High Expression of miR-218-5p in the Peripheral Blood Stream and Tumor Tissues of Pediatric Patients with Sarcomas.

Sarcomas are malignant tumors that may metastasize and the course of the disease is highly aggressive in children and young adults. Because of the rare incidence of sarcomas and the heterogeneity of tumors, there is a need for non-invasive diagnostic and prognostic biomarkers in sarcomas. The aim of the study was to investigate the level of miR-218-5p in peripheral blood and tumor tissue samples of Ewing's sarcoma, osteosarcoma, spindle cell sarcoma patients, and healthy controls, and assessed whether the corresponding molecule was a diagnostic and prognostic biomarker. The study was performed patients (n = 22) diagnosed and treated with Ewing's sarcoma and osteosarcoma and in a control group of 22 healthy children who were matched for age, gender, and ethnicity with the patient group. The expression level of miR-218-5p in RNA samples from peripheral blood and tissue samples were analyzed using the RT-PCR and the expression level of miR-218-5p was evaluated by comparison with the levels in patients and healthy controls. The expression level of miR-218-5p was found to be statistically higher (3.33-fold, p = 0.006) in pediatric patients with sarcomas and when the target genes of miR-218-5p were investigated using the bioinformatics tools, the miR-218-5p was found as an important miRNA in cancer. In this study, the miR-218-5p was shown for the first time to have been highly expressed in the peripheral blood and tumor tissue of sarcoma patients. The results suggest that miR-218-5p can be used as a diagnostic and prognostic biomarker in sarcomas and will be evaluated as an important therapeutic target.

Gastroenteropancreatic neuroendocrine tumors in children and adolescents.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare in children and adolescents. Standard management of these tumors has not been well established due to their rarity in this age group. We aimed to report the clinical and pathological characteristics of patients with this rare disease followed and treated between the years 1993-2022. MATERIALS AND METHODS: The medical records of patients with GEP-NETs were reviewed. RESULTS: Fourteen patients (11 girls, 3 boys) were diagnosed with GEP-NET. The median age was 13 (9-18) years. Tumor localization was the appendix in 12, stomach in one and pancreas in one patient. Mesoappendix invasion was detected in four patients two of whom underwent right hemicolectomy (RHC) and lymph node dissection (LND). Of those, one patient had lymph node involvement. The other two had not further operations. Somatostatin was used in one with pancreatic metastatic disease and the other with gastric disease after surgery. No additional treatment was given in other patients. All patients are under follow-up without evidence of disease at a median follow-up of 85 months (7-226 months). CONCLUSION: GEP-NETs should be considered in the differential diagnosis of acute appendicitis and in cases with persistent abdominal pain. In children, there is invariably a favorable prognosis, and additional surgical interventions other than simple appendectomies generally do not provide benefits. Mesoappendix invasion may not necessitate RHC and LND.

Gliomatosis cerebri in children: A poor prognostic phenotype of diffuse gliomas with a distinct molecular profile.

BACKGROUND: The term Gliomatosis cerebri (GC), a radiology-defined highly infiltrating diffuse glioma, has been abandoned since molecular GC-associated features have not been established yet. METHODS: We conducted a multinational retrospective study of 104 children and adolescents with GC providing comprehensive clinical and (epi-)genetic characterization. RESULTS: Median overall survival (OS) was 15.5 months (interquartile range, 10.9-27.7) with a 2-years survival rate of 28%. Histopathological grading correlated significantly with median OS: CNS WHO grade II: 47.8 months (25.2-55.7); grade III: 15.9 months (11.4-26.3); grade IV: 10.4 months (8.8-14.4). By DNA methylation profiling (n=49), most tumors were classified as pediatric-type diffuse high-grade glioma (pedHGG), H3-/IDH-wildtype (n=31/49, 63.3%) with enriched subclasses pedHGG_RTK2 (n=19), pedHGG_A/B (n=6), and pedHGG_MYCN (n=5), but only one pedHGG_RTK1 case. Within the pedHGG, H3-/IDH-wildtype subgroup, recurrent alterations in EGFR (n=10) and BCOR (n=9) were identified. Additionally, we observed structural aberrations in chromosome 6 in 16/49 tumors (32.7%) across tumor types. In the pedHGG, H3-/IDH-wildtype subgroup TP53 alterations had a significant negative effect on OS. CONCLUSION: Contrary to previous studies, our representative pediatric GC study provides evidence that GC has a strong predilection to arise on the background of specific molecular features (especially pedHGG_RTK2, pedHGG_A/B, EGFR and BCOR mutations, chromosome 6 rearrangements).

