Turan Bayhan

Sorafenib-induced Posterior Reversible Encephalopathy Syndrome in a Child With FLT3-ITD-positive Acute Myeloid Leukemia.

Background: Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiologic condition characterized by headache, seizures, impaired vision, acute hypertension, and typical cranial MRI findings. Observation: A 10-year-old boy with FLT3-ITD-positive acute myelogenous leukemia who developed PRES during sorafenib treatment has been presented here. In English literature, there are 2 adult patients with metastatic cholangiocarcinoma or hepatocellular carcinoma who developed PRES under sorafenib treatment. Our patient is the first pediatric case with the diagnosis of acute myelogenous leukemia who developed PRES that might be attributed to sorafenib use. Conclusions: Thus, PRES might be a rare, potentially serious, but manageable, side effect of sorafenib that should be kept in mind by pediatric hematologists and oncologists.

Foetal and neonatal intracranial haemorrhage in term newborn infants: Hacettepe University experience.

In this study, we aimed to evaluate the incidence, risk factors, causes and clinical management of intracranial haemorrhage (ICH) diagnosed during foetal life or in the first month of life in term neonates with a discussion of the role of haematological risk factors. This study included term neonates (gestational age 37–42 weeks) with ICH diagnosed, treated and followed up in the Neonatal Intensive Care Unit of Hacettepe University, Ankara, Turkey, between January 1994 and January 2014. Medical follow-up was obtained retrospectively from hospital files and prospectively from telephonic interviews and/or clinical visits. During the study period, 16 term neonates were identified as having ICH in our hospital. In six (37.5%) neonates, ICH was diagnosed during foetal life by obstetric ultrasonography, and in 10 (62.5%) neonates, it has been diagnosed after birth. Haemorrhage types included intraventricular haemorrhage (IVH) in eight (50.0%), intraparenchymal haemorrhage in six (37.5%), subarachnoid haemorrhage in one (6.2%) and subdural haemorrhage in one (6.2%) neonate. IVH was the most common (n = 5/6, 83.3%) haemorrhage type among neonates diagnosed during foetal life. Overall, haemorrhage severity was determined as mild in three (18.7%) neonates, moderate in three (18.75%) neonates and severe in 10 (62.5%) neonates. During follow-up, one infant was diagnosed as afibrinogenemia, one diagnosed as infantile spasm, one cystic fibrosis, one orofaciodigital syndrome and the other diagnosed as Friedrich ataxia. Detailed haematological investigation and search for other underlying diseases are very important to identify the reason of ICH in term neonates. Furthermore, early diagnosis, close monitoring and prompt surgical interventions are significant factors to reduce disabilities.

Chronic lymphocytic leukemia in a child: a challenging diagnosis in pediatric oncology practice.

Chronic lymphocytic leukemia/lymphoma (CLL) is an extremely rare disease during childhood. We report a 16‐year‐old female who presented with lymphadenopathies and she was diagnosed as T cell lymphoblastic lymphoma. Her chemotherapy response was minimal and clinical findings were unusual. Therefore, her biopsy specimen was re‐examined and diagnosis was changed to CLL. Chemotherapy protocol including fludarabine, cyclophosphamide, rituximab was administrated and good response was observed. In our patient deletion at 1q21.2 region that includes aryl hydrocarbon receptor nuclear translocator (ARNT) gene was detected via comparative genomic hybridization method. ARNT gene deletion may be a new mutation in chronic lymphocytic leukemia development. Pediatr Blood Cancer 2014;61:933–935.

Heavy metal levels in patients with ineffective erythropoiesis

OBJECTIVES Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls. RESULTS Blood samples were obtained from 68 patients (51 patients with TM, 8 with TI, 9 with CDA), and a control group that included 65 volunteers. Patients with TM were found to have lower Al, Pb, and Zn, and higher Cd levels compared with the control group. The patients treated with deferasirox were further analyzed and Pb and Zn levels were found lower compared with the control group. DISCUSSION Patients with TM had tendency to have elevated levels of plasma cadmium; however, the median level was not at a toxic level. Increased metal-ion transporter 1 activity may cause heavy metal accumulation, but deferasirox chelation may be protective against heavy metals besides iron.

