Genomic alterations in a cohort of pediatric acute myeloid leukemia patients at two cancer centers in Colombia.

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.

Pharmacogenetics of ABCB1, CDA, DCK, GSTT1, GSTM1 and outcomes in a cohort of pediatric acute myeloid leukemia patients from Colombia.

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.

Philadelphia-like acute lymphoblastic leukemia: Characterization in a pediatric cohort in a referral center in Colombia.

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, non-receptor 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.

Compromiso vesical en paciente pediátrico con poliarteritis nodosa: primera descripción / Bladder involvement in a paediatric patient with polyarteritis nodosa: First description

RESUMEN La poliarteritis nudosa (PAN) es una vasculitis necrosante, rara en la infancia, caracterizada por el compromiso de vasos pequeños/medianos y de múltiples órganos. Presentamos a una paciente que inició a los 4 arios con síndrome febril prolongado, dolor abdominal crónico, mialgias incapacitantes y compromiso en la piel, quien luego de 2 años de cuadro clínico completa criterios clínicos para PAN. Recibió tratamiento con corticoide sistêmico por vía oral e intravenosa, 6 meses de ciclofosfamida por vía intravenosa y manejo de mantenimiento con inmunosupresores convencionales sin respuesta adecuada, logrando control de la enfermedad únicamente con ciclofosfamida por vía oral y corticoide a largo plazo. Luego de 5 años y de recibir una dosis alta acumulada de ciclofosfamida, inicia con cuadros de hematuria macroscópica. Se evaluaron, entre otras causas, la toxicidad por ciclofosfamida y la actividad de la enfermedad. El estudio incluyó biopsia vesical, con hallazgo de vas-culitis necrosante de paredes vesicales. La vasculitis vesical es raramente reportada en la literatura (3-5 casos en adultos) y en lo consultado no hay reportes en niños. Se describe, en nuestro conocimiento, el primer caso de compromiso vesical asociado a vasculitis sistêmica reportado en la edad pediátrica.

A B S T R A C T Polyarteritis nodosa (PAN) is a necrotising vasculitis, rare in childhood, and characterized by the inflammation of small and medium vessels and multiple organ involvement. The case is presented of a 4 year old girl with prolonged febrile syndrome, chronic abdominal pain, disabling myalgia, and skin involvement. After 2years of symptoms, she met clinical criteria for PAN. She received treatment with oral and intravenous systemic corticosteroids, 6 months of intravenous cyclophosphamide and maintenance with conventional immuno-suppressants without an adequate response. However, she showed clinical improvement with oral cyclophosphamide and long-term corticosteroids. She had several relapses during follow-up visits due to irregular treatment requiring a high cumulative dose of cyclophosphamide. Five years later she presented with macroscopic haematuria, and was assessed for, among other causes, cyclophosphamide toxicity and disease activity. The workup included cystoscopy and bladder biopsy with findingof necrotising vasculitis of bladder wall. Bladder vasculitis is rarely reported in the literature (3-5 cases in adults) and in that consulted there are no reports in children. To our knowledge, this is the first case of bladder involvement associated with systemic vasculitis reported in the paediatric age.

Neurofibroma del hipogloso en un niño colombiano. Reporte de caso / Hypoglossal neurofibroma in a Colombian child: case report

Resumen Se presenta el caso de un paciente masculino de 14 años de edad, con antecedente de dos intervenciones quirúrgicas debidas a la presencia de una masa a nivel sublingual -la primera a los 8 meses de edad y la segunda a los 13 años- y sin información de estudios histopatológicos. Cerca de 8 meses después de la última intervención quirúrgica es valorado por el Servicio de Cirugía Maxilofacial de la Fundación Hospital Pediátrico de La Misericordia en Bogotá D.C., Colombia, por crecimiento acelerado de la misma lesión y por problemas en la deglución y el lenguaje. En la revisión del paciente se encuentra una masa importante sublingual, dificultad en el lenguaje, deformidad mandibular y alteraciones en la mordida, por lo que se decide intervenir quirúrgicamente de nuevo. El resultado de la biopsia es un tumor mesenquimal benigno característico de neurofibroma, que por su ubicación sugiere probable compromiso del nervio hipogloso.

Abstract This article presents the case of a 14-year-old male patient, with a history of two surgical procedures due to the presence of a mass at sublingual level -the first performed at the age of 8 months and the second at 13 the age of years- and without information of histopathological studies. About 8 months after the last surgical procedure, the patient was assessed by the Maxillofacial Surgery Service of the Fundación Hospital Pediátrico de La Misericordia, in Bogotá D.C. - Colombia, due to the rapid growth of the same lesion and swallowing and language disorders. On physical examination, a significant sublingual mass, difficulty in language, mandibular deformity and malocclusion were observed, so a new surgical intervention was indicated. The result of the biopsy revealed a benign mesenchymal tumor, typically seen in neurofibroma, which suggested a possible involvement of the hypoglossal nerve due to its location.

Leiomiositis inflamatoria como causa de pseudoobstrucción intestinal y vólvulo recidivante de sigmoides: reporte de un caso y revisión de la literatura / Chronic intestinal pseudo-obstruction and recurrent sigmoid volvulus due to inflammatory leiomyositis: Case report and review of the literature

La leiomiositis intestinal es una causa rara de pseudoobstrucción intestinal crónica (POIC) y no está descrita asociada a vólvulo de sigmoides. Reportamos el caso de un paciente de 12 años con episodios recurrentes de POIC en quien se descartó enfermedad del sistema nervioso entérico. Las biopsias endorrectales y posteriormente una sigmoidectomía por vólvulo recidivante evidenciaron una miopatía con infiltrado inflamatorio de linfocitos y eosinófilos limitado a la capa muscular propia. Los estudios complementarios descartaron enfermedad sistémica. El diagnóstico final fue leiomiositis inflamatoria, una entidad rara, con muy pocos casos reportados en la literatura, de probable etiología inmunológica y pronóstico variable (AU)

Intestinal leiomyositis is a rare cause of chronic intestinal pseudo-obstruction (CIPO) and is not described associated with sigmoid volvulus. We report the case of a 12 year old patient with recurrent episodes of CIPO. Rectal biopsies were performed to rule out enteric nervous system disease. These biopsies and subsequently a sigmoidostomy made by recurrent sigmoid volvulus evidenced a myopathy with inflammatory infiltrate of lymphocytes and eosinophils limited to the muscularis propia, atrophy of myocytes and intersticial fibrosis. Complementary studies ruled out systemic disease. The final diagnosis was inflammatory leiomyositis, a rare entity, with very few cases reported in the literature that seems to have an immune etiology and variable prognosis (AU)