Objectives Fever is a known complication in pediatric cancer patients when on chemotherapy for which prompt initiation of empiric antibiotics is the single most important life-saving intervention. Nearly two-thirds of all children are treated without identifying the source of fever. Molecular diagnostics can improve management of febrile episodes and reduce unnecessary antibiotic use. The purpose of our study was to evaluate the pathogenic etiology of febrile episodes and analyze their clinical characteristics. Materials and Methods We conducted a prospective observational study at our tertiary care institution from January 2019 to March 2020, to identify the etiology of febrile episodes with or without neutropenia in pediatric cancer patients and to study their clinical outcomes. Results Forty febrile episodes were observed among 27 patients over a period of 15 months. The mean age group was 5 years. In 28 febrile episodes without a focus (70%), a respiratory organism (virus, bacteria, or coinfection) was detected. Rhinovirus was the most common single respiratory isolate (47.36%), followed by Streptococcus pneumoniae (21.05%) and six episodes had multiple viral isolates (21.42%). There was no prolonged hospitalization, need for intensive care unit or oxygen requirement, or mortality. The most common antibiotic used in empiric management was piperacillin-tazobactam. Aminoglycosides were added when there was a clinical suspicion of resistant organism. Conclusion Around 70% of febrile episodes without a focus or documented infection in cancer children had a respiratory pathogen identified in nasopharyngeal swab. Molecular diagnostics greatly enhances diagnostic sensitivity and thereby individualizes the management of febrile illness in these children.

Introduction Febrile neutropenia is a dreadful complication associated with malignancies. Knowledge of locally prevalent pathogens and their resistance pattern is of paramount importance in guiding antimicrobial therapy. Aims/Objectives The aim of the study was to identify the common infectious agent, antibiotic susceptibility of culture positive patients, and outcome Methods We conducted a single-center prospective observational study. Forty-three children with febrile neutropenia episodes admitted in KKCTH, Chennai, were included in the study. The duration of the study was 1 year. Relevant patient and disease specific details were obtained, results were analyzed, and conclusions were drawn. Results There were 90 episodes of febrile neutropenia. Overall culture positivity was identified in 37 cases (41.11%). Bacteremia (23.3%) was the most common cause of microbiologically documented infection. Gram-positive organisms (60%) were more commonly documented. Among the gram-positive organisms, coagulase-negative Staphylococcus aureus was the predominant isolate followed by Streptococcus . Central line-associated bloodstream infections were documented in 13.33%. Chemo-port removal was done in four children. Three had invasive fungal disease. The majority of the gram-negative isolates were resistant strains. Morbidity was significantly more in gram-negative infections. Overall outcome was good though three children succumbed to sepsis. Conclusion A vigilant management of illness is essential. Chemo-port carries risk of severe infection. Protocol-based management of catheter-related bloodstream infection (CRBSI) can limit the number of chemo-port removal. Though gram-positive organisms are in the rise, gram-negative organisms are still responsible for significant morbidity. Early initiation of broad-spectrum empirical antibiotics with optimal gram-positive coverage is crucial. Children with suspected fungal infections should be aggressively evaluated and treated. An organized approach is the key in successful management.

Abstract Background: Although renal complications are well-known in hematological malignancies, they occur mostly after initiation of steroids and chemotherapy. We describe an unusual scenario of isolated renal complications as a presenting feature in children with acute lymphoblastic leukemia (ALL). Clinical Description: A 2-year-old girl presented with abdominal distension due to bilateral palpable renal masses associated with stage 2 hypertension. Investigations revealed ALL and impaired renal functions with enlarged kidneys on ultrasound, with no involvement of any other organ or lymph node. Management and Outcome: She required three antihypertensives for normalizing her blood pressure (BP). After initiation of chemotherapy, BP improved, kidney sizes reduced, and acute kidney injury resolved. Conclusion: Renal functions, BP and imaging for kidney sizes should not be missed in the initial work-up in children with ALL.

Background: The incidence of brain tumours in India equate to half of those in the developed world. Delayed diagnosis is associated with a higher risk of life-threatening neurological complications at presentation and poor cognitive outcomes amongst survivors. Early detection and treatment is crucial for improving outcomes. Aims: The aim of this study was to analyse baseline diagnostic intervals for paediatric brain tumours in Tamil Nadu. Methods: Data for this retrospective study was collected via questionnaire across 8 different hospitals in Tamil Nadu. It consisted of 14 questions where doctors were asked to record data items including the date of symptom onset, first presentation to healthcare and date of diagnosis. Results: 114 children were diagnosed with a brain tumour between January 2018 – October 2020. The average diagnostic interval was 9.3 weeks (median 3.5 weeks), and the average patient interval is 6.1 weeks (median 0.6 weeks.). Low-grade tumours had the longest median total diagnostic interval of 6.6 weeks. The median total diagnostic interval was significantly higher in villages (7.9 weeks), as compared to patients located in District (4.8 weeks) and cities (2.3 weeks). Conclusion: Overall, the diagnostic interval for paediatric brain tumours were comparable to data in the UK. Moreover, all patients received an MRI within a day, indicating excellent infrastructure.. However, many low-grade and optic pathway tumours were unaccounted for. Tamil Nadu has one of the best healthcare systems in India and extending this methodology to areas with poorer healthcare provisions, is required to get representative national data.

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.

Teratoid Wilms tumor (TWT) is a variant of Wilms tumor. 30 cases have been reported so far. The extrarenal TWT variant has only been 5 in number. We are reporting a case of retroperitoneal TWT in a 6-year-old female child with diagnostic and therapeutic challenges.

