Search

Your search keyword '"Göhring, G"' showing total 300 results
Start Over Author "Göhring, G" Search Limiters Full Text
300 results on '"Göhring, G"'

1. Randomized phase-II trial evaluating induction therapy with idarubicin and etoposide plus sequential or concurrent azacitidine and maintenance therapy with azacitidine

Author

Schlenk, R. F., Weber, D., Herr, W., Wulf, G., Salih, H. R., Derigs, H. G., Kuendgen, A., Ringhoffer, M., Hertenstein, B., Martens, U. M., Grießhammer, M., Bernhard, H., Krauter, J., Girschikofsky, M., Wolf, D., Lange, E., Westermann, J., Koller, E., Kremers, S., Wattad, M., Heuser, M., Thol, F., Göhring, G., Haase, D., Teleanu, V., Gaidzik, V., Benner, A., Döhner, K., Ganser, A., Paschka, P., and Döhner, H.

Published
2019
Full Text
View/download PDF

2. European standard clinical practice - Key issues for the medical care of individuals with familial leukemia

Author

Förster, A, Davenport, C, Duployez, N, Erlacher, M, Ferster, A, Fitzgibbon, J, Göhring, G, Hasle, H, Jongmans, M, Kolenova, A, Kronnie, G, Lammens, T, Mecucci, C, Mlynarski, W, Niemeyer, C, Sole, F, Szczepanski, T, Waanders, E, Biondi, A, Wlodarski, M, Schlegelberger, B, Ripperger, T, Förster, Alisa, Davenport, Claudia, Duployez, Nicolas, Erlacher, Miriam, Ferster, Alina, Fitzgibbon, Jude, Göhring, Gudrun, Hasle, Henrik, Jongmans, Marjolijn C, Kolenova, Alexandra, Kronnie, Geertruijte, Lammens, Tim, Mecucci, Cristina, Mlynarski, Wojciech, Niemeyer, Charlotte M, Sole, Francesc, Szczepanski, Tomasz, Waanders, Esmé, Biondi, Andrea, Wlodarski, Marcin, Schlegelberger, Brigitte, Ripperger, Tim, Förster, A, Davenport, C, Duployez, N, Erlacher, M, Ferster, A, Fitzgibbon, J, Göhring, G, Hasle, H, Jongmans, M, Kolenova, A, Kronnie, G, Lammens, T, Mecucci, C, Mlynarski, W, Niemeyer, C, Sole, F, Szczepanski, T, Waanders, E, Biondi, A, Wlodarski, M, Schlegelberger, B, Ripperger, T, Förster, Alisa, Davenport, Claudia, Duployez, Nicolas, Erlacher, Miriam, Ferster, Alina, Fitzgibbon, Jude, Göhring, Gudrun, Hasle, Henrik, Jongmans, Marjolijn C, Kolenova, Alexandra, Kronnie, Geertruijte, Lammens, Tim, Mecucci, Cristina, Mlynarski, Wojciech, Niemeyer, Charlotte M, Sole, Francesc, Szczepanski, Tomasz, Waanders, Esmé, Biondi, Andrea, Wlodarski, Marcin, Schlegelberger, Brigitte, and Ripperger, Tim

Abstract

Although hematologic malignancies (HM) are no longer considered exclusively sporadic, additional awareness of familial cases has yet to be created. Individuals carrying a (likely) pathogenic germline variant (e.g., in ETV6, GATA2, SAMD9, SAMD9L, or RUNX1) are at an increased risk for developing HM. Given the clinical and psychological impact associated with the diagnosis of a genetic predisposition to HM, it is of utmost importance to provide high-quality, standardized patient care. To address these issues and harmonize care across Europe, the Familial Leukemia Subnetwork within the ERN PaedCan has been assigned to draft an European Standard Clinical Practice (ESCP) document reflecting current best practices for pediatric patients and (healthy) relatives with (suspected) familial leukemia. The group was supported by members of the German network for rare diseases MyPred, of the Host Genome Working Group of SIOPE, and of the COST action LEGEND. The ESCP on familial leukemia is proposed by an interdisciplinary team of experts including hematologists, oncologists, and human geneticists. It is intended to provide general recommendations in areas where disease-specific recommendations do not yet exist. Here, we describe key issues for the medical care of familial leukemia that shall pave the way for a future consensus guideline: (i) identification of individuals with or suggestive of familial leukemia, (ii) genetic analysis and variant interpretation, (iii) genetic counseling and patient education, and (iv) surveillance and (psychological) support. To address the question on how to proceed with individuals suggestive of or at risk of familial leukemia, we developed an algorithm covering four different, partially linked clinical scenarios, and additionally a decision tree to guide clinicians in their considerations regarding familial leukemia in minors with HM. Our recommendations cover, not only patients but also relatives that both should have access to adequate medical

Published
2023

4. Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis

Author

Thol, F, Klesse, S, Köhler, L, Gabdoulline, R, Kloos, A, Liebich, A, Wichmann, M, Chaturvedi, A, Fabisch, J, Gaidzik, V I, Paschka, P, Bullinger, L, Bug, G, Serve, H, Göhring, G, Schlegelberger, B, Lübbert, M, Kirchner, H, Wattad, M, Kraemer, D, Hertenstein, B, Heil, G, Fiedler, W, Krauter, J, Schlenk, R F, Döhner, K, Döhner, H, Ganser, A, and Heuser, M

