Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.

Risk Factors for Surgical Site Infections in Elective Orthopedic Foot and Ankle Surgery: The Role of Diabetes Mellitus.

Surgical site infection (SSI) after elective orthopedic foot and ankle surgery is uncommon and may be higher in selected patient groups. Our main aim was to investigate the risk factors for SSI in elective orthopedic foot surgery and the microbiological results of SSI in diabetic and non-diabetic patients, in a tertiary foot center between 2014 and 2022. Overall, 6138 elective surgeries were performed with an SSI risk of 1.88%. The main independent associations with SSI in a multivariate logistic regression analysis were an ASA score of 3-4 points, odds ratio (OR) 1.87 (95% confidence interval (CI) 1.20-2.90), internal, OR 2.33 (95% CI 1.56-3.49), and external material, OR 3.08 (95% CI 1.56-6.07), and more than two previous surgeries, OR 2.86 (95% CI 1.93-4.22). Diabetes mellitus showed an increased risk in the univariate analysis, OR 3.94 (95% CI 2.59-5.99), and in the group comparisons (three-fold risk). In the subgroup of diabetic foot patients, a pre-existing diabetic foot ulcer increased the risk for SSI, OR 2.99 (95% CI 1.21-7.41), compared to non-ulcered diabetic patients. In general, gram-positive cocci were the predominant pathogens in SSI. In contrast, polymicrobial infections with gram-negative bacilli were more common in contaminated foot surgeries. In the latter group, the perioperative antibiotic prophylaxis by second-generation cephalosporins did not cover 31% of future SSI pathogens. Additionally, selected groups of patients revealed differences in the microbiology of the SSI. Prospective studies are required to determine the importance of these findings for optimal perioperative antibiotic prophylactic measures.

Upregulation of T-Cell-Specific Transcription Factor Expression in Pediatric T-Cell Acute Lymphoblastic Leukemia (T-ALL).

OBJECTIVE: T-cell acute lymphoblastic leukemia (T-ALL) is associated with recurrent chromosomal aberrations andabnormal ectopic gene expression during T-cell development. In order to gain insight into the pathogenesis of T-ALLthis study aimed to measure the level of expression of 7 T-cell oncogenes (LMO2, LYL1, TAL1, TLX1, TLX3, BMI1, andCALM-AF10) in pediatric T-ALL patients Material and Methods: LMO2, LYL1, TLX1, TLX3, BMI1, TAL1, and CALM-AF10 expression was measured usingquantitative real-time PCR in 43 pediatric T-ALL patients. RESULTS: A high level of expression of LMO2, LYL1, TAL1, and BMI1 genes was observed in a large group of T-ALL.Several gene expression signatures indicative of leukemic arrest at specific stages of normal thymocyte development(LYL1 and LMO2) were highly expressed during the cortical and mature stages of T-cell development. Furthermore,upregulated TAL1 and BMI1 expression was observed in all phenotypic subgroups. In all, 6 of the patients had TLX1and TLX3 proto-oncogene expression, which does not occur in normal cells, and none of the patients had CALM-AF10fusion gene transcription. Expression of LYL1 alone and LMO2-LYL1 co-expression were associated with mediastinalinvolvement; however, high-level oncogene expression was not predictive of outcome in the present pediatric T-ALLpatient group, but there was a trend towards a poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 protooncogeneexpression. CONCLUSION: Poor prognostic impact of TAL1 and/or LMO2 and/or LYL1 proto-oncogene expression indicate the needfor extensive study on oncogenic rearrangement and immunophenotypic markers in T-ALL, and their relationship totreatment outcome. CONFLICT OF INTEREST: None declared.

Analysis of Chromosomal Aberrations and FLT3 gene Mutations in Childhood Acute Myelogenous Leukemia Patients.

OBJECTIVE: To identify the well-known common translocations and FLT3 mutations in childhood acute myelogenousleukemia (AML) patients in Turkey. MATERIAL AND METHODS: The study included 50 newly diagnosed patients in which t(15;17), t(8;21), and inv(16)chromosomal translocations were identified using real-time PCR and FLT3 gene mutations were identified via direct PCR amplification PCR-RE analysis. RESULTS: In all, t(15;17) chromosomal aberrations were observed in 4 patients (8.0%), t(8;21) chromosomal aberrationswere observed in 12 patients (24.0%), inv(16) chromosomal aberrations were observed in 3 patients (6.0%), and FLT3-ITD mutations were observed in 2 patients (4.0%); FLT3-D835 point mutation heterozygosity was observed in only 1patient (2.0%) patient. CONCLUSION: Despite of the known literature, a patient with FLT3-ITD and FLT3-D835 double mutation shows a bettersurvival and this might be due to the complementation effect of the t(15;17) translocation. The reportedmutation ratein this article (4%) of FLT3 gene seems to be one of the first results for Turkish population.

