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اورام الخلايا الجنينية تجربة 7 سنوات في مستشفى حماية الاطفال التعليمي خلفية الدراسة: اورام الخلايا الجنينية خارج القحف هي نادرة ومجموعة غير متجانسة من السرطانات التي تصيب الأطفال ولكن يمكن علاجها. هدف الدراسة: دراسة الاعراض السريرية والمرضية للمرضى الذين يعانون من أورام الخلايا الجنينية وتقييم النتائج في المرضى الذين تم إدخالهم إلى وحدة الأورام في مستشفى تعليمي رعاية الأطفال خلال فترة سبع سنوات بين 2009- 2015. طريقة العمل: أجريت دراسة بأثر رجعي على 61 مريضا يعانون من ورم الخلايا الجنينية للأطفال الذين ادخلوا الى مستشفى حماية الاطفال التعليمي خلال السنوات 2009-2015.في هذه الدراسة، تم مراجعة المعلومات المتعلقة بالجنس والعمر والتشخيص والعلامات السريرية والنتائج المرضية والعلاج. النتائج: متوسط عمر المرضى كان 4.2 سنوات (بدءا من 1 شهر الى 14 سنة). كانت هناك 45 انثى و16 ذكر. كان الألم في البطن العرض الأكثر شيوعا في 17 مريضا يليه كتلة أسفل الظهر في 16 مريضا. وتشمل المواقع الأساسية خارج الغدد التناسلية (18 عجز عصعصي، كتلة حوضية 5، المهبل 4، الألوية 3، داخل القلب، المنصف، محجر العين والمستقيم واحدة لكل منهما)، والغدد التناسلية (18 المبيض، 9 الخصية). بعد متوسط متابعة من 42 شهرا. معدل البقاء على قيد الحياة في 1 سنة 59٪. وقد تم دراسة عوامل الخطورة وفقا لكابلان- ما ير والمتغير الاحادي. أحادي المتغير تحليلات تحديد العوامل الهامة التي تؤثربقوةعلى نظام التشغيل: مرحلة (ع = 0.01)، مجموعة المخاطر (ف

Iraq's health care system has gradually declined after several decades of wars, terrorism, and UN economic sanctions. The Oncology Unit at Children's Welfare Teaching Hospital (CWTH) in Baghdad was lacking basic facilities and support. To address this shortcoming, a humanitarian and educational partnership was established between CWTH and Sapienza University of Rome (SUR).We investigated the outcomes of 80 online and 16 onsite educational sessions and 142 teleconsultation sessions from 2006 to 2014. We also determined the outcomes of pathology reviews by SUR of 1216 tissue specimens submitted by CWTH from 2007 until 2019 for second opinions. The primary outcomes were discordance, concordance, and changes among clinical diagnoses and pathology review findings. The measures included the frequency of teleconsultation and tele-education sessions, the topics discussed in these sessions, and the number of pathology samples requiring second opinions.A total of 500 cases were discussed via teleconsultations during the study period. The median patient age was 7 years (range, 24 days to 16·4 years), and the cases comprised 79 benign tumors, 299 leukemias, 120 lymphomas, and 97 solid tumors. The teleconsultation sessions yielded 27 diagnostic changes, 123 confirmed diagnoses, and 13 equivocal impacts. The pathology reviews by SUR were concordant for 996 (81·9%) cases, discordant for 186 (15·3%), and inconclusive for 34 (2·8%). The major cause of discordance was inadequate immunohistochemical staining. The percentage of discordance markedly decreased over time (from 40% to 10%). The cause of the improvement is multifactorial: training of two CWTH pathologists at SUR, better immunohistochemical staining, and the ongoing clinical and pathologic telemedicine activities. The partnership yielded 12 publications, six posters, and three oral presentations by CWTH investigators.The exchange of knowledge and expertise across continental boundaries meaningfully improved the diagnoses and management of pediatric cancer at CWTH.

