Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study.

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0-9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey.

Assestment of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) is of utmost importance both for risk classification and tailoring of the therapy. The data of pediatric ALL patients that received treatment with Berlin-Frankfurt-Münster (BFM) protocols were retrospectively collected from 5 university hospitals in Turkey. Of the 1388 patients enrolled in the study 390 were treated according to MRD-based protocols. MRD assestment was with real time quantitative polymerase chain reaction (qPCR) in 283 patients and with multiparametric flow cytometry (MFC)-MRD in 107 patients. MRD monitoring had upstaged a total of 8 patients (2%) from intermediate risk group to high-risk group. Univariate analysis revealed age 10 years or above, prednisone poor response, PCR-MRD ≥10-3 on day 33 and on day 78 as poor prognostic factors affecting event-free survival (EFS). Detection of >10% blasts on day 15 with MFC (MFC-high-risk group) was not shown to affect EFS and/or overall survival (log-rank P=0.339). Multiple logistic regression analysis revealed PCR-MRD ≥10-3 on day 78 as the only poor prognostic factor affecting EFS (odds ratio: 8.03; 95% confidence interval: 2.5-25; P=0.000). It is very important to establish the infrastructure and ensure necessary standardization for both MRD methods for optimal management of children with ALL.

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.

Impact of having a sibling with cancer or type I diabetes mellitus on psychopathology and self-conscious emotions in adolescents: a comparative study including controls.

BACKGROUND: OBJECTIVE: Having a child diagnosed with cancer is stressful for the whole family and may cause significant psychological impact on parents and siblings. Chronic, life-altering diseases may also have similar effects in siblings due to the daily life changes in the family to accommodate the child with chronic disease. We investigated the impact of having a sibling with cancer or type 1 diabetes mellitus (T1DM) on the psychological features of adolescents, with particular focus on self-conscious emotions such as guilt and shame-which are associated with the development of psychopathologies. METHOD: Sixty-four children who were siblings of patients diagnosed with cancer (CS group), 54 children who were siblings of patients diagnosed with T1DM (DMS group), and 200 adolescents with siblings who did not have any chronic disease (control group) were included in the study. The CS group was also divided into two subgroups with respect to cancer type (leukemia and non-leukemia). Feelings of guilt and shame were evaluated via the Test of Self-Consciousness Affect for Adolescents (TOSCA-A). The Children's Depression Inventory (CDI) and the State-Trait Anxiety Inventory (STAI) were used to determine the levels of depression and anxiety symptoms. Comparisons between groups were performed and within-group directional relationships between scores were analyzed. RESULTS: Guilt scores were significantly higher in CSs than controls (p = 0.009), and the guilt scores of CSs and DMSs were similar (p = 0.508). Other subdimension scores obtained from the TOSCA-A and the CDI and STAI scores were similar in all three groups. In the CS group, externalization scores of siblings with leukemia were significantly higher than that of siblings with non-leukemia cancer. Although shame scores were similar in the CS, DMS, and control groups, shame scores were found to be positively correlated with CDI and STAI total scores in each group (p < 0.05 for all), whereas guilt scores did not demonstrate any significant correlations. CONCLUSION: Our results support prior studies in showing that CSs feel a greater level of guilt compared to adolescents without disease-stricken siblings, whereas, interestingly, CSs and DMSs were found to experience similar levels of guilt. Despite lack of significant increase in the CS and DMS groups, shame levels were positively correlated with depression and anxiety scores in all groups, but the lower correlation coefficients for the CS group indicate the presence of other factors influencing this relationship. We believe our results warrant the need for future studies evaluating the needs of the siblings of children with other chronic diseases, preferably with longitudinal follow-up to determine situations associated with need for psychosocial support.

Effect of platelet count and platelet transfusion on fever duration in patients with febrile neutropenia.

