Incidence trends of childhood acute lymphoblastic leukemia in Saudi Arabia: Increasing incidence or competing risks?

INTRODUCTION: The incidence of childhood acute lymphoblastic leukemia (cALL) varies between countries likely as a result of competing risks including infections, access-to-care, socioeconomic influences, and/or ethnicity. However, little is known about disease burden in high-income Arab countries offering free-of-charge healthcare. The hypothesis was that, due to population characteristics (young age, high fertility and parental consanguinity rate), the incidence of cALL in Saudi Arabia is equal or higher than that observed in high-income Western countries. METHODS: Saudi databases were used to calculate the incidence of cALL from 2001 to 2014. Incidence trends over time of children with ALL, 14-years of age or younger, were analyzed and compared with those reported in USA. RESULTS: The age-adjusted incidence over the years was lower in Saudi Arabia compared to USA. However, the incidence trend of cALL in Saudi Arabia was increasing at a rate higher than that observed in USA (p < 0.001). The overall incidence of cALL in Saudi Arabia increased from 1.58/100,000 in 2001 to 2.35/100,000 population in 2014. The median annual increase was 4.58 %. The incidence in males increased from 1.88 to 2.71/100,000, and from 1.21 to 1.86/100,000 population in females. CONCLUSIONS: The reported incidence of cALL in Saudi Arabia is rapidly increasing. The increasing trend may reflect evolving socioeconomic structure, improved access-to-cancer care, and improved diagnosis/ reporting capacity. This highlights the need for better understanding of cALL causes and the need for the formation of separate national pediatric cancer registries in different countries to monitor childhood cancer incidence trends.

The influence of polymorphisms in the drug transporter, ABCB1 on the toxicity of glucocorticoids in Saudi children with acute lymphoblastic leukaemia.

BACKGROUND: Glucocorticoids play essential roles in the treatment of childhood acute lymphoblastic leukaemia (ALL); however, treatment with these agents can result in severe side-effects. This study, the first of its kind in a Saudi population, investigates associations of ABCB1 gene polymorphisms (pharmacodynamics and pharmacokinetic) with the development of toxicity and side effects (glucose abnormality, liver toxicity and infection) in a small population of Saudi children with ALL. METHODS: Three single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs 3213619 T129C, rs 2032582 G2677T and rs1045642 C3435T) were analysed in 70 Saudi children with ALL and 60 control subjects. Participants were treated according to the ALL 2000 study protocol. Toxicities were assessed and associations with genotypes were evaluated according to Common Toxicity Criteria (NCI-CTC). RESULTS: Significant associations were observed among carriers and the mutated genotype C3435T (ABCB1), which had an incidence of infection (p = 0.05). Although no correlations were found between liver toxicity and glucose abnormalities for patients carrying ABCB1 SNPs, risk factors for liver toxicity were elevated by a factor of three for patients carrying the SNP G2677T, OR 3.00 (1.034-8.702). The risk factor of glucose abnormality toxicity for the patients carring T129C were increased three times OR 3.06 (0.486-19.198). CONCLUSIONS: In terms of infection incidence, polymorphism C3435T may contribute to potential life-threatening infections during paediatric ALL therapy, through glucocorticoid usage.