Background: MYCN amplification represents a powerful prognostic factor in neuroblastoma (NB) and may occasionally account for intratumoral heterogeneity. Radiomics is an emerging field of advanced image analysis that aims to extract a large number of quantitative features from standard radiological images, providing valuable clinical information Procedure: In this retrospective study, we aimed to create a radiogenomics model by correlating computed tomography (CT) radiomics analysis with MYCN status and overall survival (OS). NB lesions were segmented on pre-therapy CT scans and radiomics features subsequently extracted using a dedicated library. Dimensionality reduction/features selection approaches were then used for features procession and logistic regression models have been developed for the considered outcome. Results: Seventy-eight patients were included in this study, 24 presented MYCN amplification. In total, 232 radiomics features were extracted. Eight features were selected through Boruta algorithm and 2 features were lastly chosen through Pearson correlation analysis: mean of voxel intensity histogram (p=0.0082) and zone size non-uniformity (p=0.038). Five-times repeated 3-fold cross-validation logistic regression models yielded an Area Under the Curve (AUC) value of 0.879 on the training and 0.865 on the testing set for MYCN. No statistical significant difference has been observed comparing radiomics predicted and actual OS data. Conclusions: CT based radiomics is able to predict MYCN amplification status and OS in NB, paving the way to the in depth analysis of imaging based biomarkers that could enhance outcomes prediction.

Comment On: Sarcopenia is a Prognostic Outcome Marker in Children with High-Risk Hepatoblastoma

Introduction: Several studies on late effects of childhood cancer have been conducted during the past decades. To ensure external validation of a study population, the participation rate must be high. This study investigated demographic data in late effect studies and potential factors impacting on participation rates such as cancer type, time since diagnosis and duration of clinical examinations. Procedure: By searching the databases PubMed, Embase and Web of Science and by contacting researchers and clinicians, we identified studies including an invitation to a clinical examination for late effects after childhood cancer. Studies conducted from January 2010 - March 2020 in the Nordic countries were included. Results: We found 80 published studies originating from 16 cohorts. The overall participation rates ranged between 27 and 100%. The majority of studies (eleven studies) were conducted more than ten years after the cancer diagnosis and primarily on hematologic malignancies (seven studies). The highest participation rates were seen in studies of survivors with solid tumors (92%) and the lowest in survivors with hematologic malignancies (67%) and central nervous system tumors (73%). Neither duration of the clinical examination nor time since diagnosis seemed to affect the participation rate. Conclusion: A trend of lower participation rates when recruiting survivors of hematologic malignancies and central nervous system tumors was found. We encourage future studies to describe the recruitment process more thouroughly to improve understanding of the factors influencing participation rates.

Background The long-term impact of childhood cancer treatment on dietary intake is likely to be complex and the length of time dietary behaviours are affected after childhood cancer treatment is unknown. Aim The aim of this study was to determine the diet quality in childhood cancer survivors recently off treatment and identify possible contributing factors that may affect diet quality in this population. Methods Participants were 65 parents and/or carers of childhood cancer survivors (CCS) (aged 2-18 years), recently off treatment and 81 age-matched controls. Methods Participants completed two self-administered dietary intake and eating behaviour questionnaires. Study data was explored to determine between group differences, bivariate analysis using Spearman’s correlations was used to determine the relationship between diet quality and identified variables, and hierarchical cluster analysis was completed to characterise specific variables into clusters. Results CCS had a significantly poorer diet quality score than the age-matched controls (t=-2.226, p=0.028). Childhood cancer survivors had significantly higher parent-reported rates of ‘picky eating’ behaviour than the control group (t=0.106 p=0.044). Factors such as picky eating, emotional overeating and Body Mass Index z-score appeared to drive diet quality in survivors. Conclusions A CCS with picky eating behaviours could avoid complete food groups, have strong food preferences/aversions and over- consume high energy foods to maintain their energy intake, possibly affecting diet quality. The outcomes highlighted the need for a tailored intervention aimed at improving healthy eating behaviours in CCS after treatment for cancer.

