Hematopoietic stem cell transplant(HSCT) is the only modality that, if performed in the early- stages of cerebral X-linked adrenoleukodystrophy(X-ALD) can lead to good outcomes. Loes- score, calculated based on the findings of the magnetic resonance imaging(MRI) of the brain, helps in the selection of patients for HSCT. As per recommendations, the Loes-score should be <10 for a patient to be eligible for HSCT. Here we report a child of cerebral X-ALD with Loes of 12, but a good neurological function score(NFS), who was treated with HSCT, and had good outcomes. It is therefore important to utilize other parameters along with the Loes score, in selecting patients for HSCT in X-ALD.

Background: Juvenile Myelomonocytic leukemia(JMML) is a rare and aggressive malignancy found in children. The genomic landscape of the JMML shows that the most common mutated genes found in the RAS. The risk stratification and the management of JMML patients is determined by the precise evaluation of the underlying genetic mutations. The co-occurring mutations along with the RAS pathway mutations may affect the outcomes of the disease. PTPN11 is the most common mutation found in JMML. In this study, we describe the outcomes of JMML patients who had an underlying PTPN11 mutation along with a mutation in the SETBP1 gene. Methods: DNA was extracted from the 43 cases with JMML after confirmation of the diagnosis. Whole exome sequencing was performed to find out the underlying germline and somatic mutations. Results: We found that about 35%(n=14) of patients harboured a PTPN11 somatic mutation. A coexisting SETBP1 mutation was found in 5 patients out of 14 cases. In our cohort of patients, we found that the SETBP1 was exclusively associated with PTPN11 and all 5 patients transformed into AML. The median time to AML transformation was 12 months (13 days-35 months). PTPN11 mutation with co-existing SETBP1 mutation showed a worse outcome compared to other PTPN11 positive patients and all 5 patients died within 3 months of transformation. Conclusion: In with PTPN11 positive JMML a coexisting SETBP1 mutation confers a poorer prognosis. These patients have a high risk of AML transformation. These patients should be candidate for consideration of early hematopoietic stem cell transplantation (HSCT).

Background Chemotherapy related mucosal toxicity is a major hindrance to successful therapy in pediatric cancers. The role of gut dysbiosis in modulation of chemotherapy related gastrointestinal toxicity is poorly understood. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for neutropenic enterocolitis (NEC) with CECT abdomen. Clinical features, fecal calprotectin and microbiological data were analysed. Fecal Gut microbiota was evaluated in children with NEC and compared with children where NEC was excluded and healthy controls using conventional culture method. Results Of 590 children receiving chemotherapy during study period, 44 were diagnosed with NEC. Significantly higher frequency of isolation of Bacteroides was observed in children with NEC (42%) as compared to non- NEC group (14%) and healthy controls (13%). Isolation of Lactobacilli was infrequent in NEC group (26%) than non- NEC group (74%) and healthy controls (80%). There was nonsignificant trend towards higher isolation of Clostridium in children with NEC. Clostridiodes difficle or Clostridium septicum were not identified in any group. Isolation of other bacterial flora was similar in the sub groups. No significant association of survival with gut dysbiosis could be established. Isolation of Lactobacilli was associated with reduction in duration of intravenous alimentation by 2.4 days, whereas isolation of Bacteroides prolonged the requirement of bowel rest by 2.2 days. Conclusion Gut dysbiosis was significantly higher in NEC group and associated with higher morbidity suggesting its role in pathogenesis. This highlights role of interventions towards gut dysbiosis like prebiotics and probiotics in pediatric cancer patients.

The second wave of COVID 19, far outnumbered the first, in cases and deaths. We report outcome of pediatric cancer patients with COVID-19 during the second wave, from a tertiary center in India. Out of 41 patients who tested positive; 51% were asymptomatic, 36% had mild symptoms, 12 required admissions in ward and 4 in intensive care. Mechanical ventilation, systemic steroids, Remdesivir and IVIG were required in those admitted to intensive care unit. Out of 4 deaths (9.7%), 3 occurred in adolescent age and 2 had superimposed bacterial/viral infections. Other contributors to mortality were: cachexia, airway obstruction, disease relapse.