Platelets play a role in hemostasis, thrombosis, and vascular integrity. They also play a major role in the development of inflammation and the activation of immune responses. They have phagocytic activity, stimulate the secretion of immune modulators, and activate other immune cells, which results in platelet-neutrophil aggregation, platelet-induced neutrophil degranulation, and the formation of neutrophil extracellular traps. Data on 124 febrile neutropenia attacks were retrospectively examined. Patients' age, sex, diagnosis, and relapse history were obtained. The complete blood count levels on the first and last febrile day of the febrile neutropenia attacks, duration of fever, and number, type, and timing of thrombocyte suspension transfusions were recorded. The patients were divided into three groups according to the day of fever when the platelet suspension was administered (1 day, 2-3 days, and >3 days); the duration of fever was compared between the three groups. The fever duration of those who were transfused with platelet suspension on the first day of fever was found to be significantly shorter (p = 0.03 and p < 0.001, respectively). When treating a patient with febrile neutropenia, if thrombocyte suspension transfusion is indicated, transfusing thrombocytes in the first days of fever shortens the fever duration and improves the prognosis of febrile neutropenia attack, supporting the hypothesis that not only neutrophils but also platelets may play a role in fighting against microorganisms.

Neurofibromatosis type 1: Expanded variant spectrum with multiplex ligation-dependent probe amplification and genotype-phenotype correlation in 138 Turkish patients.

OBJECTIVE: To investigate the variant spectrum and genotype-phenotype correlations in a Turkish cohort with Neurofibromatosis Type-1 (NF1). MATERIALS AND METHODS: We retrospectively investigated the clinical and molecular data of 138 NF1 patients from 129 families who had been followed-up for a median of 3.9 (1.25-18.5) years. RESULTS: NF1 sequencing revealed 73 different intragenic variants, 19 of which were novel. Seven large deletions were detected by multiplex ligation-dependent probe amplification (MLPA) analyses. The total detection rate of pathogenic NF1 variants was found to be 87.1%. Comparing age groups, cutaneous neurofibromas, freckling, and Lisch nodules were more prevalent in patients older than 12 years (p > .05). Optic glioma detected in 17.3% of the patients and was significantly more common before the age of 6 (p > .001). Other solid tumors developed in 5% of the patients. There was no genotype-phenotype correlation between patients with truncating and nontruncating variants. However, six out of seven patients with large deletions had significant developmental delay, one patient with the c.2970_2972delAAT (p.Met992del) variant had only typical pigmentary features, and another patient with the c.4267A > G (p.Lys1423Glu) variant had CALMs, freckling, neurofibromas, and Noonan-like phenotype. CONCLUSIONS: We described 19 novel variants and seven large deletions in NF1. Applying MLPA assay in NF1 is useful in expanding the molecular diagnosis. Although very limited genotype-phenotype correlation has been reported in NF1, the fact that specific phenotypic findings were observed in our patients with large deletions and two intragenic variants supports the studies published recently.

Investigation of (epi)genotype causes and follow-up manifestations in the patients with classical and atypical phenotype of Beckwith-Wiedemann spectrum.

Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder, characterized by macroglossia, abdominal wall defects, lateralized overgrowth, and predisposition to embryonal tumors. It is caused by the defect of imprinted genes on chromosome 11p15.5, regulated by imprinting control (IC) domains, IC1, and IC2. Rarely, CDKN1C and chromosomal changes can be detected. The aim of this study is to retrospectively evaluate 55 patients with BWS using the new diagnostic criteria developed by the BWS consensus, and to investigate (epi)genetic changes and follow-up findings in classic and atypical phenotypes. Loss of methylation in IC2 region (IC2-LoM), 11p15.5 paternal uniparental disomy (pUPD11), and methylation gain in IC1 region (IC1-GoM) are detected in 31, eight, and five patients, respectively. Eleven patients have had no molecular defects. Thirty-five patients are classified as classical and 20 as atypical phenotype. Patients with classical phenotype are more frequent in the IC2-LoM (25/31), while patients with atypical phenotype are common in the pUPD11 group (5/8). Malignant tumors have developed in six patients (10.9%); three of these patients have IC1-GoM, two pUPD11, one IC2-LoM genotype, and four an atypical phenotype. We observed that the face was round in the infantile period and elongated as the child grew-up, developing prognathism and becoming asymmetrical if hemi-macroglossia was present in the classical phenotype. These findings were mild in the atypical phenotype. These results support the importance of using the new diagnostic criteria to facilitate the diagnosis of patients with atypical phenotype who have higher tumors risk. This study also provides important information about facial gestalt.