Background: Vitamin D deficiency and insufficiency have been associated with poorer health outcomes. Children with cancer are at high risk for Vitamin D deficiency and insufficiency. At our institution, we identified high variability in Vitamin D testing and supplementation in this population. Of those tested, 65% were Vitamin D deficient/insufficient. We conducted a quality improvement (QI) initiative with aim to improve Vitamin D testing and supplementation among children aged 2-18 years old with newly-diagnosed cancer to ≥ 80% over 6 months. Methods: An inter-professional team reviewed baseline data, then developed and implemented interventions using Plan-Do-Study-Act (PDSA) cycles. Barriers were identified using QI tools, including lack of automated triggers for testing and inconsistent supplementation criteria and follow-up testing post-supplementation. Interventions included an institutional Vitamin D guideline, clinical decision-making tree for Vitamin D deficiency, insufficiency and sufficiency, electronic medical record triggers, and automated testing options. Results: Pre-intervention: N=26 patients, four (15%) had baseline Vitamin D testing; two (8%) received appropriate supplementation. Post-intervention: N=33 patients; 32 (97%) had baseline Vitamin D testing; 33 (100%) received appropriate supplementation and completed follow-up testing timely (6-8 weeks post-supplementation). Change was sustained over 24 months. Conclusions: We achieved and sustained our aim for Vitamin D testing and supplementation in children with newly-diagnosed cancer through inter-professional collaboration of hematology/oncology, endocrinology, hospital medicine, pharmacy, nursing, and information technology. Future PDSA cycles will address patient compliance with Vitamin D supplementation and impact on patients’ Vitamin D levels.

Background: To describe how parents and families of children with cancer evaluate the benefits and risks of using social media (SM) and how they navigate disagreements between oncologists’ advice and information found on SM. Procedure: Parents of children who had been previously diagnosed with cancer, and who had used SM for a purpose related to that child’s health were recruited through SM sites and nonprofit organizations across the U.S. and were invited to complete questionnaires about their experiences using SM; a subset of participants also completed a follow-up in-depth interview. Open-ended responses and interviews were analyzed using thematic analysis. Results: 90 parents completed written questionnaires; 21 completed follow-up interviews. 70% described experiencing a situation in which information shared on SM conflicted with information provided by their child’s oncologist. Although 86% discussed it with the oncologist and 70% described the response as positive, 78% retained negative feelings about the experience. Openness to discussing SM, honesty, transparency and humility regarding the limits of medicine, and shared decision-making regarding information found on SM were connected with reported trust in the oncologist. Conclusions: Parents offered valuable insights regarding their experiences navigating SM, including 8 recommendations for how pediatricians might approach discussing parental SM use. Future studies will evaluate the utility of these recommendations for pediatric clinicians.