Published
2017
Full Text
View/download PDF

9. Clinical impact of GATA2 mutations in acute myeloid leukemia patients harboring CEBPA mutations: a study of the AML study group

Author

Theis, F, Corbacioglu, A, Gaidzik, V I, Paschka, P, Weber, D, Bullinger, L, Heuser, M, Ganser, A, Thol, F, Schlegelberger, B, Göhring, G, Köhne, C-H, Germing, U, Brossart, P, Horst, H-A, Haase, D, Götze, K, Ringhoffer, M, Fiedler, W, Nachbaur, D, Kindler, T, Held, G, Lübbert, M, Wattad, M, Salih, H R, Krauter, J, Döhner, H, Schlenk, R F, and Döhner, K

Published
2016
Full Text
View/download PDF

10. P816: TRANSIENT MONOSOMY 7 IN SAMD9/9L SYNDROMES: IS IT SAFE TO WATCH AND WAIT?

Author

Erlacher, M., primary, Andresen, F., additional, Yoshimi, A., additional, Sukova, M., additional, Stary, J., additional, de Moerloose, B., additional, Dworzak, M., additional, Polychronopoulou, S., additional, Göhring, G., additional, Kratz, C., additional, van der Werff ten Bosch, J., additional, Seidel, M., additional, Strahm, B., additional, Wlodarski, M., additional, and Niemeyer, C., additional

Published
2022
Full Text
View/download PDF

11. Frequency and prognostic impact of casein kinase 1A1 mutations in MDS patients with deletion of chromosome 5q

Author

Heuser, M, Meggendorfer, M, Cruz, M M A, Fabisch, J, Klesse, S, Köhler, L, Göhring, G, Ganster, C, Shirneshan, K, Gutermuth, A, Cerny-Reiterer, S, Krönke, J, Panagiota, V, Haferlach, C, Koenecke, C, Platzbecker, U, Thiede, C, Schroeder, T, Kobbe, G, Ehrlich, S, Stamer, K, Döhner, K, Valent, P, Schlegelberger, B, Kroeger, N, Ganser, A, Haase, D, Haferlach, T, and Thol, F

Published
2015
Full Text
View/download PDF

12. Prognostic effect of calreticulin mutations in patients with myelofibrosis after allogeneic hematopoietic stem cell transplantation

Author

Panagiota, V, Thol, F, Markus, B, Fehse, B, Alchalby, H, Badbaran, A, Lehmann, U, Koenecke, C, Shahswar, R, Chaturvedi, A, Stadler, M, Eder, M, Göhring, G, Koenigsmann, M, Kloos, A, Trummer, A, Schroeder, T, Kobbe, G, Thiede, C, Platzbecker, U, Schlegelberger, B, Kreipe, H-H, Ganser, A, Kröger, N, and Heuser, M

Published
2014
Full Text
View/download PDF

13. The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS

Author

Aalbers, A M, van der Velden, V H J, Yoshimi, A, Fischer, A, Noellke, P, Zwaan, C M, Baumann, I, Beverloo, H B, Dworzak, M, Hasle, H, Locatelli, F, De Moerloose, B, Göhring, G, Schmugge, M, Stary, J, Zecca, M, Langerak, A W, van Dongen, J J M, Pieters, R, Niemeyer, C M, and van den Heuvel-Eibrink, M M

Published
2014
Full Text
View/download PDF

15. Clinical evolution, genetic landscape and trajectories of clonal hematopoiesis in SAMD9/SAMD9L syndromes

Author

Sahoo SS, Pastor VB, Goodings C, Voss RK, Kozyra EJ, Szvetnik A, Noellke P, Dworzak M, Starý J, Locatelli F, Masetti R, Schmugge M, De Moerloose B, Català-Temprano A, Kállay K, Turkiewicz D, Hasle H, Buechner J, Jahnukainen K, Ussowicz M, Polychronopoulou S, Smith OP, Fabri O, Barzilai S, de Haas V, Baumann I, Schwarz-Furlan S, European Working Group of MDS in Children (EWOG-MDS), Niewisch MR, Sauer MG, Burkhardt B, Lang P, Bader P, Beier R, Müller I, Albert MH, Meisel R, Schulz A, Cario G, Panda PK, Wehrle J, Hirabayashi S, Derecka M, Durruthy-Durruthy R, Göhring G, Yoshimi-Noellke A, Ku M, Lebrecht D, Erlacher M, Flotho C, Strahm B, Niemeyer CM, and Wlodarski MW

Subjects
congenital, hereditary, and neonatal diseases and abnormalities
Abstract

