Childhood medulloblastoma

Medulloblastoma is the most common malignant brain tumour in children and is a major cause of mortality and morbidity, particularly in low- and middle-income countries. It has been risk-stratified on the basis of clinical (age, metastasis and extent of resection) and histological subtypes (classic, desmoplastic and anaplastic). However, recently medulloblastoma has been sub-grouped by using a variety of different genomic approaches, such as gene expression profiling, micro-ribonucleic acid profiling and methylation array into 4 groups, namely Wingless, Sonic hedgehog, Group 3 and Group 4. This new sub-grouping has important therapeutic and prognostic implications. After acute leukaemia, brain tumour is the second most common malignancy in the paediatric age group. The improvement in outcome of acute lymphoblastic leukaemia in low- and middle-income countries reflects the relative simplicity of diagnostic procedures and management. Unlike leukaemia, the management of brain tumours requires a complex multidisciplinary approach, including neuro-radiologists, neurosurgeons with a paediatric expertise, neuropathologists, radiation oncologists and neuro-oncologists. In addition, the equipment required for the diagnosis (magnetic resonance imaging scan, histological, molecular and genetic techniques) and the management (operating room, radiation facilities) is a limiting factor in countries with limited resources. In Pakistan, there are very few centres able to treat children with brain tumours. The current literature review was planned to provide an update on the management of this tumour

A retrospective review on antibiotic use in acute watery diarrhea in children in a tertiary care hospital of Karachi, Pakistan

Introduction: Responsible for at least one in nine pediatric deaths, diarrheal diseases are the leading, global cause of death. Further abetted by improper antibiotic use in a hospital setting, children with acute watery diarrhea can see prolonged hospital stays, and unwanted adverse effects such as antibiotic resistance. Hence, this study is aimed to identify the association between antibiotic usage for the treatment of acute watery diarrhea in children, and the impact this line of management has on the duration of their hospital stay.Methods: A retrospective review was conducted at the department of Pediatric of Aga Khan University Hospital (AKUH) in Karachi. A total of 305 records of children aged 6 months to 5 years who were admitted with a diagnosis of acute watery diarrhea from June 2017 -December 2018 was screened, of which 175 fulfilled the eligibility criteria. A predesigned questionnaire was used to collect demographic information, comorbidities, and clinical features, severity of dehydration, clinical examination, treatment received, and laboratory investigations. The primary outcome of this study was the length of hospital stay measured against the number of hours a child stayed in hospital for treatment of acute watery diarrhea. The statistical analysis was carried out using STATA version 14 to reach conclusive results.Results: 175 patients presented with acute watery diarrhea, out of which 106 (60.6%) did not receive antibiotics. The median (IQR) age of the group that did not receive antibiotics was 12.0 (12.0) months compared to 15.0 (12.0) months for the group that did receive antibiotics. In both groups, there were more males than females, less than 15% of the patients were severely malnourished (WHZ score -3SD) and less than 10% of the patients were severely dehydrated. The median (IQR) length of hospital stay (hours) was 32.0 (19.0) respectively for the group that did not receive antibiotic and 41.0 (32.0) for the group that did receive antibiotic therapy. The expected length of hospital stay for the group that received antibiotic therapy was 0.22 hours higher than the group that did not. Finally, as compared to females, hospital stay for males was longer by 0.25 hours.Conclusion: In conclusion, antibiotic use was associated with a prolonged hospital stay in children with acute watery diarrhea as compared to children who did not receive antibiotics. Large scale robust prospective studies are needed to establish this association using this observational data

Poster # 306 PRF1-Related familial hemophagocytic lymphohistiocyctosis in a Pakistani family: Importance of molecular testing