TITLE PAGETitle: Retiring as a Physician during the 2020 Coronavirus PandemicAuthor: Philippa G. Sprinz, MD, MScHasbro Children’s HospitalDivision of Pediatric Hematology/Oncology593 Eddy StProvidence, RI. [email protected] Author: Philippa G. Sprinz, MD, MScHasbro Children’s HospitalDivision of Pediatric Hematology/Oncology593 Eddy StProvidence, RI. [email protected]: (401) 444-5171fax: (401) 444 -8845Main Text Word Count: 1194 wordsNo Tables, Figures or other materialKeywords: Retiring, Pandemic, COVID 19,Congratulations! Well done! Bravo! Our compliments and best wishes! I sat outside, looking up at the night sky trying to make sense of everything. I could not. I had hoped, in the silence of night, that I might be able to find some peace and understanding, something positive to hold on to, some equipoise with where I was at in my life, in the midst of a global pandemic. Unfortunately, the cloud ceiling was too low; there were no stars to be seen, to add perspective to my life. I could not grasp my retirement from clinical practice, at this globally distressing time.My retirement was planned before Covid-19 was a name in the medical lexicon.I thought I had planned appropriately. Our son-in-law matched for his clinical fellowship some 2600 miles away. I was 65 years old, and had had a wonderful career as a pediatric hematologist/oncologist, training in the UK but moving to and practicing in the US for almost 40 years. My new job was going to be to help with grandchildren, so our children could pursue their own medical careers. As I clearly could not work and commute 2600 miles on a regular basis, I reasoned that I should retire from clinical practice.Practicing as a physician has been incredibly satisfying. It has been my identity. It is how I presented myself to my family, colleagues and friends. I have given so much of my life to my work. At the same time, unfortunately, I had not taken the time to develop other skills that were anywhere near as rewarding. I acquired some hobbies: diversions from the responsibilities of helping and supporting ‘my’ patients and colleagues, but not skills to keep my mind or body active when I stopped working. As I contemplated no longer working clinically, I developed an anxiety for ‘my’ patients. I knew I had excellent colleagues to hand my patients on to, but I could not escape the thought that I would be letting my patients down by not continuing to care for them, myself. I argued that I knew their health care needs ‘best’. Only, surely I was doing right by our kids and grandkids by helping them at this time.I found myself thinking over my years in practice. During that time, I saw the five-year survival rate of children with a cancer diagnosis increase from 58% to 86% (1); Hodgkin Lymphoma essentially became straightforwardly curable (5 year survival rate of 99.5% by 2016) (1). Even brain tumors experienced a twenty percent increase in their overall cure rate, (57.2% to 76.3%)(1). For individuals with sickle cell disease (SCD) (my particular area of expertise) the survival gain has been more modest: in the 1970s (ten years before the start of my fellowship) 80% of individuals with SCD died by age 30 years (2). In the 1990s females with sickle cell anemia had an average life expectancy of 48 years and males 42 years (3). Despite these improvements, the care of individuals with SCD still needs new drugs and better curative approaches. Life expectancy, for patients with SCD, is currently 54 years for both sexes (4). This is still signifiantly less than the non-SCD population of 76 years in the US(4). I do, nevertheless, look to the future in my field with optimism. Immunotherapy is in the forefront of cancer care, and sensitive molecular tests are allowing earlier diagnoses and hopefully, more successful treatments. There are a number of new, albeit expensive, drugs now being marketed for SCD. Stem cell transplantation is accepted as a ‘curative’ option for the disease, and gene therapy is not too far in the future.Then February 2020: SARS-CoV-2 arrived in the US. This virus has impacted so many lives in so many ways, in circumstances much, much worse than mine. For me, however, it reformatted my retirement. I could not travel to help our children: borders were closed and international travel all but halted. I would stop work with ‘nothing to do’. I suddenly needed to understand ‘Retirement from being a full time MD’, without a ‘plan B’. I recognised that not having to share life-threatening diagnoses with families, would take a weight off my shoulders. Instead, nonetheless, I would cease to be one of a team working painstakingly to help children and their families understand life-impacting illnesses: to hopefully feel better, for at least some periods of time. Despite sadnesses, ‘pedi heme-onc’ definitely has many rewards. Retirement from it includes the loss of deep family relationships and also daily interactions and stimulating meetings with friends and colleagues.I then wondered: why does one retire when one has a secure job (and no new occupation to move on to), with rewarding work, and a sense of serving ‘the greater good’. This, particularly if one is without ‘burn-out’ that over the years I have watched some of my colleagues experience? Does one really have to retire? A critical aspect of retirement may be to afford practices the opportunity to replenish the workforce with younger, more adaptable workers. Individuals trained recently on newer, clinical approaches and disease management present new skills and may improve efficiency. Does the fact that junior doctors have lesser salaries than those who have been in practice for many years make a difference? Recognising my predicament, I suggested I could help part-time during the pandemic. The coronavirus was not causing so many childhood illnesses, however, to need more pediatric staff and I am no expert in adult medicine.Notwithstanding concerns over my retirement, I did have an excitement to think that my leaving would afford a younger physician the opportunity to take a leading role in patients’ care and eventually have as rewarding a career in pediatric hematology/oncology as I had. So, I took stock: maybe I could volunteer in the community? I reached out to a number of organisations, all of which were very happy to have my help, ‘just not now’, in the middle of a pandemic. I listened in to as many medical and non-medical on-line lectures as I could. I ‘attended’ virtual conferences, easily, regionally and nationally, without any travel, and contributed to ‘Zoom’ teaching at my own institution. I worked for an online publishing company and reviewed manuscripts. I was in touch with ‘everyone’ and tried to support all the vulnerable people I knew.Ten months into the pandemic, nevertheless, I am still struggling to come to terms with not being a clinician. Did I devote too much time to my patients – that could not be? Should I have paid more attention to hobbies and have developed a ‘Plan B’? Probably ‘yes’. Will there be a time, after the pandemic has passed, when again I can contribute to ‘the greater good’ and do more clinical work? Perhaps it is true: ‘once a doctor, always a doctor’. But it is more than that: having spent all of my working days caring for others, with responsibilities of making accurate diagnoses, recommending potentially curative management and providing compassionate care when the cure did not come, I now have to learn a new life: a life of giving back without the rewards of clinical practice.References:SEER (Surveillance, Epidemiology and End Results program,) 2017Platt O et al Mortality in sickle cell disease. Life expectancy and risk factors for early death: N Eng J Med. 1994, Jun 9; 330(23):1639-443) Lanzkron S, Carroll CP, Haywood C Jr. Mortality rates and age at death from sickle cell disease: US, 1979 – 2005. Public Health Rep. 2013; 128: 110-116 4) Lubek et al Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease: JAMA Network Open. 2019;2(11):e1915374. doi:10.1001/jamanetworkopen.2019.15374, accessed 12/26/2020

