Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant.

INTRODUCTION: Mercaptopurine (6-MP) is the backbone of the consolidation and maintenance therapy for paediatric acute lymphoblastic leukaemia (ALL). Nevertheless, it can cause critical myelosuppression. Predicting adverse reactions to 6-MP often involves the investigation of pharmacogenetic variants; in particular thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15). Lately, NUDT15 variants have been shown to play a significant pharmacogenetic role in predicting 6-MP intolerance in children of Asian descent. CASE REPORT: We present a six-year-old male child of Indian origin with persistent cytopenia after treatment. This prompted targeted sequencing of the genes TPMT and NUD15. The results revealed two copies of the variant of NUD15 rs116855232, that is, NUDT15*2 genotype. MANAGEMENT AND OUTCOME: Since the NUDT15*2 allele classified the patient as a poor metabolizer, he was restarted on a low dose of 6-MP, which he tolerated. DISCUSSION: Individuals with the NUDT15*2allele (*2/*2 genotype) are poor metabolizers of thiopurines which results in an adverse reaction to 6-MP. About 3.5% of Indians show variations in the TPMT gene as compared to 19.4% variations observed in NUDT15, which makes the latter a more reliable disease marker.

Sporadic Burkitt Lymphoma Involving the Orbit - A Report of Two Cases and Review of Literature.

Burkitt lymphoma (BL) is an aggressive, rapidly growing B-cell non-Hodgkin lymphoma found predominantly in children and has three clinical subtypes. The sporadic subtype, seen in non-endemic areas, typically presents as an abdominal mass. Primary orbital involvement is rarely reported. We report two cases of sporadic orbital BL manifesting as unilateral rapidly progressive proptosis with orbit being the initial site of presentation. Following an incision biopsy, BL was confirmed on histopathology and immunohistochemistry. Both patients demonstrated a remarkable improvement with systemic chemotherapy. Burkitt lymphomas grow rapidly with the potential for vision loss. Albeit rare, clinicians should be aware of this entity as timely diagnosis and initiation with chemotherapy display a dramatic response.

Choice of Place of the Death of Children with Cancer during End-of-Life Care - Parent's Perspectives in a Developing Country.

Objectives: The place of a child's death is an indicator of the quality of paediatric palliative and end-of-life care. This study aimed to identify the choices of parents about the place of death of their children with cancer and to evaluate whether they had any regrets about their choices retrospectively. Material and Methods: All children who were treated in our centre for the past 9 years with palliative intent treatment to improve their quality of life were included in this study. For the children whose place of death was the hospital, data were collected from the case records. For the children who passed away at home, a telephone call was made to the families, informing them of the study, allowing time for there to be any clarifications. A verbal consent was requested for the study. Data were collected through the telephone conversation. Results: Out of the 59 children who died during the study period from 2012 to 2021, 31 children (52.5%) died in hospital settings. Eighteen (58.1%) families who had opted hospital as the place of death had regretted their choices. Families who chose home as a place of death were upset about inadequate pain management. The majority of the families had desired home care services for adequate symptom control and to keep the child comfortable in a familiar environment. Conclusion: Most children with life-limiting conditions continue to die in the hospital setting in developing countries due to a lack of dedicated palliative care services and home care. Most of the families retrospectively, regretted their choices of place of death. Most of the families, however, would prefer home as the place of death, if there was better end-of-life care support for symptom control at home. Specific policies institutional and nationwide need to be formulated to provide guidance to the professionals on the discussion of goals of care and place of care, with a supporting network to ensure its provision.

Renal Primitive Neuroectodermal Tumor Mimicking Wilms' Tumor in a Young Boy: A Case Report of a Rare Entity with Review of the Literature.

Primary renal primitive neuroectodermal tumors (PNET) are an extremely rare entity. The tumor is very aggressive presenting with metastasis and carries a dismal prognosis. We describe the case of renal PNET in an 11-year-old boy with a solid cystic lesion in the right kidney with a thrombus in the inferior vena cava and lung nodules, mimicking Wilms' tumor.

Cytogenetic and Fluorescence in situ Hybridization Profile of Pediatric Acute Lymphoblastic Leukemia in a University Hospital in South India.

OBJECTIVE: The purpose of this study was to evaluate the cytogenetic and fluorescent in situ hybridization (FISH) profile in children with acute lymphoblastic leukemia (ALL), referred to a university hospital in a 5-year 6-month period. SUBJECTS AND METHODS: Cytogenetic analysis of the bone marrow aspirate specimens of 91 patients was performed by standard Giemsa (G)-banding and interphase FISH (iFISH). RESULTS: The frequency of chromosomal abnormalities detected by G-banding was 29.5%, and the frequency of nonrandom abnormalities with independent prognostic significance identified by iFISH was 46.4%. The abnormality with the highest frequency was gain of RUNX1 (n = 18, 21.4%), followed by ETV6/RUNX1 fusion (n = 7, 8.3%), and gain of KMT2A (n = 6, 7.1%). Additionally, rarely reported gains of ETV6, PBX1, and ABL1 were observed at a frequency of 6% (n = 5), and the deletion of ETV6 and TCF3 was seen at a frequency of 3.6% (n = 3) and 2.3% (n = 2), respectively. A 10-year old with intrachromosomal amplification of chromosome 21 was also observed. CONCLUSIONS: This study strengthens and widens the current knowledge of the cytogenetic landscape of pediatric ALL.