The effect of therapeutic play on fear, anxiety, and satisfaction levels of pediatric oncology patients receiving chemotherapy.

OBJECTIVE: This study aimed to examine the effect of therapeutic play on the levels of fear and anxiety towards chemotherapy in pediatric oncology patients and evaluate the satisfaction of children and parents regarding therapeutic play. METHODS: The study was conducted with a one-group pretest-post-design and was developed as a prospective quasi-experimental study. The study was conducted with 40 pediatric oncology patients aged 5-12 and their parents. Data were collected by Child Information Form, Child Fear Scale (CFS), Child State Anxiety (CSA), and Visual Satisfaction Scale. RESULTS: The mean age was 8.98 ± 2.76, 65% were males. The CSA score was decreased at the end of the second cycle compared to the first (p < 0.001). The CFS score was reduced at the end of the second cycle compared to the first (p < 0.001). There was a statistically significant decrease in CFS scores at the end of the first cycle compared to the beginning (p < 0.001). The decrease in CFS scores at the end of the second cycle compared to the beginning was statistically significant (p < 0.001). CONCLUSION: The results of the study show that there was a significant decrease in the fear and anxiety levels of children against chemotherapy in the pre-and post-treatment evaluations. Children and their families were satisfied with the therapeutic play intervention. PRACTICE IMPLICATIONS: Therapeutic play may be an effective method to reduce fear and anxiety levels against chemotherapy in pediatric oncology patients. The use of therapeutic play from the moment of diagnosis is recommended to reduce children's fear and anxiety related to chemotherapy.

The role of International Society of Paediatric Oncology (SIOP) in advancing global childhood cancer care.

The Société Internationale d'Oncologie Pédiatrique [International Society of Paediatric Oncology] (SIOP), founded in 1969, aims to improve the lives of children and adolescents with cancer through global collaboration, education, training, research and advocacy. The annual congress provides the opportunity to share late-breaking research, clinical experiences and debate, with experts worldwide. SIOP's six Continental Branches represent their constituent members in North America, Oceania, Latin America, Africa, Europe and Asia and bring best practices and recent research findings of value to their specific patient populations. In 1990, the SIOP Board of Directors addressed the formerly predominantly European/North American society transforming into a global association by establishing a scholarship program to bring low- and middle-income country (LMIC) paediatric oncologists and nurses to SIOP meetings. A major achievement was SIOP's acceptance as a World Health Organisation (WHO) non-state actor in official relations in 2018, joining 220 non-governmental organisations, international business associations and philanthropic foundations with this privilege. SIOP supports advocacy with WHO member states and civil society to highlight the specific needs of cancer in this age-group through key programs especially supporting the WHO Global Initiative for Childhood Cancer. Sustained improvement in childhood cancer outcomes has paralleled the integration of research with care; thus, SIOP launched a Programme for Advancing Research Capacity for funding selected clinical trial groups in LMICs. SIOP supports south-south partnerships, and the principles elegantly expressed in SIOP Africa's checklist for co-branding projects, that include the prioritisation of local needs, cultivation of local expertise and commitment to equitable partnerships. SIOP now counts approximately 3,000 members from over 128 countries; 39% are from more than 60 LMICs. SIOP members have multidisciplinary expertise on all aspects of childhood cancer care working in collaboration with key stakeholders including governments, civil society organisations and funders to improve the lives of children/adolescents with cancer everywhere in all ways.

Investigation of the methylation changes in the promoter region of RB1 gene in retinoblastoma: Unraveling the epigenetic puzzle in retinoblastoma.

Retinoblastoma is an infrequent neoplasm that arises during childhood from retinal nerve cells and is attributed to the biallelic inactivation of the RB1 gene. In conjunction with anatomical anomalies, it is widely acknowledged that epigenetic modifications play a significant role in the pathogenesis of cancer. The association between methylation of the RB1 gene promoter and tumor formation has been established; however, there is currently no scholarly evidence to substantiate the claim that it is responsible for the inheritance of retinoblastoma. The initial hypothesis posited for this work was that familial retinoblastoma disease would be similarly observed in cases with RB1 promotor gene methylation, akin to RB1 mutations. The RB1 gene promoter region was subjected to methylation screening using real-time PCR in individuals diagnosed with familial retinoblastoma but lacking RB1 mutations. The study involved a comparison of the germline methylation status of the RB1 gene in the peripheral blood samples of 50 retinoblastoma patients and 52 healthy individuals. The healthy individuals were carefully selected to match the retinoblastoma patients in terms of age, sex, and ethnicity. The data obtained from both groups were subjected to statistical analysis. The study revealed that the methylation level in a cohort of 50 individuals diagnosed with retinoblastoma and 52 healthy control participants was determined to be 36.1% and 33.9%, respectively. As a result, there was no statistically significant disparity observed in RB1 promoter methylation between the patient and control groups (p = 0.126). The methylation of the promoter region of the RB1 gene in familial retinoblastoma does not exert any influence on the hereditary transmission of the disease.

