Our findings substantiate and expand the spectrum of clinical presentations of perforin deficiency, linking PRF1 missense mutations to lymphoma susceptibility and highlighting clinical variability within families. PRF1 mutations should, therefore, be considered as a cause of several diseases disparate to HLH.

F-FDG PET-CT imaging is more sensitive than BMB for BMI detection in pHL staging. BMB should be limited to those with normal marrow uptake in the presence of poor risk factors or those with diffusely increased uptake to exclude marrow involvement in the background of reactive marrow.

Introduction: Pediatric oncology patients are at increased risk of contracting healthcare-associated infections (HAIs), which are responsible for increased morbidity and mortality rates as well as treatment costs.  This study aimed to identify the frequency of HAIs among pediatric oncology patients and their outcome. Methodology: Pediatric oncology patients admitted between January 2009 and June 2010 in a pediatric ward at Aga Khan University Hospital, Karachi, Pakistan, who developed HAIs, were analyzed. Results: A total of 90 HAIs were identified in 32 patients in 70 admissions. The HAI rate among pediatric oncology patients was 3.1/100 admission episodes. Bloodstream infections (63 episodes, 90.0%) were the most common, followed by urinary tract infection (two episodes, 2.9%). Gram-positive infections were seen in 54 (60%) patients, followed by Gram-negative infection in 34 (37.8%), and fungi in 2 (2.8%) cases. Coagulase negative staphylococci was the most common Gram-positive and Escherichia coli and Pseudomonas aeruginosa were most common Gram-negative infections. Mortality rate among pediatric oncology patients who developed HAIs was 12.5% (4/32). Total parental nutrition use and length of stay longer than 30 days were the identified risk factors associated with increased mortality among pediatric oncology patients who developed HAIs. Conclusion: We report an HAI rate among pediatric oncology patients of 3.1/100 admission episodes with a mortality rate of 12.5% in Pakistan. Further studies should be done, especially in the developing world, to identify the risk factors associated with increased mortality among pediatric oncology patients so that adequate measures can be taken to reduce the mortality among these patients.

Background: Low-and middle-income countries sustain the majority of pediatric cancer burden, with significantly poorer survival rates compared to high-income countries.Collaboration between institutions in low-and middle-income countries and highincome countries is one of the ways to improve cancer outcomes.Methods: Patient characteristics and effects of a pediatric neuro-oncology twinning program between the Hospital for Sick Children in Toronto, Canada and several hospitals in Karachi, Pakistan over 7 years are described in this article.Results: A total of 460 patients were included in the study. The most common primary central nervous system tumors were low-grade gliomas (26.7%), followed by medulloblastomas (18%), high-grade gliomas (15%), ependymomas (11%), and craniopharyngiomas (11.7%). Changes to the proposed management plans were made in consultation with expert physicians from the Hospital for Sick Children in Toronto, Canada. On average, 24% of the discussed cases required a change in the original management plan over the course of the twinning program. However, a decreasing trend in change in management plans was observed, from 36% during the first 3.5 years to 16% in the last 3 years. This program also led to the launch of a national pediatric neuro-oncology telemedicine program in Pakistan.

Background:            Outcomes of pediatric mature B cell NHL in resource challenged countries are negatively affected by increased rate of early and toxic deaths. Aim of this study is to assess rate of acute mortality and define significant risk factors present in children with mature B Cell NHL. Methods: A retrospective analysis was done of patients with B cell NHL from January 2012 till December 2016. Risk factors studied for acute mortality were malnutrition, stage, prior surgery with open laparotomy, LDH levels, tumor lysis syndrome, sepsis and fungal infection Results: Total 233 patients were enrolled in the study. Eighty five (36.4%) were below 15th percentile.  Treatment was started in 226 patients. Eighty eight percent children showed 20% response after COP pre-phase. Tumor lysis syndrome was developed in 20.6 % (n = 48) children and 42.9% (n = 100) patients had sepsis, 71/100 patients had culture proven sepsis. 19.7% (n = 46) patients developed fungal infection. There was 19.7% (n = 46) acute mortality.  Most common cause of death was sepsis (n = 22, 47.8%) followed by acute renal failure secondary to tumor lysis syndrome. On multivariate analysis, three independent variables found significant for early death are malnutrition, sepsis and tumor lysis syndrome. Conclusion: Rate of acute mortality in B cell NHL is high in our set up and significant risk factors are tumor lysis syndrome, sepsis and malnourishment at time of presentation.

Osteosarcoma is the most common primary malignant bone tumor in children. In addition to pulmonary metastasis, computed tomography frequently detects indeterminate pulmonary nodules (IPN). We conducted this study to determine the clinical significance of IPN in terms of progression to pulmonary metastasis and its impact on survival. It was a retrospective cohort study of pediatric nonmetastatic osteosarcoma patients treated from January 2005 to December 2018. Baseline computed tomography scans were reviewed for the presence of IPN (defined as a single nodule of <10 mm or ≥3 nodules of <5 mm). Subsequent scans were reviewed for the development of pulmonary metastasis. Of 155 patients, 31.6% (n=49) had IPN at baseline. A total of 43% (n=21) of those with IPN subsequently progressed to pulmonary metastasis compared with only 26% (n=28) of those without IPN (P<0.001) with a relative risk of 1.6 (1.03 to 2.5) in the IPN group. Patients with ≥3 IPN at baseline were at significantly greater risk of pulmonary metastasis as compared with <3 IPN (P=0.013). Overall and event-free survival in patients with and without IPN was 58% and 35%, and 72% and 46%, respectively. Our results suggest that patients with IPN may be at greater risk for progressing to pulmonary metastasis.