Background: Posterior reversible encephalopathy syndrome (PRES) is associated with a range of medical conditions and medications.Objectives: In this retrospective analysis we attempted to identify predisposing factors for PRES in children with cancer on chemotherapy.Design/Method: We identified 19 patients, 4 females and 15 males. These patients were diagnosed with PRES on clinical and radiological features. Patient charts were reviewed from January 2013 to June 2016 after authorization from the Institutional review board (IRB).Results: The average age of patients with PRES was 7-years. Primary diagnosis of these patients included non-hodgkin lymphoma (n = 9), acute pre-B-leukemia (n = 5), relapsed pre-B-leukemia (n = 2), hodgkin-lymphoma (n = 2) and Ewing sarcoma (n = 1). PRES occurred during induction chemotherapy in 12 patients. Sixteen patients had hypertension when they developed PRES. Most of these patients (n = 14) were on steroids when they were diagnosed with PRES. Common clinical features included hypertension, seizures and altered mental status. Excluding 3 patients all others required anti-epileptic therapy. 10 of these patients got re-imaged with an MRI. Ten of our patients are still alive.Conclusion: PRES is becoming a commonly recognized complication in pediatric patients with cancer. Patients presenting to our center with signs and symptoms of hypertension, seizures, visual loss or altered mental status get an MRI. PRES was mostly seen in patients undergoing systemic induction chemotherapy, intra-thecal chemotherapy and on steroids. Despite reversal of clinical and radiological findings most patients could not be weaned off anti-epileptics

Upshaw-Schulman syndrome with c.2728C\u3eT Mutation in ADAMTS13 Gene

Congenital thrombotic thrombocytopenic purpura is a rare autosomal recessive disorder presenting with hemolytic anemia, thrombocytopenia, micro vascular thrombosis, and end organ damage. Here, we present a case of a 7-year-old girl having recurrent neonatal hemolysis, developmental delay, frequent seizures, and thrombocytopenia. Characteristic clinical picture and gene sequencing of a disintegrin and metalloproteinase with thrombospondin motifs 13 confirmed the diagnosis of Upshaw-Schulman syndrome. She was treated successfully with plasma infusion. The patient is alive at 6-month post follow-up, and on regular plasma therapy. Congenital thrombotic thrombocytopenic purpura should be considered in the differential diagnosis of thrombocytopenia with hemolytic anemia in infants

Clinical features and treatment outcomes of children With anaplastic large cell lymphoma in Pakistan: A multicenter study

Background: different approaches have been adopted in the treatment of anaplastic large cell lymphoma (ALCL); there is a lack of consensus with regard to standard treatment. Because of paucity of data from low and middle-income countries, we reviewed the clinical features and treatment outcomes of children with ALCL. Method: all ALCL patients under 16 years of age diagnosed from 2005 to 2015 at Aga Khan University Hospital and The Indus Hospital were identified. Clinical features and treatment outcomes were analyzed. Result: thirty-two (n=32) patients met the inclusion criteria. Cervical Lymphadenopathy was the most common presentation (34.3%, n=11). Advanced disease was seen in 68.7% (n=22) (stages III and IV). Fourteen (42.4%) were treated on ALCL-99, 30.3% (n=10) on multicenter protocol-842 regimen, 9% (n=3) on adriamycin-prednisolone-oncovin (doxorubicin, prednisone, vincristine) regimen, and 16% (n=5) were treatment abandonments. Five-year overall survival was 70.6% (95% confidence interval: 47.8%-84.9%), and 5-year event-free survival (EFS) considering treatment abandonment and death as an event was 52.3 % (95% confidence interval: 23.5%-74.8%). Conclusion: significant therapy-related mortality (27.7%) was observed. Treatment abandonment and therapy-related toxicity were the major barriers for better outcomes. However, less intensive outpatient regimens, such as adriamycin-prednisolone-oncovin regimen, may decrease the number of hospitalizations, hence reducing treatment abandonment in the low and middle-income country

Poster # 052 Risk stratification and outcomes based on cytogenetic profile in acute myeloid leukemias in Pakistan

