Genetic polymorphisms of the lymphotoxin alpha gene are associated with increased risk for lethal infections during induction therapy for childhood acute leukemia: a case-control study.
Specific mutations of the TNF-alpha (TNF-alpha) and Lymphotoxin-alpha (LT-alpha) genes are correlated to the outcome of patients during serious infections. This study aimed at correlating these polymorphisms to lethal infections during childhood acute lymphoblastic leukemia (ALL). A matched case-control study of 34 patients who died due to infections during ALL treatment and 68 ALL patients without lethal infections was performed. Genomic DNA was isolated from blood smears and specific fragments including the polymorphic site of each gene were amplified. In the total study population, 23/102 (22.5%) of the children carried at least two variant alleles (high-producer haplotype). The variant genotypes were equally distributed between cases and controls [relative risk (RR) 1.17 (CI 0.33-2.22, P = 0.752)]. With regard to infective organisms, no statistically significant differences could be detected between the groups for bacterial infections [RR 1.59 (CI 0.56-4.50), P 0.379]. Patients with a LT-alpha (10.5 kb/5.5 kb; 5.5 kb/5.5 kb) haplotype, however, seemed to have a significant higher risk of attracting a lethal infection during induction/consolidation chemotherapy (RR 2.98, CI 0.98-9.01, P = 0.05). These results support a role of specific genetic polymorphisms on lethal infections during induction chemotherapy of ALL treatment.
Kidas
Ekaterini
E
Department of Paediatric Haematology and Oncology, OE 6780, Medizinische Hochschule Hannover, Hannover, Germany.
Möricke
Anja
A
Beier
Rita
R
Welte
Karl
K
Schrappe
Martin
M
Stanulla
Martin
M
Grigull
Lorenz
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007239:Infections / Q000139:chemically induced / Q000235:genetics* / Q000401:mortality; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications* / Q000188:drug therapy; D012306:Risk
D008233:Lymphotoxin-alpha