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.

PURPOSE: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration. MAIN OUTCOME MEASURES: Enucleation and death. RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Taboo words in pediatric oncology: Communication experiences of nurses and physicians with dying children and their families.

PURPOSE: Despite the numerous benefits of effective communication between patients, families, and healthcare professionals, there are still substantial barriers and communication challenges. This study investigated the experiences of nurses and doctors working in different pediatric hematology-oncology units in Turkey communicating with children and their parents about end-of-life issues. METHOD: This qualitative study was conducted with twenty-four physicians and nurses. A descriptive phenomenological approach was used. Data were analyzed using Braun and Clarke's six-step reflexive thematic analysis. The MAXQDA software was used to facilitate data management. RESULTS: The findings revealed three main themes describing end-of-life communication experiences of physicians and nurses: Avoiding communication with a dying child, Everyone knows but nobody talks, and Complicating aspects of the setting. CONCLUSIONS: Communication with dying children and their families is essential. However, multiple barriers remain for healthcare providers to do so. That issue burdens the child and their family more during the end-of-life, which is already a challenging experience to handle. Healthcare professionals need urgent training in communication with the dying children and their families.

Late Relapse in Neuroblastoma: Case Report and Review of the Literature.

BACKGROUND: Neuroblastoma is the most common extra-cranial solid tumor in children. The survival rate of relapsed/refractory neuroblastoma is dismal. Late recurrence may occur rarely. CASE PRESENTATION: We have, herein, presented a case with stage IV neuroblastoma who relapsed after 11 years and had a subsequent relapse after 15 years from the initial diagnosis, and reviewed cases with late relapsed (after >5 years) neuroblastoma in the literature. The case presented with recurrent disease at the T7 vertebra after 11 years from the initial diagnosis. The patient received surgery, chemotherapy, MIBG treatment, and antiGD2 combined with chemotherapy, and had a further local recurrence in the paravertebral area of the removed T7 vertebra after three years. The patient was operated, received anti-GD2 combined with chemotherapy, and is still alive with no symptoms for 19 months after the last relapse. CONCLUSION: There is not a well-established treatment regimen for the majority of these patients. MIBG treatment and antiGD2 combined with chemotherapy may be promising options for relapsed/ refractory neuroblastoma.

RB1 gene mutations and genetic spectrum in retinoblastoma cases.

The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.

18 F-FDG-PET/CT imaging in diagnostic workup of pediatric precursor B-cell lymphoblastic lymphoma.

18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) imaging is currently not used in standard diagnostics for B-cell precursor lymphoblastic lymphoma (BCP-LBL), and it is unknown whether PET/CT imaging would lead to agreement between detection of lesions with the gold standard imaging methods. Therefore, we performed a retrospective cohort study in which we included 32 pediatric BCP-LBL patients and determined localizations by reviewing local imaging reports. There was a disagreement between protocol-based imaging and PET/CT in 59% of the patients, and the discrepancies mostly comprise of additional lesions detected with PET/CT, typically in lymph node and bone or the absence of bone marrow involvement with PET/CT. If PET/CT was leading in determining definite stage of disease, this would lead to a different stage and therapy branch in 31% and 28% of the patients, respectively.

A rare cause of intestinal obstruction in children: signet-ring cell adenocarcinoma of the colon.

