Optimising Palliative Care for Children with Metastatic Neuroblastoma and the Paediatrician's Role in a Shared Care Model - Proposal from a Regional Cancer Centre in India.

Objectives: The burden of advanced and metastatic cancer is high among children in developing countries, and palliative care (PC) services for children are sparsely available and poorly accessed. To estimate the burden of PC requirements in children with metastatic neuroblastoma (NB), and to evaluate the PC services offered. Materials and Methods: Retrospective analysis of case records of children 1-14 years diagnosed with metastatic NB from 1 January 2008 to 31 December 2017. Results: One hundred and nineteen patients with metastatic NB were included, of which 87 patients received PC consultation. Early PC referral occurred only in 13 patients (14.9%), and pain was the most prominent symptom. Shifting of care from oncology to PC occurred at disease relapse in 58 patients (66.6%) and at end-of-life in 16 patients (18.3%). Nausea/vomiting, constipation and abdominal distension were the most common symptoms during end-of-life. Seventy-one patients (85%) died of disease, median time to death being 9 months from diagnosis and 4 months from relapse. The mean time from initiation of PC to death was 4.2 months. Conclusion: Timely integration of PC and shared care incorporating the oncology team, PC team and local paediatricians can ease out transition in care, ensure a continuum of care and improve the quality of treatment delivered to children with metastatic cancer.

Clinical profile and outcome of children with anaplastic large cell lymphoma treated with short-course chemotherapy - ten years experience from a tertiary care center in a LMIC.

Anaplastic large-cell lymphoma (ALCL) constitutes 10-15% of non-Hodgkin lymphoma in children. With short-course chemotherapy, outcome has improved up-to 90% in developed-countries. There is limited-data on outcome of pediatric ALCL treated with ALCL99 protocol from low-middle income countries. Children ≤14 years, diagnosed with ALCL between 1st January 2007 and 31st December 2016 were analyzed. Details regarding clinical-presentation and treatment were recorded and outcome was analyzed. Fourteen-children were diagnosed. Median-age was 114 months (range 24 - 162 months). Male:female ratio was 3.6:1. Stage-I, II and III disease was seen in three (21.4%), three (21.4%), and eight (57.1%) children, respectively. Low, standard and high-risk disease was seen in two (14.2%), six (42.9%) and six (42.9%), respectively. All children were treated using ALCL99 protocol. Three (21.4%) children had disease-progression/relapse and five (35.7%) died (three from treatment-related mortality, and two from disease). At median follow-up of 54-months, four-year EFS and OS were 64.3% and 64.3%, respectively. Log-rank test demonstrated female gender (p = 0.005), stage-III disease (p < 0.001), visceral-organ involvement (p = 0.035), high-risk disease (p = 0.016) and, serum albumin ≤3.5 g/dL (p = 0.031) associated with significantly worse 4-year EFS. Cox-regression analysis demonstrated female gender associated with poor EFS (p = 0.02) and female gender and visceral-organ involvement associated with poor OS (p = 0.02, p = 0.011, respectively). Good survival could be achieved for children with ALCL using uniform treatment protocol in a resource-limited setting, especially among low and standard-risk children. Female-sex, high-risk disease, stage-III disease, visceral organ involvement and low albumin levels were associated with poor outcome, however these findings need to be corroborated in larger studies.

Outcomes of pediatric mixed phenotype acute leukemia treated with lymphoid directed therapy: Analysis of an institutional series from India.

