Deniz Yilmaz Karapinar

Iliopsoas haemorrhage in patients with haemophilia: results from one centre.

Summary.  Iliopsoas haematoma is a well‐recognized complication of haemophilia, and is considered as potentially life threatening and significantly associated with morbidity. There are only rare reports on the incidence or outcomes of iliopsoas bleeding since the widespread usage of modern therapies for haemophilia. In this study, we present the experience of Ege University Haemophilia Centre with iliopsoas bleeding and its early and late complications. We reviewed 146 haemophiliacs (106 haemophilia A, 40 haemophilia B). Fourteen iliopsoas bleeding episodes were identified in eight haemophiliacs. Three patients (37%) had one episode, four (50%) had two episodes and one (13%) had three episodes. Two patients had a high titre inhibitor against factor VIII and accounted for three bleeding episodes (21%). We did not observe any episodes in six patients receiving prophylaxis. Iliopsoas haematomas were confirmed by ultrasonography in all patients. In physical examination, the most common symptoms were thigh, hip and groin pain, hip flexion contracture, abdominal tenderness and paraesthesia in the distribution of the femoral nerve. The mean duration of therapy with clotting factor concentrate was 7.8 ± 1.6 days. The mean duration of hospitalization was 4.8 ± 2.0 days. All patients started to receive a physical therapy program 6.0 ± 2.4 days after the initiation of haemostatic therapy which lasted 20.0 ± 6.0 days. Ultrasonographic findings related to iliopsoas haematoma disappeared in all patients within 3 months from the initial episodes. Only in one patient with mild haemophilia A, heterotopic bone formation (myositis ossificans) developed as a long‐term complication. In conclusion, pain around the hip joint, femoral neuropathy and hip flexion contracture in a patient with haemophilia should alert the physician to the possibility of an iliopsoas haematoma. Early and effective factor replacement therapy is essential in the prevention of the complications.

Meropenem Plus Amikacin Versus Piperacillin-Tazobactam Plus Netilmicin as Empiric Therapy for High-Risk Febrile Neutropenia in Children

The aim of this study was to evaluate the efficacy and safety of meropenem plus amikacin compared with piperacillin-tazobactam plus netilmicin for initial empirical antibiotic treatment of high-risk febrile neutropenia in children with cancer. Patients with hematologic malignancy (leukemia or stage III/IV non-Hodgkin lymphoma) who presented with fever and neutropenia (ANC < 500/mm3) and patients with solid tumors who presented with fever and severe neutropenia (ANC < 100/mm3) were considered to be at high risk and eligible for this study. In this prospective study, 33 patients with 50 febrile neutropenic episodes received iv meropenem (20 mg/kg every 8 h) plus amikacin (15 mg/kg/d in 2 divided doses) (in 31 episodes) or piperacillin/tazobactam (100 mg/4 mg/kg every 8 h) plus netilmicin (7 mg/kg every 24 h) (in 19 episodes). Clinical response was determined at 72 h and at completion of the therapy. The groups were comparable in terms of age, sex, initial ANC, use of growth factors, and classification of the infections. An infection was documented microbiologically in 12 episodes (39%) in the meropenem plus amikacin group and in 8 episodes (42%) in the piperacillin/tazobactam plus netilmicin group. Of the 22 microbiological isolates, 37% were gram-positives, 45% were gram-negatives, and 18% were fungi. Most of the clinically documented infections were of lower respiratory tract, gastrointestinal mucosa, or urinary tract origin. The mean duration of neutropenia was 9 days in both groups. Fever persisted for 1–30 days (mean 3 vs. 5 days). The success rate with initial empiric therapy was 52% in the meropenem plus amikacin and 42% in the piperacillin/tazobactam plus netilmicin group, respectively (p= .5). Total success rate (with or without modification) was 97% vs. 90% in the episodes. Three patients died due to infection (1 vs. 2 patients). No major adverse effects were observed in each group. Empirical therapy with meropenem plus amikacin or piperacillin/tazobactam plus netilmicin for high-risk febrile neutropenia is equally effective and safe in pediatric cancer patients.