Background Neutropenic enterocolitis (NEC) is a dreaded complication of chemotherapy. There is scant literature regarding incidence, clinical features, and determinants. The understanding of gut dysbiosis in NEC and pediatric cancer is evolving. Methods Pediatric cancer patients with neutropenia and gastrointestinal symptoms were evaluated for NEC with CECT abdomen. Clinical, imaging, and laboratory features were analysed. Fecal samples were analysed for fecal calprotectin by sandwich ELISA and gut microbiota by conventional culture and compared with healthy controls and children without NEC. Results NEC was diagnosed in 44 children based on clinical and imaging features with incidence of 7.4% (Four had recurrent episodes). Common manifestations included fever(98%), pain abdomen(88%), and diarrhoea(83%). Hypoalbuminemia was observed in 78% patients. Large bowel involvement(94%) with diffuse bowel involvement(63%) and pancolitis(64%) were common. Fecal calprotectin was significantly elevated in NEC group than non-NEC group and healthy controls (median 87, 53, and 42 µg/g respectively). Higher degree of gut dysbiosis was observed in children with NEC with higher isolation of Bacteroides and infrequent isolation of Lactobacilli.. Mortality rate of 23% was observed. Only presence of free fluid predicted higher mortality. Though levels of fecal calprotectin and gut dysbiosis were higher in NEC, they didn’t increase mortality. Isolation of Bacteroides and absence of Lactobacilli predicted longer duration of intravenous alimentation. Conclusion NEC caused significant morbidity and mortality in pediatric cancer patients. Gut dysbiosis was significantly higher in NEC group suggesting role in pathogenesis and influencing outcome. This highlights role of targeted interventions towards gut dysbiosis like prebiotics and probiotics.

Xeroderma pigmentosum (XP) is a rare genodermatosis characterized by defective DNA repair, leading to hypersensitivity to ultraviolet (UV) sunlight and predisposes to various cutaneous and non-cutaneous malignancies. Platinum compounds are used against cutaneous cancers as concurrent chemoradiotherapy. But the XP gene polymorphism has a potential role in metabolism of these agents and their susceptibility. Here, we report a case of cutaneous squamous cell carcinoma in a patient with XP who had severe toxicity to chemotherapy. We also discuss other similar cases reported in literature of this entity, to highlight this potentially lethal pharmacogenomic association.

Paraneoplastic neurologic syndromes (PNS) are rare in pediatrics and are understood to be consequences of cross-reactivity against various neuroendocrine antigens expressed on cancer cells. Here, we report a case of autoimmune encephalitis, a type of paraneoplastic neurologic syndrome that was associated with a case of adrenocortical carcinoma and had some clinical response to immunosuppressive therapy. Adrenocortical carcinoma is a rare tumor with controversial tissue of origin but expresses various neuroendocrine antigens that could be the possible mechanism for this rare yet interesting association.

Background: Childhood cancer survivors are 8.8 times more likely to die of pulmonary causes when compared to general population: an aspect of concern. Pulmonary dysfunction is the third leading cause of non recurrence related cause of death among Hodgkin lymphoma survivors. Methods: A cross section study on Hodgkin lymphoma survivors in complete remission, who completed treatment within last 5 years was done. All children were subjected to detail history including drugs, past history of respiratory illnesses, physical and respiratory system examination followed by spirometry and three minute step test under supervision. Pulmonary dysfunction was determined as presence of obstructive, restrictive or mixed pattern on spirometry or abnormality in three minute step test. Subclinical pulmonary dysfunction was determined as patients who were clinically asymptomatic but had pulmonary dysfunction Results: A total of 60 children were enrolled (Mean age of 11.3 years and 53 were boys) Abnormal pulmonary function tests were documented in 11 (18.3%) of HL survivors at a median time of 2 years (IQR 1,3) from treatment completion. Restrictive pattern was documented in 10 (16.67%) and obstructive pattern in only one patient (1.67%), mostly mild in severity. Older age at start of chemotherapy and radiotherapy and past history of respiratory illness were found to be significantly associated with pulmonary dysfunction. Conclusion: Majority of Hodgkin lymphoma survivors had subclinical pulmonary dysfunction at median follow up of 2 years from treatment completion. Hodgkin lymphoma survivors require long term follow up for timely detection of pulmonary dysfunction and improve quality of life.

