Experience with Generic Pegylated L-asparaginase in Children with Acute Lymphoblastic Leukemia from a Tertiary Care Oncology Center in South India.

Dhaarani JayaramanBackground Acute lymphoblastic leukemia (ALL) is a common type of leukemia in children. The innovator pegylated L-asparaginase has several advantages over native L-asparaginase; however, its use in India is limited due to availability and cost. Therefore, a generic pegylated L-asparaginase can be considered as an alternative to the innovator molecule. Methods A retrospective study was conducted to assess the outcome (minimal residual disease [MRD]) and toxicity of a generic pegylated L-asparaginase (Hamsyl) at the end of induction therapy. Results Eighty-eight (80.7%) and 21 (19.3%) patients had received generic pegylated L-asparaginase and conventional asparaginase, respectively, as a part of their treatment protocol. Nearly 82% of patients had B-type ALL. Eight-one percent of children had a white blood cell count of fewer than 50,000/mm 3 . At the end of induction, 80.7% (88) of children were minimal residual disease (MRD)-negative, and at the end of augmented consolidation therapy, 20.2% were MRD-negative. Ten percent of patients exhibited allergic reactions. Two children had pancreatitis, and one child had central venous thrombosis. Conclusion The generic pegylated L-asparaginase (Hamsyl) was effective and safe for use in pediatric ALL.

Evaluation of cytogenetic and molecular markers with MTX-mediated toxicity in pediatric acute lymphoblastic leukemia patients.

PURPOSE: Pediatric acute lymphoblastic leukemia (pALL) patients have better overall survival and methotrexate (MTX) is an effective drug used in their treatment. However, the treatment-related adverse effects (TRAEs) have a bigger impact on the therapy. In this study, we have evaluated the association of polymorphisms in genes encoding proteins engaged in MTX metabolism, and the cytogenetic aberrations with TRAEs. METHODS: A total of 115 patients between the age of 1 and 18 years (average: 6.6) under maintenance therapy were selected for the study. SLC19A1 (c.80G > A), MTHFR (c.677C > T; c.1298A > C), and TYMS (c.*450_*455del) genotypes were determined using PCR techniques and Sanger sequencing. Cytogenetic and SNP findings were analyzed for any association with the reported toxicities using odds ratio, chi-square test, multifactor dimensionality reduction (MDR) analysis for synergistic effect and, multinomial logistic regression analysis for the likelihood of adverse events. RESULTS: Among the evaluated genetic variations, SLC19A1 (c.80G > A) was significantly associated with TRAEs (OR = 5.71, p = 0.002). Multinomial logistic regression analysis (chi-sq = 16.64, p < 0.001) and MDR analysis (chi-sq = 10.51 p < 0.001) confirmed the finding. On the other hand, no significant association was observed between adverse events and any specific cytogenetic aberration. CONCLUSION: SLC19A1 facilitates the import of cyclic dinucleotides and reduced folates, evaluating genotypes in this gene can help in better management of patients on methotrexate treatment. Assessing a broader gene panel can help in finding more associated markers and delivering personalized medicine to the patients.

Precocious puberty in a child: A rare cause and review of literature.

Precocious puberty (PP) in pediatric office practice is challenging as the cause varies from benign to malignant conditions. Adrenocortical tumors are rare in childhood and pseudo-precocious puberty is the most common clinical presentation in children. We report a case of a 5-year-old boy who presented with features of abdominal distention and virilization, and his abdominal magnetic resonance imaging (MRI) revealed an adrenal tumor which was confirmed as adrenocortical carcinoma by biopsy. This case report highlights the importance of the awareness among general practioners and pediatricians to rule out adrenocortical tumors while evaluating a child with PP.

A Journey Across Oceans With a Heavy Heart: Rare Presentation of a Pediatric Malignancy.

Myeloid sarcoma, due to extramedullary deposition of myeloblasts, is one of the rare presentations in acute myeloid leukemia. We present an extremely rare case of a 5-year-old boy with cardiac myeloid sarcoma. Noninvasive mode of diagnosis, timely initiation of chemotherapy and meticulous supportive care are the keys to successful outcome. (Level of Difficulty: Intermediate.).

Pharmacogenetic evaluation of 6-mercaptopurine-mediated toxicity in pediatric acute lymphoblastic leukemia patients from a South Indian population.

Aim: To evaluate the variants in the genes coding for the proteins involved in thiopurine and folate metabolism with treatment related adverse effects (TRAEs). Materials & methods: Eleven variants in seven candidate genes were genotyped in 127 pediatric acute lymphoblastic leukemia patients under 6-mercaptopurine (6-MP) treatment to infer the association of selected genotypes with TRAEs. Results: Among the genotypes inspected, NUDT15 (c.415C>T) and SLC19A1 (c.80G>A) showed a significant association with the TRAEs (odds ratio = 4.01, p = 0.002 and odds ratio = 7.78, p = 0.002). Conclusion:SLC19A1 and NUDT15 play an important role in the metabolism of 6-MP and it is necessary to spot other variants in associated pathways and investigate the factors that can impact 6-MP metabolism.

Secondary acute myeloid leukemia in a child treated for retinoblastoma: A case report with review of literature.

