High-throughput sequencing of immunoglobulin heavy chain for minimal residual disease detection in B-lymphoblastic leukemia.

INTRODUCTION: Minimal residual disease (MRD) is a cornerstone for stratification of upfront B-lymphoblastic leukemia (B-ALL) treatment protocols to decrease relapse risk. Although its detection by flow cytometry (FC) and real-time quantitative polymerase has clinical usefulness, evidence suggests that methods with increased sensitivity could lead to improved outcomes. The aim of this study was to develop an amplicon-based assay followed by high-throughput sequencing of the immunoglobulin heavy chain variable region for MRD detection in B-ALL. METHODS: We analyzed 84 samples, 27 from diagnosis, 5 from relapse, 40 from post-treatment samples, and 12 from healthy controls. RESULTS: Our assay was able to identify more neoplastic clones at diagnosis than Sanger sequencing including incomplete DJ rearrangements. From the 40 MRD samples evaluated 21 were positive by our new approach on high-throughput sequencing assay, but only 15 of these were positive by FC. The remaining 19 were negative by the two techniques. CONCLUSION: We have developed a novel approach on high-sensitive assay for MRD detection in B-ALL, which could add clinical value in the management of patients, especially in cases negative for MRD by FC.

Caesarean sections, prenatal and postnatal conditions and childhood acute lymphoblastic leukaemia: A case-control study in the State of São Paulo, Brazil.

INTRODUCTION: Brazil has high rates of caesarean sections, which has been suggested as a risk factor for acute lymphoblastic leukaemia (ALL). In addition, some pre- and postnatal conditions have been identified as relevant in the etiology of ALL. OBJECTIVES: Investigate the association of caesarean sections, pre- and postnatal conditions with childhood ALL in the State of São Paulo. METHODS: Population-based case-control study including children that are below10 years old. Information on study variables was obtained through face to face interviews, through a questionnaire, and the State of São Paulo Declarations of Live Births database. The conditional and unconditional logistic regression approaches were used to calculate the odds ratio (OR) of the associations between caesarean sections, pre- and postnatal conditions with ALL, and 95 % confidence intervals (95 % CI). RESULTS: We observed a weak and non-statistically significant risk for ALL among children exposed to caesarean sections (unconditional logistic regression OR 1.08; 95 % CI 0.70-1.66; conditional logistic regression OR 1.21; 95 % CI 0.72-2.02), but among children under 3 years old and born through a caesarean sections, the risk of ALL was greater (unconditional logistic regression OR 1.70; 95 % CI 0.69-4.21). A negative association for ALL was observed among children with mothers who reported 12 years of schooling or more (unconditional logistic regression OR 0.34; 95 % CI 0.16-0.69). CONCLUSIONS: We found a tenuous suggestive association between caesarean sections and childhood ALL. The mother's high level of education showed an inverse association with ALL.

Exposure to magnetic fields and childhood acute lymphocytic leukemia in São Paulo, Brazil.

BACKGROUND: Epidemiological studies have identified increased risks of leukemia in children living near power lines and exposed to relatively high levels of magnetic fields. Results have been remarkably consistent, but there is still no explanation for this increase. In this study we evaluated the effect of 60 Hz magnetic fields on acute lymphocytic leukemia (ALL) in the State of São Paulo, Brazil. METHODS: This case-control study included ALL cases (n=162) recruited from eight hospitals between January 2003 and February 2009. Controls (n=565) matched on gender, age, and city of birth were selected from the São Paulo Birth Registry. Exposure to extremely low frequency magnetic fields (ELF MF) was based on measurements inside home and distance to power lines. RESULTS: For 24h measurements in children rooms, levels of ELF MF equal to or greater than 0.3microtesla (µT), compared to children exposed to levels below 0.1 µT showed no increased risk of ALL (odds ratio [OR] 1.09; 95% confidence interval [95% CI] 0.33-3.61). When only nighttime measurements were considered, a risk (OR 1.52; 95% CI 0.46-5.01) was observed. Children living within 200 m of power lines presented an increased risk of ALL (OR 1.67; 95% CI 0.49-5.75), compared to children living at 600 m or more of power lines. For those living within 50 m of power lines the OR was 3.57 (95% CI 0.41-31.44). CONCLUSIONS: Even though our results are consistent with the small risks reported in other studies on ELF MF and leukemia in children, overall our results do not provide support for an association between magnetic fields and childhood leukemia, but small numbers and likely biases weaken the strength of this conclusion.