Germline SAMD9 and SAMD9L mutations (SAMD9/9L(mut)) predispose to myelodysplastic syndromes (MDS) with propensity for somatic rescue. In this study, we investigated a clinically annotated pediatric MDS cohort (n = 669) to define the prevalence, genetic landscape, phenotype, therapy outcome and clonal architecture of SAMD9/9L syndromes. In consecutively diagnosed MDS, germline SAMD9/9L(mut) accounted for 8% and were mutually exclusive with GATA2 mutations present in 7% of the cohort. Among SAMD9/9L(mut) cases, refractory cytopenia was the most prevalent MDS subtype (90%); acquired monosomy 7 was present in 38%; constitutional abnormalities were noted in 57%; and immune dysfunction was present in 28%. The clinical outcome was independent of germline mutations. In total, 67 patients had 58 distinct germline SAMD9/9L(mut) clustering to protein middle regions. Despite inconclusive in silico prediction, 94% of SAMD9/9L(mut) suppressed HEK293 cell growth, and mutations expressed in CD34(+) cells induced overt cell death. Furthermore, we found that 61% of SAMD9/9L(mut) patients underwent somatic genetic rescue (SGR) resulting in clonal hematopoiesis, of which 95% was maladaptive (monosomy 7 ± cancer mutations), and 51% had adaptive nature (revertant UPD7q, somatic SAMD9/9L(mut)). Finally, bone marrow single-cell DNA sequencing revealed multiple competing SGR events in individual patients. Our findings demonstrate that SGR is common in SAMD9/9L(mut) MDS and exemplify the exceptional plasticity of hematopoiesis in children.

Published
2021

25. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N, Emerenciano, M, Pombo-De-Oliveira, M, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, Van Der Velden, V, Delabesse, E, Park, T, Oh, S, Silva, M, Lund-Aho, T, Juvonen, V, Moore, A, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B, Kubetzko, S, Madsen, H, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J, Clappier, E, Alonso, C, Zwaan, C, Van Den Heuvel-Eibrink, M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O, Panzer-Grümayer, R, Sedék, L, Szczepa, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Meyer, C., Burmeister, T., Gröger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-De-Oliveira, M. S., Barbieri Blunck, C., Almeida Lopes, B., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Corral Abascal, L., Van Der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., Zur Stadt, U., Lentes, J., Göhring, G., Kustanovich, A., Aleinikova, O., Schäfer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., Van Den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Möricke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Grümayer, R., Sedék, L., Szczepa, T., Caye, A., Suarez, L., Cavé, H., Marschalek, R., Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N, Emerenciano, M, Pombo-De-Oliveira, M, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, Van Der Velden, V, Delabesse, E, Park, T, Oh, S, Silva, M, Lund-Aho, T, Juvonen, V, Moore, A, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B, Kubetzko, S, Madsen, H, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J, Clappier, E, Alonso, C, Zwaan, C, Van Den Heuvel-Eibrink, M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O, Panzer-Grümayer, R, Sedék, L, Szczepa, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Meyer, C., Burmeister, T., Gröger, D., Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N. C., Emerenciano, M., Pombo-De-Oliveira, M. S., Barbieri Blunck, C., Almeida Lopes, B., Zuna, J., Trka, J., Ballerini, P., Lapillonne, H., De Braekeleer, M., Cazzaniga, G., Corral Abascal, L., Van Der Velden, V. H. J., Delabesse, E., Park, T. S., Oh, S. H., Silva, M. L. M., Lund-Aho, T., Juvonen, V., Moore, A. S., Heidenreich, O., Vormoor, J., Zerkalenkova, E., Olshanskaya, Y., Bueno, C., Menendez, P., Teigler-Schlegel, A., Zur Stadt, U., Lentes, J., Göhring, G., Kustanovich, A., Aleinikova, O., Schäfer, B. W., Kubetzko, S., Madsen, H. O., Gruhn, B., Duarte, X., Gameiro, P., Lippert, E., Bidet, A., Cayuela, J. M., Clappier, E., Alonso, C. N., Zwaan, C. M., Van Den Heuvel-Eibrink, M. M., Izraeli, S., Trakhtenbrot, L., Archer, P., Hancock, J., Möricke, A., Alten, J., Schrappe, M., Stanulla, M., Strehl, S., Attarbaschi, A., Dworzak, M., Haas, O. A., Panzer-Grümayer, R., Sedék, L., Szczepa, T., Caye, A., Suarez, L., Cavé, H., and Marschalek, R.

Abstract

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients

Published
2018

27. Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency

Author

Kozyra, E., Pastor, V., Lefkopoulos, S., Sahoo, S., Busch, H., Voss, R., Erlacher, M., Lebrecht, D., Szvetnik, E., Hirabayashi, S., Pasaulienė, R., Pedace, L., Tartaglia, M., Klemann, C., Metzger, P., Boerries, M., Catala, A., Hasle, H., de Haas, V., Kállay, K., Masetti, R., Moerloose, B., Dworzak, M., Schmugge, M., Smith, O., Starý, J., Mejstrikova, E., Ussowicz, M., Morris, E., Singh, P., Collin, M., Dereka, M., Göhring, G., Flotho, C., Strahm, B., Locatelli, F., Niemeyer, C., Trompouki, E., Wlodarski, M., and EWOG-MDS, W.

Abstract

Deficiency of the transcription factor GATA2 is a highly penetrant genetic disorder predisposing to myelodysplastic syndromes (MDS) and immunodeficiency. It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymous GATA2 variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations in GATA2. In total, we identified nine individuals with five heterozygous synonymous mutations: c.351C>G, p.T117T (N = 4); c.649C>T, p.L217L; c.981G>A, p.G327G; c.1023C>T, p.A341A; and c.1416G>A, p.P472P (N = 2). They accounted for 8.2% (9/110) of cases with GATA2 deficiency in our cohort and resulted in selective loss of mutant RNA. While for the hotspot mutation (c.351C>G) a splicing error leading to RNA and protein reduction was identified, severe, likely late stage RNA loss without splicing disruption was found for other mutations. Finally, the synonymous mutations did not alter protein function or stability. In summary, synonymous GATA2 substitutions are a new common cause of GATA2 deficiency. These findings have broad implications for genetic counseling and pathogenic variant discovery in Mendelian disorders.