The most devastating late adverse effect of childhood cancer treatment is development of second malignancies. Retinoblastoma is the most common ocular malignancy of childhood and has a very good cure rate. Children with hereditary retinoblastoma have an increased risk of developing second malignancies due to the genetic cancer predisposition status and the additional risk factors are exposure to chemotherapy (alkylating agents and topoisomerase II inhibitors) and external beam radiotherapy during treatment. The common chemotherapy regimen of retinoblastoma consisting of etoposide, an epipodophyllotoxin is associated with risk of secondary AML (s-AML). We report a case of child with bilateral retinoblastoma who developed secondary AML after being treated for retinoblastoma.

Clinicopathological profile of hepatoblastoma: An experience from a tertiary care center in India.

BACKGROUND: Hepatoblastoma is the most common primary hepatic malignancy in the pediatric population. Advances in pathological evaluation, imaging, risk stratification, neo-adjuvant chemotherapy, and surgery including transplantation have improved survival of these children in the western countries. However, a successful outcome in developing countries such as India with limited resources poses great challenges to the clinician and the family. Histology plays a major role in determining the prognosis of these patients. METHODS: A retrospective study was done on 10 children diagnosed with hepatoblastoma between January 2010 and December 2015 in our institution. Clinical, laboratory, radiological, histopathological diagnoses, treatment, and outcome data were collected and analyzed. RESULTS: The median age of these children at diagnosis was 11 months, and only 1 child was premature at birth. Most children were presented with abdominal distension. One child had lung metastasis at presentation. Elevated alpha fetoprotein levels were present in 90% of the children. The histological types were fetal, embryonal, macrotrabecular, and mixed epithelial-mesenchymal types. SIOPEL risk stratification was done, which showed 40% of the children to be of high risk. Three children had PRETEXT 1, 2, and 4, respectively. CONCLUSION: Our study is significant with respect to the information on PRETEXT staging, risk status, and histological favorability. In developing countries with limited resources and low-socioeconomic status, it is important to have a multidisciplinary team approach and tailor treatment to manage these patients effectively and improve the overall survival.

Financial Burden Faced by Families due to Out-of-pocket Expenses during the Treatment of their Cancer Children: An Indian Perspective.

CONTEXT: Life-saving cancer therapy is costly and may result in financial burden for these families. Financial costs for treating childhood cancer care are traditionally assessed based on the amount spent for diagnostic tests, hospitalization, and chemotherapy. The financial costs for travel, accommodation, out-of-pocket expenses for food, phone bills, and loss of income due to reduction or termination of parental employment are hidden nonmedical expenses that are rarely accounted for. Studies on the financial implications of pediatric cancer treatment are based on the Western model of healthcare with good government/state insurance coverage and hence literature on lifestyle implications for families in developing nations with limited resources is still scarce. AIMS: The aim of this study is to find out the details of out-of-pocket expenses incurred by the families during their treatment of cancer children and its implications on their quality of life. Settings and Design: This study was conducted in a tertiary care center for pediatric malignancies for over 1-year period. SUBJECTS AND METHODS: About seventy families whose children were diagnosed with acute leukemia and undergoing treatment at our center were asked to fill a questionnaire detailing their out-of-pocket expenses. RESULTS: Nonmedical expenses accounts for about 46% of their monthly household income of parents from rural areas and 22% of their household income from urban areas. On an average, a family from rural area spends four times the normal amount spent on home for their daily food expenditure. Thirty-eight percent of families have borrowed money from money lenders with an average interest rate of about 12.5% which pushes them to a state of debt for the next few years. CONCLUSIONS: Out-of-pocket expenses contribute a significant proportion to the financial burden of the families with childhood malignancies and these invisible expenses should be recognized and provide adequate support to lessen the burden of this economic impact.

Indian Pediatric Postgraduate's Perspective on Future Career Intentions.

OBJECTIVE: To determine the factors that influence Pediatric residents to pursue a subspecialty career and establish their choice of future workplace. METHODS: The present questionnaire based study was conducted during a National level pediatric post graduate exam refresher course in Chennai, India and involved Pediatric residents from all parts of India. Datas was analysed with the statistical package for social sciences (SPSS, version 18.0). RESULTS: Seventy five respondents participated in the study. Eighty-nine percent of the female students reported that marriage has an influence on whether or not to do sub specialisation and their choice of it while 92% of the male students found it irrelevant. Fifty-one (male - 75%, female - 58%) students pragmatically cited "interest in the subject Pediatrics" when asked for the reason choosing Pediatrics as their future career. Neonatology was the most chosen speciality followed by Critical Care and Cardiology. When asked to indicate the most important factors that is likely to influence their decision whether or not to pursue sub speciality program, the largest proportion of students identified "financial reasons" (31; 41%) followed by "job opportunities" (16; 21%). CONCLUSIONS: Pediatric residents should compulsorily be exposed to all subspecialties during their post-graduation. Adequate career guiding and exposure to various subspecialties will make the residents pursue subjects like Pediatric Nephrology, Hemato-oncology, Developmental Pediatrics and Hepatology which have less takers.

Langerhans cell histiocytosis as an unusual cause of back pain in a child: A case report and review of literature.

Low back pain in children and adolescents are usually attributed to mechanical causes and faulty positions. Although most of them are self-limiting, physicians should be aware of the red flag signs that warrant complete evaluation to rule out malignant causes of back pain. As delay in the diagnosis of vertebral lytic lesion may have sequelae in the growing children, pain disproportionate to the signs should have low threshold levels for evaluation. We report a case of 6-year-old boy who presented with worsening back pain. Initially evaluated for tuberculosis spine, he was diagnosed to have Langerhans cell histiocytosis of spine. He improved symptomatically with chemotherapy and spine orthosis and is in complete remission now.