After administration of PEG-ASNase the prevalence of anti-PEG antibodies decreased to 4.2% for anti-PEG IgG and to 4.5% for anti-PEG IgM. Pre-existing anti-PEG antibodies did not inhibit PEG-ASNase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner. Although pre-existing anti-PEG antibodies did not boost, pre-existing anti-PEG IgG were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2) (p.
- Published
- 2022
13. Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium
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Buchmann, S, Schrappe, M, Baruchel, A, Biondi, A, Borowitz, M, Campbell, M, Cario, G, Cazzaniga, G, Escherich, G, Harrison, C, Heyman, M, Hunger, S, Kiss, C, Liu, H, Locatelli, F, Loh, M, Manabe, A, Mann, G, Pieters, R, Pui, C, Rives, S, Schmiegelow, K, Silverman, L, Stary, J, Vora, A, Brown, P, Buchmann S., Schrappe M., Baruchel A., Biondi A., Borowitz M., Campbell M., Cario G., Cazzaniga G., Escherich G., Harrison C. J., Heyman M., Hunger S. P., Kiss C., Liu H. -C., Locatelli F., Loh M. L., Manabe A., Mann G., Pieters R., Pui C. -H., Rives S., Schmiegelow K., Silverman L. B., Stary J., Vora A., Brown P., Buchmann, S, Schrappe, M, Baruchel, A, Biondi, A, Borowitz, M, Campbell, M, Cario, G, Cazzaniga, G, Escherich, G, Harrison, C, Heyman, M, Hunger, S, Kiss, C, Liu, H, Locatelli, F, Loh, M, Manabe, A, Mann, G, Pieters, R, Pui, C, Rives, S, Schmiegelow, K, Silverman, L, Stary, J, Vora, A, Brown, P, Buchmann S., Schrappe M., Baruchel A., Biondi A., Borowitz M., Campbell M., Cario G., Cazzaniga G., Escherich G., Harrison C. J., Heyman M., Hunger S. P., Kiss C., Liu H. -C., Locatelli F., Loh M. L., Manabe A., Mann G., Pieters R., Pui C. -H., Rives S., Schmiegelow K., Silverman L. B., Stary J., Vora A., and Brown P.
- Abstract
Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.
- Published
- 2022
14. Outcome for Children and Young Adults With T-Cell ALL and Induction Failure in Contemporary Trials
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Raetz, E, Rebora, P, Conter, V, Schrappe, M, Devidas, M, Escherich, G, Imai, C, De Moerloose, B, Schmiegelow, K, Burns, M, Elitzur, S, Pieters, R, Attarbaschi, A, Yeoh, A, Pui, C, Stary, J, Cario, G, Bodmer, N, Moorman, A, Buldini, B, Vora, A, Valsecchi, M, Raetz, Elizabeth A, Rebora, Paola, Conter, Valentino, Schrappe, Martin, Devidas, Meenakshi, Escherich, Gabriele, Imai, Chihaya, De Moerloose, Barbara, Schmiegelow, Kjeld, Burns, Melissa A, Elitzur, Sarah, Pieters, Rob, Attarbaschi, Andishe, Yeoh, Allen, Pui, Ching-Hon, Stary, Jan, Cario, Gunnar, Bodmer, Nicole, Moorman, Anthony V, Buldini, Barbara, Vora, Ajay, Valsecchi, Maria Grazia, Raetz, E, Rebora, P, Conter, V, Schrappe, M, Devidas, M, Escherich, G, Imai, C, De Moerloose, B, Schmiegelow, K, Burns, M, Elitzur, S, Pieters, R, Attarbaschi, A, Yeoh, A, Pui, C, Stary, J, Cario, G, Bodmer, N, Moorman, A, Buldini, B, Vora, A, Valsecchi, M, Raetz, Elizabeth A, Rebora, Paola, Conter, Valentino, Schrappe, Martin, Devidas, Meenakshi, Escherich, Gabriele, Imai, Chihaya, De Moerloose, Barbara, Schmiegelow, Kjeld, Burns, Melissa A, Elitzur, Sarah, Pieters, Rob, Attarbaschi, Andishe, Yeoh, Allen, Pui, Ching-Hon, Stary, Jan, Cario, Gunnar, Bodmer, Nicole, Moorman, Anthony V, Buldini, Barbara, Vora, Ajay, and Valsecchi, Maria Grazia
- Abstract
PURPOSE Historically, patients with T-cell acute lymphoblastic leukemia (T-ALL) who fail to achieve remission at the end of induction (EOI) have had poor long-term survival. The goal of this study was to examine the efficacy of contemporary therapy, including allogeneic hematopoietic stem cell transplantation (HSCT) in first remission (CR1).METHODSInduction failure (IF) was defined as the persistence of at least 5% bone marrow (BM) lymphoblasts and/or extramedullary disease after 4-6 weeks of induction chemotherapy. Disease features and clinical outcomes were reported in 325 of 6,167 (5%) patients age 21 years and younger treated in 14 cooperative study groups between 2000 and 2018.RESULTSWith a median follow-up period of 6.4 years (range, 0.3-17.9 years), the 10-year overall survival (OS) was 54.7% (SE = 2.9), which is significantly higher than the 27.6% (SE = 2.9) observed in the historical cohort from 1985 to 2000. There was no significant impact of sex, age, white blood cell count, central nervous system disease status, T-cell maturity, or BM disease burden at EOI on OS. Postinduction complete remission (CR) was achieved in 93% of patients with 10-year OS of 59.6% (SE = 3.1%) and disease-free survival (DFS) of 56.3% (SE = 3.1%). Among the patients who achieved CR, 72% underwent HSCT and their 10-year DFS (with a 190-day landmark) was significantly better than nontransplanted patients (63.8% [SE = 3.6] v 45.5% [SE = 7.1]; P =.005), with OS of 66.2% (SE = 3.6) versus 50.8% (SE = 6.8); P =.10, respectively.CONCLUSIONOutcomes for patients age 21 years and younger with T-ALL and IF have improved in the contemporary treatment era with a DFS benefit among those undergoing HSCT in CR1. However, outcomes still lag considerably behind those who achieve remission at EOI, warranting investigation of new treatment approaches.
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- 2023
15. Preexisting conditions in pediatric ALL patients: Spectrum, frequency and clinical impact
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Schütte, P., Möricke, A., Zimmermann, M., Bleckmann, K., Reismüller, B., Attarbaschi, A., Mann, G., Bodmer, N., Niggli, F., Schrappe, M., Stanulla, M., and Kratz, C.P.
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- 2016
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16. Lebendspende-Lebertransplantation beim Kind
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Dreßke, B., Schulze, M., Braun, F., Walter, J., Kohl, M., Schulz-Jürgensen, S., Krause, M., Schrappe, M., Burdelski, M., and Bröring, D.C.