There is limited data regarding pediatric mixed phenotype acute leukemia (MPAL) and there is no global consensus on its management yet. In this retrospective study, we analyzed the outcomes of children diagnosed with MPAL at our institute. This study included children ≤ 14 years with MPAL who presented to a tertiary cancer center in India from January 1st 2009 to December 31st 2015. Over a seven-year period, 1390 patients with leukemia presented to our institute of which 22 patients (1.5%) had MPAL. Sixteen patients (72.7%) had B/myeloid leukemia, while 4 (18.1%) and 2 (9%) patients had T/myeloid and B/T leukemia respectively. Twenty-one patients were treated with a modified BFM ALL 95 protocol. 76.1% (n = 16) of patients had a good prednisolone response (GPR) on day 8 and end-of-induction (EOI) marrow was in remission in 90.5% (n = 19). A poor prednisolone response (PPR) on day 8 correlated with an inferior relapse-free survival (25% vs 79.5%, P=.025). The 4-year event-free survival (EFS) and overall survival (OS) for the entire group was 60.8% and 64.9% respectively while the EFS for patients who had a GPR and remission at the EOI (n = 15) was 80% as compared to 16.7% in patients with PPR or induction failure. Lymphoid directed chemotherapy is seen to have good survival outcomes in pediatric MPAL. However, a PPR on day 8 or a positive EOI marrow may be an indication for more aggressive treatment.

Effect of imatinib on growth in children with chronic myeloid leukemia.

Imatinib is a preferred drug for pediatric Chronic Myeloid Leukemia (CML). Long-term use has inhibitory effects on other tyrosine kinase pathways causing off-target complications such as growth impairment. Our aim was to evaluate impact of long-term use on longitudinal growth in children with CML in Kerala. We hypothesized that the impact would be lesser compared to Northern India as Kerala has the lowest rates of underweight and stunting, with a high literacy rate and per capita income. Children ≤14 years of age, diagnosed with CML and received imatinib for at least 1 year were included. Girls >9 years of age and boys >11 years were considered pubertal. Height Z scores were derived using WHO AnthroPlus. Paired t test compared difference of Z scores in prepubertal and postpubertal age groups. Height Z scores were compared with mid-parental height and sibling height Z scores. Thirty-six children were included (M = 21; F = 15). Median duration of imatinib exposure was 84 months. Decrease in longitudinal growth affected children in both prepubertal and postpubertal age groups. Decrease in height Z scores was more in prepubertal age group when imatinib therapy was initiated (p = .0018). Of 10 patients currently above 19 years (of whom 8 were in pubertal age and 2 in prepubertal age at start of imatinib) none are stunted. Patient's height Z scores was lesser compared to sibling height Z scores (p = .027). Children on continuous imatinib showed a significant stunting when treatment was initiated during prepubertal age. There is a catch-up of growth as the final height reached is within normal limits of WHO reference values.

Intensifying Insulin Therapy in Type 2 Diabetes: Choices & Challenges.

Insulin therapy remains the cornerstone of effective diabetes management. Timely intensification of insulin therapy reduces the progression of diabetes and the development of diabetes-related complications. Given that overall hyperglycaemia is a relative contribution of both fasting and postprandial hyperglycaemia, use of basal insulin alone may not achieve optimal glucose control due to its inability to cover postprandial glucose excursions. Intensifying therapy with addition of bolus insulin or switching to premixed insulin is a viable option in patients failing on basal alone therapy. Although the benefits of early insulin treatment are well established, a considerable delay in intensifying insulin therapy in patients with sub-optimal glycaemic control is still observed. Most of the patients and physicians are reluctant to intensify therapy due to the fear of hypoglycaemia, regimen complexity, and increased burden of multiple daily injections. In this context, there is a need for a flexible, alternative intensification option taking into account individual patient considerations to achieve or maintain individual glycaemic targets. An ideal insulin regimen should mimic physiological insulin release while providing optimal glycaemic control with low risk of hypoglycaemia, weight gain and fewer daily injections. The current paper reviews the challenges of insulin intensification in patients with type 2 diabetes mellitus poorly controlled on current treatment regimens.

Hopkins syndrome and phantom hernia: a rare association.

Acute flaccid paralysis (AFP), other than paralytic poliomyelitis, are usually due to demyelination like Guillian Barre syndrome (GBS), transverse myelitis and traumatic neuritis. Poliomyelitis like illness, Hopkins syndrome or Post Asthmatic Amotrophy, associated with bronchial asthma and hyperIgEemia has been reported in literature. We present a two and a half year old child who developed AFP with phantom hernia following an episode of bronchial asthma.