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C Eckert, N Hagedorn, L Sramkova, G Mann, R Panzer-Grümayer, C Peters, J-P Bourquin, T Klingebiel, A Borkhardt, G Cario, J Alten, G Escherich, K Astrahantseff, K Seeger, G Henze, A von Stackelberg
The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4...
August 2015: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Moneeb A K Othman, Joana B Melo, Isabel M Carreira, Martina Rincic, Eyad Alhourani, Kathleen Wilhelm, Bernd Gruhn, Anita Glaser, Thomas Liehr
Cytogenetic classification of acute lymphoblastic leukemia (ALL) is primarily based on numerical and structural chromosomal abnormalities. In T-cell ALL (T-ALL), chromosomal rearrangements are identified in up to 70% of the patients while the remaining patients show a normal karyotype. In the present study, a 16-year-old male was diagnosed with T-precursor cell ALL and a normal karyotype after standard GTG-banding, was studied retrospectively (>10 years after diagnosis) in frame of a research project by molecular approaches...
February 2015: Oncology Reports
Julie Irving, Elizabeth Matheson, Lynne Minto, Helen Blair, Marian Case, Christina Halsey, Isabella Swidenbank, Frida Ponthan, Renate Kirschner-Schwabe, Stefanie Groeneveld-Krentz, Jana Hof, James Allan, Christine Harrison, Josef Vormoor, Arend von Stackelberg, Cornelia Eckert
For most children who relapse with acute lymphoblastic leukemia (ALL), the prognosis is poor, and there is a need for novel therapies to improve outcome. We screened samples from children with B-lineage ALL entered into the ALL-REZ BFM 2002 clinical trial (, #NCT00114348) for somatic mutations activating the Ras pathway (KRAS, NRAS, FLT3, and PTPN11) and showed mutation to be highly prevalent (76 from 206). Clinically, they were associated with high-risk features including early relapse, central nervous system (CNS) involvement, and specifically for NRAS/KRAS mutations, chemoresistance...
November 27, 2014: Blood
Cornelia Eckert, Günter Henze, Karlheinz Seeger, Nikola Hagedorn, Georg Mann, Renate Panzer-Grümayer, Christina Peters, Thomas Klingebiel, Arndt Borkhardt, Martin Schrappe, André Schrauder, Gabriele Escherich, Lucie Sramkova, Felix Niggli, Johann Hitzler, Arend von Stackelberg
PURPOSE: In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT). PATIENTS AND METHODS: In the Acute Lymphoblastic Leukemia-Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10(-3) (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10(-3) (n = 109) continued to receive chemotherapy...
July 20, 2013: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
G Henze, A v Stackelberg, C Eckert
The BFM studies for relapsed childhood acute lymphoblastic leukemia (ALL) were started in 1983, at a time when cure rates for ALL were still lower and the number of children with ALL relapse equaled about the number of children with newly diagnosed neuroblastoma. Today, relapses have become relatively rare events in ALL although, because of the frequency of ALL, they are still a significant cause of death in children and adolescents. With currently used treatment modalities, cure rates of about 50% after relapse can be achieved, and, together with the improved results of front-line therapy, the survival rate of childhood ALL is now about 90%...
May 2013: Klinische Pädiatrie
Cornelia Eckert, Arend von Stackelberg, Karl Seeger, Tom W L Groeneveld, Christina Peters, Thomas Klingebiel, Arndt Borkhardt, Martin Schrappe, Gabriele Escherich, Günter Henze
PURPOSE: This blinded prospective study was performed to optimise the risk assessment of children with a late isolated, combined or an early combined bone marrow (BM) relapse of precursor B-cell acute lymphoblastic leukaemia (ALL). The aim was to develop a reliable tool to identify patients with an intermediate risk relapse who are in need of haematopoietic stem cell transplantation (HSCT). METHODS: Included were 80 children and adolescents with first intermediate risk BM relapse of ALL recruited in trial ALL-REZ BFM P95/96...
April 2013: European Journal of Cancer
Ninela Irga, Malgorzata Mysliwiec, Marcelina Osak, Malgorzata Szmigiero-Kawko, Elzbieta Adamkiewicz-Drozynska, Radoslaw Jaworski
INTRODUCTION: The majority of hyperglycaemic incidents in oncohaematological patients treated with glucocorticosteroids remain undiagnosed. The aim of our study was to work out a detailed protocol for the control of carbohydrate metabolism and to evaluate whether such a protocol can help in diagnosis of carbohydrate metabolism disturbances in oncohaematological paediatric patients. MATERIAL AND METHODS: A one hundred and twenty-eight children treated for proliferative diseases of the haematopoietic system and severe aplastic anaemia with therapeutic protocols including glucocorticosteroids were divided into two groups...