Published
2020

28. 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, Biondi, A, 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

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 ≥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 (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).

Published
2020

29. Generation of an induced pluripotent stem cell line (MHHi018-A) from a patient with Cystic Fibrosis carrying p.Asn1303Lys (N1303K) mutation

Author

Merkert, S. (Sylvia), Schubert, M. (Madline), Haase, A. (Alexandra), Janssens, H.M. (Hettie), Scholte, B.J. (Bob), Lachmann, N. (Nico), Göhring, G. (Gudrun), Martin, U. (Ulrich), Merkert, S. (Sylvia), Schubert, M. (Madline), Haase, A. (Alexandra), Janssens, H.M. (Hettie), Scholte, B.J. (Bob), Lachmann, N. (Nico), Göhring, G. (Gudrun), and Martin, U. (Ulrich)

Abstract

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene which encodes for a chloride ion channel regulating the balance of salt and water across secretory epithelia. Here we generated an iPSC line from a CF patient homozygous for the p.Asn1303Lys mutation, a Class II folding defect mutation. This iPSC line provides a useful resource for disease modeling and to investigate the pharmacological response to CFTR modulators in iPSC derived epithelia.

Published
2020
Full Text
View/download PDF

33. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

Author

Hanfstein, B, Müller, M C, Hehlmann, R, Erben, P, Lauseker, M, Fabarius, A, Schnittger, S, Haferlach, C, Göhring, G, Proetel, U, Kolb, H-J, Krause, S W, Hofmann, W-K, Schubert, J, Einsele, H, Dengler, J, Hänel, M, Falge, C, Kanz, L, Neubauer, A, Kneba, M, Stegelmann, F, Pfreundschuh, M, Waller, C F, Branford, S, Hughes, T P, Spiekermann, K, Baerlocher, G M, Pfirrmann, M, Hasford, J, Sauele, S, and Hochhaus, A

Published
2012
Full Text
View/download PDF

38. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C., Burmeister, T., Gröger, D. (D.), Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N., Emerenciano, M. (M.), Pombo-De-Oliveira, M.S. (M. S.), Barbieri Blunck, C. (C.), Almeida Lopes, B. (B.), Zuna, J., Trka, J. (Jan), Ballerini, P. (P.), Lapillonne, H. (H.), Braekeleer, E. de, Cazzaniga, G. (Gianni), Corral Abascal, L. (L.), Velden, V.H.J. (Vincent) van der, Delabesse, E., Park, T.S. (T. S.), Oh, S.H. (S.), Silva, M.L.M. (M. L M), Lund-Aho, T. (T.), Juvonen, V. (V.), Moore, A.S. (A.), Heidenreich, O., Vormoor, J. (J.), Zerkalenkova, E. (E.), Olshanskaya, Y. (Y.), Bueno, C. (C.), Menéndez, P. (Pablo), Teigler-Schlegel, A., zur Stadt, U., Lentes, J. (J.), Göhring, G. (Gudrun), Kustanovich, A. (A.), Aleinikova, O. (O.), Schäfer, B.W. (B. W.), Kubetzko, S. (S.), Madsen, H.O., Gruhn, B. (B.), Duarte, X. (X.), Gameiro, P., Lippert, E. (Eric), Bidet, A. (A.), Cayuela, J.-M. (Jean-Michel), Clappier, E., Alonso, C.N. (Cristina), Zwaan, C.M. (Michel), Heuvel-Eibrink, M.M. (Marry) van den, Izraeli, S. (Shai), Trakhtenbrot, L., Archer, P. (P.), Hancock, J., Möricke, A., Alten, J. (J.), Schrappe, M. (Martin), Stanulla, M. (Martin), Strehl, S., Attarbaschi, A. (Andishe), Dworzak, M.N. (Michael), Haas, O.A. (O. A.), Panzer-Grümayer, R. (Renate), Sedek, L. (Lukasz), Szczepa, T. (T.), Caye, A. (Aurélie), Suarez, L. (L.), Cavé, H. (Helene), Marschalek, R. (Rolf), Meyer, C., Burmeister, T., Gröger, D. (D.), Tsaur, G., Fechina, L., Renneville, A., Sutton, R., Venn, N., Emerenciano, M. (M.), Pombo-De-Oliveira, M.S. (M. S.), Barbieri Blunck, C. (C.), Almeida Lopes, B. (B.), Zuna, J., Trka, J. (Jan), Ballerini, P. (P.), Lapillonne, H. (H.), Braekeleer, E. de, Cazzaniga, G. (Gianni), Corral Abascal, L. (L.), Velden, V.H.J. (Vincent) van der, Delabesse, E., Park, T.S. (T. S.), Oh, S.H. (S.), Silva, M.L.M. (M. L M), Lund-Aho, T. (T.), Juvonen, V. (V.), Moore, A.S. (A.), Heidenreich, O., Vormoor, J. (J.), Zerkalenkova, E. (E.), Olshanskaya, Y. (Y.), Bueno, C. (C.), Menéndez, P. (Pablo), Teigler-Schlegel, A., zur Stadt, U., Lentes, J. (J.), Göhring, G. (Gudrun), Kustanovich, A. (A.), Aleinikova, O. (O.), Schäfer, B.W. (B. W.), Kubetzko, S. (S.), Madsen, H.O., Gruhn, B. (B.), Duarte, X. (X.), Gameiro, P., Lippert, E. (Eric), Bidet, A. (A.), Cayuela, J.-M. (Jean-Michel), Clappier, E., Alonso, C.N. (Cristina), Zwaan, C.M. (Michel), Heuvel-Eibrink, M.M. (Marry) van den, Izraeli, S. (Shai), Trakhtenbrot, L., Archer, P. (P.), Hancock, J., Möricke, A., Alten, J. (J.), Schrappe, M. (Martin), Stanulla, M. (Martin), Strehl, S., Attarbaschi, A. (Andishe), Dworzak, M.N. (Michael), Haas, O.A. (O. A.), Panzer-Grümayer, R. (Renate), Sedek, L. (Lukasz), Szczepa, T. (T.), Caye, A. (Aurélie), Suarez, L. (L.), Cavé, H. (Helene), and Marschalek, R. (Rolf)

