Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

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.

CARMIL2 Immunodeficiency with Epstein Barr Virus Associated Smooth Muscle Tumor (EBV-SMT). Report of a Case with Comprehensive Review of Literature.

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

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.

Rosette-forming Glioneuronal Tumor in the Optic Pathway of a Child.

Rosette-forming glioneuronal tumor is a rare World Health Organization grade I neoplasm, primarily involving the posterior fossa. Most cases have been reported in young adults. Although maximal surgical resection is advocated, a precise treatment modality is yet to be established. We describe an unusual presentation of rosette-forming glioneuronal tumor occurring in the optic pathway in a child. As the site of the tumor was not amenable to resection, he underwent radiotherapy and is currently well on follow-up.

Surveillance of adverse drug reactions and drug-drug interactions with pediatric oncology patients in a south Indian tertiary care hospital.

OBJECTIVE: The present study was conducted to evaluate the pattern of occurrence of adverse drug reactions and drug-drug interaction in a pediatric oncology unit of a tertiary care hospital. METHODS: A prospective, observational study was conducted in the Department of Pediatric Oncology, Sri Ramachandra Medical College and Hospital, India. Patients were monitored actively for the occurrences of any adverse drug reaction during the study period. Patient's demographic details, clinical, and treatment data were collected for drug-drug interaction analysis. The detected adverse drug reaction was assessed for causality, severity, and preventability. Drug-drug interaction identified was rated based on their level of urgency and the nature of actions necessary to respond to an interaction. RESULTS: Of 176 patients, 118 were detected for the occurrence of various adverse drug reaction. The majority of the cases were suffering with acute lymphocytic leukemia (67.9%). Vincristine was noted for a maximum number of adverse drug reaction in cytotoxic drugs. Rash is the most frequently occurred reaction. Assessment of causality showed that the majority of cases are "probable" (60.16%). In evaluating the severity of adverse drug reactions, 57.6% reactions were moderately severe and 74.5% of the reactions were preventable. Upon assessing the drug-drug interaction, 38.13% of the prescription needs to be monitored and 10 drug-drug interactions were under the risk category of "X." The majority of the adverse drug reaction was moderately severe in nature and those were preventable. CONCLUSION: Since pediatrics are vulnerable population, they must have a thorough surveillance system for adverse drug reaction and drug-drug interaction; thereby, a positive impact on the medication-use system and improved patient care can be achieved.

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.

A Rare Case of Perinatal Intrarenal Neuroblastoma.

Perinatal neuroblastoma is the most common solid malignant tumor in infancy which comprises one fifth of all neuroblastomas. Most of them are of adrenal origin and extra-adrenal neuroblastoma is uncommon. We present a rare case of perinatal intrarenal neuroblastoma in a neonate who presented with an incidentally detected abdominal mass. These tumors cause diagnostic and therapeutic dilemma because of its uncommon location. Although very rare, neuroblastoma should be considered in the differential diagnosis of perinatally detected renal tumors.

Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18-month-old child with multisystem LCH.

Two Uncommon Paraneoplastic Neurological Syndromes in a Child With Hodgkin Lymphoma.

Paraneoplastic neurological syndromes (PNS) are rare, remote effects of cancer that are usually caused by an altered immune response to the tumor and not due to the tumor mass, metastasis, infection, ischemia, or metabolic derangements. PNSs can affect any area of the central, the peripheral, and the autonomic nervous systems. These are rare in lymphomas compared with solid tumors attributed to their presentation even in late stages and the absence of onconeural antibodies. We present a child with stage IIB Hodgkin lymphoma who presented with dual PNS, achalasia cardia, and Holmes Adie pupil occurring synchronously with the cancer.

First Counseling Revealing the Diagnosis of Childhood Cancer: Parent Preferences From an Indian Perspective.

BACKGROUND: The first counseling or the exchange between the physician and the parent(s) of children with cancer is of vital importance as it sets the tone for the rest of the treatment. The goal of our study was to find out the preferences among parents of Indian children with cancer regarding communication and breaking of bad news when fully informed about the diagnosis. MATERIALS AND METHODS: A sample of 60 parents who had been counseled within 3 months from diagnosis were interviewed with a prepared questionnaire directed at eliciting their experiences with the physicians who broke the bad news to them and also suggestions to improve the exchange. RESULTS: Sixty parents of children diagnosed with cancer participated in the study. All parents agreed on the importance of first counseling and asked for a second round of counseling to reinforce concepts learned during the first counseling. An overall 83% of parents wanted a comparison with another child having the same diagnosis, 57% wanted immediate or extended family to be present, and 92% did not want support staff to be present during counseling. In all, 68% of parents did not want to reveal the diagnosis to the child, 77% wanted as much information about the disease as possible, including estimated cost of treatment, and 90% wanted access to other information services and information about other centers where treatment was available. CONCLUSIONS: Parents have preferences about the ways in which information is presented to them during the first counseling. Knowing these preferences will help physicians to better their ability to interact with parents in the future during first counseling and help them decide a culturally appropriate course of action.

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.