Background: Hepatic metastasis from retinoblastoma (RB) is rare. We evaluated clinical features, imaging manifestations, treatment, and prognosis in these patients. Procedure: Clinical data of five patients diagnosed with hepatic metastases of RB at the Department of Pediatrics in Beijing Tongren Hospital between January 2009 and January 2019 were analyzed retrospectively. Results: Two patients had bilateral lesions, while three had unilateral lesions. Among the seven eyes with lesions, six and one were classified as stage E and C, respectively (International Integrated Reporting Council staging). On computed tomography (CT), low-density foci were observed (three, multiple foci and two, single foci). After chemotherapy, tumor regression was observed in four patients, while there was no response in one patient. Three patients who underwent enucleation were at high risk for extensive choroidal invasion. All patients had severe disease with multiple system involvement, including central nervous system (CNS) and bone metastases. Neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels were significantly elevated in all patients; after treatment, they decreased in four patients and remained unchanged in one patient with end-stage disease. Two patients died, with survival durations of 1 and 3 months following the diagnosis of hepatic metastasis. Three patients survived and continued treatment. Conclusion: Hepatic metastasis from RB is rare and usually occurs with CNS and bone metastases. On CT, hepatic foci could be indicated by low-density lesions with calcification. Chemotherapy could be effective for hepatic metastases. The prognosis of these patients is poor; however, hepatic metastasis is not a direct cause of death.

Pediatric histiocytic neoplasms are hematopoietic disorders frequently driven by the BRAF-V600E mutation. Here we identified two BRAF gene fusions (novel MTAP-BRAF and MS4A6A-BRAF) in two aggressive histiocytic neoplasms. In contrast to previously described BRAF fusions, MTAP-BRAF and MS4A6A-BRAF do not respond to the paradox breaker RAF inhibitor (RAFi) PLX8394 due to stable fusion dimerization mediated by the N-terminal fusion partners. This highlights a significant and clinically relevant shift from the current dogma that BRAF-fusions respond similarly to BRAF-inhibitors. As an alternative, we show suppression of fusion-driven oncogenic growth with the pan-RAFi LY3009120 and MEK inhibition.

Introduction: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond natural limits of the eye may lead to metastatic disease which is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. Method: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma group (EURbG) network. Extended information were gathered via personal Email communication. Results: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. Conclusion: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.