Posterior Reversible Encephalopathy Syndrome in Childhood Hematological/Oncological Diseases: Multicenter Results.

The aim of the study was to analyze the characteristics of posterior reversible encephalopathy syndrome (PRES) cases treated at 10 different institutions in our country. Fifty-eight patients diagnosed with PRES were included in this study. The data of PRES cases from 10 departments of pediatric hematology/oncology were analyzed. The mean age of the patients at the time of diagnosis of PRES was 8.95±3.66 years. Most patients (80.4%) had a primary diagnosis of acute leukemia. Patients received chemotherapy (71.4%) and/or used steroids within 14 days before the diagnosis of PRES (85.7%). Hypertension was found in 83.9% of the patients. Twenty-six patients had infections and 22 of them had febrile neutropenia. The most common electrolyte disorders were hypocalcemia, hypomagnesemia, and hypopotassemia. Six patients had tumor lysis syndrome and 4 had inappropriate antidiuretic hormone syndrome. Magnetic resonance imaging was used for diagnosis in all patients. The most commonly involved regions by magnetic resonance imaging were occipital (58%), parietal (51%), and frontal lobes (45%), respectively. Twenty-five patients required intensive care and 7 patients were intubated. In conclusion, PRES may develop during the follow-up and treatment of hematological diseases. In addition to steroid and intense combined chemotherapies, immunosuppressive agents and hypertension are also factors that may be responsible for PRES.

Comparison of outcomes of children with acute lymphoblastic leukemia treated with BMF protocol across 2 decades.

Acute lymphoblastic leukemia is the most common malignancy of childhood. The aim of this study is to compare the outcome of children with acute lymphoblastic leukemia treated with BFM protocol over two decades at our center. We retrospectively examined the files of 421 patients by dividing them into two groups by decade of treatment, 1995-2005 and 2006-2015. After excluding 117 patients, overall, 304 patients were included in the analysis. From the first to the second decade, the proportion of patients over 12 years of age increased from 7.1% to 16.8% (p < 0.04), the high-risk group increased from 15.5% to 19.5% and patients with central nervous system leukemia increased from 5.2% to 11.4%. The relapse rate remained relatively unchanged during this period (from 12.9% to 12.7%), while the mortality rate decreased from 18.7% to 15.4% (p > 0.05) and the death rate during remission induction treatment decreased from 3.9% to 0.7%. The mortality rate of high-risk and standard-risk patients decreased from 62.5% to 34.5% (p < 0.05) and 11.1% to 3.0% (p > 0.05), respectively. The 5-year overall survival and event-free survival rates for standard-, medium- and high-risk patients were 92.7% ± 6.0%, 87.9% ± 4.7%, and 54.7% ± 13.3% and 92.5% ± 6.3%, 83.2% ± 5.5%, and 48.7% ± 14.7%, respectively. For the cohort, the 5-year overall survival rate was 83.2% ± 4.1% and the event-free survival rate was 79.9% ± 4.7%. These results demonstrate the impact of a standard protocol, experience of staff, achieving better risk stratification on treatment success.

Telemedicine Applications in a Tertiary Pediatric Hospital in Turkey During COVID-19 Pandemic.

Background: A novel type of Coronavirus emerged at Wuhan in late 2019 involving preferentially the respiratory system. Owing to the rapid spread, almost 22 million people became infected and 700,000 died. Similar to other countries, the need for additional hospital beds and intensive care units required diversion of health care resources toward the care for those with COVID-19 in Turkey. Telemedicine appeared as a safe and low-cost alternative for the maintainability of pediatric health services during the pandemics. Within this context, we aimed to deliver the health services through telemedicine during the follow-up of chronic childhood diseases. Materials and Methods: This prospective study included five pediatric subspecialties, including allergy immunology, hematology and oncology, nephrology, rheumatology, and inborn metabolic disorders. After the interview, patients and involved physicians were requested to fill out a questionnaire designed to measure the level of satisfaction and the quality of the service we offered. Results: Of the 263 interviews, overall patient and physician satisfaction was 99% and 87%, respectively. As results of the interviews, 250 routine visits were performed, 181 acute complaints were assessed, drug changes were made in 118 patients, 9 patients were determined to be unable to get their drugs, and 12 who misused their drugs. The main advantage of the telemedicine declared by the patients was "not to waste time for transportation." The main concerns of the participants were inability to perform physical and laboratory examinations. Conclusion: Consequently, we considered telemedicine as a feasible alternative not only during pandemics but also in daily practice in Turkey.