Background Decades of political and economic instability have taken a significant toll on health outcomes among children in Iraq. In a health system with optimal resources, five-year rates of survival for childhood cancer would exceed 80%; however, a study in Iraq demonstrated a much lower survival rate of 50%, reflecting a disrupted health care infrastructure. Under such conditions, it is a struggle to sustain good treatment outcomes. The aims of the present study are to: i) estimate the median time from initial presentation to diagnosis of childhood cancer at a tertiary center in Iraq; and ii) examine sociodemographic and clinical factors associated with delay in diagnosis in this vulnerable population. Methods A cohort of 346 children presenting for cancer care between January 1-December 31, 2012 was included in the study. Data were obtained through structured interviews with caregivers and from medical charts. The median total delay in cancer diagnosis was calculated in addition to the median patient delay and physician delay. Factors associated with delay in diagnosis were also examined. Results The majority of the patients were less than five years of age and 59% were boys. The median number of days from the onset of symptoms to diagnosis was 55 (range: 3-1,093). This was largely due to physician delay. Clinical factors associated with a longer delay to diagnosis included number of doctors visited, as well as tumor location and type. Conclusions Despite recent advances in cancer treatment outcomes, there are persistent disparities between high-resource versus low- and middle-income countries in childhood cancer survival. Lack of access to care, medication shortages, and inadequate access to medical equipment fuel these disparities. Such factors contribute to delay in access to care and increased mortality risk for children suffering from cancer. The situation will continue unless action to improve access to quality care is taken at national and international levels.

Background The Pediatric Oncology East and Mediterranean (POEM) network, through this report, provides a snapshot view of an expected child’s treatment journey in five countries in the region. Methods Pediatric oncologists from cancer centers in Egypt, Lebanon, Iraq, Jordan, and Pakistan provided input on referral pathways, barriers to care, and patient outcomes, based on personal experience and published data. Outcome data were extracted from institutional registries. A literature review of articles and meeting abstracts was conducted, and results summarized. Results Countries across the Middle Eastern, North African, and West Asian region face common difficulties relating to the provision of pediatric oncology care. National registries are largely lacking, with unavailability of outcome data. Economic barriers are a common theme, leading to delays in patient diagnosis, and interruptions and abandonment of therapy. Insufficient infrastructure and human resources, high rates of toxic deaths, and lack of common national protocols are common. The establishment of successful fundraising organizations linked to specific cancer hospitals showcase several success stories, enhancing services, improving patient access, and leading to outcomes comparable to those in developed countries. All identified published literature is institution-based and from only one or a few hospitals. Therefore, outcomes at a national level likely differ due to disparate cancer care capabilities. Conclusion Well-designed national registries are essential for identifying gaps, and clear referral networks are needed to address delays to diagnosis and therapy. National and transversal programs to improve infrastructure, facilitate knowledge transfer, and promote advocacy, are needed to accelerate progress in the region.

Until very recently, health care in conflict settings was based on a model developed in the second half of the twentieth century. Things have changed, and present civil wars, such as those that are currently taking place in the Middle East, do not address the complexity of the ongoing armed conflicts in countries such as Syria, Iraq, and Afghanistan. These conflicts have caused a significant increase in the number of refugees in the region, as well as in Europe. Hundreds of thousands of refugees succeed in settling in mid- and north-European countries, and their health issues are becoming of great importance. Refugees in Europe in the twenty-first century do not suffer so much from infectious diseases but more from noninfectious chronic diseases such as diabetes, cardiac disease, and cancer. These facts profoundly alter the demographics and disease burden of hostility-derived migrants. Thus, host European countries face situations they have never faced before. Hence, new approaches and strategies are urgently needed to cope with this new situation. The efforts to absorb refugees of different traditions and cultural backgrounds often cause increasing ethnic and religious tensions, which frequently escort the emergence of social violence. To date, little attention has been paid to the overall load of distress being experienced, especially among the first-generation refugees. The current ongoing hostilities in the Middle East induce a long-term health impact on people expelled from their homes, communities, traditions, and cultural environment. The realization of collective suffering forces communities and governmental health agencies to develop new programs that include social determinants to overcome the severe cultural gaps of the newcomers in their new European host countries.

