Comparison of bone marrow biopsy and fluorodeoxyglucose-positron emission tomography for the assessment of bone marrow infiltration in children with Hodgkin's lymphoma.

PURPOSE: To compare bone marrow biopsy (BMB) with [18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (PET/CT) imaging in the demonstration of bone marrow involvement in children with Hodgkin's Lymphoma (HL) and to investigate the effectiveness of PET/CT imaging and thus the necessity for BMB at staging. METHODS: Pediatric patients with HL, who underwent both bilateral iliac BMB and PET/CT imaging at disease staging were retrospectively analyzed. In determining bone marrow involvement (BMinv), BMB and/or first/follow-up PET/CT imaging were eligible for review. RESULTS: Fifty-six patients were included. BMinv was detected by PET/CT imaging in 6/56 (10.7%), whereas the proportion was 3/56 (5.3%) in BMB specimens. Bone marrow biopsies and PET/CT images were concordant in 53/56 (94.6%) patients with BMB specimens missing three cases of BMinv detected by PET/CT. When diagnostic accuracy was calculated, sensitivity, specificity, positive predictive value and negative predictive values for PET/CT were 100%, 100%, 100%, 100%, respectively, and the same values for BMB were 50%, 100%, 100%, 94.3%, respectively. CONCLUSIONS: The results of PET/CT and BMB for staging of pediatric HL patients were compatible, and PET/CT imaging was found to provide high diagnostic performance in determining BMinv. In keeping with earlier research, the current study showed that BMB may not be necessary in every patient at staging, and should be reserved for cases where PET/CT is inconclusive.

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.

The effect of granulocyte colony-stimulating factors on survival parameters in pediatric patients with acute lymphoblastic leukemia: A retrospective study.

OBJECTIVE: There is a paucity of data concerning the use of granulocyte colony-stimulating factors (G-CSFs) in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of the present study was to evaluate the effect of G-CSF use on relapse-free and overall survival in 358 consecutive, newly diagnosed pediatric ALL patients uniformly treated at the same institution between April 2012 and April 2020. MATERIALS AND METHODS: Patients were evaluated in two separate periods, based on the G-CSF treatment approach. All patients who underwent ALL treatment between April 2012 and December 2016 received G-CSF (G-CSF+ arm; n: 245) in the course of the protocol for reducing the risk of febrile neutropenia and/or inducing neutrophil recovery to prevent any treatment delay. No patients after December 2016 received G-CSF, even if they belonged to the high-risk group, and these were included in the G-CSF- arm (n: 113). RESULTS: Estimated mean relapse-free (106.5 months; 95 % CI 102-110.8 vs 82 months 95 % CI 75.2-88.9; p: 0.794) and overall survival (111.4 months; 95 % CI 108-114.8 vs 85 months 95 % CI 80.4-89.8; p: 0.431) rates were similar between the G-CSF+ and G-CSF- groups. CONCLUSIONS: Our findings indicate that G-CSF use during ALL treatment had no effect on relapse rates or overall survival.

Safety and efficacy of deferasirox in patients with transfusion-dependent thalassemia: A 4-year single-center experience.

This study was organized to determine the efficacy and safety of deferasirox (DFX) in reducing the SF of patients with transfusion-dependent thalassemia (TDT). This is a retrospective, descriptive study of 101 transfusion- dependent patients with thalassemia major who were followed for 48 months. Twenty-nine patients who used an alternative chelator either alone or combined, who were not compliant to the treatment, changed the drug due to adverse reactions, and had multiple transfusions and did not complete 4 years of DFX use were excluded. A total 72 out of 101 patients completed the study. SF decreases were noted for the 6-12 and >18-year age groups, from a median of 1532 ng/mL to 1190 ng/mL, and from 1386 ng/mL to 1165 ng/mL, respectively (p > 0.05). The proportion of patients with SF concentrations >2000 ng/mL is decreased (29% at baseline decreased to 15% at the end of the study) during the 48 months. The median SF of those who used <30 mg/kg/day (n = 38) increased from 767 ng/mL to 1006 ng/mL, whereas the >30 mg/kg/day (n = 34) group's SF concentrations decreased from a median of 1575 ng/mL to 1209 ng/mL (p = 0.029). The decrease of median SF values for Syrian patients was statistically significant (p = 0.043). Most common adverse events were gastric irritation symptoms (19.4%). The total DFX discontinuation ratio was calculated as 9.7%. Although dosages between 25-30 mg/kg/day are adequate to stabilize SF concentrations higher dosages are needed to achieve a statistically significant decrease.