Spinal epidural haematoma in a patient with haemophilia B

Summary.  Spinal epidural haematoma (SEH) is a rare complication in haemophiliacs. We report the case of a 17‐year‐old boy with severe haemophilia B who presented with acute onset of neck/back pain, walking impairment and urinary retention because of an extensive SEH. The haematoma was identified by magnetic resonance imaging of the spinal column. Prompt and aggressive treatment with factor IX concentrate led to complete recovery at 3 weeks. This case calls attention to the clinical manifestation, radiological features and management options of the rarely reported SEH in haemophiliacs. Despite evidence of extensive SEH, factor replacement therapy and a multidisciplinary team approach result in complete neurological recovery without the need for surgical decompression.

Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

Dysregulation of microRNA (miRNA) expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL) to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.

Evaluation of telomerase mRNA (hTERT) in childhood acute leukemia

Human telomerase reverse transcriptase (hTERT) is the catalytic component of telomerase enzyme and has been shown to be associated with telomerase activity (TA). Although many studies in adult leukemia have established the importance of TA, very few have been reported in the children. In this study hTERT levels in childhood leukemia was evaluated and compared with the prognostic factors described before. The LightCycler instrument was used (online real-time PCR) for the quantification of hTERT in peripheral blood and bone marrow in 23 cases with acute lymphoblastic leukemia (ALL) and in 8 cases with acute myeloblastic leukemia (AML). Ten cases with normal peripheral blood (PB) and bone marrow (BM) were selected as control group. Cytogenetic analyses were available in 21 patients with leukemia. In all cases with acute leukemia and in control group, peripheral blood (PB) hTERT levels correlated significantly with bone marrow (BM) hTERT levels. Before treatment, patients with ALL had significantly higher hTERT levels than that of AML patients and control cases. Among patients with ALL, higher hTERT levels were observed in patients with pre-B leukemia, followed by B cell and T cell leukemia patients. Initially increased hTERT levels decreased to the nearly normal levels during remission in cases with ALL. No correlation was observed between the initial hTERT levels and the known prognostic factors except cytogenetic findings. Higher hTERT levels were detected in patients having karyotypic abnormalities which indicate poor prognosis. hTERT levels are significantly high in childhood ALL with the highest level of pre-B cell leukemia before treatment. Those high levels of hTERT decrease to almost normal levels in remission. hTERT levels might be useful in monitoring of leukemia in children.

The Association of minor congenital anomalies and childhood cancer.

Although the association of some congenital malformations and specific genetic syndromes is well understood, the association between minor anomalies and cancer is not well known. In recent years some researchers have reported studies establishing this association in different types of cancer. In this study, we aimed to investigate the prevalence and patterns of age‐independent minor anomalies in childhood cancer patients.

Long-term evaluation of chromosomal breakages after radioisotope synovectomy for treatment of target joints in patients with haemophilia

Summary.  Radioisotope synovectomy (RS) is defined as the intra‐articular injection of radioisotopic agents with the aim of fibrosis on hypertrophic synovium in the target joint. The aim of this study was to investigate genotoxic effects on lymphocytes and malign transformation induced by Yttrium90 (Y90) and Rhenium186 (Re186) in children with haemophilia undergone RS. Forty haemophilia patients were enrolled. The mean age was 16.4 ± 6.2 years (range: 8–40). Y90 was used for knees, Re186 was used for other joints. For safety, cytogenetic analysis was performed to determine potential chromosomal changes after RS procedure at three different time points as prior to procedure, 3rd day and 90th day. For the stimulation of chromosomal breakages, diepoxybutane was used (DEB test). Chromosomal breakages (CBs) were found in 23 patients (67.6%) prior to RS. We have found CBs additionally in nine of 11 patients who had no CBs prior to RS after 3 days of radioisotope exposure. At that time, the patients who had CBs were 29 (85.2%). At day 90, only 21 patients revealed (61.7%) CBs. The mean frequency of CBs slightly but not significantly increased in the 3rd day. However, there was a significant decreasing trend between 3rd and 90th days. Radioisotope synovectomy with Y90 and Re186 does not seem to induce the genotoxic effects significantly on peripheral blood lymphocytes. However, CBs even after one year in the re‐evaluation of four patients, significant decrease in the number of CBs between the 3rd and 90th days and de novo CBs after exposure may be accepted as warning signals for young population. It should also be pointed out that families and patients be informed properly related with historical and potential dangers of radioisotopic agents.