Novel influenza a (H1N1) infection in a Pediatric Hematology Oncology Clinic during the 2009-2010 pandemia.

Pandemic influenza A infection (2009 H1N1) was associated with a worldwide outbreak of febrile respiratory infection. Although usually it results in a mild illness, certain patient groups are at increased risk for complications. The authors reviewed their experience in a pediatric hematology-oncology unit to determine the outcome of this disease in children with hematological conditions and solid tumors. During the second outbreak (1 November 2009 to 14 January 2010), a total of 187 children from pediatric clinic were tested for H1N1 influenza A by multiplex polymerase chain reaction (PCR), 63 of them were positive. Patients' signs and symptoms were recorded prospectively. Ten (35.7%) (5 children with solid tumors, 4 with leukemia, 1 with hereditary spherocytosis) of 28 tested children with hematological conditions were diagnosed with 2009 H1N1 influenza infection. Fever (100%) and cough (90%) were the most common symptoms. Five were neutropenic (neutrophil count <1000/mm(3)), 4 had severe neutropenia (neutrophil count <500/mm(3)). Systemic antibiotics were given in 5 patients with the diagnosis of febrile neutropenia. Four were inpatients, others were hospitalized after the diagnosis. One patient required mechanical ventilation; however, he had concomitant invasive fungal infection. Eight patients were treated by oseltamivir, all tolerated the drug well. A total of 4 cases from 9 cancer patients had a delay in their planned chemotherapy for 7 to 15 days. Pandemic H1N1 influenza caused mild symptoms in children with cancer and/or hematological conditions but resulted in delay in anticancer therapy and increase in hospitalization and antibiotic usage.

Treatment of pediatric Burkitt lymphoma in Turkey.

This study aimed to assess the demographic data and treatment results of children who were diagnosed with Burkitt lymphoma and treated according to the Berlin-Frankfurt-Münster-95 (BFM) protocol in a single institution. A total of 48 patients (37 boys, 77%) with a median age of 8 years (range 2 to 16 years) at diagnosis, were evaluated. Primary tumor sites were abdomen (70.8%), head and neck (22.9%), peripheral lymph node (2%), bone (2%), and testis (2%). The 5-year overall survival (OS) and event-free survival (EFS) were 78.1±4% and 76.6±6%, respectively. In univariate analysis, hemoglobin level less than 10 g/dL, cerebrospinal fluid (CSF) positivity and dialysis requirement at diagnosis were found to be important reverse predictor factors for EFS (P; 0.001, 0.001, 0.004, respectively). In multivariate analysis, hemoglobin level less than 10 g/dL and dialysis at diagnosis were found to be important reverse predictor factors for EFS (P; 0.0001). The EFS of our patients was lower than the values achieved with BFM-95 protocol in other centers. This study provides evidence that low hemoglobin level, CSF positivity and dialysis at diagnosis were important predictor factors for EFS in children with Burkitt lymphoma.

Treatment of Wilms tumor: a report from the Turkish Pediatric Oncology Group (TPOG).

AIM: To standardize diagnosis and treatment of childhood Wilms tumor (WT) in Turkey. METHODS AND PATIENTS: Between 1998 and 2006, WT patients were registered from 19 centers. Patients <16 years with unilateral WT whose treatment started in first postoperative 3 weeks were included. Treatments were stage I favorable (FH) and unfavorable histology (UH) patients, VCR + Act-D; stage IIA FH, VCR + Act-D; stage IIB FH, VCR + Act-D + radiotherapy (RT); stage III-IV FH, VCR + Act-D + adriamycin (ADR) + RT; stages II-IV UH tumors, VCR + Act-D + ADR + etoposide + RT. RESULTS: 165/254 registered cases were eligible (bilateral, 5.9%) [median age 3.0 years; M/F: 0.99; 50/165 cases < or =2 years]. 9.7% cases had UH tumors. Disease stages were stage I 23.6%; IIA 36.4%; IIB 5.5%; III 22.4%; IV 12.1%. Cases >2 years had significantly more advanced disease. 1/11 cases with recurrent disease died; 2/165 had progressive disease, 2/165 had secondary cancers, and all 4 died. In all cases 4-year OS and EFS were 92.8 and 86.5%, respectively. Both OS and EFS were significantly worse in stage IV. CONCLUSIONS: Despite problems in patient management and follow-up, treatment results were encouraging in this first national experience with a multicentric study in pediatric oncology. Revisions and modifications are planned to further improve results and minimize short- and long-term side effects.

Association between genetic polymorphism in DNA repair genes and risk of B-cell lymphoma.