Testis Involvement in Neuroblastoma: Report of 3 Cases in the Turkish Pediatric Oncology Group-Neuroblastoma Study and Review of the Literature.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood. Primary and secondary testicular involvement is extremely uncommon in neuroblastoma. PROCEDURE: All children with neuroblastoma treated with the Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma (NB) Study and who had testis involvement either at diagnosis or at relapse were retrospectively evaluated. A review of all cases with neuroblastoma and testis involvement in the literature was done. RESULTS: There were 3 children with NB documented to have involvement of the testis, 2 at diagnosis, 1 at recurrence, within the 559 cases (0.5%) treated with the Turkish Pediatric Oncology Group (TPOG)-Neuroblastoma Protocol. All had advanced stage. Two were infants. A total of 57 cases of testicular or paratesticular neuroblastoma have been reported in children, and most cases represent metastases as in the 3 cases in our series. CONCLUSIONS: Neuroblastoma should be considered in the differential diagnosis of testicular mass and work-up for neuroblastoma should be done before orchiectomy. Scrotal ultrasonography should be used as the first diagnostic tool and abdominal ultrasonography shall be done additionally. Testis examination should be performed at diagnosis and regularly during follow-up for boys diagnosed with neuroblastoma. Testes may be sanctuary sites when neuroblastoma is metastatic, as is the case in leukemia.

Causes of Hypochromic Microcytic Anemia in Children and Evaluation of Laboratory Parameters in the Differentiation.

Most common causes of microcytic anemia in children are iron deficiency anemia (IDA) and thalassemia. Differentiation of these and detection of coexistence is essential for genetic counseling and to set a treatment plan. Aim is to characterize the frequency of IDA and thalassemia trait (TT) in children presenting with hypochromic, microcytic anemia and to define the significance of blood count parameters in differential diagnosis. Of the 200 enrolled, 107 were male (53.5%). In total 154 had IDA (77%), 27 had ß-TT (13.5%), and in 11 (5.5%) both conditions coexisted. Eight patients had α-thalassemia gene mutations, 3 of these also had IDA. RBC, MCV, Mentzer index, serum iron, TIBC, ferritin were significantly different between IDA and ß-TT patients (P<0.001); however, RDW was not different between the 2 groups (P>0.05). Sensitivity and specificity of Mentzer index for the detection of ß-TT were 100% and 69.4%, respectively. The positive and negative predictive values of Mentzer index in diagnosing ß-TT were 36.6% and 100%, respectively. Differential diagnosis of microcytic anemia is important in children, especially in regions where IDA and thalassemia are both prevalent. We found that 7% of children referred to our clinic for hypochromic, microcytic anemia had both TT and IDA. Our data showed that serum iron, ferritin, TIBC, MCV, and Mentzer index were all valuable markers in diagnosing IDA and were significantly different compared with ß-TT patients; RDW was not different between the 2 groups.

Diagnostic performances of superb microvascular imaging, shear wave elastography and shape index in pediatric lymph nodes categorization: a comparative study.