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Zusammenfassung: Die Lebertransplantation ist bei Kindern mit akutem und chronischem Leberversagen, metabolischen Lebererkrankungen und -tumoren die Therapie der Wahl. Bei den meist sehr kleinen Empfängern sind die Ressourcen größenkompatibler Vollorgantransplantate jedoch begrenzt. Die Leberlebendspende konnte bei Kindern die Wartelistenmortalität fast vollständig eliminieren und weist exzellente Patienten- und Organüberlebensdaten auf. Da 80% der kindlichen Empfänger ein Gewicht <25 kg haben, ist die Spende der linkslateralen Lebersegmente II und III meist ausreichend. Durch eine Standardisierung des chirurgischen sowie des prä-, intra- und postoperativen Managements konnte sie zu einem Verfahren entwickelt werden, welches eine sehr niedrige Spendermorbidität und -mortalität aufweist. Die kindliche Lebendspende-Lebertransplantation setzt eine hohe Expertise in der Leberchirurgie und Splitlebertransplantation voraus und erfordert aufgrund der komplexen und oft organübergreifenden Krankheitsbilder eine enge Zusammenarbeit mit einem erfahrenen pädiatrischen Team. Sie sollte deshalb ausschließlich in Transplantationszentren durchgeführt werden, die diese Voraussetzungen erfüllen.
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- 2024
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17. „AKTION Saubere Hände“
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Reichardt, C., Eberlein-Gonska, M., Schrappe, M., and Gastmeier, P.
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Zusammenfassung: In Deutschland treten ca. 500.000 Krankenhausinfektionen im Jahr auf, von denen schätzungsweise 20–30% (100.000–150.000) vermeidbar sind. Krankenhausinfektionen gehen mit einer erhöhten Sterblichkeit und einer Verlängerung der Krankenhausverweildauer einher. Im Durchschnitt muss man von einer Verlängerung der Verweildauer von ca. 4 Tagen ausgehen, dementsprechend resultieren aus Krankenhausinfektionen ca. 2 Mio. zusätzliche Krankenhausverweiltage. Bildlich gesprochen könnte man sagen, dass ca. 6 Krankenhäuser mit jeweils 1000 Betten in Deutschland ein Jahr lang nur daran arbeiten, Patienten mit Krankenhausinfektionen zu behandeln. Experten sind sich darüber einig, dass die sorgfältige Händedesinfektion die wichtigste Maßnahme zur Vermeidung der Übertragung von Krankheitserregern ist. In Untersuchungen konnte nachgewiesen werden, dass die Verbesserung der Händedesinfektion das Auftreten von Krankenhausinfektionen deutlich reduziert. Die „AKTION Saubere Hände“ hat deshalb das Ziel, als gemeinsame Kampagne des Nationalen Referenzzentrums für die Surveillance von nosokomialen Infektionen, der Gesellschaft für Qualitätsmanagement im Gesundheitswesen e. V. und des Aktionsbündnisses Patientensicherheit zu einer deutlichen Verbesserung des Händedesinfektionsverhaltens in deutschen Gesundheitseinrichtungen beizutragen.
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- 2024
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18. Population Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia: Treatment Phase Dependency and Predictivity in Case of Missing Data
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Wurthwein, G, Lanvers-Kaminsky, C, Siebel, C, Gerss, J, Moricke, A, Zimmermann, M, Stary, J, Smisek, P, Schrappe, M, Rizzari, C, Zucchetti, M, Hempel, G, Wicha, S, Boos, J, Wurthwein G., Lanvers-Kaminsky C., Siebel C., Gerss J., Moricke A., Zimmermann M., Stary J., Smisek P., Schrappe M., Rizzari C., Zucchetti M., Hempel G., Wicha S. G., Boos J., Wurthwein, G, Lanvers-Kaminsky, C, Siebel, C, Gerss, J, Moricke, A, Zimmermann, M, Stary, J, Smisek, P, Schrappe, M, Rizzari, C, Zucchetti, M, Hempel, G, Wicha, S, Boos, J, Wurthwein G., Lanvers-Kaminsky C., Siebel C., Gerss J., Moricke A., Zimmermann M., Stary J., Smisek P., Schrappe M., Rizzari C., Zucchetti M., Hempel G., Wicha S. G., and Boos J.
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Background and Objectives: The pharmacokinetics of polyethylene glycol-conjugated asparaginase (PEG-ASNase) are characterized by an increase in elimination over time, a marked increase in ASNase activity levels from induction to reinduction, and high inter- and intraindividual variability. A population pharmacokinetic (PopPK) model is required to estimate individual dose intensity, despite gaps in monitoring compliance. Methods: In the AIEOP-BFM ALL 2009 trial, two PEG-ASNase administrations (2500 U/m2 intravenously) during induction (14-day interval) and one administration during reinduction were administered in children with acute lymphoblastic leukemia. ASNase activity levels were monitored weekly. A PopPK model was used for covariate modeling and external validation. The predictivity of the model in case of missing data was tested for observations, as well as for the derived parameters of the area under the concentration time curve (AUC0-∞) and time above different thresholds. Results: Compared to the first administration in induction (1374 patients, 6069 samples), the initial clearance and volume of distribution decreased by 11.0% and 15.9%, respectively, during the second administration during induction and by 41.2% and 28.4% during reinduction. Furthermore, the initial clearance linearly increased for children aged > 8 years and was 7.1% lower for females. The model was successfully externally validated (1253 patients, 5523 samples). In case of missing data, > 52% of the predictions for observations and > 82% for derived parameters were within ± 20% of the nominal value. Conclusion: A PopPK model that describes the complex pharmacokinetics of PEG-ASNase was successfully externally validated. AUC0−∞ or time above different thresholds, which are parameters describing dose intensity, can be estimated with high predictivity, despite missing data. (www.clinicaltrials.gov, NCT01117441, first submitted date: May 3, 2010).
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- 2021
19. Intercontinental collaboration in clinical trials for children and adolescents with cancer—A systematic review by ACCELERATE
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de Rojas, T, Pearson, A, Scobie, N, Knox, L, Wariabharaj, D, Kearns, P, Vassal, G, Reaman, G, Alonzo, T, Biondi, A, Brodeur-Robb, K, Fouladi, M, Gross, T, Hunger, S, Mccowage, G, Pappo, A, Schrappe, M, Grazia Valsecchi, M, Weigel, B, Wejbora, P, Whitlock, J, Zwaan, M, Buenger, V, Ludwinski, D, Barry, E, Neville, K, Sharma, A, Karres, D, de Rojas T., Pearson A. J., Scobie N., Knox L., Wariabharaj D., Kearns P., Vassal G., Reaman G., Alonzo T., Biondi A., Brodeur-Robb K., Fouladi M., Gross T., Hunger S., McCowage G., Pappo A., Schrappe M., Grazia Valsecchi M., Weigel B., Wejbora P., Whitlock J., Zwaan M., Buenger V., Ludwinski D., Barry E., Neville K., Sharma A., Karres D., de Rojas, T, Pearson, A, Scobie, N, Knox, L, Wariabharaj, D, Kearns, P, Vassal, G, Reaman, G, Alonzo, T, Biondi, A, Brodeur-Robb, K, Fouladi, M, Gross, T, Hunger, S, Mccowage, G, Pappo, A, Schrappe, M, Grazia Valsecchi, M, Weigel, B, Wejbora, P, Whitlock, J, Zwaan, M, Buenger, V, Ludwinski, D, Barry, E, Neville, K, Sharma, A, Karres, D, de Rojas T., Pearson A. J., Scobie N., Knox L., Wariabharaj D., Kearns P., Vassal G., Reaman G., Alonzo T., Biondi A., Brodeur-Robb K., Fouladi M., Gross T., Hunger S., McCowage G., Pappo A., Schrappe M., Grazia Valsecchi M., Weigel B., Wejbora P., Whitlock J., Zwaan M., Buenger V., Ludwinski D., Barry E., Neville K., Sharma A., and Karres D.
