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MTHFR 677 (C→T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95

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Abstract

We analyzed the relationship of genetic variation within the methylenetetrahydrofolate reductase gene (MTHFR 677 C→T) with clinical characteristics, outcome, and therapy-related toxicity in pediatric non-Hodgkin’s lymphoma (NHL) in our multicenter trial NHL-BFM 95. In this trial, high-dose methotrexate (MTX) infusion regimens were randomized (4- vs 24-h infusion) in patients with B-cell lymphoma; MTX was applied as 24-h infusion in all patients with lymphoblastic lymphoma and anaplastic large cell lymphoma. Toxicity data were collected per patient and therapy course according to National Cancer Institute Common Toxicity Criteria (NCI-CTC). The genotypes in 484 pediatric patients were distributed as follows: MTHFR 677 CC, 206 patients (42.6%); MTHFR 677 CT, 214 patients (44.2%); and MTHFR 677 TT, 64 patients (13.2%). Lymphoblastic lymphoma was significantly associated with homozygosity for the MTHFR 677 T allele. No association of MTHFR 677 genotype with clinical characteristics (sex, age, and tumor stage), outcome, or therapy-related toxicity could be detected. Therefore, we conclude that the MTHFR 677 C→T polymorphism does not appear to influence outcome or therapy-associated toxicity in pediatric patients with NHL treated on BFM protocols.

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Acknowledgements

We thank E. Odenwald for expert work in cytological diagnosis and U. Meyer for excellent data management. We especially thank all doctors and nurses in participating hospitals for their continuous care for sick children and their excellent cooperation with study center NHL-BFM. Supported by the Deutsche Krebshilfe, Bonn (grant no. M 109/91/Re1) and by the Verein zur Förderung der Behandlung krebskranker Kinder Hannover e.V.

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Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625, Hannover, Germany

    Kathrin Seidemann, Marion Book, Martin Zimmermann, Karl Welte & Martin Stanulla

  2. NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children’s Hospital, Justus Liebig University Giessen, Giessen, Germany

    Ulrike Meyer & Alfred Reiter

Authors
  1. Kathrin Seidemann
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  2. Marion Book
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  3. Martin Zimmermann
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  4. Ulrike Meyer
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Correspondence to Kathrin Seidemann.

Appendix

Appendix

Reference laboratories for histopathology and immunohistochemistry

R. Parwaresch, Lymph Node Registry founded by the Society of German Pathologists, Institute of Hematopathology, University of Kiel; A. Feller, Institute of Pathology, University of Lübeck; M.L. Hansmann, Institute of Pathology, University of Frankfurt; P. Möller, Institute of Pathology, University of Ulm; H.K. Müller-Hermelink, Institute of Pathology, University of Würzburg; H. Stein, Institute of Pathology, University of Berlin; I. Simonitsch, Institute of Pathology, University of Vienna, Austria

Immunophenotyping

W.-D. Ludwig, Berlin, Germany; W. Knapp, Vienna, Austria; F. Niggli, Zürich, Switzerland

Cytomorphology

A. Reiter, Giessen, Germany; W. Haas, Vienna, Austria; F. Niggli, Zürich, Switzerland

Principal investigators

R. Mertens (Aachen), R. Angst (Aarau), A. Gnekow (Augsburg), R. Dickerhoff (St. Augustin), P. Imbach (Basel), G.F. Wuendisch (Bayreuth), W. Dörffel (Berlin-Buch), G. Henze (Berlin-Charité), U. Bode (Bonn), W. Eberl (Braunschweig), H.-J. Spaar (Bremen), I. Krause (Chemnitz), J.-D. Thaben (Coburg), D. Moebius (Cottbus), W. Wiesel (Datteln), B. Ausserer (Dornbirn), H. Breu (Dortmund), G. Weiβbach (Dresden), W. Kotte (Dresden), U. Göbel (Düsseldorf), W. Weinmann (Erfurt), J.D. Beck (Erlangen), W. Havers (Essen), G. Müller (Feldkirch), B. Kornhuber (Frankfurt), C. Niemeyer (Freiburg), F. Lampert (Gieβen), M. Lakomek (Göttingen), C. Urban (Graz), H. Reddemann (Greifswald), S. Burdach (Halle), G. Janka-Schaub (Hamburg), K. Welte (Hannover), B. Selle/A. Kulozik (Heidelberg), C. Tautz (Herdecke), N. Graf (Homburg), F.M. Fink (Innsbruck), F. Zintl (Jena), G. Neβler (Karlsruhe), H. Wehinger (Kassel), R. Schneppenheim (Kiel), H. Messner (Klagenfurt), M. Rister, (Koblenz), F. Berthold (Köln), W. Sternschulte (Köln), C. Schulte-Wissermann (Krefeld), M. Domula (Leipzig), I. Mutz (Leoben), K. Schmitt (Linz), O. Stoellinger (Linz), L. Nobile (Locarno), P. Bucsky (Lübeck), H. Ruetschele (Ludwigshafen), U. Caflisch (Luzern), U. Mittler (Magdeburg), P. Gutjahr (Mainz), O. Sauer (Mannheim), C. Eschenbach (Marburg), W. Tillmann (Minden), K.-D. Tympner (München-Harlaching), R.J. Haas (München), C. Bender-Götze (München), S. Müller-Weihrich (München), H. Jürgens (Münster), O. Schofer (Neunkirchen), A. Jobke (Nürnberg), G. Eggers (Rostock), R. Geib-König (Saarbrücken), H. Grienberger (Salzburg), H. Haas (Schwarzach), R. Schumacher (Schwerin), F.-J. Göbel (Siegen), R. Ploier (Steyr), A. Feldges (St. Gallen), J. Treuner (Stuttgart), H. Rau (Trier), D. Niethammer (Tübingen), K.-M. Debatin (Ulm), D. Franke (Vechta), H. Gadner (Wien), F. Haschke (Wien), J. Weber (Wiesbaden), D. Dohrn (Wuppertal), J. Kühl (Würzburg), F. Niggli (Zürich).

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Seidemann, K., Book, M., Zimmermann, M. et al. MTHFR 677 (C→T) polymorphism is not relevant for prognosis or therapy-associated toxicity in pediatric NHL: results from 484 patients of multicenter trial NHL-BFM 95. Ann Hematol 85, 291–300 (2006). https://doi.org/10.1007/s00277-005-0072-2

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