Medical Marijuana in Pediatric Oncology: What Your Patients Are ThinkingDavid Brumbaugh, MD MSCS FAAPDepartment of Pediatrics, University of Colorado School of MedicineChildren’s Hospital Colorado13123 E. 16th Avenue, B290Aurora, CO [email protected] count: 837Short Running Title: Medical Marijuana in Pediatric OncologyKeywords: marijuana, cannabis, complementary, pediatricsAbbreviations:MM Medical MarijuanaAYA Adolescent/young adultTHC TetrahydrocannabinolUse of complementary therapies occurs by up to 40-80% of pediatric oncology patients.1,2 Although cannabis is hardly new to the scene as a complementary treatment, legalization of both medical and recreational marijuana in many states has made these products ubiquitous. Use of and interest in medical marijuana (MM) by hospitalized pediatric patients appears to be concentrated in oncology units for the purpose of relieving symptoms such as nausea, pain, and anorexia.3 Yet clinical practitioners are still limited by the absence of high-quality research in MM to guide them. FDA approval of Epidiolex™ for specific pediatric epilepsy syndromes was an important research milestone, but marijuana remains classified as a Drug Enforcement Administration Schedule I drug, imposing an enormous barrier for clinical researchers.So how should pediatric oncology programs approach the topic of MM? In this issue of Pediatric Blood and Cancer , Ananth and colleagues used a qualitative research design to characterize patient and family perception of MM from a single institution in a state with permissive rules towards both medical and recreational marijuana. The authors interviewed both parents of younger children as well as adolescent/young adult (AYA) patients. In this cohort of pediatric oncology patients/families, although the proportion of subjects using MM was only 27%, a higher proportion were interested in MM, though with concerns about safety and effectiveness.In the Ananth study, patients/families were primarily using or interested in MM for treatment of nausea, anorexia, and anxiety. A concerning number of families in this study expressed a hope that MM would be effective as anti-cancer therapy. With the absence of high-quality randomized controlled trials of MM for treatment of cancer or treatment-related symptoms in children to inform practitioners on safety, dosing, and toxicity, there is no evidence base for pediatric oncologists to base a recommendation of MM. But should we be dissuading interested families from using MM products because they are harmful?Regarding safety of MM use, most parents and nearly all AYA patients minimized risks. When expressed, safety concerns of MM were perceived as less than with alcohol, illicit drugs, or other prescribed medications. This is not surprising, as perceived risk of marijuana in AYA has been steadily failing over last five years in the National Survey on Drug Use and Health.4 Understandably, in this study safety concerns focused on the potential for addiction, which would be associated with MM products enriched in Tetrahydrocannabinol (THC), the principal psychoactive cannabinoid found in cannabis. However, cannabis is a complex plant with over 70 distinct cannabinoids, and the MM industry now contains a broad range of different types of products that have varying concentrations of THC and consequent psychoactive potential. Carver and colleagues noted in their study of 19 hospitalized patients actively using MM, the majority were using products enriched in Cannabidiol with low concentration of THC. One limitation of the study by Ananth, et al. is that there was no attempt to classify the type of MM either being actively used or of interest to patients and parents, so the appropriateness of the concern for addiction cannot be assessed. Absent in patients/families’ perception of risk was any potential for interaction with chemotherapeutics or other prescribed medications. Since both THC and Cannabidiol can impact drug bioactivation and metabolism through multiple pathways, this potential safety concern should be known to the patient and treatment team.Despite the high level of interest in MM in their study population, the minority of patients/families had discussed MM with their oncologist and in those cases, the patient/family initiated the conversation. Absent advice from their treatment team, there was reliance on friends, family, and the internet for more information. A majority of parents desired the involvement of their physician team in any consideration of MM, and previous research has shown a high level of willingness amongst pediatric oncology providers to consider MM use by their patients, particularly when patients are seriously ill, so what stands in the way of talking about it? Providers are concerned about the absence of good research and are less knowledgeable in the domain of rules/laws regulating access to MM, particularly at the state level where there has been so much change over the last decade.5 These gaps may explain why we don’t bring up the topic of MM with our patients and families as often as they would like.Institutions may consider designating a multidisciplinary team of providers to develop greater experience in the legal and pharmacologic aspects of MM use. This team can support providers in the shared decision-making process around MM. In some institutions, it may make sense to house this expertise within the pediatric palliative care program supporting oncology patients.In summary, MM presently is an important part of the complementary therapeutic options available to pediatric oncology patients and their families, who desire the involvement of their provider team in decision making around MM. Despite the lack of evidence supporting use of MM, many patients are using MM products or may in the future, so we should invite this discussion as this will strengthen our therapeutic partnership.1. Fernandez CV, Stutzer CA, MacWilliam L, Fryer C. Alternative and complementary therapy use in pediatric oncology patients in British Columbia: prevalence and reasons for use and nonuse. J Clin Oncol. 1998;16(4):1279-1286.2. Kelly KM, Jacobson JS, Kennedy DD, Braudt SM, Mallick M, Weiner MA. Use of unconventional therapies by children with cancer at an urban medical center. J Pediatr Hematol Oncol. 2000;22(5):412-416.3. Carver AE, Jorgensen J, Barberio MW, Lomuscio CE, Brumbaugh D. A Pediatric Hospital Policy for Medical Marijuana Use. Pediatrics.2020;146(2).4. Administration SAaMHS. 2019 NSDUH Detailed Tables. samhsa.gov/data/report/2019-nsduh-detailed-tables. Published 2019. Accessed.5. Ananth P, Ma C, Al-Sayegh H, et al. Provider Perspectives on Use of Medical Marijuana in Children With Cancer. Pediatrics.2018;141(1).

Emicizumab is a recombinant, humanized, and bispecific monoclonal antibody that bridges activated factor (F) IX and FX in place of FVIII to restore hemostasis in persons with hemophilia A (PHA). Data on the efficacy and safety of emicizumab in young children is limited. Immunologic naivety, physiologically decreased production of vitamin K dependent proteins, specifically FIX, and enhanced clearance of emicizumab in infants may support decreased emicizumab effectiveness. We report on the facilitation of care rendered by using emicizumab in young PHA with inhibitors and extend data on the efficacy and safety in PHA < 3 years.

