Meryem Albayrak

Invasive fungal infections in pediatric leukemia patients receiving fluconazole prophylaxis.

Children with acute leukemia have increased risk for invasive fungal infections (IFI) but the role of long term antifungal prophylaxis (AFP) in morbidity and mortality of IFI is not well‐known.

A novel single point mutation of the LYST gene in two siblings with different phenotypic features of Chediak Higashi syndrome.

Chediak Higashi syndrome (CHS) is an autosomal‐recessive disorder characterized by oculocutaneous albinism, recurrent infections and a progressive primary neurological disease. Here, we describe two siblings with CHS due to a novel homozygous R1836X mutation in the LYST gene associated with loss of NK cell degranulation and cytotoxicity. While one sibling was born with fair skin and hair and died of hemophagocytic lymphohistiocytosis (HLH) at 5 months of age, the other sibling had dark black hair and skin and developed HLH at the age of 4 years. Pediatr Blood Cancer 2011;56:1136–1139.

Heart Rate Variability in Neonates with Hypoxic Ischemic Encephalopathy

ObjectiveTo evaluate the changes in heart rate variability (HRV) in newborns with hypoxic-ischemic encephalopathy (HIE).MethodsTwenty-two newborns (14 boys, 8 girls) with moderate or severe HIE and 24 term neonates with similar gestational and postnatal age for control were included in this study. Normalized low and high frequency components of HRV and their ratio were evaluated for 24-h in newborns with HIE and control subjects.ResultsThe newborns with hypoxic-ischemic encephalopathy had significantly lower normalized low frequency (LFn) and low frequency (LF) / high frequency (HF) values and higher normalized high frequency (HFn) values when compared with the control babies. In addition, when the cases with severe HIE are compared with those of moderate HIE, decreased LFn, LF/HF values and also increased HFn values were present in the severe cases.ConclusionsHIE is associated with reduced sympathetic nervous system activity, and increased parasympathetic nervous system activity and these activities also correlate with the severity of the disease.

The Frequency of Menorrhagia and Bleeding Disorders in University Students

Study Objective: Menorrhagia is an important health problem in women of reproductive age. The aims of this study were to assess the prevalence of menorrhagia and hemostatic abnormalities associated with menorrhagia in university students. Methods: The pictorial blood assessment chart (PBAC) was used to identify students with menorrhagia. Those with a PBAC score > 100 were examined by pelvic ultrasound and laboratory tests including complete blood count, levels of clotting factors, von Willebrand factor antigen, and ristocetin cofactor activity and Platelet Function Analyser-100 (PFA-100). Platelet aggregation was studied in students with prolonged PFA-100 closure time. Results: Menorrhagia was identified in 82 (21.8%) of 376 students. Six of 82 students who had pelvic pathologies were excluded. Eleven (14.5%) of the remaining 76 students were found to have bleeding disorders, including von Willebrand disease in five (6.5%), platelet function disorder in four (5.2%), and clotting factor deficiencies in two (2.6%). Conclusions: Menorrhagia is a common but mostly unrecognized and untreated problem among university students. Underlying bleeding disorders are not rare and require comprehensive hemostatic evaluation for identification.

Assessment of clinical and laboratory presentations of familial hemophagocytic lymphohistiocytosis patients with homozygous W374X mutation

Homozygous W374X mutation was identified in unrelated 13 patients (6M/7F) from consanguineous families, 62% of which had history of deceased sibling. Haplotype analysis provided evidence for the probable existence of a founder effect. Age at disease onset ranged from 1 day to 5.5 months (median 2 months). Hepatic dysfunction was observed in 69%, ascite 62%, hypertriglyceridemia 77%, each hyperferritinemia and hypofibrinogenemia 85%, CNS involvement 46% of patients while birth weights were in normal range. Those with very high ferritin (>20,000ng/ml) had extremely low fibrinogen levels. Two-thirds of patients receiving HLH protocol died within 20 days of therapy.

Prognostic Factors and Long-Term Outcome in 52 Turkish Children With Hemophagocytic Lymphohistiocytosis.

