Background and Aim: Different studies have shown pharmacogenetic variants related to drug toxicity in acute myeloid leukemia (AML) patients. Our aim was to identify the association between ABCB1, CDA, DCK, GSTT1, and GSTM1 variants with clinical outcomes and toxicity in pediatric patients with AML.Methods: Fifty-one confirmed de novo AML pediatric patients were included. A SNaPshot™ assay and conventional PCR were used to evaluate ABCB1, CDA, DCK, GSTT1, and GSTM1 variants. Clinical outcomes and toxicity associations were evaluated using odds ratios and Chi-square analysis.Results: Patients carrying ABCB1 (1236C > T, rs1128503) GG genotype in had a 6.8 OR (CI 95% 1.08-42.73, p = .044) for cardiotoxicity as compared to patients carrying either AA or GA genotypes 0.14 OR (CI 95% 0.023-0.92, p = .044). For ABCB1 (1236G > A rs1128503/2677C > A/T rs2032582/ 3435G > A rs1045642) AA/AA/AA combined genotypes had a strong association with death after HSTC OR 13.73 (CI 95% 1.94-97.17, p = .009). Combined genotypes GG/CC/GG with CDA (79A > C, rs2072671) CA genotype or CDA (-451G > A, rs532545) CT genotype, had a 4.11 OR (CI 95% 2.32-725, p = .007) and 3.8 OR (CI 95% 2.23-6.47, p = .027) with MRD >0.1% after first chemotherapy cycle, respectively. Conclusion:Our results highlight the importance of pharmacogenetic analysis in pediatric AML, particularly in populations with a high degree of admixture, and might be useful as a future tool for patient stratification for treatment.

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Background: Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a subtype of pediatric leukemia with high risk factors and poor outcome. There are few reports of its prevalence in Latin America.Aim: This study evaluated the frequency and clinical and biological characteristics of Ph-like ALL in a pediatric cancer center in Colombia. Methods:The Ph-like genetic profile was analyzed by a low-density array (LDA).Samples from patients with Ph-like ALL were analyzed by fluorescent in situ hybridization for cytokine receptor like factor 2 (CRLF2) and ABL proto-oncogene 1, nonreceptor tyrosine kinase (ABL1) rearrangements. Copy number variations were assessed by multiplex ligation probe amplification.Results: Data from 121 patients were analyzed. Fifteen patients (12.4%) had Ph-like ALL, and these patients had significantly higher leukocyte counts at diagnosis and higher levels of minimal residual disease on days 15 and 33 of induction than patients without the Ph-like subtype. There were no significant differences in sex, age, or response to prednisone at day 8 between the two groups. CRLF2 rearrangements were identified in eight patients, and ABL1 rearrangements were identified in two patients. Other genetic alterations alone or in combination were identified in 77% of patients, including deletions in cyclin dependent kinase inhibitor 2 A/B (46.2%), IKAROS family zinc finger 1 (38.3%), and paired box 5 (30.8%).Conclusions: Ph-like ALL had a 12.4% prevalence in our cohort of patients with pediatric ALL. The identification of this group of patients has importance for risk stratification and future targeted therapy.Adriana Linares and Luz Karime Yunis contributed equally as first authors.

Few studies identifying genomic aspects in pediatric acute myeloid leukemia patients in Latin American countries have been reported. The aim of this study was to identify genomic alterations, clinical characteristics and outcomes in a cohort of pediatric AML patients. This descriptive observational cohort study included patients with confirmed de novo acute myeloid leukemia up to 18 years of age. Cytogenetics and conventional FISH analysis, next-generation sequencing and PCR testing were performed. The correlation of genomic data with treatment response and outcomes were analyzed. Of the 51 patients analyzed, 67.4% had a cytogenetic abnormality and 74.5% had a genetic variant. FLT3 variants (ITD or TKD D835) were found in 27.4%, followed by NRAS (21.6%), KRAS (13.7%) and WT1 and KIT (11.8%). Patients were stratified by risk (66.6% high-risk) after the end of induction. FLT3-ITD was associated with relapse (OR 11.25; CI 1.89–66.72, p 0.006) and NRAS with death during induction (OR 16.71; CI 1.51–184.59, p 0.022). Our study highlights the importance of rapid incorporation of genetic testing in pediatric AML in Colombia, as it directly affects treatment decisions and outcomes. Incorporation of targeted therapies with conventional chemotherapy is an increasingly urgent need in pediatric patients.