Abstract

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.

Published
2018
Full Text
View/download PDF

39. Front-line imatinib treatment in children and adolescents with chronic myeloid leukemia: Results from a phase III trial

Author

Suttorp, M, Schulze, P, Glauche, I, Göhring, G, Von Neuhoff, N, Metzler, M, Sedlacek, P, De Bont, E, Balduzzi, A, Lausen, B, Aleinikova, O, Sufliarska, S, Henze, G, Strauss, G, Eggert, A, Kremens, B, Groll, A, Berthold, F, Klein, C, Groß-Wieltsch, U, Sykora, K, Borkhardt, A, Kulozik, A, Schrappe, M, Nowasz, C, Krumbholz, M, Tauer, J, Claviez, A, Harbott, J, Kreipe, H, Schlegelberger, B, Thiede, C, Suttorp, Meinolf, Schulze, Philipp, Glauche, Ingmar, Göhring, Gudrun, Von Neuhoff, Nils, Metzler, Markus, Sedlacek, Petr, De Bont, Eveline S. J. M., Balduzzi, Adriana, Lausen, Birgitte, Aleinikova, Olga, Sufliarska, Sabina, Henze, Günter, Strauss, Gabriele, Eggert, Angelika, Kremens, Bernhard, Groll, Andreas H., Berthold, Frank, Klein, Christoph, Groß-Wieltsch, Ute, Sykora, Karl Walter, Borkhardt, Arndt, Kulozik, Andreas E., Schrappe, Martin, Nowasz, Christina, Krumbholz, Manuela, Tauer, Josephine T., Claviez, Alexander, Harbott, Jochen, Kreipe, Hans H., Schlegelberger, Brigitte, Thiede, Christian, Suttorp, M, Schulze, P, Glauche, I, Göhring, G, Von Neuhoff, N, Metzler, M, Sedlacek, P, De Bont, E, Balduzzi, A, Lausen, B, Aleinikova, O, Sufliarska, S, Henze, G, Strauss, G, Eggert, A, Kremens, B, Groll, A, Berthold, F, Klein, C, Groß-Wieltsch, U, Sykora, K, Borkhardt, A, Kulozik, A, Schrappe, M, Nowasz, C, Krumbholz, M, Tauer, J, Claviez, A, Harbott, J, Kreipe, H, Schlegelberger, B, Thiede, C, Suttorp, Meinolf, Schulze, Philipp, Glauche, Ingmar, Göhring, Gudrun, Von Neuhoff, Nils, Metzler, Markus, Sedlacek, Petr, De Bont, Eveline S. J. M., Balduzzi, Adriana, Lausen, Birgitte, Aleinikova, Olga, Sufliarska, Sabina, Henze, Günter, Strauss, Gabriele, Eggert, Angelika, Kremens, Bernhard, Groll, Andreas H., Berthold, Frank, Klein, Christoph, Groß-Wieltsch, Ute, Sykora, Karl Walter, Borkhardt, Arndt, Kulozik, Andreas E., Schrappe, Martin, Nowasz, Christina, Krumbholz, Manuela, Tauer, Josephine T., Claviez, Alexander, Harbott, Jochen, Kreipe, Hans H., Schlegelberger, Brigitte, and Thiede, Christian

Abstract

A total of 156 patients (age range 1.3-18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib up-front (300, 400, 500 mg/m 2 , respectively) within a prospective phase III trial. Therapy response, progression-free survival, causes of treatment failure, and side effects were analyzed in 148 children and adolescents with complete data. Event-free survival rate by 18 months for patients in CML-CP (median follow-up time 25 months, range: 1-120) was 97% (95% CI, 94.2-99.9%). According to the 2006 ELN-criteria complete hematologic response by month 3, complete cytogenetic response (CCyR) by month 12, and major molecular response (MMR) by month 18 were achieved in 98, 63, and 59% of the patients, respectively. By month 36, 86% of the patients achieved CCyR and 74% achieved MMR. Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response or intolerance (N = 9). In all, 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N = 3) or SCT-related complications (N = 2). This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective.