BACKGROUND: Neurocognitive deficits are an important late effect in survivors of acute lymphoblastic Leukemia(ALL). Data from low middle income countries is scarce and highly influenced by biological and cultural variations. Such data would be useful for highlighting the importance of early intervention in an already disadvantaged population. PROCEDURE: 70 consecutive survivors of childhood ALL were evaluated for neurocognitive deficits by the Indian adaptation of Wechsler Intelligence Scale for Children-Fourth Edition(WISC-INDIA). Prevalence of neurocognitive deficits was calculated based on Full Scale Intelligence Quotient(FSIQ) and scores in discrete domains like Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed were calculated and compared to baseline characteristics, chemotherapy and radiation dose received. RESULTS: The mean FSIQ was 86.1 ± 20.5, with significant neurocognitive deficit(FSIQ <90) being prevalent in 50%(95% CI 38% to 62%) of the cohort. The proportion of survivors with deficits in individual domains of verbal comprehension, perceptual reasoning, working memory and processing speed were 49%, 50%, 47% and 44% respectively. The odds of having deficits in neurocognitive function was higher when a child belonged to lower socioeconomic strata, had parents with less than primary school education and whose birth order was higher(All p<0.05). Age at diagnosis, current age at assessment, receiving lower or higher dose of radiotherapy, high dose methotrexate or cytarabine did not have a direct impact on neurocognitive function. CONCLUSIONS AND RELEVANCE: The current need is to develop country specific neurocognition assessment tools to initiate early screening and develop culturally appropriate preventive and rehabilitative interventions.

Ketamine is a dissociative anesthetic agent, with excellent analgesic properties and a favorable safety profile. Although it acts predominantly through NMDA receptor antagonism, numerous other molecular targets have been characterized, rendering anti-inflammatory, anti-depressant, and thus expanding its scope for new clinical applications. The noticeable safety of ketamine in children enables its widespread use in pediatric oncology, chiefly for procedural sedation. Its value for chronic pain management in children with cancer is being increasingly recognized but requires more evidence. The topical use of ketamine is largely in investigational stages.. Rational medical use of ketamine is largely free from significant long-term neurological side effects but may have some troublesome short-term effects such as vomiting, palpitations, urinary retention, and hallucinations. This review will provide a brief account of the pharmacology of ketamine and primarily focus on the relevant aspects of ketamine in pediatric oncology.

Data on the prevalence and outcomes of coronavirus disease (COVID-19) in children with cancer is limited, more so from developing countries. We aimed to evaluate the prevalence, severity and outcome of COVID-19 in pediatric oncology patients by implementing a screening and testing plan. Among 104 children tested, the rate of COVID-19 positivity was 15% and 3% in symptomatic and asymptomatic respectively. Majority had mild illness with uneventful recovery, whereas neutropenia increased the risk of serious illness. Prolonged virus shedding with a median time to negativity of 21 days was observed.

Background and aims: Oral mucositis (OM) is common and distressing toxicity in children on chemotherapy. There is limited number of safe and effective therapeutic options available for OM. Ketamine oral rinse has shown promising results in few studies in adults. This randomized, double-blind placebo-controlled trial aimed to test the efficacy of ketamine mouthwash in reducing chemotherapy-induced severe OM pain in children. Methods: Children aged 8-18 years with severe OM were randomized to a single dose of ketamine mouthwash (4 mg/ml solution; dose 1 mg/kg) or a placebo. A sample size of 44 patients was determined. Pain score (6-point faces scale) was noted at baseline and 15, 30, 45, 60, 120, 180, and 240 min. The outcome variables were a reduction in pain score, need for rescue medications, and adverse events. Results: The baseline characteristics were comparable in the two groups. The mean OM pain at 60 min decreased by 1.64 points (CI 1.13-2.14) in the ketamine group and 1.32 points (CI 0.76-1.87) in the placebo group (p=0.425), with a group difference of 0.32 points. Rescue pain medication (at 60 min) was required in 13.6% in the ketamine group and 18.2% in the placebo group (p=1.000). There were no significant adverse events observed. Conclusions: Among children on cancer chemotherapy with severe OM, ketamine mouthwash at a dose of 1 mg/kg did not significantly reduce OM pain. It did not decrease the need for rescue pain medications. Further research is warranted to test higher doses of ketamine for a clinically significant effect.