Objective: To analyze the effect of a novel second-line escalating treatment strategy (high-dose dexamethasone (HDD), low-dose rituximab to eltrombopag) for children with severe chronic immune thrombocytopenia (SCITP). Materials and Methods: This study was a single-center, retrospective cohort study. The second-line escalating strategy included 3 steps: Step I (6 courses high-dose dexamethasone: HDD), Step II (HDD combined with low-dose rituximab), and Step III (eltrombopag). Results: A total of 30 cases (18 males and 12 females) were included; the median age was 8.83 (1.42-13.9) year-old, the duration time of ITP was 20.5 (12.0-96.0) months, and the platelet counts were 15 (3-29) ×109/L. After the median 14 (12-37) months’ treatment, the remission rate was 36.7% (11/30), and the sustained response (SR) rate was 68.2% (15/22). In eltrombopag (step III) cases, 47.5% (8/17) maintained platelet ≥50×109/L, 37.5% (3/8) dose tapering, and 25% (2/8) were successfully discontinued from medication. The number of patients at 12th, 24th, and 36th months was 30, 7, and 2, with the total response (TR) and remission rates of 80% (36.7%), 57.1% (28.6%), and 50% (50%), respectively. The total relapse rate was 26.7% (8/30)，three cases(75%, 3/4)from Step II and 5 cases (41.7% ,5/12)from Step III, none in Step I. Conclusion: The new second-line escalating strategy for children SCITP has an effective improving rate with 36.7% remission and 68.2% SR; 30% could benefit and retain stable response from HDD treatment. Combined treatment with eltrombopag can reduce the relapse rate of low-dose rituximab.

A document by Jonathan Marron. Click on the document to view its contents.

Sickle cell disease (SCD) patients are immunocompromised with multiple comorbidities and a hypercoagulation state. On the other hand COVID-19 is associated with cytokine storm and hypercoagulability. To find the susceptibility and the clinical course of COVID-19 in SCD patients we surveyed related published papers from USA, Europe, Middle East, few African patients and international SCD registry. The COVID-19 presentation was mild in children and moderate in many SCD adults. To explain these findings, possible benefits of high HbF level, and hydroxyurea therapy could be considered. The obtained results should be interpreted considering low cases from sub-Saharan people, younger age of SCD patients compared to general population, a bias toward registry of more severe form of the disease, the influence of preexisting comorbidities with multisystem organ damage in exacerbation of the COVID-19 and the fatality rate in SCD patients and the role of health socio-economic determinants.

Complex lymphatic anomalies are congenital diseases of the lymphatic circulation system that are associated with significant morbidity and early mortality. While guidelines for the comprehensive evaluation of the complex lymphatic anomalies were recently published, the diagnostic approach and medical management are not standardized. The current manuscript presents the clinical features of 4 complex lymphatic anomalies: Gorham-Stout disease, generalized lymphatic anomaly, kaposiform lymphangiomatosis, and central collecting lymphatic anomaly. We also offer three cases from the authors’ practice and our views on diagnostic testing and disease management including supportive care, medical therapies and other interventions.

BACKGROUND: Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. METHODS: Retrospective review of 114 children (3-18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively. Overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS: The male/female ratio was 1.32 and the median age at diagnosis was 8.2 years. Headache (83%) and nausea/vomiting (78%) were the most common presenting symptoms. Overall survival (5y) was 59,1% and EFS (5y) was 58,4%. The OS for standard-risk patients was 69% and 53% for high-risk patients. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.25). Patients who lived >40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS: The epidemiological characteristics of this series possibly explain the differences in survival that medulloblastoma patients have in Brazil. Issues related to limited health care resources, poverty, delayed diagnosis, treatment abandonment, and malnutrition are reflected in inferior survival outcomes when compared to high-income countries. Despite the difficulties encountered in an upper-middle income country, it was possible to deliver treatment with good results.

Cytopenias are common among neonates in neonatal intensive care units (NICU). Although, bone marrow aspirations (BMA) are often performed as part of diagnostic work up but trephine marrow biopsies (BMB) have not been reported from living neonates. BMB is indispensable to accurately assess the cellularity and architecture. There is paucity of literature regarding the technique of BMB in neonates. In this report, for the first time, we describe trephine BMB from Posterior superior iliac crest (PSIC) using 18 guage BMA needle in six living neonates admitted to NICU where bone marrow biopsy findings helped in understanding the underlying mechanism and diagnosis of cytopenias.