Published
2018

40. Reduced-Intensity delayed intensification in standard-Risk pediatric acute lymphoblastic leukemia defined by undetectable minimal residual disease: Results of an international randomized trial (AIEOP-BFM ALL 2000)

Author

Schrappe, M, Bleckmann, K, Zimmermann, M, Biondi, A, Möricke, A, Locatelli, F, Cario, G, Rizzari, C, Attarbaschi, A, Valsecchi, M, Bartram, C, Barisone, E, Niggli, F, Niemeyer, C, Testi, A, Mann, G, Ziino, O, Schäfer, B, Panzer-Grümayer, R, Beier, R, Parasole, R, Göhring, G, Ludwig, W, Casale, F, Schlegel, P, Basso, G, Conter, V, Valsecchi, MG, Bartram, CR, Testi, AM, Ludwig, WD, Schlegel, PG, Schrappe, M, Bleckmann, K, Zimmermann, M, Biondi, A, Möricke, A, Locatelli, F, Cario, G, Rizzari, C, Attarbaschi, A, Valsecchi, M, Bartram, C, Barisone, E, Niggli, F, Niemeyer, C, Testi, A, Mann, G, Ziino, O, Schäfer, B, Panzer-Grümayer, R, Beier, R, Parasole, R, Göhring, G, Ludwig, W, Casale, F, Schlegel, P, Basso, G, Conter, V, Valsecchi, MG, Bartram, CR, Testi, AM, Ludwig, WD, and Schlegel, PG

Abstract

Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (6 SE) was 89.2 6 1.3% and 92.3 6 1.2% (P = .04); cumulative incidence of relapse, 8.7 6 1.2% and 6.4 6 1.1% (P = .09); and overall survival, 96.1 6 0.8% and 98.0 6 0.6% (P = .06). Patients with ETV6-RUNX1–positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 6 0.5% and 0.6 6 0.4% for P-III and P-II, respectively (P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity o

Published
2018

41. The MLL recombinome of acute leukemias in 2017

Author

Hubrecht Institute with UMC, Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N C, Emerenciano, M, Pombo-de-Oliveira, M S, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, van der Velden, V H J, Delabesse, E, Park, T S, Oh, S H, Silva, M L M, Lund-Aho, T, Juvonen, V, Moore, A S, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B W, Kubetzko, S, Madsen, H O, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J M, Clappier, E, Alonso, C N, Zwaan, C M, van den Heuvel-Eibrink, M M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O A, Panzer-Grümayer, R, Sedék, L, Szczepański, T, Caye, A, Suarez, L, Cavé, H, Marschalek, R, Hubrecht Institute with UMC, Meyer, C, Burmeister, T, Gröger, D, Tsaur, G, Fechina, L, Renneville, A, Sutton, R, Venn, N C, Emerenciano, M, Pombo-de-Oliveira, M S, Barbieri Blunck, C, Almeida Lopes, B, Zuna, J, Trka, J, Ballerini, P, Lapillonne, H, De Braekeleer, M, Cazzaniga, G, Corral Abascal, L, van der Velden, V H J, Delabesse, E, Park, T S, Oh, S H, Silva, M L M, Lund-Aho, T, Juvonen, V, Moore, A S, Heidenreich, O, Vormoor, J, Zerkalenkova, E, Olshanskaya, Y, Bueno, C, Menendez, P, Teigler-Schlegel, A, Zur Stadt, U, Lentes, J, Göhring, G, Kustanovich, A, Aleinikova, O, Schäfer, B W, Kubetzko, S, Madsen, H O, Gruhn, B, Duarte, X, Gameiro, P, Lippert, E, Bidet, A, Cayuela, J M, Clappier, E, Alonso, C N, Zwaan, C M, van den Heuvel-Eibrink, M M, Izraeli, S, Trakhtenbrot, L, Archer, P, Hancock, J, Möricke, A, Alten, J, Schrappe, M, Stanulla, M, Strehl, S, Attarbaschi, A, Dworzak, M, Haas, O A, Panzer-Grümayer, R, Sedék, L, Szczepański, T, Caye, A, Suarez, L, Cavé, H, and Marschalek, R

Published
2018

42. Validation of the revised IPSS at transplant in patients with myelodysplastic syndrome/transformed acute myelogenous leukemia receiving allogeneic stem cell transplantation

Author

Scheid, C. (Christof), de Wreede, L.C. (Liesbeth C.), Biezen, A. (Anja) van, Koenecke, C. (Christian), Göhring, G. (Gudrun), Volin, L. (Liisa), Maertens, J. (Johan), Finke, J. (Jürgen), Passweg, J. (Jakob Robert), Beelen, D.W. (Dietrich), Cornelissen, J.J. (Jan), Itälä Remes, M. (Maija), Chevallier, P. (Patrice), Russell, N. (Nigel), Petersen, E.J. (Eefke), Milpied, N., Richard Espiga, C. (Carlos), Peniket, A. (A.), Sierra, J. (Jorge), Mufti, G.J. (Ghulam), Crawley, C. (C.), Veelken, J. (Joan), Ljungman, P., Cahn, J.Y. (J. Y.), Alessandrino, E.P., Witte, T. de, Robin, M. (Marie), Kröger, N. (Nicolaus), Scheid, C. (Christof), de Wreede, L.C. (Liesbeth C.), Biezen, A. (Anja) van, Koenecke, C. (Christian), Göhring, G. (Gudrun), Volin, L. (Liisa), Maertens, J. (Johan), Finke, J. (Jürgen), Passweg, J. (Jakob Robert), Beelen, D.W. (Dietrich), Cornelissen, J.J. (Jan), Itälä Remes, M. (Maija), Chevallier, P. (Patrice), Russell, N. (Nigel), Petersen, E.J. (Eefke), Milpied, N., Richard Espiga, C. (Carlos), Peniket, A. (A.), Sierra, J. (Jorge), Mufti, G.J. (Ghulam), Crawley, C. (C.), Veelken, J. (Joan), Ljungman, P., Cahn, J.Y. (J. Y.), Alessandrino, E.P., Witte, T. de, Robin, M. (Marie), and Kröger, N. (Nicolaus)