Expression of the latent membrane protein-1 (LMP1) of Epstein-Barr virus (EBV) was investigated in 153 cases of EBV+ classic Hodgkin lymphoma (cHL); 120 cases were pediatric patients (< 14years of age) from Iraq, and 33 cases were adult patients from Italy. We describe for the first time the presence of LMP1 protein in EBV-encoded RNA (EBER)-negative follicular dendritic cells (FDCs) of reactive germinal centers (GC) associated with EBV+ cHL. Presence of LMP1+ GCs was independent of geographic region and age of patients. Variable numbers of reactive GCs were present in 22.2% of cases (34 of 153), whereas LMP1 staining of FDCs was present in about a third of cases (10 of 34) with reactive GC. Most cases with LMP1+ GC were mixed-cellularity (MC) subtype, but some nodular sclerosis (NS) was also present. GC cells with LMP1+ FDCs were surrounded by numerous EBV-infected cells which were positive for EBER, LMP1, and CD30. Double immunolocalization analysis revealed that LMP1 was associated with CD63, an exosomal marker, and with CD21. The possibility is discussed that peri-follicular EBV-infected cells release LMP1 protein, perhaps through exosomes, and that the protein is then captured by FDCs and is presented to EBER-negative GC B cells.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. In order to guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population. METHODS: Next Generation Sequencing of 10 target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, NMYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled. RESULTS: Mutations were detected in previously described WT “hot spots” (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range, 6 to 78 months). CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.

Epstein-Barr virus (EBV)-related lymphoproliferative disorders are relatively common in Iraqi children. Burkitt lymphoma (BL) accounted for 40% of lymphoma cases. The mean age of 125 BL cases was 5.9 ± 3.1 years, and the male-to-female ratio was 3.6:1. Clinical presentation was abdominal in 66% and head and neck in 34%. Bone marrow involvement was higher (P

The lack of molecular diagnosis in the field of cancer in Iraq has motivated us to perform a genetic analysis of pediatric acute myelogenous leukemia (AML), including class I and II aberrations. Peripheral blood or bone marrow cells were collected from 134 AML children aged ≤15 years. Flinders Technology Associates (FTA) filter paper cards were used to transfer dried blood samples from five Iraqi hospitals to Japan. DNA sequencing was performed to identify class I mutations. Nested RT-PCR was used to detect class II aberrations, except that MLL rearrangement was detected according to long distance inverse-PCR. NPM1 and FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations were analyzed by GeneScan using DNA template. Among 134 Iraqi pediatric AML samples, the most prevalent FAB subtype was M2 (33.6 %) followed by M3 (17.9 %). Class I mutations: 20 (14.9 %), 8 (6.0 %), and 8 (6.0 %) patients had FLT3-ITD, FLT3-TKD, and KIT mutations, respectively. Class II mutations: 24 (17.9 %), 19 (14.2 %), and 9 (6.7 %) children had PML-RARA, RUNX1-RUNX1T1, and CBFB-MYH11 transcripts, respectively. MLL rearrangements were detected in 25 (18.7 %) patients. NPM1 mutation was detected in seven (5.2 %) cases. Collectively, approximately 30 % of AML children were proved to carry favorable prognostic genetic abnormalities, whereas approximately 10 % had high FLT3-ITD allelic burden and needed a special treatment plan including allogeneic hematopoietic stem cell transplantation. Acute promyelocytic leukemia (APL) was frequent among Iraqi pediatric AML. It is likely that molecular diagnosis using FTA cards in underdeveloped countries could guide doctors towards an appropriate treatment strategy.