OBJECTIVES: The authors evaluated the possible effect of DNA repair genes, XPD (Xeroderma pigmentosum group D) codon (312 and 751) and XRCC1 (X-ray repair cross-complementing group 1) codon (194 and 399) SNPs (single-nucleotide polymorphisms) on the risk of childhood B-cell lymphoma. METHODS: The polymorphisms were analyzed in 33 patients with BL cases and in 52 healthy, age-matched controls using PCR-RFLP method. RESULTS: The authors observed no association between variation in the XPD codon Asp312Asn, Lys751Gln, and XRCC1 codon Arg399Gln polymorphisms and B-cell lymphoma for any parameter. In contrast, tryptophan allele frequency in control and patient groups was 0.10 and 0.03 respectively (p = .04). The frequency of XRCC1 194Arg/Trp genotype in B-cell lymphoma was significantly lower than that in controls (p = .005). No significant relationship was found between genotypes and stage, lactate dehydrogenase, or bone marrow involvement. CONCLUSIONS: XRCC1 194Trp allele may be associated with a protective effect against development of childhood B-cell lymphoma. However, these results were based on a small number of case and further studies should be done.

First observation of homozygote Hb Q-Iran (alpha 75 (EF4) Asp-His).

The first observation of homozygote Hb Q-Iran (α1 75(EF4) Asp-His) is presented in this report. The clinical and hematological data of the index case, his father and mother showed that homozygous or heterozygous Hb Q-Iran has no clinical importance.

Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience.

AIM: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. MATERIAL AND METHODS: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients' files. RESULTS: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. CONCLUSIONS: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving survival. Evaluation of febrile neutropenia results by hematology-oncology units in years will be directive in early and successful treatment.

The Role of Epstein-Barr Virus LMP-1 Immunohistochemical Staining in Childhood Hodgkin Lymphoma.

BACKGROUND: There are a few published studies about prognostic markers of Epstein-B virus (EBV) related to outcomes in pediatric Hodgkin Lymphoma (HL). OBJECTIVES: We aimed to investigate the prognostic value and effect of EBV on survival by using biopsy materials in children and adolescents diagnosed with HL. PATIENTS AND METHODS: EBV LMP-1 expression was examined using immunohistochemical methods in 58 tumor samples. Clinical features, overall survival (OS) and failure free survival time (FFS) were compared between EBV LMP-1 positive and negative patients. RESULTS: In 20 (35%) patients tumors were LMP-1 positive. When compared with patients above 10 years old, EBV LMP-1 was often positive in patients under 10 years old (30% vs. 70%, P = 0.02). In our most cases having B symptoms and advanced stage, EBV positiveness in Hodgkin Reed-Stenberg cells (H-RS) was not a significant determinant for survival (P = 0.78). Half of the past clinical trials in childhood HL reported longer survival rates in EBV LMP-1 positive patients. In some trials similar to our results there was no significant relationship between EBV and prognosis. CONCLUSIONS: The reason of diminished EBV positiviness may be related to technical methods such as not using immunohistochemical and in situ hybridization for EBER antigen but in laboratory conditions painting of control tissues with EBV impair this probability. In addition, cases enrolled to our study were living in Istanbul where social and economical factors are improved rather than generally.

Anemic or not?

Laboratory data obtained from blood analysis by an electronic cell counter is a routine test along with physical evaluation. We assessed the hematological characteristics of schoolchildren to establish the prevalence of anemia in Istanbul. The study was performed on 1,600 students between the ages of 6-16. Hematological parameters of all the students were measured by an electronic cell counter on blood taken intravenously. Anemia prevalence was primarily determined according to Dallman's criteria. The results showed that if hemoglobin (Hb) was used as the primary criterion to define anemia, 423 students (27.6%) were found anemic; if hematocrit (Hct) was used, 625 students (40.8%) were found anemic and if mean corpuscular volume (MCV) was taken as a criterion to define microcytosis, 121 students (7.9%) remained below the normal level. The difference of anemia prevalence was high (p < 0.001) when two evaluation criteria (Hb or Hct) were compared. Furthermore it is known that a 3% difference occurs when automated and spun Hct values are compared. When a correction was made by adding this 3% to our series' Hct values, the anemic students' number decreased to 418 and the ratio became 27.3%, quite similar to Hb criterion ratio. Population based screening surveys for anemia must be designed and compared cautiously taking into account the method used (electronic counters or gravity based centrifuges), otherwise misleading results can be achieved. We evaluated the data of the survey according to different cut-off values and tried to select the proper one for our conditions.

[Malignant rhabdoid tumor of the orbit]. / Orbital Malign Rabdoid Tümör.