Abstract

The International Prognostic Scoring System has been revised (IPSS-R) to predict prognosis of patients with myelodysplastic syndromes at diagnosis. To validate the use of the IPSS-R assessed

Published
2017
Full Text
View/download PDF

43. The MLL recombinome of acute leukemias in 2017

Author

Meyer, C, primary, Burmeister, T, additional, Gröger, D, additional, Tsaur, G, additional, Fechina, L, additional, Renneville, A, additional, Sutton, R, additional, Venn, N C, additional, Emerenciano, M, additional, Pombo-de-Oliveira, M S, additional, Barbieri Blunck, C, additional, Almeida Lopes, B, additional, Zuna, J, additional, Trka, J, additional, Ballerini, P, additional, Lapillonne, H, additional, De Braekeleer, M, additional, Cazzaniga, G, additional, Corral Abascal, L, additional, van der Velden, V H J, additional, Delabesse, E, additional, Park, T S, additional, Oh, S H, additional, Silva, M L M, additional, Lund-Aho, T, additional, Juvonen, V, additional, Moore, A S, additional, Heidenreich, O, additional, Vormoor, J, additional, Zerkalenkova, E, additional, Olshanskaya, Y, additional, Bueno, C, additional, Menendez, P, additional, Teigler-Schlegel, A, additional, zur Stadt, U, additional, Lentes, J, additional, Göhring, G, additional, Kustanovich, A, additional, Aleinikova, O, additional, Schäfer, B W, additional, Kubetzko, S, additional, Madsen, H O, additional, Gruhn, B, additional, Duarte, X, additional, Gameiro, P, additional, Lippert, E, additional, Bidet, A, additional, Cayuela, J M, additional, Clappier, E, additional, Alonso, C N, additional, Zwaan, C M, additional, van den Heuvel-Eibrink, M M, additional, Izraeli, S, additional, Trakhtenbrot, L, additional, Archer, P, additional, Hancock, J, additional, Möricke, A, additional, Alten, J, additional, Schrappe, M, additional, Stanulla, M, additional, Strehl, S, additional, Attarbaschi, A, additional, Dworzak, M, additional, Haas, O A, additional, Panzer-Grümayer, R, additional, Sedék, L, additional, Szczepański, T, additional, Caye, A, additional, Suarez, L, additional, Cavé, H, additional, and Marschalek, R, additional

Published
2017
Full Text
View/download PDF

44. Acute myeloid leukemia derived from lympho-myeloid clonal hematopoiesis

Author

Thol, F, primary, Klesse, S, additional, Köhler, L, additional, Gabdoulline, R, additional, Kloos, A, additional, Liebich, A, additional, Wichmann, M, additional, Chaturvedi, A, additional, Fabisch, J, additional, Gaidzik, V I, additional, Paschka, P, additional, Bullinger, L, additional, Bug, G, additional, Serve, H, additional, Göhring, G, additional, Schlegelberger, B, additional, Lübbert, M, additional, Kirchner, H, additional, Wattad, M, additional, Kraemer, D, additional, Hertenstein, B, additional, Heil, G, additional, Fiedler, W, additional, Krauter, J, additional, Schlenk, R F, additional, Döhner, K, additional, Döhner, H, additional, Ganser, A, additional, and Heuser, M, additional

Published
2016
Full Text
View/download PDF

45. Mutational landscape in children with myelodysplastic syndromes is distinct from adults: specific somatic drivers and novel germline variants

Author

Pastor, V, primary, Hirabayashi, S, additional, Karow, A, additional, Wehrle, J, additional, Kozyra, E J, additional, Nienhold, R, additional, Ruzaike, G, additional, Lebrecht, D, additional, Yoshimi, A, additional, Niewisch, M, additional, Ripperger, T, additional, Göhring, G, additional, Baumann, I, additional, Schwarz, S, additional, Strahm, B, additional, Flotho, C, additional, Skoda, R C, additional, Niemeyer, C M, additional, and Wlodarski, M W, additional

Published
2016
Full Text
View/download PDF

46. Impact of the revised international prognostic scoring system cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: A retrospective multicenter study of the European society of blood and marrow transplantation