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry.

BACKGROUND: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. METHOD: Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. RESULTS: The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow-up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. CONCLUSION: In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

Pediatric Stroke: A Single-Center Experience.

The aim of this study was to evaluate the clinical characteristics, risk factors, treatment, and outcomes of pediatric stroke cases. A total of 118 patients diagnosed with arterial ischemic stroke (AIS), hemorrhagic stroke, and sinovenous thrombosis (SVT) between January 2000 and December 2011 were included. Neonatal cases were excluded. Demographic and clinical findings were retrospectively examined from medical records. We identified 118 patients with stroke. The age of the patients ranged from 1 to 215 months (17.92 y), with a mean age of 5.19±5.25 years. AIS accounted for the majority of cases (n=69, 58.5%), and the major etiology was cardiac disease (17%). Hemorrhagic stroke accounted for 19.5% (n=23) of the cases, and late hemorrhagic disease of the newborn was the major etiology (43%, n=10). SVT accounted for 22% (n=26) of the cases, and the major etiology was otitis media-mastoiditis (27%, n=7). Hemiplegia and headache were the most frequent symptoms for AIS and SVT, respectively. Stroke is rare in children compared with adults; however, it is detected more frequently with better imaging techniques and increased awareness. We found that children with AIS presented more commonly with hemiplegia and children with SVT with headache and strabismus. We did not find an association between thrombophilia and stroke.

Hepatosplenic Fungal Infections in Children With Leukemia-Risk Factors and Outcome: A Multicentric Study.

BACKGROUND: Invasive fungal infections, including hepatosplenic fungal infections (HSFI), cause significant morbidity and mortality in children with leukemia. There are not enough data to support for the best approach to diagnosis of HSFI in children, nor for the best treatment. PROCEDURE: In this multicentric study, we assessed the demographic data, clinical and radiologic features, treatment, and outcome of 40 children with leukemia and HSFI from 12 centers. RESULTS: All cases were radiologically diagnosed with abdominal ultrasound, which was performed at a median of 7 days, of the febrile neutropenic episode. Mucor was identified by histopathology in 1, and Candida was identified in blood cultures in 8 patients. Twenty-two had fungal infection in additional sites, mostly lungs. Nine patients died. Four received a single agent, and 36 a combination of antifungals. CONCLUSIONS: Early diagnosis of HSFI is challenging because signs and symptoms are usually nonspecific. In neutropenic children, persistent fever, back pain extending to the shoulder, widespread muscle pain, and increased serum galactomannan levels should alert clinicians. Abdominal imaging, particularly an abdominal ultrasound, which is easy to perform and available even in most resource-limited countries, should be recommended in children with prolonged neutropenic fever, even in the absence of localizing signs and symptoms.

Frequency of ALK and GD2 Expression in Neuroblastoma.

Background: The aim of this study was to elucidate the significance of immunohistochemical staining patterns of ALK and GD2 in peripheral neuroblastic tumors with different stages and favorable/unfavorable features. Materials and methods: 32 neuroblastomas, 7 ganglioneuroblastomas, and 1 ganglioneuroma cases were immunohistochemically stained with ALK and GD2, and the expressions were graded and correlated with differentiation, size, and favorable/unfavorable histology. Results: There was no statistically significant correlation between ALK immunopositivity and tumor differentiation or stage. Although there was no statistically significant correlation between GD2 immunopositivity and stage, the intensity and prevalence of GD2 immunostaining were statistically significantly higher in the well differentiated group and in tumors which were smaller than 10 cm. Conclusion: GD2 immunostaining levels correlated with tumor differentiation and size. ALK immunostaining was not related to tumor differentiation or stage.

