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Klin Padiatr 2003; 215(6): 327-331
DOI: 10.1055/s-2003-45496
Therapeutische Maßnahmen
Originalarbeit
© Georg Thieme Verlag Stuttgart · New York

Methylenetetrahydrofolate Reductase Gene Polymorphism and Glucocorticoid Intake in Children with ALL and Aseptic Osteonecrosis

Methylentetrahydrofolat-Reduktase-Gen-Polymorphismus und Glukokortikoid-Behandlung bei Kindern mit ALL und aseptischer OsteonekroseB.  Bernbeck1 , C.   Mauz-Körholz1 , R.  B.  Zotz2 , U.  Göbel1
  • 1Department of Paediatric Oncology, Haematology and Immunology, Heinrich Heine University Medical Center Düsseldorf, Germany
  • 2Department of Haemostasis and Transfusion Medicine, Heinrich Heine University Medical Center Düsseldorf, Germany
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Publication History

Publication Date:
15 December 2003 (online)

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Zusammenfassung

Hintergrund: Methotrexat ist essenzieller Bestandteil der Behandlung der akuten lymphoblastischen Leukämie (ALL). Aufgrund guten Langzeitüberlebens der Patienten gewinnen die Spätfolgen der Behandlung wie BME (bone marrow edema) und AON (aseptic osteonecrosis) zunehmend an Interesse. Ziel der Untersuchung war es, herauszufinden, ob ein Polymorphismus des Methylentetrahydrofolsäure-Reduktase-(MTHFR)-Gens prädisponierend für die Entstehung von BME und/oder AON ist. Zusätzlich wurde die kumulativ verabreichte Prednisondosis dieser Patienten errechnet und in einer Matched-pairs-Analyse verglichen. Patienten und Methoden: 87 Patienten wurden retrospektiv auf einen MTHFR-Polymorphismus hin untersucht (48 männlich, 43 weiblich). Bei 14/87 Patienten waren ein BME und/oder eine AON diagnostiziert worden (16 %). Ergebnisse: 42/73 Patienten ohne BME und/oder AON (43 männlich, 34 weiblich, mittleres Alter 5,3 Jahre) sowie 10/14 der Patienten mit BME/AON (5 männlich, 9 weiblich, mittleres Alter 10,2 Jahre) wiesen einen MTHFR-Polymorphismus auf (p = 0.28). 14,3 % der Patienten mit MTHFR-Polymorphismus aber ohne BME und/oder AON (6/42) und 70 % der Patienten mit MTHFR-Polymorphismus und mit BME und/oder AON (7/10) waren über 10 Jahre bei ALL-Diagnose (p = 0,002). Die mittlere kumulativ verabreichte Menge an Prednison betrug in einer Matched-pairs-Analyse 98,0 mg/kg KG respektive 100,0 mg/kg KG. Schlussfolgerung: Das Alter der Patienten bei ALL-Diagnose scheint einen Risikofaktor für die Entstehung von BME und/oder AON darzustellen, was auch durch voran gegangene Untersuchungen bestätigt wird. Weiterhin ergibt sich der Hinweis auf einen Zusammenhang zwischen dem MTHFR-Polymorphismus und der Entstehung von BME/AON. Dieser Aspekt ist wert, an einer größeren Fallzahl unter Berücksichtigung der MTX-Pharmakokinetik und der Leukovorin-Rescue überprüft zu werden.

Abstract

Backround: Methotrexate is an essential part of the treatment of acute lymphoblastic leukaemia (ALL). Due to an increased survival of ALL patients, complications like BME (bone marrow edema) and AON (aseptic osteonecrosis) have become a matter of increasing importance. The aim of the study was to find out if a polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene predisposes to the development of BME and/or AON. Furthermore the cumulative prednisone equivalent dose per kilogram body weight was compared in a matched-pairs analysis. Patients and methods: A retrospective analysis of the MTHFR polymorphism of 87 patients was performed (48 male, 43 female). 14/87 patients were diagnosed with BME and/or AON (16 %). Results: 42/73 patients without BME and/or AON (43 male, 34 female, median age 5.3 yrs) and 10/14 patients with BME/AON (5 male, 9 female, median age 10.2 years) presented with a MTHFR-polymorphism (p = 0.28). 14,3 % of the patients with MTHFR-polymorphism but without BME and/or AON (6/42) and 70 % of the patients with MTHFR-polymorphism and with BME and/or AON (7/10) were over 10 years of age at ALL diagnosis (p = 0.002). The mean cumulative prednisone equivalent dose per kilogram body weight was 98.0 mg, compared with 100.0 mg in the matched pairs group. Conclusions: The age of the patients at diagnosis seems to be a risk factor for the development of BME and/or AON as also seen in previous studies. If MTHFR polymorphism is an additional risk factor it was not borne out by this study, possible due to the small number of patients analyzed. This aspect is worth to be proven with a large group of patients considering the MTX pharmacokinetic and leucovorine rescue.

Schlüsselwörter

MTHFR-Polymorphismus - Knochenmarksödem - Aseptische Osteonekrosen - Glukokortikoide - ALL

Key words

MTHFR-polymorphism - bone marrow edema - aseptic osteonecrosis - glucocorticoids - ALL

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Benedikt Bernbeck, MD 

Department of Paediatric Oncology, Haematology and Immunology; Children’s Hospital, Heinrich-Heine-University, Medical Center

Moorenstr. 5

40225 Düsseldorf, Germany

Phone: +49/211/811 9108

Fax: +49/211/811 6038

Email: bernbeck@med.uni-duesseldorf.de

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