Author

Koenecke, C. (Christian), Göhring, G. (Gudrun), de Wreede, L.C. (Liesbeth C.), Biezen, A. (Anja) van, Scheid, C. (Christof), Volin, L. (Liisa), Maertens, J. (Johan), Finke, J. (Jürgen), Schaap, N. (Nicolaas), Robin, M. (Marie), Passweg, J. (Jakob Robert), Cornelissen, J.J. (Jan), Beelen, D.W. (Dietrich), Heuser, M. (Michael), Witte, T. de, Kröger, N. (Nicolaus), Koenecke, C. (Christian), Göhring, G. (Gudrun), de Wreede, L.C. (Liesbeth C.), Biezen, A. (Anja) van, Scheid, C. (Christof), Volin, L. (Liisa), Maertens, J. (Johan), Finke, J. (Jürgen), Schaap, N. (Nicolaas), Robin, M. (Marie), Passweg, J. (Jakob Robert), Cornelissen, J.J. (Jan), Beelen, D.W. (Dietrich), Heuser, M. (Michael), Witte, T. de, and Kröger, N. (Nicolaus)

Abstract

The aim of this study was to determine the impact of the revised 5-group International Prognostic Scoring System cytogenetic classification on outcome after allogeneic stem cell transplantation in patients with myelodysplastic syndromes or secondary acute myeloid leukemia who were reported to the European Society for Blood and Marrow Transplantation database. A total of 903 patients had sufficient cytogenetic information available at stem cell transplantation to be classified according to the 5-group classification. Poor and very poor risk according to this classification was an independent predictor of shorter relapse-free survival (hazard ratio 1.40 and 2.14), overall survival (hazard ratio 1.38 and 2.14), and significantly higher cumulative incidence of relapse (hazard ratio 1.64

Published
2015
Full Text
View/download PDF

48. Outcomes in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with isolated deletion 5q treated with lenalidomide: A subset analysis from the MDS-004 study

Author

Giagounidis, A. (Aristoteles), Mufti, G.J. (Ghulam), Mittelman, M. (Moshe), Sanz, G. (Guillermo), Platzbecker, U. (Uwe), Muus, P. (P.), Selleslag, D., Beyne-Rauzy, O. (Odile), Boekhorst, P.A.W. (Peter) te, Cañizo, C. (Consuelo) del, Guerci-Bresler, A. (Agnes), Nilsson, L. (Lars), Lübbert, M. (Michael), Quesnel, B. (Bruno), Ganser, A. (Arnold), Bowen, D. (David), Schlegelberger, B. (Brigitte), Göhring, G. (Gudrun), Fu, T. (Tommy), Benettaib, B. (Bouchra), Hellström-Lindberg, E. (Eva), Fenaux, P. (Pierre), Giagounidis, A. (Aristoteles), Mufti, G.J. (Ghulam), Mittelman, M. (Moshe), Sanz, G. (Guillermo), Platzbecker, U. (Uwe), Muus, P. (P.), Selleslag, D., Beyne-Rauzy, O. (Odile), Boekhorst, P.A.W. (Peter) te, Cañizo, C. (Consuelo) del, Guerci-Bresler, A. (Agnes), Nilsson, L. (Lars), Lübbert, M. (Michael), Quesnel, B. (Bruno), Ganser, A. (Arnold), Bowen, D. (David), Schlegelberger, B. (Brigitte), Göhring, G. (Gudrun), Fu, T. (Tommy), Benettaib, B. (Bouchra), Hellström-Lindberg, E. (Eva), and Fenaux, P. (Pierre)

Abstract

Objective: A subset analysis of the randomised, phase 3, MDS-004 study to evaluate outcomes in patients with International Prognostic Scoring System (IPSS)-defined Low-/Intermediate (Int)-1-risk myelodysplastic syndromes (MDS) with isolated del(5q). Methods: Patients received lenalidomide 10 mg/d (days 1-21; n = 47) or 5 mg/d (days 1-28; n = 43) on 28-d cycles or placebo (n = 45). From the placebo and lenalidomide 5 mg groups, 84% and 58% of patients, respectively, crossed over to lenalidomide 5 or 10 mg at 16 wk, respectively. Results: Rates of red blood cell-transfusion independence (RBC-TI) ≥182 d were higher in the lenalidomide 10 mg (57.4%; P < 0.0001) and 5 mg (37.2%; P = 0.0001) groups vs. placebo (2.2%). Cytogenetic response rates (major + minor responses) were 56.8% (P < 0.0001), 23.1% (P = 0.0299) and 0%, respectively. Two-year cumulative risk of acute myeloid leukaemia progression was 12.6%, 17.4% and 16.7% in the lenalidomide 10 mg, 5 mg, and placebo groups, respectively. In a 6-month landmark analysis, overall survival was longer in lenalidomide-treated patients with RBC-TI ≥182 d vs. non-responders (P = 0.0072). The most common grade 3-4 adverse event was myelosuppression. Conclusions: These data support the clinical benefits and acceptable safety profile of lenalidomide in transfusion-dependent patients with IPSS-defined Low-/Int-1-risk MDS with isolated del(5q).

Published
2014
Full Text
View/download PDF

49. T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS

Author

Aalbers, A M, primary, van den Heuvel-Eibrink, M M, additional, Baumann, I, additional, Beverloo, H B, additional, Driessen, G J, additional, Dworzak, M, additional, Fischer, A, additional, Göhring, G, additional, Hasle, H, additional, Locatelli, F, additional, De Moerloose, B, additional, Noellke, P, additional, Schmugge, M, additional, Stary, J, additional, Yoshimi, A, additional, Zecca, M, additional, Zwaan, C M, additional, van Dongen, J J M, additional, Pieters, R, additional, Niemeyer, C M, additional, van der Velden, V H J, additional, and Langerak, A W, additional

Published
2014
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results