Treatment of plasminogen deficiency patients with fresh frozen plasma.

Congenital plasminogen (Plg) deficiency leads to the development of ligneous membranes on mucosal surfaces. Here, we report our experience with local and intravenous fresh frozen plasma (FFP). We retrospectively reviewed medical files of 17 patients and their eight first-degree relatives. Conjunctivitis was the main complaint. Thirteen patients were treated both with intravenous and conjunctival FFP. Venous thrombosis did not develop in any. Genetic evaluation revealed heterogeneous mutations as well as polymorphisms. Diagnosis and treatment of Plg deficiency is challenging; topical and intravenous FFP may be an alternative treatment.

Coagulation Disturbances in Patients with Argininemia.

BACKGROUND: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. METHODS: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. RESULTS: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. CONCLUSIONS: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

Homozygous protein C deficiency presenting as neonatal purpura fulminans: management with fresh frozen plasma, low molecular weight heparin and protein C concentrate.

Purpura fulminans in neonates is a rapidly progressive thrombotic disorder manifesting as hemorrhagic skin infarction and disseminated intravascular coagulation. Being inherited in an autosomal dominant manner, it is a medical emergency. Clinical presentations of patients may vary depending on the genetic mutations. Retinal and intracranial hemorrhages are the worst clinical scenarios with persistent morbidity. During acute phase, fresh frozen plasma, protein C concentrates and anticoagulant therapy should be administered rapidly. Here we report a patient with homozygous protein C deficiency.

Evaluation of high-risk features of primary enucleation of patients with retinoblastoma in a tertiary center of a developing country in the era of intra-arterial chemotherapy.

PURPOSE: To evaluate the frequency of high-risk histopathologic factors in Turkish children enucleated for retinoblastoma and to analyze the association between growth pattern, rosetta formation, tumor thickness, presence of necrosis, calcification, neovascularization, rate of mitosis, and high-risk histopathologic factors. METHODS: Pathology reports of 59 eyes who had received enucleation for retinoblastoma were reviewed retrospectively. The histopathologic data included presence of choroidal invasion, optic nerve invasion, scleral extension, tumor thickness, presence of necrosis, calcification, neovascularization, rosetta formation and lymphocyte infiltration, rate of mitosis, and growth pattern. RESULTS: This study included 59 eyes from 30 (50.8%) male and 29 (49.2%) female patients. The mean age was 22.87 ± 18.99 months. There were 30 (50.8%) eyes with choroidal invasion, 30 (50.8%) eyes with optic nerve invasion, and 5 (8.5%) eyes with scleral invasion. Endophytic growth pattern was seen in 27 (45.8%) eyes, exophytic growth pattern was seen in 2 (3.4%) eyes, and combined growth pattern was seen in 30 (50.8%) eyes. Exophytic growth pattern was found statistically related to choroidal invasion (p = 0.00). Although tumor with greater thickness tended to have more choroidal invasion (p = 0.02), there was no relation between tumor thickness and optic nerve invasion (p = 0.09). CONCLUSIONS: Incidences of choroidal and optic nerve invasion showed similarity with other developing countries. Because of higher incidence of high-risk factors, intra-arterial chemotherapy with its targeted effect should be preferred carefully.

Sinusoidal Obstruction Syndrome During Chemotherapy of Pediatric Cancers and its Successful Management With Defibrotide.

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication generally occurring after hematopoietic stem cell transplantation. SOS after standard dose chemotherapy in malignancies is rare. Between the year 1995 and 2016, 414 patients were diagnosed with acute lymphoblastic leukemia and 113 patients were diagnosed with Wilms tumor in our institution. Among these patients, 4 patients with acute lymphoblastic leukemia (0.96%) and 2 patients with Wilms tumor (1.7%) developed SOS during treatment. SOS behaves like a local disseminated intravascular coagulation. Defibrotide has proved to be effective in SOS. In this article, we report our experience with defibrotide in SOS.