September 8, 2012: Archives of Medical Science: AMS
S Krentz, J Hof, A Mendioroz, R Vaggopoulou, P Dörge, C Lottaz, J C Engelmann, T W L Groeneveld, G Körner, K Seeger, C Hagemeier, G Henze, C Eckert, A von Stackelberg, R Kirschner-Schwabe
Despite risk-adapted treatment, survival of children with relapse of acute lymphoblastic leukemia (ALL) remains poor compared with that of patients with initial diagnosis of ALL. Leukemia-associated genetic alterations may provide novel prognostic factors to refine present relapse treatment strategies. Therefore, we investigated the clinical relevance of 13 recurrent genetic alterations in 204 children treated uniformly for relapsed B-cell precursor ALL according to the ALL-REZ BFM 2002 protocol. The most common alterations were deletions of CDKN2A/2B, IKZF1, PAX5, ETV6, fusion of ETV6-RUNX1 and deletions and/or mutations of TP53...
February 2013: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Alex Wing Kwan Leung, Lee Vincent, Alan Kwok Shing Chiang, Anselm Chi Wai Lee, Frankie Wai Tsoi Cheng, Daniel Ka Leung Cheuk, Chung Wing Luk, Siu Cheung Ling, Chi Kong Li
BACKGROUND: In 2000, the Hong Kong Pediatric Hematology Oncology Study Group started a new relapsed acute lymphoblastic leukemia (ALL) treatment protocol based on modified ALL-REZ BFM 96 protocol aiming at improving the treatment outcome in Chinese children. PROCEDURE: All patients in Hong Kong with first relapse of childhood ALL were included. Patients were stratified into four risk groups (S1, S2, S3, and S4) and the treatment consisted of intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if indicated...
September 2012: Pediatric Blood & Cancer
Michael E Rytting
No abstract text is available yet for this article.
March 2012: Current Hematologic Malignancy Reports
Andrea Willer, Joachim Gerss, Thorsten König, Dieter Franke, Hans-Jürgen Kühnel, Günter Henze, Arendt von Stackelberg, Anja Möricke, Martin Schrappe, Joachim Boos, Claudia Lanvers-Kaminsky
Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < ...
November 24, 2011: Blood
Shabnam Shalapour, Jana Hof, Renate Kirschner-Schwabe, Lorenz Bastian, Cornelia Eckert, Javier Prada, Günter Henze, Arend von Stackelberg, Karl Seeger
BACKGROUND: Resistance to therapy and subsequent relapse remain major challenges in the clinical management of relapsed childhood acute lymphoblastic leukemia. As the bone marrow environment plays an important role in survival and chemotherapy resistance of leukemia cells by activating different signaling pathways, such as the VLA-4 and PI3K/Akt pathways, we studied the prognostic and biological impact of VLA-4 expression in leukemia cells from children with relapsed B-cell precursor acute lymphoblastic leukemia and its influence on the sensitivity of the leukemia cells to drugs...
November 2011: Haematologica
Jana Hof, Stefanie Krentz, Claudia van Schewick, Gabriele Körner, Shabnam Shalapour, Peter Rhein, Leonid Karawajew, Wolf-Dieter Ludwig, Karl Seeger, Günter Henze, Arend von Stackelberg, Christian Hagemeier, Cornelia Eckert, Renate Kirschner-Schwabe
PURPOSE: In the clinical management of children with relapsed acute lymphoblastic leukemia (ALL), treatment resistance remains a major challenge. Alterations of the TP53 gene are frequently associated with resistance to chemotherapy, but their significance in relapsed childhood ALL has remained controversial because of small studies. PATIENTS AND METHODS: Therefore, we systematically studied 265 first-relapse patients enrolled in the German Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Mü nster 2002 (ALL-REZ BFM 2002) trial for sequence and copy number alterations of the TP53 gene by using direct sequencing and multiplex ligation-dependent probe amplification...
August 10, 2011: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Arend von Stackelberg, Enrico Völzke, Jörn-Sven Kühl, Karl Seeger, André Schrauder, Gabriele Escherich, Günter Henze, Gesche Tallen et al.
AIM OF THE STUDY: Non-response (NR) to treatment of childhood relapsed acute lymphoblastic leukaemia (ALL) is an end-point of protocol therapy. Subsequent management has not yet been standardised. This study analyses different approaches after NR to aid optimising future strategies. PATIENTS AND METHODS: Ninety-three children with NR to treatment according to ALL relapse-protocols of the Berlin/Frankfurt/Muenster (BFM) Study Group (03/1990-2006/1999) were retrospectively assigned to a curative (C: intensive polychemotherapies, stem cell transplantation (SCT); n=51), palliative (P: 1-2 antineoplastic agents; n=23) or supportive (S: no antineoplastic therapy; n=19) treatment approach...