Multidisciplinary management of hepatoblastoma in children: Experience from a developing country.

BACKGROUND: Advances in chemotherapy, liver resection techniques, and pediatric liver transplantation have vastly improved survival in children with hepatoblastoma (HB). These are best managed by a multidisciplinary team (MDT) in a setting where all treatment options are available. Until recently, this was difficult to achieve in India. METHODS: All children (<16 years) with HB treated in a pediatric liver surgery and transplantation unit between January 2011 and July 2016 were reviewed. Data regarding the clinical presentation, preoperative management, surgical treatment, postoperative course, and outcomes were extracted from a prospectively managed database. RESULTS: Thirty children were treated for HB during the study period. Nine children were PRETEXT 4, 7 were PRETEXT 3, 13 were PRETEXT 2, and 1 was PRETEXT 1 (where PRETEXT is pretreatment extension). All children received a neoadjuvant chemotherapy before surgery followed by an adjuvant chemotherapy. Nineteen children had complete resection, while six underwent primary living donor liver transplantation. There were six mortalities including five children who poorly responded to chemotherapy with progressive tumor extension. At a median follow-up of 30 months, two children who underwent resection and one child who underwent liver transplant had disease recurrence. CONCLUSION: Improved outcomes can be achieved in children with HB even in countries with limited resources when they are managed by MDTs with expertise in pediatric oncology, liver resection, and liver transplantation.

Parent's Perspectives on the End-of-life Care of their Child with Cancer: Indian Perspective.

CONTEXT: Parents report that end-of-life decisions are the most difficult treatment-related decisions that they face during their child cancer experience. Research from the parent's perspective of the quality of end-of-life care of their cancer children is scarce, particularly in developing countries like India. AIMS: This study aimed to identify the symptoms (medical/social/emotional) that most concerned parents at the end-of-life care of their cancer child and to identify the strategies parents found to be helpful during this period. SETTINGS AND DESIGN: We wanted to conduct this to focus on the parents perspectives on their cancer child's end-of-life care and to address the issues that could contribute to the comfort of the families witnessing their child's suffering. MATERIALS AND METHODS: The study was conducted at Sri Ramachandra University, Chennai, a Tertiary Care Pediatric Hemato Oncology Unit. Parents who lost their child to cancer, treated in our institution were interviewed with a validated prepared questionnaire. Statistical analysis was performed using SAS statistical software package. RESULTS: Toward death, dullness (30%), irritability (30%), and withdrawn from surroundings (10%) were the most common symptoms encountered. About 30% of the children had fear to be alone. About 50% of the children had the fear of death. Pain, fatigue, loss of appetite were the main distressful symptoms that these children suffered from parents' perspective. Though the parents accepted that the child was treated for these symptoms, the symptom relief was seldom successful. CONCLUSION: The conclusion of the study was that at the end of their child's life, parents value obtaining adequate information and communication, being physically present with the child, preferred adequate pain management, social support, and empathic relationships by the health staff members.

Impact of cancer support groups on childhood cancer treatment and abandonment in a private pediatric oncology centre.

AIMS: To analyze the impact of two cancer support groups in the treatment and abandonment of childhood cancer. MATERIALS AND METHODS: This is a retrospective review of children with cancer funded and non-funded who were treated at Kanchi Kamakoti CHILDS Trust Hospital from 2010 to 2013. A total of 100 patients were funded, 57 by Ray of Light Foundation and 43 by Pediatric Lymphoma Project and 70 non-funded. RESULTS: The total current survival of 80%, including those who have completed treatment and those currently undergoing treatment, is comparable in both the groups. Abandonment of treatment after initiating therapy was not seen in the financially supported group whereas abandonment of treatment after initiation was seen in one child in the non-funded group. CONCLUSIONS: Besides intensive treatment with good supportive care, financial support also has an important impact on compliance and abandonment in all socioeconomic strata of society. Financial support from private cancer support groups also has its impact beyond the patient and family, in reducing the burden on government institutions by non-governmental funding in private sector. Improvement in the delivery of pediatric oncology care in developing countries could be done by financial support from the private sector.

Kimura's Disease: A Rare Cause of Chronic Lymphadenopathy in a Child.