Proven and probable invasive fungal infections in children with acute lymphoblastic leukaemia: results from an university hospital, 2005–2013

Despite improvements in diagnosis and treatment, invasive fungal infections (IFIs) are still a major cause of morbidity and mortality in immunocompromised patients. The data on IFI among children with acute lymphoblastic leukaemia (ALL) are still scarce, and our aim was to estimate the risk, aetiology and outcome of proven and probable IFIs in children with ALL who did not receive primary prophylaxis over an 8‐year period. Between January 2005 and February 2013, 125 children who were treated for ALL at the Pediatric Hematology Department of the Medical School of Ege University were retrospectively reviewed. Proven and probable IFIs were defined according to revised definitions of the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. The proven and probable IFI incidence was 30/125 (24%). Profound neutropenia was detected in 18 (60%) patients, and prolonged neutropenia was detected in 16 (53.3%) of the patients. The most isolated agents were non‐albicans Candida spp. The crude and attributable mortality was 20% and 13.3% respectively. Profound neutropenia was associated with mortality (P < 0.05). The younger patients were especially at risk for proven IFI. Prolonged neutropenia, to be in the induction phase of chemotherapy, and profound neutropenia were found to be the most common predisposing factors for IFI episodes.

The investigation of relationship between joint findings and serum angiogenic and inflammatory factor levels in severe hemophilia A patients.

Despite the use of primary prophylactic Factor VIII replacement in severe hemophilia A patients, bleeding into joints cannot be prevented completely and early diagnosis and treatment of the joint bleedings are important for prevention of permanent joint damage. Recent studies have shown that neoangiogenesis plays important role in development of synovitis after recurrent joint bleedings. This study aimed to investigate the relationship between joint findings and levels of serum angiogenic and inflammatory factors in severe hemophilia A patients.The patient groups consisted of 10 severe hemophilia A patients with acute joint bleeding and 25 severe hemophilia A patients without acute joint bleeding. They were all inhibitor negative. The control group consisted of 22 healthy male children. Complete blood cell count analysis, C-reactive protein (CRP), serum ferritin, lactic acid, and ELISA-based detection of vascular endothelial growth factor (VEGF), intercellular adhesion molecule-1, thrombomodulin, macrophage migration inhibitory factor (MIF), and endostatin were performed from peripheral blood of patient and the control groups. CRP and MIF levels were detected significantly higher in hemophilia patients with acute joint bleeding than patients without acute joint bleeding. There was a positive correlation between serum thrombomodulin, VEGF, and MIF levels. In this study, we demonstrated that serum CRP and MIF levels increases in acute bleeding period regardless of the presence of previous joint damage in children with severe hemophilia. CRP elevation may be a useful and rapid marker for acute bleeding in these patients.

The Influence of the ABO Blood Type on the Distribution of von Willebrand Factor in Healthy Children With no Bleeding Symptoms

The purpose of this study was to determine the effect of ABO blood groups on von Willebrand factor–ristocetin cofactor activity (vWF-RCo) and on vWF–antigen (vWF-Ag) in children who have no personal or familial history of bleeding. Material and methods: A survey and testing were performed on 200 children with no personal or familial history of bleeding. In all, 100 of them belonged to blood group O, and the remaining 100 belonged to other blood groups. The blood samples were stored at −80°C for a maximum period of 2 weeks to detect vWF-RCo and vWF-Ag levels. Results: The mean vWF-Ag (±2 standard deviation [SD]) level in children with blood group O was 86% (±20%); and for those with non-O blood group, it was 98.8% (±25%). There was a significant difference between the 2 groups (P < .001). The mean vWF-RCo (±2 SD) level in children with blood group O was 89% (±23%); and for those with non-O blood group, it was 103% (±17%). There was a significant difference between those in the 2 groups (P < .001). The lowest value of vWF-Ag and vWF-RCo levels in children with blood group O was found to be 50%. In conclusion, we showed that the selection of normal ranges based on the ABO group might influence the clinical diagnosis of vWD and that while the approach of using ABO group ranges for a vWF-Ag level lower than 50 IU/dL is scientifically sound, it might not be useful to assist a clinician in identifying people at increased risk of bleeding.