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Background: Since pediatric cancer drug development is a global enterprise, we sought to provide an overview of the landscape of intercontinental clinical trials in pediatric oncology opened over the last decade. Methods: ClinicalTrials.gov was systematically searched to identify all clinical therapeutic trials which opened between 2010 and 2020 and recruited pediatric patients (<18 years) with cancer. Results: Over the last 10 years, 295 (8.7%) of 3383 therapeutic pediatric cancer trials were international and 182 (5.4%) were intercontinental. Most intercontinental trials were phase-1 or 2, with 25% late-phase, 65% were sponsored by industry, and North America was involved in 92%. Industry-sponsored proportionally more phase-1 trials than academia (41% vs. 25%); conversely, academia sponsored more phase-2 and late-phase trials (39% and 31% vs. 36% and 21%, respectively) (p = 0.020). North America–Europe collaboration was predominantly industry sponsored as opposed to North America–Oceania and Europe–Oceania collaboration, more frequently academic (p < 0.0001). Most late-phase trials (18/20, 90%) focusing on pediatric malignancies were conducted by academic sponsors and 10 of these were conducted by Children's Oncology Group (COG)/National Cancer Institute in the United States and Oceania. There was no significant increase over time of intercontinental trials and a trend for a reduction in academic trials. Conclusions: Despite the relative rarity of childhood malignancies, especially within molecular subtypes, only 5.4% of pediatric cancer trials were intercontinental. The number of intercontinental trials remains small, with no significant increase over the last decade. The ACCELERATE International Collaboration Working Group aims to identify existing hurdles and propose solutions to improve intercontinental collaboration in clinical research for the benefit of children and adolescents with cancer.
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- 2021
20. Outcomes of paediatric patients with B-cell acute lymphocytic leukaemia with ABL-class fusion in the pre-tyrosine-kinase inhibitor era: a multicentre, retrospective, cohort study
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den Boer, M, Cario, G, Moorman, A, Boer, J, de Groot-Kruseman, H, Fiocco, M, Escherich, G, Imamura, T, Yeoh, A, Sutton, R, Dalla-Pozza, L, Kiyokawa, N, Schrappe, M, Roberts, K, Mullighan, C, Hunger, S, Vora, A, Attarbaschi, A, Zaliova, M, Elitzur, S, Cazzaniga, G, Biondi, A, Loh, M, Pieters, R, den Boer M. L., Cario G., Moorman A. V., Boer J. M., de Groot-Kruseman H. A., Fiocco M., Escherich G., Imamura T., Yeoh A., Sutton R., Dalla-Pozza L., Kiyokawa N., Schrappe M., Roberts K. G., Mullighan C. G., Hunger S. P., Vora A., Attarbaschi A., Zaliova M., Elitzur S., Cazzaniga G., Biondi A., Loh M. L., Pieters R., den Boer, M, Cario, G, Moorman, A, Boer, J, de Groot-Kruseman, H, Fiocco, M, Escherich, G, Imamura, T, Yeoh, A, Sutton, R, Dalla-Pozza, L, Kiyokawa, N, Schrappe, M, Roberts, K, Mullighan, C, Hunger, S, Vora, A, Attarbaschi, A, Zaliova, M, Elitzur, S, Cazzaniga, G, Biondi, A, Loh, M, Pieters, R, den Boer M. L., Cario G., Moorman A. V., Boer J. M., de Groot-Kruseman H. A., Fiocco M., Escherich G., Imamura T., Yeoh A., Sutton R., Dalla-Pozza L., Kiyokawa N., Schrappe M., Roberts K. G., Mullighan C. G., Hunger S. P., Vora A., Attarbaschi A., Zaliova M., Elitzur S., Cazzaniga G., Biondi A., Loh M. L., and Pieters R.
- Abstract
Background: ABL-class fusion genes other than BCR–ABL1 have been identified in approximately 3% of children with newly diagnosed acute lymphocytic leukaemia, and studies suggest that leukaemic cells carrying ABL-class fusions can be targeted successfully by tyrosine-kinase inhibitors. We aimed to establish the baseline characteristics and outcomes of paediatric patients with ABL-class fusion B-cell acute lymphocytic leukaemia in the pre-tyrosine-kinase inhibitor era. Methods: This multicentre, retrospective, cohort study included paediatric patients (aged 1–18 years) with newly diagnosed ABL-class fusion (ABL1 fusion-positive, ABL2 fusion-positive, CSF1R fusion-positive, and PDGFRB fusion-positive) B-cell acute lymphocytic leukaemia enrolled in clinical trials of multidrug chemotherapy done between Oct 3, 2000, and Aug 28, 2018, in which tyrosine-kinase inhibitors had not been given as a first-line treatment. Patients from 14 European, North American, and Asia-Pacific study groups of the Ponte di Legno group were included. No patients were excluded, and patients were followed up by individual study groups. Through the Ponte di Legno group, we collected data on the baseline characteristics of patients, including IKZF1, PAX5, and CDKN2A/B deletion status, and whether haematopoietic stem cell transplantation (HSCT) had been done, as well as treatment outcomes, including complete remission, no response, relapse, early death, and treatment-related mortality, response to prednisone, and minimal residual disease (MRD) at end of induction therapy. 5-year event-free survival and 5-year overall survival were estimated by use of Kaplan-Meier methods, and the 5-year cumulative incidence of relapse was calculated by use of a competing risk model. Findings: We identified 122 paediatric patients with newly diagnosed ABL-class fusion B-cell acute lymphocytic leukaemia (77 from European study groups, 25 from North American study groups, and 20 from Asia-Pacific study groups). 64 (52
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- 2021
21. An extensive quality control and quality assurance (QC/QA) program significantly improves inter-laboratory concordance rates of flow-cytometric minimal residual disease assessment in acute lymphoblastic leukemia: An I-BFM-FLOW-network report