BACKGROUND: Signet-ring cell adenocarcinoma of the colon is well-recognized in adult patients who are extremely rare and not well-documented in children. Our study aims to raise awareness about this rare disease and its long-term outcomes. METHODS: We retrospectively evaluated patients with signet-ring cell colon adenocarcinoma. RESULTS: Six patients, three boys and three girls, with a mean age of 14.83 (range, 13-17 years), presented with signs of intesti-nal obstruction and were diagnosed with signet-ring cell colon adenocarcinoma. All patients had air-fluid levels on abdominal X-ray. Abdominal ultrasonography of all patients revealed subileus. Abdominal computed tomography was performed in five patients, and pre-operative colonoscopy was conducted in two patients before the emergency intervention. All of the patients underwent emergent exploratory laparotomy with the preliminary diagnosis of acute abdomen. In two patients, debulking surgery followed by a stoma was performed. The remaining four patients were treated with anastomosis following intestinal resection. All girls had metastases on the ovary. One of the patients died due to the burden of multiple metastases in the early period, and three died in the sixth post-operative year. We have been following the remaining two patients since then. CONCLUSION: Although signet-ring cell carcinomas (SRCCs) are rare, they should be considered in the differential diagnosis of acute abdomen and intestinal obstruction in pediatric patients. Despite early diagnosis and treatment, SRCC has a poor prognosis in the pediatric population.

Long-Term Endocrinologic Follow-Up of Children with Brain Tumors and Comparison of Growth Hormone Therapy Outcomes: A SingleCenter Experience.

OBJECTIVE: Brain tumors in childhood carry a high risk for endocrine disorders due to the direct effects of the tumor and/or surgery and radiotherapy. Somatotropes are vulnerable to pressure and radiotherapy; therefore, growth hormone deficiency is one of the most frequent abnormalities. This study aimed to evaluate endocrine disorders and recombinant growth hormone treatment outcomes in brain tumor survivors. MATERIALS AND METHODS: In this study, 65 (27 female) patients were classified into 3 groups as craniopharyngioma (n = 29), medulloblastoma (n = 17), and others (n = 19). "Others" group included astrocytoma, ependymoma, germinoma, pineoblastoma, and meningioma patients. Anthropometric data and endocrine parameters of patients and their growth outcome with/without recombinant growth hormone therapy were collected from medical records, retrospectively. RESULTS: Mean age at the first endocrinological evaluation was 8.7 ± 3.6 years (range: 1.0- 17.1 years). Height, weight, and body mass index standard deviation score, mean ± standard deviation (median) values were -1.7 ± 1.7 (-1.5), -0.8 ± 1.9 (-0.8), and 0.2 ± 1.5 (0.4), respectively. Hypothyroidism (central 86.9%, primary 13.1%) was detected during follow-up in 81.5% of patients. Primary hypothyroidism in medulloblastoma (29.4%) was significantly higher compared to other groups (P = .002). The frequency of hypogonadotropic hypogonadism, central adrenal insufficiency, and diabetes insipidus was significantly high in the craniopharyngioma cases. CONCLUSION: In our study, endocrine disorders other than growth hormone deficiency were also frequently observed. In craniopharyngioma cases, the response to recombinant growth hormone therapy was satisfactory. However, there was no improvement in height prognosis during recombinant growth hormone therapy in medulloblastoma patients. A multidisciplinary approach to the care of these patients, referral for endocrine complications, and guidelines on when recombinant growth hormone therapy is required.

Comparison of Heparin and Saline for Prevention of Central Venous Catheter Occlusion in Pediatric Oncology: A Systematic Review and Meta-Analysis.

OBJECTIVE: The management of central venous catheter (CVC) occlusion remains an area without clear evidence-based guidelines. Studies have been conducted that compare the use of heparin and normal saline for reducing thrombosis, but the evidence is not strong enough to suggest a significant advantage of one over the other. Therefore, the study aimed to assess the effectiveness of heparin and normal saline flushing in preventing CVC occlusion in pediatric patients with cancer. DATA SOURCES: A comprehensive search was conducted in PubMed, Web of Science, Cochrane, MEDLINE, CINAHL, Embase, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov platform using specific keywords. The search was conducted until March 2022. Five randomized controlled trials are included in this study. CONCLUSION: Five studies with a total of 316 pediatric cancer patients met the inclusion criteria. The studies were found to be heterogeneous due to variations in the types of cancer, heparin concentration, flushing frequency of CVCs, and methods used to measure occlusion. Despite these differences, there was no significant difference in the effect of flushing with heparin and normal saline in preventing CVC occlusion. The analysis revealed that normal saline is as effective as heparin in preventing CVC occlusion among pediatric cancer patients. IMPLICATIONS FOR NURSING PRACTICE: This systematic review and meta-analysis demonstrated that there is no significant difference between the use of heparin and normal saline flushing in preventing CVC occlusion among pediatric cancer patients. Considering the potential risks of heparin, the use of normal saline flushing may be recommended to prevent CVC obstruction.

Tandem high-dose chemotherapy followed by autologous stem cell transplantation: An infant with trilateral retinoblastoma.