This study estimated the incidence of viral hepatitis in children treated for cancer, to identify variables that could affect this incidence and to assess the role of hepatitis B virus (HBV) vaccination in preventing infection. Between September 2007 and June 2008, 256 children in the haemato-oncology unit at the Children's Welfare Teaching Hospital, Baghdad, were studied prospectively. Demographic and clinical data and vaccination history were recorded. Patients were tested for HBV at the time of diagnosis (all were negative) and after starting chemotherapy. On admission to the unit, 231 patients (90.2%) were revaccinated. At reassessment after treatment for cancer, HBV infection was found in 70 patients (27.3%). The variables that significantly increased the risk for HBV infection were a diagnosis of leukaemia and receiving more than 3 units of blood. A higher number of HBV vaccinations in hospital reduced the risk for HBV infection. The high rate of acquisition of HBV infection found in this study indicates the need for better screening of blood products and adherence to aseptic techniques in management of this group of patients.

There has been a lot of news coming out of Iraq in recent decades, but most of it ignores the situation for people on the ground: ordinary men, women and children who continue trying to live their lives in spite of wars, economic sanctions, violence, and social, political and cultural collapse. The challenges of maintaining and sustaining health in an environment where everything—the human spirit, education and health care systems and the health-sustaining infrastructures of housing, water purification and the electric grid—is damaged or broken are enormous.

Background: Human parvovirus B19 (B19V) is the only human pathogenic parvovirus, It is highly erythrotropic and preferentially replicates in erythroid progenitor cells (EPCs). Recently the effects of B19 infection have been well studied in children with acute lymphoblastic leukemia (ALL). Objective: To detect parvovirus B19 among children with ALL. Methods: A cross sectional study involved forty five patients with ALL (21 patients were newly diagnosed ALL and 24 children who underwent chemotherapy) who were attending department of oncology in Children's Welfare Teaching Hospital in Baghdad Medical City between December 2012 and April 2013, compared to forty five of apparently healthy children as a control group, age and sex were matched. A serological and molecular detection of parvovirus B19 were done using enzyme linked immunosorbant assay (ELISA) and Real-time PCR. Results: B19-IgM, IgG and DNA were detected in study cases as (15.6%, 40% and 13.3%) compared to control group (4.4%, 13 % and 0%) respectively. B19-IgG and B19-IgM were detected in newly diagnosed cases in (41.7% and 19.05%) as well as in (38.1% and 12. 5%) of cases on chemotherapy respectively, all cases with B19-DNA signals were underwent chemotherapy (25%) with mean viral load of (36x104 copies/ml). Conclusion: children who suffering from ALL are at increased risk of B19 infection. Notable percentage of persistent B19 infection was recorded among children with ALL who are receiving ongoing treatment.

p JP A 4-year-old boy presented with a history of abdominal pain lasting 3 months. Computerized tomography scan detected a large, rounded jejunal mass (7 cm) that was surgically removed. Histology showed a pleomorphic gastrointestinal stromal tumor (GIST); at immunohistochemistry, neoplastic cells markedly expressed KIT protein (CD117) (Fig. 1) and CD34 with a high (10%) Ki67 proliferative activity. Based on prognostic criteria identified in adult GISTs (1,2), a diagnosis of high-risk GIST with malignant clinical behavior was established. Mutational analysis and direct sequencing of KIT gene exons 9 and 11 demonstrated a deletion of 19 codons (from 554 to 572) in exon 11 with no mutations in exon 9 (Fig. 2). No mutations i n exons 12 and 18 of the PDGFRA gene were identified. The child remained disease free for the subsequent 18 months, when a local relapse caused intestinal obstruction. The parents refused further treatment and the child died at home.