Aims The aim was to study cytogenetics and molecular genetic profile in pediatric B-acute lymphoblastic leukemia (ALL) and correlate it with induction outcomes. Subjects and Methods A retrospective study of cytogenetics and molecular genetics of 98 children with B-cell ALL from January 2013 to May 2018 was done. Cytogenetics and molecular genetics were done in the bone marrow using multiplex reverse transcription polymerase chain reaction and G-banded karyotyping, respectively. Minimal residual disease (MRD) assessment was done at the end of induction by flowcytometry. Results Of the 98 children, 83 (84.6%) had evaluable cytogenetics, with 11 (13.25%) being abnormal karyotypes. Of the 11 abnormal karyotypes, seven children (8.4%) had hyperdiploidy, one had hypodiploidy, and three had miscellaneous findings. In molecular genetics, TEL-AML1 (ETV6/RUNX1)[t(12;21)] was the most common fusion gene abnormality (12.2% [12/98]), followed by E2A-PBX1 [t(1;19)] (5%), BCR/ABL1 [t(9;22)] (3%), and MLL-AF4 [t(4;11)] (1%). All the 98 children attained morphologic remission at the end of induction. All children with hyperdiploidy (7/7) attained remission and MRD negativity, but one expired during maintenance chemotherapy of disseminated tuberculosis. The child with hypodiploidy was MRD-positive. Three (25%) children with t (12;21) were MRD-positive. All children with Ph + ALL, t(1:19), and t(4;11) were MRD-negative. Fifty-two children had no detected abnormalities, six of whom had MRD positivity (11.5%). Conclusion Cytogenetic and molecular genetic subgrouping prognosticates ALL outcomes. Although 25% of TEL-AML + children had MRD positivity, larger studies are required to validate the same. End-of-induction MRD outcomes did not correlate with chromosomal aberrations.

Background: Early diagnosis of sepsis in children with febrile neutropenia remains difficult owing to non-specific clinical and laboratory signs of infection. There is a need to assess the utility of inflammatory markers in clinical risk assessment for their ability to discriminate between low-risk and high-risk neutropenic patients since presently there is insufficient data to recommend their routine use. Methods: This is a prospective study of children on therapy admitted with febrile neutropenia and sampled for serum procalcitonin (PCT), interleukin-6 (IL-6), and interleukin-8 (IL-8) at admission. The febrile neutropenia episodes were categorized into two groups - Group I: no focus of infection and Group II: clinically/microbiologically documented infection. Statistical analyses for comparison were performed using Z-test and receiver operating curves at various cut-off levels. Results: A total of 46 episodes of febrile neutropenia in 33 children were analyzed. In total, 76% were categorized as group I and 24% as group II. The mean value of PCT in group II was higher (28.07 ng/mL) than group I (1.03 ng/mL) though there was no significant statistical difference. At a cut-off level of 2 ng/mL for PCT, sensitivity of 63%, specificity of 91%, positive predictive values (PPV) of 70%, and negative predictive value (NPV) of 88% were observed. There was no significant difference in the IL-6 and IL-8 levels between both the groups. However, at an optimal cut-off value of 50 pg/mL, IL-6 had an NPV of 80% and at a cut-off level of 130 pg/mL, IL-8 had an NPV of 73%, however, with low sensitivity and specificity. Conclusion: IL-6, IL-8, and PCT can be utilized to define a group of patients with a low risk of sepsis in view of their favorable NPV. The use of these biomarkers together can facilitate early discharge from the hospital, and the use of oral antimicrobial therapy, in turn, reducing the cost of supportive therapy in a developing country.

Introduction Most Indian centers use Adriamycin/Bleomycin/Vinblastine/Dacarba-zine (ABVD) chemotherapy for pediatric Hodgkin lymphoma (pHL). To reduce the late toxicity, robust predictive markers are needed to risk stratify pHL patients, thereby limiting the number of chemotherapy cycles and omitting radiation for low-risk and intensifying treatment for high-risk children. Objective This study was conducted to analyze the outcome of pHL patients treated with ABVD and various factors predicting the outcome. Materials and Methods This retrospective study analyzed the outcome of 113 consecutive pHL children treated with ABVD chemotherapy from 11 tertiary care centers in South India from 2009 to 2019. Results The median duration of follow-up was 2.73 years. The median age was 13 years. B symptoms are seen in 50.5% patients, bulky disease in 23%, and stage IV in 28.3%. Of 113 pHL, 69% had a positron emission tomography (PET) and 31% had computed tomography (CT)-based staging. Stage IV (37.1%) and extranodal involvement (31.2%) were seen more often with PET than with CT staging (8.5 and 2.8%, respectively). Among 64 patients with interim PET scan after two cycles (iPET2), 20.3% did not achieve complete remission (CR) and no factors were significantly associated. The 4-year event-free survival (EFS) rate of the entire cohort was 86%. The 4-year EFS rate was 93% for patients with CR in iPET2 and 52% for patients not achieving CR. The only independent predictor of low EFS was iPET2 response (p < 0.05). Conclusion Our study confirms the prognostic role of PET scan staging and response assessment. Not achieving CR on the iPET2 scan indicates poor prognosis and warrants clinical trial enrollment for a better outcome.

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.

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.

Pyoderma gangrenosum (PG) is a sterile neutrophilic dermatosis which occurs either idiopathically or associated with various systemic diseases and malignancies. Although the association of PG with myeloid malignancies is well known, its association with lymphoid malignancy especially in children is extremely rare. We describe PG in association with acute lymphoblastic leukemia in a 4-year-old child, an occurrence which has been reported just once previously to the best of our knowledge.