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Maurer-Granofszky, M, Schumich, A, Buldini, B, Gaipa, G, Kappelmayer, J, Mejstrikova, E, Karawajew, L, Rossi, J, Suzan, A, Agriello, E, Anastasiou-Grenzelia, T, Barcala, V, Barna, G, Batinic, D, Bourquin, J, Bruggemann, M, Bukowska-Strakova, K, Burnusuzov, H, Carelli, D, Deniz, G, Dubravcic, K, Feuerstein, T, Gaillard, M, Galeano, A, Giordano, H, Gonzalez, A, Groeneveld-Krentz, S, Hevessy, Z, Hrusak, O, Iarossi, M, Jakso, P, Prevodnik, V, Kohlscheen, S, Kreminska, E, Maglia, O, Malusardi, C, Marinov, N, Martin, B, Moller, C, Nikulshin, S, Palazzi, J, Paterakis, G, Popov, A, Ratei, R, Rodriguez, C, Sajaroff, E, Sala, S, Samardzija, G, Sartor, M, Scarparo, P, Sedek, L, Slavkovic, B, Solari, L, Svec, P, Szczepanski, T, Taparkou, A, Torrebadell, M, Tzanoudaki, M, Varotto, E, Vernitsky, H, Attarbaschi, A, Schrappe, M, Conter, V, Biondi, A, Felice, M, Campbell, M, Kiss, C, Basso, G, Dworzak, M, Maurer-Granofszky M., Schumich A., Buldini B., Gaipa G., Kappelmayer J., Mejstrikova E., Karawajew L., Rossi J., Suzan A. C., Agriello E., Anastasiou-Grenzelia T., Barcala V., Barna G., Batinic D., Bourquin J. -P., Bruggemann M., Bukowska-Strakova K., Burnusuzov H., Carelli D., Deniz G., Dubravcic K., Feuerstein T., Gaillard M. I., Galeano A., Giordano H., Gonzalez A., Groeneveld-Krentz S., Hevessy Z., Hrusak O., Iarossi M. B., Jakso P., Prevodnik V. K., Kohlscheen S., Kreminska E., Maglia O., Malusardi C., Marinov N., Martin B. M., Moller C., Nikulshin S., Palazzi J., Paterakis G., Popov A., Ratei R., Rodriguez C., Sajaroff E. O., Sala S., Samardzija G., Sartor M., Scarparo P., Sedek L., Slavkovic B., Solari L., Svec P., Szczepanski T., Taparkou A., Torrebadell M., Tzanoudaki M., Varotto E., Vernitsky H., Attarbaschi A., Schrappe M., Conter V., Biondi A., Felice M., Campbell M., Kiss C., Basso G., Dworzak M. N., Maurer-Granofszky, M, Schumich, A, Buldini, B, Gaipa, G, Kappelmayer, J, Mejstrikova, E, Karawajew, L, Rossi, J, Suzan, A, Agriello, E, Anastasiou-Grenzelia, T, Barcala, V, Barna, G, Batinic, D, Bourquin, J, Bruggemann, M, Bukowska-Strakova, K, Burnusuzov, H, Carelli, D, Deniz, G, Dubravcic, K, Feuerstein, T, Gaillard, M, Galeano, A, Giordano, H, Gonzalez, A, Groeneveld-Krentz, S, Hevessy, Z, Hrusak, O, Iarossi, M, Jakso, P, Prevodnik, V, Kohlscheen, S, Kreminska, E, Maglia, O, Malusardi, C, Marinov, N, Martin, B, Moller, C, Nikulshin, S, Palazzi, J, Paterakis, G, Popov, A, Ratei, R, Rodriguez, C, Sajaroff, E, Sala, S, Samardzija, G, Sartor, M, Scarparo, P, Sedek, L, Slavkovic, B, Solari, L, Svec, P, Szczepanski, T, Taparkou, A, Torrebadell, M, Tzanoudaki, M, Varotto, E, Vernitsky, H, Attarbaschi, A, Schrappe, M, Conter, V, Biondi, A, Felice, M, Campbell, M, Kiss, C, Basso, G, Dworzak, M, Maurer-Granofszky M., Schumich A., Buldini B., Gaipa G., Kappelmayer J., Mejstrikova E., Karawajew L., Rossi J., Suzan A. C., Agriello E., Anastasiou-Grenzelia T., Barcala V., Barna G., Batinic D., Bourquin J. -P., Bruggemann M., Bukowska-Strakova K., Burnusuzov H., Carelli D., Deniz G., Dubravcic K., Feuerstein T., Gaillard M. I., Galeano A., Giordano H., Gonzalez A., Groeneveld-Krentz S., Hevessy Z., Hrusak O., Iarossi M. B., Jakso P., Prevodnik V. K., Kohlscheen S., Kreminska E., Maglia O., Malusardi C., Marinov N., Martin B. M., Moller C., Nikulshin S., Palazzi J., Paterakis G., Popov A., Ratei R., Rodriguez C., Sajaroff E. O., Sala S., Samardzija G., Sartor M., Scarparo P., Sedek L., Slavkovic B., Solari L., Svec P., Szczepanski T., Taparkou A., Torrebadell M., Tzanoudaki M., Varotto E., Vernitsky H., Attarbaschi A., Schrappe M., Conter V., Biondi A., Felice M., Campbell M., Kiss C., Basso G., and Dworzak M. N.
- Abstract
Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.
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- 2021
22. Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol
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Driessen, E MC, de Lorenzo, P, Campbell, M, Felice, M, Ferster, A, Hann, I, Vora, A, Hovi, L, Escherich, G, Li, C K, Mann, G, Leblanc, T, Locatelli, F, Biondi, A, Rubnitz, J, Schrappe, M, Silverman, L, Stary, J, Suppiah, R, Szczepanski, T, Valsecchi, M, and Pieters, R
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- 2017
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23. Akute lymphoblastische Leukämie
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Ritter, J., Möricke, A., Riehm, H., Schrappe, M., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
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- 2006
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24. Tumortherapie bei HIV-Infektion
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Ruhnke, M., Lüke, C., Schrappe, M., Peters, H. D., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
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- 2006
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25. Outcome of relapsed infant acute lymphoblastic leukemia treated on the interfant-99 protocol
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Driessen, E M C, de Lorenzo, P, Campbell, M, Felice, M, Ferster, A, Hann, I, Vora, A, Hovi, L, Escherich, G, Li, C K, Mann, G, Leblanc, T, Locatelli, F, Biondi, A, Rubnitz, J, Schrappe, M, Silverman, L, Stary, J, Suppiah, R, Szczepanski, T, Valsecchi, M, and Pieters, R
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- 2016
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26. Prognostic value of rare IKZF1 deletion in childhood B-cell precursor acute lymphoblastic leukemia: an international collaborative study
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Boer, J M, van der Veer, A, Rizopoulos, D, Fiocco, M, Sonneveld, E, de Groot-Kruseman, H A, Kuiper, R P, Hoogerbrugge, P, Horstmann, M, Zaliova, M, Palmi, C, Trka, J, Fronkova, E, Emerenciano, M, do Socorro Pombo-de-Oliveira, M, Mlynarski, W, Szczepanski, T, Nebral, K, Attarbaschi, A, Venn, N, Sutton, R, Schwab, C J, Enshaei, A, Vora, A, Stanulla, M, Schrappe, M, Cazzaniga, G, Conter, V, Zimmermann, M, Moorman, A V, Pieters, R, and den Boer, M L
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- 2016
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27. Zum Zusammenhang zwischen Führung, Arbeitsbedingungen und Qualität der Krankenhausarbeit
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Schrappe, M., Badura, Bernhard, editor, Schellschmidt, Henner, editor, and Vetter, Christian, editor
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- 2005