OBJECTIVE: To determine the diagnostic utility of a vascularity index via superb microvascular imaging in lymph nodes of children with malignant lymphoma and acute lymphadenitis compared to normal lymph nodes. METHODS: We performed a retrospective study for multiparametric lymph node (LN) evaluation. Malignant lymphoma diagnosed via histopathological examination and lymph nodes receiving an acute lymphadenitis diagnosis based on clinical and laboratory findings constituted the study subgroups. We calculated a shape index [SI (percent of shortest to longest diameter)] using grayscale ultrasonography and elasticity and velocity values via shear wave elastography (SWE) as well as a vascularity index (VI) using superb microvascular imaging (SMI) for comparison with normal lymph nodes. RESULTS: 45 lymph nodes diagnosed with malignant lymphoma, 72 lymph nodes diagnosed with acute lymphadenitis and 146 normal lymph nodes were evaluated. For differentiating lymphoma from normal lymph nodes, vascularity index cut-off values higher than 15% represented a diagnostic accuracy of 95%; cut-off elasticity values higher than 17 kPa exhibited a diagnostic accuracy of 99%. Optimal VI, elasticity, velocity and SI cut-off values in differentiating lymphoma from lymphadenitis were 15%, 17 kPa, 2.45 m sn-1 (p < 0.001) and 65% (p < 0.002) with calculated diagnostic accuracies of 83, 87, 88 and 68%, respectively. CONCLUSION: Vascularity index values obtained via superb microvascular imaging and SWE would be reasonably useful in differentiating malignant lymphoma and acute lymphadenitis from normal LNs. SWE would be more efficient in distinguishing malignant lymph nodes from acute lymphadenitis compared with superb microvascular imaging. Advances in knowledge: Vascularity index by superb microvascular imaging would be a novel Doppler parameter in differentiating both lymphoma from lymphadenitis and also lymphadenitis from normal lymph nodes.

Congenital Factor Deficiencies in Children: A Report of a Single-Center Experience.

Congenital factor deficiencies (CFDs) refer to inherited deficiency of coagulation factors in the blood. A total of 481 patients with CFDs, who were diagnosed and followed at our Pediatric Hematology and Oncology Clinic between 1990 and 2015, were retrospectively evaluated. Of the 481 cases, 134 (27.8%) were hemophilia A, 38 (7.9%) were hemophilia B, 57 (11.8%) were von Willebrand disease (vWD), and 252 (52.3%) were rare bleeding disorders (RBDs). The median age of the patients at the time of diagnosis and at the time of the study was 4.1 years (range: 2 months to 20.4 years) and 13.4 years (range: 7 months to 31.3 years), respectively. The median duration of the follow-up time was 6.8 years (range: 2.5 months to 24.8 years). One hundred nineteen (47.2%) of 252 patients with RBDs were asymptomatic, 49 (41.1%) of whom diagnosed by family histories, 65 (54.6%) through preoperative laboratory studies, and 5 (4.2%) after prolonged bleeding during surgeries. Consanguinity rate for the RBDs was 47.2%. Prophylactic treatment was initiated in 80 patients, 58 of whom were hemophilia A, 7 were hemophilia B, 13 were RBDs, and 2 were vWD. Significant advances have been achieved during the past 2 decades in the treatment of patients with CFDs, particularly in patients with hemophilias. The rarity and clinical heterogeneity of RBDs lead to significant diagnostic challenges and improper management. In this regard, multinational collaborative efforts are needed with the hope that can improve the management of patients with RBDs.

Treatment of high-risk neuroblastoma: National protocol results of the Turkish Pediatric Oncology Group.

BACKGROUND: The national protocol aimed to improve the outcome of the high risk neuroblastoma patients by high-dose chemotherapy and stem cell rescue with intensive multimodal therapy. MATERIALS AND METHODS: After the 6 induction chemotherapy cycles, patients without disease progression were nonrandomly (by physicians' and/or parent's choices) allocated into two treatment arms, which were designed to continue the conventional chemotherapy (CCT), or myeloablative therapy with autologous stem cell rescue (ASCR). RESULTS: Fifty-six percent (272 patients) of patients was evaluated as high risk. Response rate to induction chemotherapy was 71%. Overall event-free survival (EFS) and overall survival (OS) at 5 years were 28% and 36%, respectively. "As treated" analysis documented postinduction EFS of 41% in CCT arm (n = 138) and 29% in ASCR group (n = 47) (P = 0.042); whereas, OS was 45% and 39%, respectively (P = 0.05). Thirty-one patients (11%) died of treatment-related complications. CONCLUSION: Survival rates of high-risk neuroblastoma have improved in Turkey. Myeloablative chemotherapy with ASCR has not augmented the therapeutic end point in our country's circumstances. The adequate supportive care and the higher patients' compliance are attained, the better survival rates might be obtained in high-risk neuroblastoma patients received myeloablative chemotherapy and ASCR.