Malignant rhabdoid tumor is a rare and malignant tumor of childhood. Generally it originates from the kidney and central nervous system, but occasionally it may arise from the orbit. Differential diagnosis from other childhood soft tissue sarcomas should be done. We report here an 8-week-old female infant with malignant rhabdoid tumor of the orbit who was treated with chemotherapy and surgery. The 8 week-old girl was referred to our hospital with a history of right proptosis first noted at birth. Physical and laboratory evaluation of the patient was normal except for right proptosis. The mass was removed surgically. Histopathologic examination and immunohistochemical findings of the specimen were evaluated as malignant rhabdoid tumor. Chemotherapy was administered. While in clinical remission, she succumbed during a febrile episode. Malignant rhabdoid tumor can rarely originate from the orbit. Malignant rhabdoid tumor should be kept in mind in the differential diagnosis of orbital masses, and surgery, chemotherapy and local radiotherapy should be used as combined therapy due to the poor prognosis.

Erythrocyte membrane protein defects in hereditary spherocytosis patients in Turkish population.

Hereditary spherocytosis (HS) is a congenital hemolytic anemia which is characterized by spherocytes in peripheral blood and increased osmotic fragility test. The disease is caused by defects in red cell membrane cytoskeleton. In this study, we investigated erythrocyte membrane protein defects in 50 Turkish HS patients and 42 controls. We used sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) to identify the protein defects causing HS. The patients were from 27 families (39 kindred and 11 unrelated patients). They were aged between 6 months and 53 years and the mean age was 18.75 (±14.70) years. Protein deficiencies related to HS were demonstrated in 42% of study group. There was not any statistically significant relation between the protein deficiency and hemoglobin levels. Isolated or combined spectrin deficiency was the most common protein abnormality among our patients. Spectrin deficiency was detected in 22% of cases (11/50), ankyrin deficiency in 8% (4/50), protein 4.2 deficiency in 8% (4/50), combined spectrin and protein 4.2 deficiency in 2% (1/50), combined spectrin and ankyrin deficiency in 2% (1/50). Fifty-eight percent of cases (29/50) showed normal protein contents.

Evaluation of PAX5 gene in the early stages of leukemic B cells in the childhood B cell acute lymphoblastic leukemia.

B-lineage acute lymphoblastic leukemia (B-ALL) is a common subtype of acute leukemia in children. PAX5 plays a central role in B-cell development and differentiation. In this study, we analyzed PAX5 expression levels, transactivation domain mutations/deletions in B-ALL patients (n=115) and healthy controls (n=10). Relative PAX5 mRNA levels were significantly increased in B-ALL patients (p<0.0001). PAX5 expression was also evaluated in three different B-ALL subgroups (pro B, Common B and Pre B ALL) and showed stage specific expression levels. Pro B (p=0.04) and pre B (p=0.04) patients showed significantly high PAX5 mRNA levels compared to stage specific controls. At least one deletion of exons 7-8 or 9 has been identified in the 41% of the patients. CD34 positivity in patients and presence of large deletions (Δ7/8/9) showed a significant correlation (p=0.05). None of our patients showed PAX5 point mutations, but two previously identified SNPs (rs3780135 and rs35469494) were detected. Our results support that PAX5 is a critical factor in B-ALL development and aberrant PAX5 expression especially at early stages may leads to leukemic transformation.

Prognostic significance of NOTCH1 and FBXW7 mutations in pediatric T-ALL.

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T-ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.

DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute lymphoblastic leukemia.

Polymorphisms have been identified in several DNA repair genes. These polymorphisms may effect DNA repair capacity and modulate cancer susceptibility. In this study, we aimed to determine the four polymorphisms in two DNA repair genes, xeroderma pigmentosum complementation group D (XPD) and X-ray repair cross-complementing group 1 (XRCC1), in a sample of Turkish patients with childhood acute lymphoblastic leukemia (ALL), and evaluate their association with childhood ALL development. We used polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), to analyze XPD Asp312Asn, XPD Lys751Gln, XRCC1 Arg194Trp, and XRCC1 Arg399Gln polymorphisms in 70 patients with childhood ALL and in 75 disease-free controls, who were of a similar age. No significant differences were observed among the study groups with regard to the XPD codon 312, XPD codon 751, XRCC1 codon 194, and XRCC1 codon 399 polymorphisms. However, the combined XRCC1 Arg194Trp/Trp194Trp variant genotypes were associated with increased risk for ALL in females (OR=5.47; 95% CI=1.49-20.10; p=0.008). This finding indicates that females carrying XRCC1 194Trp allele are at increased risk of developing childhood ALL. These results suggest that the risk of childhood ALL may be associated with DNA repair mechanisms, and understanding these mechanisms will help identify individuals at increased risk of developing childhood ALL, and also should be lead to improved treatment of ALL.