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28. Effects of p38α/β inhibition on acute lymphoblastic leukemia proliferation and survival in vivo
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Alsadeq, A, Strube, S, Krause, S, Carlet, M, Jeremias, I, Vokuhl, C, Loges, S, Aguirre-Ghiso, J A, Trauzold, A, Cario, G, Stanulla, M, Schrappe, M, and Schewe, D M
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- 2015
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29. S108: PEDIATRIC T- ALL RELAPSE: CONSTITUTIONAL CANCER PREDISPOSITION AND HYPERMUTATATOR PHENOTYPES
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Richter-Pechanska, P., primary, Kunz, J., additional, Rausch, T., additional, Erarslan-Uysal, B., additional, Bornhauser, B., additional, Frismantas, V., additional, Assenov, Y., additional, Zimmermann, M., additional, Happich, M., additional, von Knebel-Doeberitz, C., additional, von Neuhoff, N., additional, Koehler, R., additional, Stanulla, M., additional, Schrappe, M., additional, Cario, G., additional, Escherich, G., additional, Kischner-Schwabe, R., additional, Eckert, C., additional, Avigad, S., additional, Pfister, S., additional, Muckenthaler, M., additional, Bourquin, J.-P., additional, Korbel, J., additional, and Kulozik, A., additional
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- 2022
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30. P305: COMPREHENSIVE TRANSCRIPTIONAL AND CYTOGENETIC PROFILING IMPROVES CLASSIFICATION AND DETECTION OF RISK-STRATIFYING MARKERS IN THE B-OTHER PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
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Antić, Ž., primary, Chouvarine, P., additional, Lentes, J., additional, Schröder, C., additional, Alten, J., additional, Möricke, A., additional, Brüggemann, M., additional, Carrillo-de Santa Pau, E., additional, Illig, T., additional, Laguna, T., additional, Schewe, D. M., additional, Stanulla, M., additional, Tang, M., additional, Zimmermann, M., additional, Schrappe, M., additional, Schlegelberger, B., additional, Cario, G., additional, and Bergmann, A. K., additional
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- 2022
- Full Text
- View/download PDF
31. Prognostic significance of minimal residual disease prior to reinduction in intermediate risk patients with ALL
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Dzajic, E, additional, Alten, J, additional, Zimmermann, M, additional, Möricke, A, additional, Schrappe, M, additional, and Cario, G, additional
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- 2022
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32. Prognostic relevance of persisting minimal residual disease in children with ALL and slow early response to chemotherapy
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Nofcz, L, additional, Alten, J, additional, Zimmermann, M, additional, Koehler, R, additional, Möricke, A, additional, Schrappe, M, additional, and Cario, G, additional
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- 2022
- Full Text
- View/download PDF
33. IKZF1plus under investigation: Optical Genome Mapping to detect additional alterations
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Lühmann, JL, additional, Kater, J, additional, Wendeburg, L, additional, Möricke, A, additional, Cario, G, additional, Schrappe, M, additional, Schlegelberger, B, additional, Stanulla, M, additional, and Steinemann, D, additional
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- 2022
- Full Text
- View/download PDF
34. Akute lymphatische Leukämie bei Erwachsenen und Kindern
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Hoelzer, D., Gökbuget, N., Schrappe, M., Hiddemann, Wolfgang, Huber, Heinz, and Bartram, Claus R.
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- 2004
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35. Flash survey on severe acute respiratory syndrome coronavirus-2 infections in paediatric patients on anticancer treatment
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Hrusak, O, Kalina, T, Wolf, J, Balduzzi, A, Provenzi, M, Rizzari, C, Rives, S, del Pozo Carlavilla, M, Alonso, M, Dominguez-Pinilla, N, Bourquin, J, Schmiegelow, K, Attarbaschi, A, Grillner, P, Mellgren, K, van der Werff ten Bosch, J, Pieters, R, Brozou, T, Borkhardt, A, Escherich, G, Lauten, M, Stanulla, M, Smith, O, Yeoh, A, Elitzur, S, Vora, A, Li, C, Ariffin, H, Kolenova, A, Dallapozza, L, Farah, R, Lazic, J, Manabe, A, Styczynski, J, Kovacs, G, Ottoffy, G, Felice, M, Buldini, B, Conter, V, Stary, J, Schrappe, M, Hrusak O., Kalina T., Wolf J., Balduzzi A., Provenzi M., Rizzari C., Rives S., del Pozo Carlavilla M., Alonso M. E. V., Dominguez-Pinilla N., Bourquin J. -P., Schmiegelow K., Attarbaschi A., Grillner P., Mellgren K., van der Werff ten Bosch J., Pieters R., Brozou T., Borkhardt A., Escherich G., Lauten M., Stanulla M., Smith O., Yeoh A. E. J., Elitzur S., Vora A., Li C. -K., Ariffin H., Kolenova A., Dallapozza L., Farah R., Lazic J., Manabe A., Styczynski J., Kovacs G., Ottoffy G., Felice M. S., Buldini B., Conter V., Stary J., Schrappe M., Hrusak, O, Kalina, T, Wolf, J, Balduzzi, A, Provenzi, M, Rizzari, C, Rives, S, del Pozo Carlavilla, M, Alonso, M, Dominguez-Pinilla, N, Bourquin, J, Schmiegelow, K, Attarbaschi, A, Grillner, P, Mellgren, K, van der Werff ten Bosch, J, Pieters, R, Brozou, T, Borkhardt, A, Escherich, G, Lauten, M, Stanulla, M, Smith, O, Yeoh, A, Elitzur, S, Vora, A, Li, C, Ariffin, H, Kolenova, A, Dallapozza, L, Farah, R, Lazic, J, Manabe, A, Styczynski, J, Kovacs, G, Ottoffy, G, Felice, M, Buldini, B, Conter, V, Stary, J, Schrappe, M, Hrusak O., Kalina T., Wolf J., Balduzzi A., Provenzi M., Rizzari C., Rives S., del Pozo Carlavilla M., Alonso M. E. V., Dominguez-Pinilla N., Bourquin J. -P., Schmiegelow K., Attarbaschi A., Grillner P., Mellgren K., van der Werff ten Bosch J., Pieters R., Brozou T., Borkhardt A., Escherich G., Lauten M., Stanulla M., Smith O., Yeoh A. E. J., Elitzur S., Vora A., Li C. -K., Ariffin H., Kolenova A., Dallapozza L., Farah R., Lazic J., Manabe A., Styczynski J., Kovacs G., Ottoffy G., Felice M. S., Buldini B., Conter V., Stary J., and Schrappe M.