Kimura's disease is an uncommon entity that affects adults, with a predilection for the Asian population. This may rarely be encountered in children, and the knowledge of this fact is essential to rule out the remote possibility of Kimura's disease in children with a slow-growing painless mass in the head and neck region. In this case report, we document this disease in an 8-year-old boy with a slow-growing swelling in the right posterior auricular region.

Evaluation of Pathway to Diagnosis of Pediatric Brain Tumors in Tamil Nadu, India.

PURPOSE: Delayed diagnosis and poor awareness are significant barriers to the early intervention of pediatric brain tumors. This multicenter observational study aimed to evaluate the baseline routes and time to diagnosis for pediatric brain tumors in Tamil Nadu (TN), with the goal of promoting early diagnosis and timely referrals in the future. METHODS: A standard proforma was used to retrospectively collect information on demographics, diagnosis, referral pathways, and symptoms of incident pediatric brain tumor cases between January 2018 and October 2020 across eight tertiary hospitals in TN. Dates of symptom onset, first presentation of health care, and diagnosis were used to calculate total diagnostic interval (TDI), patient interval (PI), and diagnostic interval (DI). RESULTS: A total of 144 cases (mean age, 6.64 years; range, 0-15.1 years) were included in the analysis. Among those, 94% (135/144) were from city/district areas, 40% (55/144) were self-referred, and 90% (129/144) had one to three health care professional visits before diagnosis. Median TDI, PI, and DI were 3.5 (IQR, 1-9.3), 0.6 (IQR, 0.1-4.6), and 0.6 (IQR, 0-3.3) weeks, respectively. Low-grade gliomas had the longest median TDI (6.6 weeks), followed by medulloblastomas (4.6 weeks) and high-grade gliomas (3.3 weeks). Average number of symptoms recorded was 1.7 at symptom onset and 1.9 at diagnosis. CONCLUSION: Although there are some similarities with data from the United Kingdom, many low-grade and optic pathway tumors were unaccounted for in our study. DIs were relatively short, which suggests that infrastructure may not be a problem in this cohort. Increased training and establishment of proper cancer registries, combined with proper referral pathways, could enhance early diagnosis for these children.

Primary pulmonary diffuse large B-cell non-Hodgkin's lymphoma in a child.

A 3-year-old girl presented with a history of intermittent fever of six months duration associated with respiratory symptoms consisting of recurrent cough, fever, wheeze and a suspected history of contact with tuberculosis (TB). Chest radiograph revealed pulmonary infiltrates mimicking miliary TB. She was started on anti-tuberculous treatment, but in view of clinical deterioration, a further work-up including a lung biopsy revealed non-Hodgkin's lymphoma (NHL). This case documents the extremely rare occurrence of pulmonary involvement and miliary infiltrates on the chest radiograph in NHL.

Short stature and an interesting association.

Untreated hypothyroidism in children usually results in delayed puberty, but juvenile hypothyroidism causes isosexual precocious puberty in a rare syndrome called Van Wyk Grumbach syndrome, with a complete reversal to the pre pubertal state following thyroid hormone replacement therapy. We report here, a 7-year-old girl who presented with short stature, constipation and isosexual precocious puberty due to the long standing untreated severe hypothyroidism with this syndrome.

Role of Polymerase Chain Reaction-Based Diagnosis of Respiratory Viruses in Febrile Neutropenic Patients.

Background Neutropenic patients are commonly affected by respiratory infections, whereas respiratory viral infections causing high morbidity and mortality are routinely diagnosed in developing countries like India. Our study aimed to investigate the prevalence of respiratory viral infections in pediatric cancer patients with febrile neutropenia.  Methods This prospective study was performed on 45 neutropenia patients with hematological malignancies. Nasal swabs were collected and analyzed by real-time multiplex polymerase chain reaction (PCR), covering the following viruses: influenza A virus, influenza B virus, human parainfluenza virus (subtypes 1-4), human respiratory syncytial virus A and B, enterovirus, human-coronavirus (HCoV: HKU1, NL63, 229E, and OC43), human bocavirus, adenovirus, human rhinovirus, human-metapneumovirus A and B, human paraechovirus, and a bacterium Mycoplasma pneumoniae. Patients enrolled in the study since the COVID-19 pandemic was also detected for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results Of the 45 cases included in our study, 26 cases showed the presence of at least one positivity by PCR (57.7%): 23 patients had monoinfection with only one virus, two patients were found positive for coinfection with two viruses, and one patient was found positive for three viruses. The most detected viruses were human rhinovirus (26.9%, n=7) and coronavirus 19 (19.2%, n=5). A total of 11.5% of the patients had multiple viral infections. About 19 (42.2%) of the patients enrolled in our study had no viral pathogen detected. Conclusion We found that respiratory viruses contribute significantly to the development of neutropenic fever, as evidenced by the results of our prospective study. Individualizing infection treatment can reduce antibiotic use in immunocompromised patients. Thus, routine screening for viremia may be warranted in this clinical setting.

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.