BACKGROUND: Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Advanced RB, associated with exceedingly poor prognosis, requires more intensive multiagent chemotherapy than conventional regimens. Rescue of the bone marrow after intensive chemotherapy is achieved with stem cell transplantation. The sequential courses (tandem transplantation) of high-dose chemotherapy followed by autologous stem cell transplantation allow for even greater dose intensity in consolidation with the potential to use different active chemotherapeutics at each transplant and have proven feasible and successful in treating children with recurrent/refractory solid tumors. CASE DESCRIPTION: We report an infant with trilateral high-risk RB who received tandem high-dose chemotherapy (HDC) followed by autologous stem cell transplantation after the conventional chemotherapy. A 5-month-old female patient presented with strabismus, and the ophthalmoscopic examination showed intraocular tumoral lesions in both eyes. Magnetic resonance imaging (MRI) concluded the trilateral retinoblastoma diagnosis due to a tumoral mass in the optic chiasm. The follow-up ophthalmologic examinations and the MRI detected stable disease after six cycles of multiagent chemotherapy. CONCLUSIONS: Rescue with autologous stem cell transplantation after HDC allows for an increase in chemotherapy intensity. Tandem transplantation provides the chance to perform different chemotherapeutics at each transplant and enables an increase in the chemotherapy intensity, thus providing a positive effect on disease-free survival.

Neurofibromatosis Type I and Hodgkin Lymphoma: Case Report and Review of the Literature.

OBJECTIVE: Neurofibromatosis 1 is an autosomal dominant inherited tumor susceptibility syndrome. Individuals with neurofibromatosis 1 have a 4-5 times increased risk of malignancy compared to the general population. Central nervous system and soft tissue tumors are common non-hematological malignancies in individuals with neurofibromatosis 1. Although the association of leukemia and non-Hodgkin lymphoma as hematologic malignancies in neurofibromatosis 1 has been reported frequently in the literature in these individuals, association with Hodgkin lymphoma has been reported very rarely. MATERIALS AND METHODS: We presented a patient with neurofibromatosis 1 who further developed Hodgkin lymphoma and reviewed the literature. CONCLUSION: Although rare, Hodgkin lymphoma can develop in individuals with neurofibromatosis 1. Hodgkin lymphoma should be kept in mind in cervical/supraclavicular lymphadenomegalies when evaluating patients with neurofibromatosis 1.

Desires vs. conditions: A qualitative study exploring the factors affecting the place of death of child with cancer in Turkey.

OBJECTIVE: The purpose of this study was to describe factors affecting the place of death of children with cancer at the end of life. METHODS: The descriptive phenomenological approach was used. Eighteen mothers who lost their children to cancer participated in in-depth interviews. Data were analysed using MAXQDA software version. Codes and categories were developed inductively from participants' narratives. RESULTS: The factors affecting the place of death of children were categorised into two main themes: (1) desires and (2) conditions. Most of the mothers reported that their deceased children wanted to be with their families at the end of life and they wanted to go home. The conditions related to health services were defined as the barriers to the death of their children in the places of death preferred by the mothers. CONCLUSION: The desire to be close to the child was the main factor affecting the parents' decisions. The findings revealed the prevailing circumstances in the death place decision beyond parental desires. These were the child's health conditions, physical conditions of hospitals, and the lack of home care and paediatric palliative care services, which were factors related to the system, and the lack of other options for parents.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Pediatric Precursor B-Cell Lymphoblastic Malignancies: From Extramedullary to Medullary Involvement.

B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are the malignant counterparts of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment protocols have changed over the last decades, whereas treatment for BCP-LBL has stayed roughly the same. Clinical characteristics of 364 pediatric patients with precursor B-cell malignancies were studied, consisting of BCP-LBL (n = 210) and BCP-ALL (n = 154) patients. Our results indicate that based on the clinical presentation of disease, B-cell malignancies probably represent a spectrum ranging from complete isolated medullary disease to apparent complete extramedullary disease. Hepatosplenomegaly and peripheral blood involvement are the most important discriminators, as both seen in 80% and 95% of the BCP-ALL patients and in 2% of the BCP-LBL patients, respectively. In addition, we show that the overall survival rates in this cohort differ significantly between BCP-LBL and BCP-ALL patients aged 1−18 years (p = 0.0080), and that the outcome for infants (0−1 years) with BCP-LBL is significantly decreased compared to BCP-LBL patients of all other pediatric ages (p < 0.0001).