Successful treatment of multiresistant Achromobacter xylosoxidans bacteremia in a child with acute myeloid leukemia.

Achromobacter xylosoxidans is an aerobic gram-negative bacillus and important cause of bacteremia in immunocompromised patients. We describe a leukemia pediatric patient with severe neutropenia who developed bacteremia with A xylosoxidans resistant to multiple antibiotics, and treated the patient with tigecycline and piperacillin-tazobactam in addition to supportive medications.

Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

How do we encounter rare factor deficiencies in children? Single-centre results from Turkey.

BACKGROUND: Rare factor deficiencies (RFDs) are autosomal recessively inherited coagulation factor deficiencies encountered at a frequency of between one in 500, 000 and one in two million. MATERIALS AND METHODS: One hundred and ninety-two patients, diagnosed as having RFD, followed and treated in our clinic between 1990 and 2013 were retrospectively evaluated in this study. RESULTS: From the 192 patients, 142 had FVII, 15 had FX, 14 had FXI, 10 had fibrinogen, six had FV, two had FXIII, two had FV + FVIII and one had FII deficiency. One hundred and thirty of the cases were boys and 62 were girls. The age range was 2 weeks to 24 years and the ages at the admission were between 2 weeks and 16 years. The rate of consanguinity was 49.4%. Eighty-eight of our patients were asymptomatic (45.8%) and 104 were symptomatic (54.2%). Asymptomatic patients were diagnosed by family histories (39.8%), preoperative laboratory studies (54.6%) and operational bleeding (5.6%). Sixty-eight of our symptomatic patients displayed grade II (65.4%) and 36 displayed grade III bleeding symptoms (34.6%). First bleeding regions were skin (33%), nose (28%), central nervous system (CNS) (15.5%), oral cavity (10.5%), soft tissue (6%), joint (3%), urinary system (2%) and gastrointestinal system (GIS) (2%), respectively. The bleeding prevalence rates of our symptomatic patients are listed as epistaxis 62.5%, skin bleedings 53%, oral cavity bleeding 28.8%, haematomas 18.3%, CNS bleedings 17.3%, haemarthrosis 14.4%, GIS bleedings 3.8%, menorrhagia 2.9%, haematuria 1.9%, bleeding because of operations 1.9% and iliopsoas bleedings 1.9%. CNS bleedings (41%) take the first place among the serious bleedings of our cases, followed by haemarthrosis (36.4%), GIS bleedings (18.1%) and iliopsoas bleedings (4.5%). Prophylaxy was applied to nine patients (five patients with FVII, two patients with fibrinogen and one each with FV and FX deficiency). CONCLUSIONS: The characteristics of clinical presentations, first bleeding attacks, bleeding prevalence and severe bleedings as well as prophylactic approaches are discussed in this article.

Cardiac T2* MRI assessment in patients with thalassaemia major and its effect on the preference of chelation therapy.

The aim of the study is to assess the relationship between T2* magnetic resonance imaging (MRI) values and age, serum ferritin level, left ventricular ejection fraction (LVEF), splenectomy status, and to identify appropriate modifications to chelation therapy based on T2* MRI results of children with thalassaemia major. Sixty-four patients with thalassaemia major (37 girls/27 boys) older than 8 years of age were enrolled in the study. Based on the first T2* MRI, the patients' myocardial iron depositions were classified into three groups: T2* MRI <10 ms (high risk group), T2* MRI 10-20 ms (medium-risk group) and T2* MRI >20 ms (low-risk group). There was no significant relationship between T2* MRI value and ages, serum ferritin levels and splenectomy status of thalassaemia major patients. The mean LVEFs were 60, 75, and 72.5 % in the high-, medium-, and low-risk groups, respectively (P = 0.006). The mean cardiac iron concentrations calculated from the T2* MRI values were 4.96 ± 1.93, 1.65 ± 0.37, and 0.81 ± 0.27 mg/g in the high-, medium-, and low-risk groups, respectively. Chelation therapies were re-designed in 24 (37.5 %) patients according to cardiac risk as assessed by cardiac T2* MRI. In conclusion, until recently, T2* MRI has been employed to demonstrate cardiac siderosis without a direct relationship with the markers used in follow-up of patients with thalassaemia. However, modifications of chelation therapies could reliably be planned according to severity of iron load displayed by T2* MRI.

