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AIMSAcute lymphoblastic leukemia (ALL) is the most common of all paediatric cancers. Aside from predisposing to ALL, polymorphisms could also be associated with poor outcome. Indeed, genetic variations involved in drug metabolism could, at least partially, be responsible for heterogeneous responses to standardized leukemia treatments, hence requiring more personalized therapy. The aims of this study were to (a) to determine the prevalence of seven common genetic polymorphisms including those that affect the folate and/or thiopurine metabolic pathways, i.e. cyclin D1 (CCND1-G870A), γ-glutamyl hydrolase (GGH-C452T), methylenetetrahydrofolate reductase (MTHFR-C677T and MTHFR-A1298C), thymidylate synthase promoter (TYMS-TSER), thiopurine methyltransferase (TPMT*3A and TPMT*3C) and inosine triphosphate pyrophosphatase (ITPA-C94A), in Caucasian (n = 94, age < 20) and Vietnamese (n = 141, age < 16 years) childhood ALL and (b) to assess the impact of a multilocus genetic risk score (MGRS) on relapse-free survival (RFS) using a Cox proportional-hazards regression model. RESULTSThe prevalence of MTHFR-677TT genotype was significantly higher in Caucasians (P = 0.008), in contrast to the prevalence of TYMS-TSER*3R/3R and ITPA-94AA/AC genotypes which were significantly higher in Vietnamese (P < 0.001 and P = 0.02, respectively). Compared with children with a low MGRS (≤3), those with a high MGRS (≥4) were 2.06 (95% CI = 1.01, 4.22; P = 0.04) times more likely to relapse. Adding MGRS into a multivariate Cox regression model with race/ethnicity and four clinical variables improved the predictive accuracy of the model (AUC from 0.682 to 0.709 at 24 months). CONCLUSIONIncluding MGRS into a clinical model improved the predictive accuracy of short and medium term prognosis, hence confirming the association between well determined pharmacogenotypes and outcome of paediatric ALL. Whether variants on other genes associated with folate metabolism can substantially improve the predictive value of current MGRS is not known but deserves further evaluation.

Introduction: Non-syndromic hearing loss (NSHL) in children, which has numerous causes, can impede or even postpone the acquisition of spoken language. In Vietnam, screening programs and genetic testing for NSHL are rarely applied. In this study, 31 pediatric patients had their medical histories collected alongside sequencing results for the GJB2 and TECTA genes to determine the prevalence of these mutations in the community and their associations with potential risk factors. Methods: Information and blood samples were collected from 31 severe-to-profound pediatric NSHL patients. DNA was extracted, amplified by polymerase chain reaction (PCR), and directly sequenced for the detection of GJB2 (connexin 26) and TECTA mutations. Results: No TECTA gene mutations were detected. GJB2 mutations were identified in eight patients (25.8%), with three (9.7%) cases of heterozygous c.109G>A (V37I), four (12.9%) cases of homozygous c.109G>A (V37I), and one (3.2%) case of heterozygous c.299-300delAT. There were no significant associations between having mutated GJB2 genes and living in urban areas, having a family history of prelingual deafness, or having an abnormal obstetric history (p > 0.05, Fisher's exact tests). Conclusion: Our study addresses the high prevalence of GJB2 mutations as causative factors in hearing loss in diagnosed patients at the Otorhino-laryngology Hospital in Ho Chi Minh City, Viet Nam. Further studies are required to obtain a better understanding of the genetic spectrum of NSHL and to articulate its relationship with various risk factors.

Introduction:The most common sensory disorder, hearing loss, may result from genetic causes. Various inheritance patterns exist, such as X-linked, autosomal dominant, autosomal recessive, and mitochondrial. However, the genetic underpinnings of racial distinctiveness and regional variation were incompletely understood. To fully evaluate the ethnic specificity of gap junction protein beta 2 (GJB2) and tectorin alpha (TECTA) mutations in this region, data from all GJB2 and TECTA gene studies on Asian children with hearing impairment were pooled and used in this research. Methods: All nonsyndromic hearing loss studies on the prevalence of GJB2 or TECTA mutations published between 1990 and 2022 were retrieved from the PubMed database, evaluated for risk of bias, and meta-analyzed. Results: Twelve studies were chosen, representing twelve prevalence estimates. The prevalence of GJB2 and TECTA mutations in Asian patients with nonsyndromic hearing loss was 13.36% (95% confidence interval [CI]: 7.74%-20.14%), varying significantly among trials (I 2 = 96.74%; P < 0.001). The pooled prevalence of TECTA and GJB2 mutations was 3.6% (95% CI: 1.9%-5.7%) and 24.06% (95% CI: 11.43%-31.35%), respectively. Conclusions: There was an association between TECTA/GJB2 mutations and hearing impairment, but there were also regional and ethnic differences in mutation prevalence. Studies with larger sample sizes and genetic analyses based on long-read sequencing are needed to understand the mutations resulting in hearing loss.

4292 Introduction Acute lymphoblastic leukaemia (ALL) is the most common type of childhood cancer in East Asian, Caucasians and in the United States. Previous studies have shown poorer survival from childhood ALL among Asian compared to Caucasian populations. The US National Cancer Institute's Surveillance, Epidemiology and End Results program from 1998 to 2008 showed that poorer prognosis waseven observed in East Asian children living in the United States, compared to non-Hispanic Whites. This finding is interesting in that Asian ethnic groups are not socioeconomically disadvantaged in the United States relative to non-Hispanic whites as shown by US Census data. Aim The primary goal of this study was to compare the outcome of Belgian and Vietnamese children with ALL, treated with the same protocol (French acute lymphoblastic leukemia protocol FRALLE). Patients and Methods The Belgian series included 107 patients (aged less than 19 at diagnosis) followed at Cliniquesuniversitaires Saint-Luc (UCL), Brussels, Belgium between 2001 and 2011. The Vietnamese series included 166 patients from Blood Transfusion and Hematology Hospital, University of Medicine Pham Ngoc Thach (UPNT) at Ho Chi Minh city, Vietnam (aged less than 16 at diagnosis) and followed between 2005 and 2011. Clinical andbiologicalvariables and survival rates were compared using Cox Proportional Hazards Regression model. The association between clinicaland biological variables and both adverse drug reactions and relapse free survival were analyzed using Log-Binomial Regression model. All statistical analysis was performed using the ‘Epi’ and the ‘Survival’ package of the R 2.15.0 software. Results The two populations were comparable regarding age at diagnosis, sex ratio, initialwhite blood cell count, cytogenetic and steroid responsiveness at day 8. A higher prevalence of L2 type-ALL according to the FAB classification was found in Vietnamese children (81.3 % L2 in Vietnam vs 44.9% in Belgium). Vietnamese patients had a significantly lower survival than Belgian patients (p<0.001) (figure 1). In the multivariate analysis model, relative risk of death for Vietnamese children was 2.61 (95% CI= 1.03–6.65) (p = 0.04). Compared to the Belgian cohort, Vietnamese children had a lower relapse free survival (figure 2) and a higher relativerisk of relapse of 3.01 (95% CI = 1.53–5.93). They also disclosed a higher incidence of methotrexate-related grade 3 or 4 side effects (36.2% vs 5.6%). Conclusions Compared to Caucasians treated with the same protocol, a poorer overall survival was confirmed in children with ALL treated in Vietnam. Relapse free survival was lower and adverse reaction rate higher among Vietnamese children. Racial differences in pharmacogenetics of drugs as well as additional factors such as social status, lack of antibiotic prophylaxis or delayed access to care due to remoteness may explain these observations. Appendix Disclosures: No relevant conflicts of interest to declare.