An adapted LMB 96 derived protocol for B-cell non-Hodgkin lymphoma (NHL) was implemented at the pediatric oncology unit of the Children Welfare Teaching Hospital in Baghdad (Iraq) from 2000 to present. The purpose was to evaluate the feasibility and efficacy of this intensive therapeutic regimen in a limited resource country.Patients15 years of age with high grade B-cell NHL were included. A modified LMB 96 regimen was employed with a reduction of cyclophosphamide and methotrexate dosages due to inadequate laboratory facilities and supportive care.Between 2000 and 2005, 261 children with non-lymphoblastic NHL were registered; 239 were eligible for the analysis. Two patients had stage I disease, 20 stage II, 179 stage III, and 38 stage IV. Fifty-two patients (22%) had bulky disease. Twelve children were assigned to therapeutic group A (low risk), 184 to group B (intermediate risk), and 43 to group C (high risk). One hundred and eighty-four patients (77%) had a complete response after the COP pre-phase. Sixty-nine patients (29%) died during treatment. Twenty-nine patients abandoned treatment. At 24 months, the overall survival rate of the entire patient population was 66% (CI 95%: 62.2-70.6) and the event-free survival rate 53.3% (CI 95%: 50.0-56.8).The treatment schedule proved effective, but the treatment-related mortality due to infections and metabolic complications was very high owing to the limited supportive care available. The high rate of treatment abandonment was also an important cause of failure, especially for children living far away from the hospital.

Abstract 2132 The overall cure rates for children with acute lymphoblastic leukemia (ALL) treated and managed in high-income countries have reached approximately 80% over the last two decades. Unfortunately, these advances in survival have not fully translated into low-income countries where the survival rates remain significantly lower ( Our experience confirms that a protocol-based care of children with ALL has to include the prednisone pre-phase that in low-income countries may contribute to a better risk definition and also to a significant reduction of early TRM. Disclosures: Foa: Roche: Consultancy, Speakers Bureau.

There was an increase in childhood mortality in Iraq following the UN sanctions in 1990. The sanctions created a widespread shortage of medications, particularly chemotherapy drugs. We examined the effect of chemotherapy shortage on outcome of ALL in Iraqi children. Between 1990 and 2002, 670 children with ALL were treated at Children Welfare Teaching Hospital in Baghdad. Detailed records were available for review, including documentation of missed doses of chemotherapy and reason(s) for missing it. Excluded from the analysis were patients who refused or discontinued therapy or were lost to follow up prior to the completion of therapy. ALL risk classification analysis was based on the NCI risk grouping; children were treated per the UKALL X and XI (1990–1997) and MRC 97 (1998–2002) protocols. Therapy consisted of 4 phases: induction, consolidation/interim maintenance, intensification and maintenance. Drug shortage was defined as decrease or elimination of medication solely due to unavailability of medication, and not due to myelosuppression or other toxicities. Because compliance with oral medications is subjective, our analysis was limited to intravenous medication during the first 3 phases of therapy. A Cox regression model was used to examine variables associated with outcome. There were 413 patients with standard risk (SR) disease with a median age of 4.9 years (range 1.08–9.83) and median presenting WBC of 9050 (range 400–47000), and 257 with high risk disease (HR) with a median age of 8 years (range 1.3–15) and median presenting WBC of 79300 (range 800–600000). Diagnosis of ALL was based on microscopic examination and cytochemical stains; cytogenetics and flow cytometry were not available. The median follow up for all patients is 4.8 years. For SR patients the disease free survival (DFS) and survival at 5 years are 63% and 68% respectively. In Cox regression model SR patients who received ≤ 50% of prescribed chemotherapy during induction had a significantly worse DFS (RR 0.494, 95% CI 0.30 to 0.814; p=0.0058). For HR patients the disease free survival (DFS) and survival at 5 years are 49% and 53% respectively. For HR patients those who received ≤ 50% of prescribed chemotherapy during consolidation/interim maintenance had a significantly worse DFS (RR 0.45, 95% CI 0.2018 to 1.0253; p= 0.057). Overall survival (OS) of patients who did not miss any chemotherapy due to shortage in the first 3 phases of therapy was superior in both SR (85% vs. 63%, p=0.0038) and HR patients (72% vs. 49% p= 0.018) at 5 years. The OS of children who received all chemotherapy was significantly better than those who missed any chemotherapy due to shortage at 5 years (81% vs. 58%) (p=0.0002). Despite the limited supportive care and diagnostic tools during the UN sanctions, Iraqi children who were able to receive all their intravenous chemotherapy had comparable outcome to that described in developed countries. These results suggest that dose intensity of chemotherapy is most important during induction for SR patients and during consolidation/interim maintenance therapy for HR patients.