- Abstract
Introduction: Since the beginning of COVID-19 pandemic, it is known that the severe course of the disease occurs mostly among the elderly, whereas it is rare among children and young adults. Comorbidities, in particular, diabetes and hypertension, clearly associated with age, besides obesity and smoke, are strongly associated with the need for intensive treatment and a dismal outcome. A weaker immunity of the elderly has been proposed as a possible explanation of this uneven age distribution. Thus, there is concern that children treated for cancer may allso be at risk for an unfavourable course of infection. Along the same line, anecdotal information from Wuhan, China, mentioned a severe course of COVID-19 in a child treated for leukaemia. Aim and methods: We made a flash survey on COVID-19 incidence and severity among children on anticancer treatment. Respondents were asked by email to fill in a short Web-based survey. Results: We received reports from 25 countries, where approximately 10,000 patients at risk are followed up. At the time of the survey, more than 200 of these children were tested, nine of whom were positive for COVID-19. Eight of the nine cases had asymptomatic to mild disease, and one was just diagnosed with COVID-19. We also discuss preventive measures that are in place or should be taken and treatment options in immunocompromised children with COVID-19. Conclusion: Thus, even children receiving anticancer chemotherapy may have a mild or asymptomatic course of COVID-19. While we should not underestimate the risk of developing a more severe course of COVID-19 than that observed here, the intensity of preventive measures should not cause delays or obstructions in oncological treatment.
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- 2020
36. Implementation of RNA sequencing and array CGH in the diagnostic workflow of the AIEOP-BFM ALL 2017 trial on acute lymphoblastic leukemia
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Schieck, M, Lentes, J, Thomay, K, Hofmann, W, Behrens, Y, Hagedorn, M, Ebersold, J, Davenport, C, Fazio, G, Moricke, A, Buchmann, S, Alten, J, Cario, G, Schrappe, M, Bergmann, A, Stanulla, M, Steinemann, D, Schlegelberger, B, Cazzaniga, G, Gohring, G, Schieck M., Lentes J., Thomay K., Hofmann W., Behrens Y. L., Hagedorn M., Ebersold J., Davenport C. F., Fazio G., Moricke A., Buchmann S., Alten J., Cario G., Schrappe M., Bergmann A. K., Stanulla M., Steinemann D., Schlegelberger B., Cazzaniga G., Gohring G., Schieck, M, Lentes, J, Thomay, K, Hofmann, W, Behrens, Y, Hagedorn, M, Ebersold, J, Davenport, C, Fazio, G, Moricke, A, Buchmann, S, Alten, J, Cario, G, Schrappe, M, Bergmann, A, Stanulla, M, Steinemann, D, Schlegelberger, B, Cazzaniga, G, Gohring, G, Schieck M., Lentes J., Thomay K., Hofmann W., Behrens Y. L., Hagedorn M., Ebersold J., Davenport C. F., Fazio G., Moricke A., Buchmann S., Alten J., Cario G., Schrappe M., Bergmann A. K., Stanulla M., Steinemann D., Schlegelberger B., Cazzaniga G., and Gohring G.
- Abstract
Risk-adapted therapy has significantly contributed to improved survival rates in pediatric acute lymphoblastic leukemia (ALL) and reliable detection of chromosomal aberrations is mandatory for risk group stratification. This study evaluated the applicability of panel-based RNA sequencing and array CGH within the diagnostic workflow of the German study group of the international AIEOP-BFM ALL 2017 trial. In a consecutive cohort of 117 children with B cell precursor (BCP) ALL, array analysis identified twelve cases with an IKZF1plus profile of gene deletions and one case of masked hypodiploidy. Genetic markers BCR-ABL1 (n = 1), ETV6-RUNX1 (n = 25), and rearrangements involving KMT2A (n = 3) or TCF3 (n = 3) were assessed by established conventional techniques such as karyotyping, FISH, and RT-PCR. Comparison of these results with RNA sequencing analysis revealed overall consistency in n=115/117 cases, albeit with one undetected AFF1-KMT2A fusion in RNA sequencing and one undetected ETV6-RUNX1 fusion in conventional analyses. The combined application of RNA sequencing, FISH, and CGH+SNP array reliably detected all genetic markers necessary for risk stratification and will be used as the diagnostic standard workflow for BCP-ALL patients enrolled in the AIEOP-BFM ALL 2017 study. Prospectively, consistent collection of genome-wide CGH+SNP array as well as RNA sequencing data will be a valuable source to elucidate new prognostic lesions beyond established markers of pediatric ALL. In this respect, RNA sequencing identified various gene fusions in up to half of the IKZF1plus (n = 6/12) and B-other (n = 19/36) cases but not in cases with hyperdiploid karyotypes (n = 35). Among these fusions, this study reports several previously undescribed in frame PAX5 fusions, including PAX5-MYO1G and PAX5-NCOA6.
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- 2020
37. Randomized post-induction and delayed intensification therapy in high-risk pediatric acute lymphoblastic leukemia: long-term results of the international AIEOP-BFM ALL 2000 trial
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Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., Schrappe M., Attarbaschi, A, Mann, G, Zimmermann, M, Bader, P, Barisone, E, Basso, G, Biondi, A, Cario, G, Cazzaniga, G, Colombini, A, Flotho, C, Kuhlen, M, Lang, P, Lauten, M, Linderkamp, C, Locatelli, F, Lo Nigro, L, Moricke, A, Niggli, F, Panzer-Grumayer, R, Parasole, R, Peters, C, Caterina Putti, M, Rizzari, C, Suttorp, M, Valsecchi, M, Conter, V, Schrappe, M, Attarbaschi A., Mann G., Zimmermann M., Bader P., Barisone E., Basso G., Biondi A., Cario G., Cazzaniga G., Colombini A., Flotho C., Kuhlen M., Lang P., Lauten M., Linderkamp C., Locatelli F., Lo Nigro L., Moricke A., Niggli F., Panzer-Grumayer R., Parasole R., Peters C., Caterina Putti M., Rizzari C., Suttorp M., Valsecchi M. G., Conter V., and Schrappe M.
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- 2020
38. Remission, treatment failure, and relapse in pediatric ALL: an international consensus of the Ponte-di-Legno Consortium
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Buchmann, S., Schrappe, M., Baruchel, A., Biondi, A., Borowitz, M., Campbell, M., Cario, G., Cazzaniga, G., Escherich, G., Harrison, C. J., Heyman, M., Hunger, S. P., Kiss, C., Liu, H. -C., Locatelli, Franco, Loh, M. L., Manabe, A., Mann, G., Pieters, R., Pui, C. -H., Rives, S., Schmiegelow, K., Silverman, L. B., Stary, J., Vora, A., Brown, P., Locatelli F. (ORCID:0000-0002-7976-3654), Buchmann, S., Schrappe, M., Baruchel, A., Biondi, A., Borowitz, M., Campbell, M., Cario, G., Cazzaniga, G., Escherich, G., Harrison, C. J., Heyman, M., Hunger, S. P., Kiss, C., Liu, H. -C., Locatelli, Franco, Loh, M. L., Manabe, A., Mann, G., Pieters, R., Pui, C. -H., Rives, S., Schmiegelow, K., Silverman, L. B., Stary, J., Vora, A., Brown, P., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Comparison of treatment strategies in de novo pediatric acute lymphoblastic leukemia (ALL) requires standardized measures of efficacy. Key parameters that define disease-related events, including complete remission (CR), treatment failure (TF; not achieving CR), and relapse (loss of CR) require an updated consensus incorporating modern diagnostics. We collected the definitions of CR, TF, and relapse from recent and current pediatric clinical trials for the treatment of ALL, including the key components of response evaluation (timing, anatomic sites, detection methods, and thresholds) and found significant heterogeneity, most notably in the definition of TF. Representatives of the major international ALL clinical trial groups convened to establish consensus definitions. CR should be defined at a time point no earlier than at the end of induction and should include the reduction of blasts below a specific threshold in bone marrow and extramedullary sites, incorporating minimal residual disease (MRD) techniques for marrow evaluations. TF should be defined as failure to achieve CR by a prespecified time point in therapy. Relapse can only be defined in patients who have achieved CR and must include a specific threshold of leukemic cells in the bone marrow confirmed by MRD, the detection of central nervous system leukemia, or documentation of extramedullary disease. Definitions of TF and relapse should harmonize with eligibility criteria for clinical trials in relapsed/refractory ALL. These consensus definitions will enhance the ability to compare outcomes across pediatric ALL trials and facilitate development of future international collaborative trials.