In pediatric population, the most common solid malignant tumor of the kidney is Wilms' tumor (WT). Incidence of Extra-Renal Wilms' Tumor (ERWT) is immensely unusual. Prognosis of ERWT is comparable to renal WT. Hence, diagnosis, staging workup and start of treatment in a timely manner is very essential. The most common location of ERWT is the retroperitoneum. The staging of ERWT is done according to National Wilms' Tumor Study group (NWTS). ERWT is considered as stage II or higher; because it is outside renal capsule. A 6-year boy presented with complaints of increased frequency of micturition and difficulty in urination for 15 months. Biopsy of bladder mass showed WT by immunohistochemistry stains such as WTI and Desmin. Cross-sectional imaging showed both kidneys clear of any tumor. Hence, the final diagnosis of ERWT was made.

Background: Human resources are essential to the sustainability and scalability of health interventions. A barrier to global cancer efforts has been the scarcity of trained pediatric hematology/oncology (PHO) professionals in low- and middle-income countries (LMIC). Studies highlight this inequity and the need to develop a global PHO workforce through allocation of financial resources, strengthening of healthcare infrastructure, and development of innovative training programs. Ethiopia is the second most populous country in Africa. Because of recent reduction in infant mortality and improved treatment of Malaria and HIV in Ethiopia, non-communicable diseases contribute an increasing proportion of childhood mortality. The annual incidence of pediatric cancer in Ethiopia is estimated to be 6000-8000 cases. Prior to 2013, no dedicated PHO programs existed in Ethiopia, and there was no formal process for training local physicians in PHO. The following intervention aimed to increase local capacity for treating childhood cancer through the creation of a formal two-year PHO fellowship. Strategy: The PHO fellowship program was created by The Aslan Project, a US non-profit led by a group of experts in PHO, pediatric oncology nursing, and pathology with experience practicing in LMIC, in collaboration with Addis Ababa University (AAU). The goal was to provide a robust educational experience for fellows within the existing resource-constrained clinical environment. Tikur Anbessa Specialized Hospital (TASH) was the initial clinical site (in 2013) for the training program with a second at Jimma University Medical Center (JUMC) in 2016. An Aslan clinical director was present throughout the first year at each location. Visiting faculty from the US and Canada provided clinical supervision, on-site didactics, and professional mentorship. The second year of training included a six-month rotation at a high-functioning cancer institution in India. Fellows were expected to complete a scholarly activity, pass a certification exam, and serve as pediatric hematologist-oncologists in Ethiopia for a minimum of two years following training. Outcomes: Since 2013, four physicians completed PHO fellowship based in Ethiopia, with extensive support of local healthcare leadership and visiting faculty. One additional fellow left training prior to completion and one fellow currently is in training. Twenty-three faculty members from 18 Universities made 51 trips to Ethiopia for onsite training of fellows from 2013-2019. Each fellow completed a rotation in India in his/her second year (Tata Memorial Hospital, Mumbai, or TMC Kolkata). Fellowship projects included a comprehensive pediatric cancer unit assessment, safe chemotherapy practices, and the role of diagnostic pathology. The four subspecialty-trained physicians have remained local, two at TASH, one at JUMC, and one returned to Gertrude's Children's Hospital in Nairobi, Kenya. JUMC now supports a 22 bed PHO unit running at 90% capacity with over 300 new diagnoses since August 2016. TASH supports a 26 bed inpatient unit and 16 additional inpatient beds at a nearby oncology center, treating over 600 new patients annually. The fellowship structure has succeeded in training subspecialty physicians to establish PHO care in Ethiopia. Discussion: Developing specialized care in LMIC requires a multifaceted approach, including nursing training, social support, health system buy-in, diagnostic expertise and facility, pharmacy services, and subspecialty physicians. Focusing on physician training for PHO in Ethiopia, we designed a training structure and curriculum to 1) teach resource appropriate medical care, 2) provide sustained clinical mentorship, 3) develop health system leadership skills, and 4) retain physicians to support local pediatric oncology units. Onsite training by visiting faculty was augmented by sending fellows to a mature, middle-income country program and the support of full-time clinical faculty/mentorship for a large portion of the program. Challenges included fellow recruitment, pathologic accuracy, chemotherapy access, nutritional support, and treatment retention. Formal subspecialty PHO training can be implemented in LMIC without established subspecialty physicians, but requires ongoing commitment of administrators, visiting faculty, local universities, and a multidisciplinary team of health professionals. Disclosures Alexander: AbbVie: Other: travel funding.