January 2011: European Journal of Cancer
Gesche Tallen, Richard Ratei, Georg Mann, Gertjan Kaspers, Felix Niggli, Alexandr Karachunsky, Wolfram Ebell, Gabriele Escherich, Martin Schrappe, Thomas Klingebiel, Ruediger Fengler, Günter Henze, Arend von Stackelberg
PURPOSE: The multicenter trial ALL-REZ BFM (ie, Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster) 90 was designed to improve prognosis for children with relapsed acute lymphoblastic leukemia (ALL) by time-to-relapse- and site-of-relapse-adapted stratification and by introduction of novel chemotherapy elements and to evaluate new prognostic parameters in a large, population-based cohort. PATIENTS AND METHODS: Five hundred twenty-five patients stratified into risk groups A (early bone marrow [BM] relapses), B (late BM relapses), and C (isolated extramedullary relapses) received alternating short-course intensive polychemotherapy (in blocks R1, R2, or R3) and cranial/craniospinal irradiation followed by maintenance therapy...
May 10, 2010: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Georg Hempel, Hans-Joachim Müller, Claudia Lanvers-Kaminsky, Gudrun Würthwein, Antje Hoppe, Joachim Boos
We analysed 1221 serum activity measurements in 168 children from the Berlin-Frankfürt-Münster acute lymphoblastic leukaemia studies, ALL-BFM (Berlin-Frankfürt-Münster) 95 and ALL-BFM REZ, in order to develop a pharmacokinetic model describing the activity-time course of pegylated (PEG)-asparaginase for all dose levels. Patients received 500, 750, 1000 or 2500 U/m(2) PEG-asparaginase on up to nine occasions. Serum samples were analysed for asparaginase activity and data analysis was done using nonlinear mixed effects modelling (NONMEM Vers...
January 2010: British Journal of Haematology
Peter Bader, Hermann Kreyenberg, Günter H R Henze, Cornelia Eckert, Miriam Reising, Andre Willasch, Andrea Barth, Arndt Borkhardt, Christina Peters, Rupert Handgretinger, Karl-Walter Sykora, Wolfgang Holter, Hartmut Kabisch, Thomas Klingebiel, Arend von Stackelberg et al.
PURPOSE: Minimal residual disease (MRD) before allogeneic stem-cell transplantation was shown to predict outcome in children with relapsed acute lymphoblastic leukemia (ALL) in retrospective analysis. To verify this, the Acute Lymphoblastic Leukemia Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group conducted a prospective trial. PATIENTS AND METHODS: Between March 1999 and July 2005, 91 children with relapsed ALL treated according to the ALL-REZ BFM 96 or 2002 protocols and receiving stem-cell transplantation in >or= second remission were enrolled...
January 20, 2009: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
A Schrauder, A von Stackelberg, M Schrappe, J Cornish, Christina Peters, , et al.
The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome...
June 2008: Bone Marrow Transplantation
Arend von Stackelberg, Reinhard Hartmann, Christoph Bührer, Rüdiger Fengler, Gritta Janka-Schaub, Alfred Reiter, Georg Mann, Kjeld Schmiegelow, Richard Ratei, Thomas Klingebiel, Jörg Ritter, Günter Henze et al.
High-dose methotrexate (MTX) has been extensively used for treatment of acute lymphoblastic leukemia (ALL). To determine the optimal dose of MTX in childhood relapsed ALL, the ALL Relapse Berlin-Frankfurt-Münster (ALL-REZ BFM) Study Group performed this prospective randomized study. A total of 269 children with a first early/late isolated (n = 156) or combined (n = 68) bone marrow or any isolated extramedullary relapse (n = 45) of precursor B-cell (PBC) ALL (excluding very early marrow relapse within 18 months after initial diagnosis) were registered at the ALL-REZ BFM90 trial and randomized to receive methotrexate infusions at either 1 g/m(2) over 36 hours (intermediate dose, ID) or 5 g/m(2) over 24 hours (high dose, HD) during 6 (or 4) intensive polychemotherapy courses...
March 1, 2008: Blood
Anja Borgmann, Christina Zinn, Reinhard Hartmann, Ralf Herold, Peter Kaatsch, Gabriele Escherich, Anja Möricke, Günter Henze, Arend von Stackelberg
PURPOSE: To investigate the cumulative incidence of and the risk factors for developing second malignant neoplasms (SMN) in children and adolescents following treatment for relapse of acute lymphocytic leukaemia (ALL). METHODS: Patients (1376) up to 18 years of age with first relapse of non-B-cell ALL were treated and achieved a 2nd complete remission (CR). The treatment followed trial protocol in five consecutive multicentre trials of the ALL-REZ BFM Study Group between March 1983 and December 2001...
January 2008: European Journal of Cancer
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