{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:34:34Z","timestamp":1778679274678,"version":"3.51.4"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"33","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,11,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To analyze the association of genetic variation within the tumor necrosis factor (TNF \u2212308 [G\u2192A]) and lymphotoxin alfa (LT-a +252 [A\u2192G]) genes with outcome in non-Hodgkin's lymphoma of childhood and adolescence. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Genotyping of the TNF \u2212308 (G\u2192A) and LT-a +252 (A\u2192G) polymorphisms in patients (n = 488) enrolled onto the German-Austrian-Swiss multicenter trial NHL-BFM 95 from April 1996 to January 2000 was performed by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis on DNA from tumor-free specimen. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> In patients with Burkitt's lymphoma (BL) and B-cell acute lymphoblastic leukemia (B-ALL; n = 219, 211 eligible patients), patients carrying at least two variant alleles (high-producer haplotypes) had an increased risk of events: probability of event-free survival (pEFS) at 3 years was 81% (SE = 5%), compared with 91% (SE = 2%) in low-producer haplotypes (P = .018). In BL\/B-ALL with high tumor load (lactate dehydrogenase [LDH] \u2265 500 U\/L; n = 104), pEFS was 69% (SE = 8%) in high-producer versus 85% (SE = 4%) in low-producer haplotypes (P = .05). In multivariate analysis including risk factors for events (LDH \u2265 500 U\/L, CNS involvement, methotrexate infusion regimen), TNF \u2212308\/LT-\u03b1 +252 haplotype kept prognostic relevance: patients with high-producer haplotypes had a 2.34-fold increase in risk of events (P = .048). The TNF \u2212308 (G\u2192A) and LT-\u03b1 +252 (A\u2192G) polymorphisms were not associated with pEFS in lymphoblastic lymphoma (n = 101), anaplastic large-cell lymphoma (n = 67), or diffuse large B-cell lymphoma (n = 65), nor with therapy-related toxicity. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> The TNF \u2212308 (G\u2192A) and LT-a +252 (A\u2192G) polymorphisms were negative prognostic factors in pediatric BL\/B-ALL. Among patients with serum LDH \u2265 500 U\/L, haplotype analysis further determined patients at risk for events. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.01.2179","type":"journal-article","created":{"date-parts":[[2005,11,18]],"date-time":"2005-11-18T00:13:12Z","timestamp":1132272792000},"page":"8414-8421","source":"Crossref","is-referenced-by-count":44,"title":["Tumor Necrosis Factor and Lymphotoxin Alfa Genetic Polymorphisms and Outcome in Pediatric Patients With Non-Hodgkin\u2019s Lymphoma: Results From Berlin-Frankfurt-M\u00fcnster Trial NHL-BFM 95"],"prefix":"10.1200","volume":"23","author":[{"given":"Kathrin","family":"Seidemann","sequence":"first","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Book","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrike","family":"Meyer","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgit","family":"Burkhardt","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl","family":"Welte","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfred","family":"Reiter","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Stanulla","sequence":"additional","affiliation":[{"name":"From the Department of Pediatric Hematology and Oncology, Children's Hospital, Hannover Medical School, Hannover; and NHL-BFM Study Center, Department of Pediatric Hematology and Oncology, University Children's Hospital, Justus-Liebig-University Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00237-9"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)00041-8"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1086\/302517"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/13.17.6361"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.22.8699"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/371508a0"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2362.1998.00244.x"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1038\/9649"},{"key":"R9","doi-asserted-by":"crossref","unstructured":"Wilson AG, di Giovine FS, Blakemore AIF, et al: Single base polymorphism in the tumor necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. 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