Background: Acute myeloid leukemia (AML) is a heterogeneous disease from morphologic, cytogenetic, immunophenotypic, molecular, and clinical perspectives. AML accounts for15% to 20% of all childhood leukemia. Cytogenetic and molecular data are recognised as the most valuable prognostic factors in AML. Most of the studies on cytogenetic profiling of AML are from Western countries and similar data from lower-middle-income countries is lacking. We conducted this retrospective study at a single cancer centre in Pakistan.Objectives: To study the cytogenetic etiology in AML and its association with treatment outcomes in pediatric patients at Aga Khan University Hospital in Karachi, Pakistan.Design/Method: Patients from birth through 18 years diagnosed from 2006 to 2017 with AML were analysed for demographics, presenting complaints, cytogenetic profiles, management plan, toxicity and treatment outcomes.Results: The cohort included 176 patients. A total of 103 patients were excluded due to incomplete data. Seventy-three patients met the inclusion criteria with median age of 13 years IQR (4-16 months). Forty-four (60%) patients were male. Fever (n = 56, 80%) was the most common presentation. From the risk stratification groups, 23 (32%) were Favorable, 36 (49%) were Intermediate, and 14 (19 %) were Adverse. Gum Hypertrophy (n = 3, 4%, p = 0.58) was seen in Intermediate and Adverse whereas Chloroma (n = 3, 4%, p = 0.031) was seen in Favorable, showing significant difference in risk group presentation. Forty-five (62%) were treated on Cytarabine, Daunorubicin, Etoposide protocol, 9 (12%) on Cytarabine and Daunorubicin, and 9 (12%) did not receive treatment. Chemotherapy toxicities included Cardiotoxicity (n = 14, 19%) and Neurotoxicity (n = 2, 3%). The median follow-up period was 9 months. Five-year overall survival for Favorable risk: 40% (95% CI: 5% - 76%), Intermediate risk: 38% (95% CI:19% - 57%), and Adverse risk: 49% (95% CI: 18% - 80%). The 5-year Event-Free Survival keeping relapse as an event for Favorable risk: 85% (95% CI: 66% - 104%), Intermediate risk: 57% (95% CI: 32% - 82%), and Adverse risk: 58% (95% CI: 22% - 94%).Conclusion: Our results suggest that risk stratification based on cytogenetic etiology did not correlate with survival outcomes. This suggests that lower survival rates in our population are not due to primary disease but possibly due to higher rates of toxicity and complications

Capacity building for pediatric neuro-oncology in Pakistan- A project by my child matters programme

Background and Aims: The landscape of Pediatric Neuro Oncology (PNO) has changed in Pakistan since 2014, when a PNO twinning program was initiated between the Aga Khan University Hospital (AKUH) and the Hospital for Sick Children (SickKids), Toronto. This twinning initiative identified the dire need of broadening the PNO services in other centers of Pakistan.Methods: The project for the Capacity building of PNO services was initiated in 2019 with the support of a ‘My Child Matters’ grant by the Sanofi Espoir Foundation. The grant\u27s main purpose was to enhance the capacity for PNO services in 13 public and private sector hospitals across Pakistan. Activities included establishment of National PNO tumor boards, educational workshops and fellowship to train and raise awareness of health care professional (HCP), patients and families.Results: Monthly tumor boards were started in 2019 covering all provinces of Pakistan. To date 223 patients have been discussed. Three PNO workshops attended by 154 HCP, 25 lectures as part of a lecture series were delivered by 13 international faculties with \u3e 1800 participants from 48 countries. Most activities were virtual amongst the mayhem of the pandemic. This project also led to the establishment of Pakistan\u27s first Pediatric neuro-oncology fellowship program at AKUH. In addition, Pakistan\u27s National Guidelines for the management of Medulloblastoma were developed endorsed by the Pakistan Society of Pediatric Oncology (PSPO) and the Pakistan Society of Neuro-oncology (PASNO). Lastly AKUH was able to host the Pakistan`s First PNO Virtual Symposium in November 2020 which brought together 29 national and international luminaries in the field of PNO, it was attended by 1126 participants from 58 countries across the globe.Conclusions: This program has shown its capacity to transform the management of pediatric brain tumors in a low middle-income country with a very large pediatric population. Further follow-up is needed to assess the impact on survival