Surgical interventions in childhood rare factor deficiencies: a single-center experience from Turkey.

Congenital rare factor deficiencies may present in infancy by life-threatening bleedings or may not show any symptoms until adulthood. It is reported more commonly in countries having consanguineous marriages. Data regarding surgical interventions of rare congenital factor deficiencies are based on case reports and records of guidelines. There are no well documented and separately prepared directories related to pre-surgical and prophylactic approaches of surgical interventions of these deficiencies. Our retrospective study consisted of 171 rare factor deficiencies that were followed up in our clinic, and of whom 61 had 88 surgical interventions between 1990 and 2012. Of these patients, 45 were having factor VII deficiency, and factor V, X, XI, XIII and fibrinogen deficiencies were present in five, four, three, two and two patients, respectively. In 23 patients, factor coagulant activities were under 5% (37.7%), in 15 it was between 5 and 30% (24.6%), and in 23 between 30 and 50% (37.7%). Twenty-eight were symptomatic and 33 were asymptomatic. Information of 51 (83.6%) male and 10 (16.4%) female patients with an age range of 5-25 years (13 ±â€Š5.27), whose age at presentation ranged between 3 weeks and 18 years (7 ±â€Š4.66), were retrieved from patient records and from the records contained in the data-processing environment introduced in 2005. The rate of familial consanguinity was 49.2%. Of the surgical interventions, 24 (27.3%) were major, 24 (27.3%) were minor and 40 (45.4%) were circumcision. We used fresh frozen plasma in 32, recombinant factor (rF)VIIa in 20, prothrombin complex concentrate in five and fibrinogen in three patients during surgical interventions. In 18 patients, antifibrinolytic agents were also used. In 27 patients, surgical interventions were applied without any replacement therapy. No additional doses were required after surgical prophylaxis doses. Thrombotic events were not observed. Antibody occurrence was not detected in these patients. In our study, we evaluated preparation for surgical procedures, factor replacement therapy before surgical intervention and postoperative follow-up in patients with rare coagulation factor deficiency.

Mucoepidermoid carcinoma of the parotid gland in childhood survivor of acute lymphoblastic leukemia with need of radiotherapy for treatment and review of the literature.

Diagnosis of secondary malignancies began with the increasing survival in childhood cancer. Children treated for acute lymphoblastic leukemia (ALL) have an increased risk for developing mucoepidermoid carcinoma (MEC) of the parotid gland. The latent period ranges from 5 to 16 years. A 2 6/12-year-old girl was treated for pro-B ALL. Treatment included multidrug chemotherapy, prophylactic intrathecal methotrexate, and cranial radiotherapy. MEC of the left parotid gland was diagnosed at the age of 8 years, 3 years after completing treatment. She was treated with multiple surgery and radiotherapy. The authors aimed to emphasize the need for concern about second cancers of the parotid gland in children treated for ALL.

Factor VII deficiency: a single-center experience.

Congenital factor VII deficiency is the most common form of rare coagulation factor deficiencies. This article presents a retrospective evaluation of 73 factor VII deficiency cases that had been followed at our center. The study consisted of 48 males and 25 females (2 months-19 years). Thirty-one (42.5%) of them were asymptomatic. Out of symptomatic patients, 17 had severe clinical symptoms, whereas 8 presented with moderate and 17 with mild symptoms. The symptoms listed in order of frequency were as follows: epistaxis, petechia or ecchymose, easy bruising, and oral cavity bleeding. The genotype was determined in 8 patients. Recombinant activated factor VII (rFVIIa) was used to treat 49 bleeding episodes in 8 patients after 2002. In 2 patients with repeated central nervous system bleeding prophylaxis with rFVIIa was administered. No allergic and thrombotic events were observed during both treatment and prophylaxis courses. Antibody occurrence was not detected in the patients during treatment.