Methylenetetrahydrofolate reductase gene polymorphism and glucocorticoid intake in children with ALL and aseptic osteonecrosis.
BACKGROUND
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.


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.
Bernbeck
B
B
Department of Paediatric Oncology, Haematology and Immunology, Heinrich Heine University Medical Center Düsseldorf, Germany. bernbeck@med.uni-duesseldorf.de
Mauz-Körholz
C
C
Zotz
R B
RB
Göbel
U
U
D000293:Adolescent; D000367:Age Factors; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage*; D001855:Bone Marrow Diseases / Q000139:chemically induced*; D002648:Child; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004487:Edema / Q000139:chemically induced*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D010020:Osteonecrosis / Q000139:chemically induced*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D011241:Prednisone / Q000008:administration & dosage*; D012189:Retrospective Studies; D012307:Risk Factors
D000964:Antimetabolites, Antineoplastic; D018931:Antineoplastic Agents, Hormonal; D005938:Glucocorticoids; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D011241:Prednisone; D008727:Methotrexate