t(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature

Several cytogenetic abnormalities identified in patients with childhood acute lymphocytic leukemia (ALL) have been associated with a poor prognosis. There are several case reports in the literature describing t(17;19) in children with ALL. This translocation has been associated with hypercalcemia, coagulopathy, and poor outcome. We present three cases of ALL with t(17;19) treated at our institution and review the outcome of children reported in the medical literature

t(17;19) in Children with Acute Lymphocytic Leukemia: A Report of 3 Cases and a Review of the Literature

Several cytogenetic abnormalities identified in patients with childhood acute lymphocytic leukemia (ALL) have been associated with a poor prognosis. There are several case reports in the literature describing t(17;19) in children with ALL. This translocation has been associated with hypercalcemia, coagulopathy, and poor outcome. We present three cases of ALL with t(17;19) treated at our institution and review the outcome of children reported in the medical literature

Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy

<div><p>Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 x 10^-7). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10^-7. Variation in this region on chromosome 6, which includes the genes <i>TBC1D32/C6orf170</i> and <i>GJA1</i> (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.</p></div

Identification of primary cohort.

<p>Electronic medical records data were searched to identify 5,665 individuals exposed to vancomycin. Automated and manual algorithms were used to determine if each satisfied inclusion / exclusion criteria, as described in the methods, resulting in 882 confirmed cases. After exclusion of those without DNA, those who failed quality control (QC), and those of non-European-American ancestry, 745 individuals remained. Of those, 489 had serum creatinine measurements for the primary analysis.</p

Association of genome-wide SNPs to peak creatinine while on vancomycin therapy in the primary cohort.

<p>A) Manhattan plot, where each dot represents a genotyped SNP, arranged along the x-axis by position of the SNP on each chromosome. The y-axis plots-log10(p-value) for the linear regression analysis of peak creatinine, adjusted for sex, age at time of vancomycin therapy, height, weight, vancomycin dose / dosing interval, vancomycin trough, and baseline serum creatinine measurements as described in the methods. B) LocusZoom plot of 6q22.31 locus, including genotyped and imputed SNPs. Each dot represents a SNP, arranged by position on chromosome 6 along the x-axis, and the color indicates degree of linkage disequilibrium with the index SNP, rs2789047. The left y-axis plots-log10(p-value) for each SNP. The blue line indicates estimated recombination rate, quantified on the right y-axis. Known genes in the region are indicted below the x-axis.</p

Meta-analysis results for chromosome 6 SNP associations to peak creatinine during vancomycin therapy.

<p>RAF—Risk Allele Frequency; SE—Standard Error.</p><p>*—Imputed SNP in Mayo and VGER cohorts.</p><p>Meta-analysis results for chromosome 6 SNP associations to peak creatinine during vancomycin therapy.</p

Cohort demographics for primary and validation cohorts investigated by genome-wide association for the outcome of peak serum creatinine during vancomycin therapy.

<p>*Median (interquartile range)</p><p>^N, %.</p><p>Cohort demographics for primary and validation cohorts investigated by genome-wide association for the outcome of peak serum creatinine during vancomycin therapy.</p