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- 2022
39. Minimal residual disease and outcome characteristics in infant KMT2A-germline acute lymphoblastic leukaemia treated on the Interfant-06 protocol
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Stutterheim, J., de Lorenzo, P., van der Sluis, I. M., Alten, J., Ancliffe, P., Attarbaschi, A., Aversa, L., Boer, J. M., Biondi, A., Brethon, B., Diaz, P., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Leung, A. W., Locatelli, Franco, Silverman, L., Stary, J., Szczepanski, T., van der Velden, V. H. J., Vora, A., Zuna, J., Schrappe, M., Valsecchi, M. G., Pieters, R., Locatelli F. (ORCID:0000-0002-7976-3654), Stutterheim, J., de Lorenzo, P., van der Sluis, I. M., Alten, J., Ancliffe, P., Attarbaschi, A., Aversa, L., Boer, J. M., Biondi, A., Brethon, B., Diaz, P., Cazzaniga, G., Escherich, G., Ferster, A., Kotecha, R. S., Lausen, B., Leung, A. W., Locatelli, Franco, Silverman, L., Stary, J., Szczepanski, T., van der Velden, V. H. J., Vora, A., Zuna, J., Schrappe, M., Valsecchi, M. G., Pieters, R., and Locatelli F. (ORCID:0000-0002-7976-3654)
- Abstract
Background: The outcome of infants with KMT2A-germline acute lymphoblastic leukaemia (ALL) is superior to that of infants with KMT2A-rearranged ALL but has been inferior to non-infant ALL patients. Here, we describe the outcome and prognostic factors for 167 infants with KMT2A-germline ALL enrolled in the Interfant-06 study. Methods: Univariate analysis on prognostic factors (age, white blood cell count at diagnosis, prednisolone response and CD10 expression) was performed on KMT2A-germline infants in complete remission at the end of induction (EOI; n = 163). Bone marrow minimal residual disease (MRD) was measured in 73 patients by real-time quantitative polymerase chain reaction at various time points (EOI, n = 68; end of consolidation, n = 56; and before OCTADAD, n = 57). MRD results were classified as negative, intermediate (<5∗10−4), and high (≥5∗10−4). Results: The 6-year event-free and overall survival was 73.9% (standard error [SE] = 3.6) and 87.2% (SE = 2.7). Relapses occurred early, within 36 months from diagnosis in 28 of 31 (90%) infants. Treatment-related mortality was 3.6%. Age <6 months was a favourable prognostic factor with a 6-year disease-free survival (DFS) of 91% (SE = 9.0) compared with 71.7% (SE = 4.2) in infants >6 months of age (P = 0.04). Patients with high EOI MRD ≥5 × 10−4 had a worse outcome (6-year DFS 61.4% [SE = 12.4], n = 16), compared with patients with undetectable EOI MRD (6-year DFS 87.9% [SE = 6.6], n = 28) or intermediate EOI MRD <5 × 10−4 (6-year DFS 76.4% [SE = 11.3], n = 24; P = 0.02). Conclusion: We conclude that young age at diagnosis and low EOI MRD seem favourable prognostic factors in infants with KMT2A-germline ALL and should be considered for risk stratification in future clinical trials.
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- 2022
40. Essential medicines for childhood cancer in Europe: a pan-European, systematic analysis by SIOPE
- Author
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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
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- 2022
41. Bone Marrow Stromal Cell Regeneration Profile in Treated B-Cell Precursor Acute Lymphoblastic Leukemia Patients: Association with MRD Status and Patient Outcome
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Oliveira, E, Costa, E, Ciudad, J, Gaipa, G, Sedek, Ł, Barrena, S, Szczepanski, T, Buracchi, C, Silvestri, D, Siqueira, P, Mello, F, Torres, R, Oliveira, L, Fay-Neves, I, Sonneveld, E, van der Velden, V, Mejstrikova, E, Ribera, J, Conter, V, Schrappe, M, van Dongen, J, Land, M, Orfao, A, Oliveira, E, Costa, E, Ciudad, J, Gaipa, G, Sedek, Ł, Barrena, S, Szczepanski, T, Buracchi, C, Silvestri, D, Siqueira, P, Mello, F, Torres, R, Oliveira, L, Fay-Neves, I, Sonneveld, E, van der Velden, V, Mejstrikova, E, Ribera, J, Conter, V, Schrappe, M, van Dongen, J, Land, M, and Orfao, A
- Abstract
For the last two decades, measurable residual disease (MRD) has become one of the most powerful independent prognostic factors in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the effect of therapy on the bone marrow (BM) microenvironment and its potential relationship with the MRD status and disease free survival (DFS) still remain to be investigated. Here we analyzed the distribution of mesenchymal stem cells (MSC) and endothelial cells (EC) in the BM of treated BCP-ALL patients, and its relationship with the BM MRD status and patient outcome. For this purpose, the BM MRD status and EC/MSC regeneration profile were analyzed by multiparameter flow cytometry (MFC) in 16 control BM (10 children; 6 adults) and 1204 BM samples from 347 children and 100 adult BCP-ALL patients studied at diagnosis (129 children; 100 adults) and follow-up (824 childhood samples; 151 adult samples). Patients were grouped into a discovery cohort (116 pediatric BCP-ALL patients; 338 samples) and two validation cohorts (74 pediatric BCP-ALL, 211 samples; and 74 adult BCP-ALL patients; 134 samples). Stromal cells (i.e., EC and MSC) were detected at relatively low frequencies in all control BM (16/16; 100%) and in most BCP-ALL follow-up samples (874/975; 90%), while they were undetected in BCP-ALL BM at diagnosis. In control BM samples, the overall percentage of EC plus MSC was higher in children than adults (p = 0.011), but with a similar EC/MSC ratio in both groups. According to the MRD status similar frequencies of both types of BM stromal cells were detected in BCP-ALL BM studied at different time points during the follow-up. Univariate analysis (including all relevant prognostic factors together with the percentage of stromal cells) performed in the discovery cohort was used to select covariates for a multivariate Cox regression model for predicting patient DFS. Of note, an increased percentage of EC (>32%) within the BCP-ALL BM stromal cell compartment at day +78 of
- Published
- 2022
42. Minimal residual disease in BCR::ABL1-positive acute lymphoblastic leukemia: different significance in typical ALL and in CML-like disease
- Author