Objectives: Hemophagocytic lymphohistiocytosis is a syndrome of pathologic immune activation that shares similar clinical and laboratory phenotypes with severe sepsis. Recent studies led to better recognition of hemophagocytic lymphohistiocytosis by clinicians, but no consensus exists on the criteria for high-risk patients. Design: We retrospectively reviewed the medical records of patients diagnosed with hemophagocytic lymphohistiocytosis to analyze the risk factors associated with poor outcome. Setting: Pediatric intensive care and hematology units of three tertiary hospitals in Turkey. Participants: Fifty-two children with hemophagocytic lymphohistiocytosis. Interventions: None. Measurement and Main Results: There were a total of 52 children meeting the diagnostic criteria of Histiocytic Society. Of them, 28 (54%) had a primary hemophagocytic lymphohistiocytosis. Mutation studies were performed in 18 of 28 patients (65%). Fourteen of them had PRF1, STX11, STXBP2, and UNC13D mutations, and four had Rab27a and LYST mutations. The remaining 24 patients (46%) were defined as having secondary hemophagocytic lymphohistiocytosis. Twenty-one of them had infection-associated hemophagocytic lymphohistiocytosis, and three had lysinuric protein intolerance. The mortality rate was significantly higher in primary hemophagocytic lymphohistiocytosis (64%) than in secondary hemophagocytic lymphohistiocytosis (16%) (p < 0.05). There were no significant differences for survival rate between hemophagocytic lymphohistiocytosis 94 (44%) and hemophagocytic lymphohistiocytosis 2004 (64%) protocols (p > 0.05). Age below 2 years, hyperferritinemia, thrombocytopenia, high disseminated intravascular coagulation score at diagnosis, and no clinical response at 2 weeks of treatment were independent prognostic factors for poor prognosis. Conclusions: Our data suggest that disseminated intravascular coagulation score greater than or equal to 5 can be used in the definition of high-risk patients. Early recognition of poor risk factors has important prognostic and therapeutic implications.

Serum Prohepcidin Levels in Children with Solid Tumors, Inflammatory Bowel Disease and Iron Deficiency Anemia

BACKGROUND Prohepcidin is one of the regulators of iron metabolism. Few studies examined its relation with solid tumors (ST), inflammatory bowel disease (IBD) and iron deficiency anemia (IDA) in children. METHODS We measured serum prohepcidin (SP), soluble transferrin receptor (sTfR), serum ferritin (SF), serum iron (SI), transferrin saturation (TS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in ST (n = 16), IBD (n = 15), IDA (n = 14) and controls (n = 18). RESULTS The mean SP was significantly higher in ST and IBD than in IDA and controls. SP was significantly correlated with SF in ST, IBD and ESR for IBD and CRP for ST and hemoglobin for ST. CONCLUSION Elevated SP may be a clinically important predictor of inflammation and leads to anemia by impairing iron utilization in IBD and ST. SP decreases in IDA and is correlated with TS but not with SF or sTfR.

Alterations in Procoagulant, Anticoagulant, and Fibrinolytic Systems Before and After Start of Induction Chemotherapy in Children With Acute Lymphoblastic Leukemia

Induction chemotherapy is associated with increased thrombosis risk in children with acute lymphoblastic leukemia (ALL). In this prospective study, we explored the effects of ALL and induction chemotherapy on the procoagulant, anticoagulant, and fibrinolytic systems in 20 children with ALL. The levels of d-dimer, factor VIII, von Willebrand factor, protein C, antithrombin III, and thrombin-activated fibrinolysis inhibitor (TAFI) were elevated at diagnosis. These changes were not related with peripheral blast count. The levels of fibrinogen, d-dimer, coagulation inhibitors, and plasminogen decreased, whereas the levels of tissue factor pathway inhibitor and plasminogen activator inhibitor 1 increased progressively following prednisolone monotherapy, administration of vincristine plus daunorubicin, and l-asparaginase. The levels of factor VIII, d-dimer, and TAFI remained elevated during the study period. In conclusion, coagulation activation and impaired fibrinolysis already exist at diagnosis, whereas induction chemotherapy leads to reactivation of coagulation and progressive impairment in fibrinolytic and anticoagulant capacities in childhood ALL.

ALL-BFM 95 Treatment in Turkish Children with Acute Lymphoblastic Leukemia—Experience of a Single Center

Little is known about the likelihood of curing children with high-dose chemotherapy regimens for treatment of childhood acute lymphoblastic leukemia (ALL) in Turkey. The authors here report their 13 years’ experience with original ALL-BFM (Berlin-Franfurt-Münster) 95 protocol in a cohort of 140 Turkish children with ALL. Complete remission rate was 97.7% with a relapse rate of 12.9% and death rate 17.9% during a median follow-up of 69 months. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) in these patients at 12 years were 75.0%, 87.1%, and 80.6%, respectively. These results show that ALL-BFM 95 protocol is equally applicable in the experienced centers, even in developing countries without substantial treatment-related toxicity. High rate of infection deaths are to be reduced with correct policies.

Severe Myelotoxicity Associated with Thiopurine S-Methyltransferase*3A/*3C Polymorphisms in a Patient with Pediatric Leukemia and the Effect of Steroid Therapy.

Myelosuppression is a serious complication during treatment of acute lymphoblastic leukemia and the duration of myelosuppression is affected by underlying bone marrow failure syndromes and drug pharmacogenetics caused by genetic polymorphisms. Mutations in the thiopurine S-methyltransferase (TPMT) gene causing excessive myelosuppression during 6-mercaptopurine (MP) therapy may cause excessive bone marrow toxicity. We report the case of a 15-year-old girl with T-ALL who developed severe pancytopenia during consolidation and maintenance therapy despite reduction of the dose of MP to 5% of the standard dose. Prednisolone therapy produced a remarkable but transient bone marrow recovery. Analysis of common TPMT polymorphisms revealed TPMT *3A/*3C.