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Zuna, J, Hovorkova, L, Krotka, J, Koehrmann, A, Bardini, M, Winkowska, L, Fronkova, E, Alten, J, Koehler, R, Eckert, C, Brizzolara, L, Trkova, M, Stuchly, J, Zimmermann, M, De Lorenzo, P, Valsecchi, M, Conter, V, Stary, J, Schrappe, M, Biondi, A, Trka, J, Zaliova, M, Cazzaniga, G, Cario, G, Zuna, Jan, Hovorkova, Lenka, Krotka, Justina, Koehrmann, Amelie, Bardini, Michela, Winkowska, Lucie, Fronkova, Eva, Alten, Julia, Koehler, Rolf, Eckert, Cornelia, Brizzolara, Lisa, Trkova, Marie, Stuchly, Jan, Zimmermann, Martin, De Lorenzo, Paola, Valsecchi, Maria Grazia, Conter, Valentino, Stary, Jan, Schrappe, Martin, Biondi, Andrea, Trka, Jan, Zaliova, Marketa, Cazzaniga, Giovanni, Cario, Gunnar, Zuna, J, Hovorkova, L, Krotka, J, Koehrmann, A, Bardini, M, Winkowska, L, Fronkova, E, Alten, J, Koehler, R, Eckert, C, Brizzolara, L, Trkova, M, Stuchly, J, Zimmermann, M, De Lorenzo, P, Valsecchi, M, Conter, V, Stary, J, Schrappe, M, Biondi, A, Trka, J, Zaliova, M, Cazzaniga, G, Cario, G, Zuna, Jan, Hovorkova, Lenka, Krotka, Justina, Koehrmann, Amelie, Bardini, Michela, Winkowska, Lucie, Fronkova, Eva, Alten, Julia, Koehler, Rolf, Eckert, Cornelia, Brizzolara, Lisa, Trkova, Marie, Stuchly, Jan, Zimmermann, Martin, De Lorenzo, Paola, Valsecchi, Maria Grazia, Conter, Valentino, Stary, Jan, Schrappe, Martin, Biondi, Andrea, Trka, Jan, Zaliova, Marketa, Cazzaniga, Giovanni, and Cario, Gunnar
- Abstract
Recently, we defined “CML-like” subtype of BCR::ABL1-positive acute lymphoblastic leukemia (ALL), resembling lymphoid blast crisis of chronic myeloid leukemia (CML). Here we retrospectively analyzed prognostic relevance of minimal residual disease (MRD) and other features in 147 children with BCR::ABL1-positive ALL (diagnosed I/2000–IV/2021, treated according to EsPhALL (n = 133) or other (n = 14) protocols), using DNA-based monitoring of BCR::ABL1 genomic breakpoint and clonal immunoglobulin/T-cell receptor gene rearrangements. Although overall prognosis of CML-like (n = 48) and typical ALL (n = 99) was similar (5-year-EFS 60% and 49%, respectively; 5-year-OS 75% and 73%, respectively), typical ALL presented more relapses while CML-like patients more often died in the first remission. Prognostic role of MRD was significant in the typical ALL (p = 0.0005 in multivariate analysis for EFS). In contrast, in CML-like patients MRD was not significant (p values > 0.2) and inapplicable for therapy adjustment. Moreover, in the typical ALL, risk-prediction could be further improved by considering initial hyperleukocytosis. Early distinguishing typical BCR::ABL1-positive ALL and CML-like patients is essential to enable optimal treatment approach in upcoming protocols. For the typical ALL, tyrosine-kinase inhibitors and concurrent chemotherapy with risk-directed intensity should be recommended; in the CML-like disease, no relevant prognostic feature applicable for therapy tailoring was found so far.
- Published
- 2022
43. A genome-wide association study identifies risk loci for childhood acute lymphoblastic leukemia at 10q26.13 and 12q23.1
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Vijayakrishnan, J, Kumar, R, Henrion, M YR, Moorman, A V, Rachakonda, P S, Hosen, I, da Silva Filho, M I, Holroyd, A, Dobbins, S E, Koehler, R, Thomsen, H, Irving, J A, Allan, J M, Lightfoot, T, Roman, E, Kinsey, S E, Sheridan, E, Thompson, P D, Hoffmann, P, Nöthen, M M, Heilmann-Heimbach, S, Jöckel, K H, Greaves, M, Harrison, C J, Bartram, C R, Schrappe, M, Stanulla, M, Hemminki, K, and Houlston, R S
- Published
- 2017
- Full Text
- View/download PDF
44. Akute lymphoblastische Leukämie im Kindesalter
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Schrappe, M., Riehm, H., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
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- 1999
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45. Maligne Non-Hodgkin-Lymphome im Kindesalter
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Schrappe, M., Reiter, A., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
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- 1999
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46. Frequent Loss of Heterozygosity on Chromosomes 6q, 9p, 11q or 12p in Childhood Acute Lymphoblastic Leukemia
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Seriu, T., Takeuchi, S., Koike, M., Slater, J., Park, S., Miller, C. W., Schrappe, M., Reiter, A., Zimmermann, M., Mori, N., Kubota, T., Golub, T. R., Gilliland, D. G., Miyoshi, I., Koeffler, H. P., Bartram, C. R., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor
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- 1998
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47. Monitoring of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia — Preliminary Data from a Prospective Study
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Seriu, T., Ludwig, W.-D., Schrappe, M., Erz, D., Stark, Y., Bartram, C. R., Hiddemann, W., editor, Büchner, T., editor, Wörmann, B., editor, Ritter, J., editor, Creutzig, U., editor, Keating, M., editor, and Plunkett, W., editor
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- 1998
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48. Risk Adapted Treatment in Childhood Acute Lymphoblastic Leukemia: Data from the Berlin-Frankfurt-Münster Group
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Schrappe, M., Reiter, A., Welte, K., Ludwig, W.-D., Harbott, J., Lampert, F., Henze, G., Riehm, H., Büchner, T., editor, Schellong, G., editor, Ritter, J., editor, Creutzig, U., editor, Hiddemann, W., editor, and Wörmann, B., editor
- Published
- 1997
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49. Maligne Non-Hodgkin-Lymphome im Kindesalter
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Schrappe, M., Reiter, A., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
- Published
- 1997
- Full Text
- View/download PDF
50. Akute lymphoblastische Leukämie im Kindesalter
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Schrappe, M., Riehm, H., Schmoll, Hans-Joachim, editor, Höffken, Klaus, editor, and Possinger, Kurt, editor
- Published
- 1997
- Full Text
- View/download PDF
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