The questioning for routine monthly monitoring of proteinuria in patients with β-thalassemia on deferasirox chelation

ABSTRACT Background: Iron chelation therapy is one of the mainstays of the management of the patients with β-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. Methods: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios. Results: The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p = 0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29 mg/kg/day, were found to have higher risk of proteinuria development (p = 0.004). Conclusion: Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29 mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.

Successful Outcome With Fludarabine-Based Conditioning Regimen for Hematopoietic Stem Cell Transplantation From Related Donor in Fanconi Anemia: A Single Center Experience From Turkey.

Fanconi anemia (FA) is a heterogeneous autosomal recessive (and rarely X linked) disorder, which is characterized by congenital malformations, progressive bone marrow failure, and predisposition to malignancies. Hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for the hematological manifestations in FA.

Assessment of Peripheral Neuropathy in Patients with β-Thalassemia via Electrophysiological Study: Reevaluation in the Era of Iron Chelators

Abstract Peripheral neuropathy is one of the complications of β-thalassemia (β-thal) that has been investigated in limited reports. We aimed to detect the rate of peripheral neuropathy and risk factors for neuropathy development in patients with β-thal. The study was performed in patients with β-thal intermedia (β-TI) or β-thal major (β-TM). Prospective electrophysiological studies were achieved via standard procedures. A total of 27 patients were enrolled in the study. Electrophysiological studies for both motor and sensory nerves were within normal range. In motor nerve studies, delayed peroneal nerve latency was found in patients with high ferritin levels, increased ulnar nerve amplitude was detected in patients ≥20 years old, and increased tibial nerve amplitude was seen in patients with low copper levels. We could not show peripheral neuropathy in our patients. Increased ferritin level, older age, and copper deficiency may cause mild changes in electrophysiological studies of motor nerves.

Hepatoblastoma and Wolf-Hirschhorn syndrome: Coincidence or a new feature of a rare disease?

Wolf–Hirschhorn syndrome (WHS) is a chromosomal disorder characterized by multiple congenital anomalies. Deletion of the distal part of chromosome 4 (4p 16.3) is the underlying cause of the disease. Typically patients have a wide nasal bridge continuing to the forehead, giving the face the appearance of a Greek warrior helmet. Patients are small for gestational age, and weight gain and growth are limited after birth. Patients usually have seizures until 3 years of age, and majority of them have mental or motor retardation. Cancer is not a frequent feature of the syndrome, but hematopoietic system malignancies and hepatic adenoma have been reported in a few cases. Herein, we report a pediatric patient with WHS who developed hepatoblastoma.

An orbital perivascular epithelioid cell tumor in a 7-year-old boy: case report and review of the literature

We report the case of a 7-year-old boy who presented with a swollen right eye. Magnetic resonance imaging revealed a right intraconal orbital mass with intense contrast enhancement. Incisional biopsy led to a diagnosis of perivascular epithelioid cell tumor (PEComa). Sirolimus was initiated but discontinued at the third week of treatment because the tumor had progressed. A minor regression of the tumor was seen after six cycles of systemic chemotherapy. Previously reported cases of PEComa were benign in nature, and full remission was achieved with surgical excision. In the present case the tumor was malignant and responded only slightly to systemic chemotherapy.

Hereditary Elliptocytosis with Pyropoikilocytosis.

A 17-day-old boy was admitted because of jaundice and anemia. He was born weighing 2900 g subsequent to a term gestation as the fourth child of first-degree cousin parents. The previous history revealed the administration of phototherapy for 4 days starting from the first day of life. Complete blood count revealed hemoglobin (Hb) of 6.9 g/dL, hematocrit of 19.8%, mean corpuscular volume (MCV) of 87.5 fL, red cell distribution width (RDW) of 37%, white blood cell count of 11.4x109/L, and platelet count of 263x109/L. Corrected reticulocyte count was 5.3%. Peripheral blood smear revealed polychromasia and pyropoikilocytosis. Direct antibody test was negative. Erythrocyte glucose-6-phosphate dehydrogenase, pyruvate kinase, and pyrimidine 5’ nucleotidase levels were normal. An erythrocyte transfusion was administered with a diagnosis of non-immune hemolytic anemia and the patient was discharged at the 26th day of life with initiation of folic acid. During his outpatient follow-up, he required erythrocyte transfusions 2 more times and the last transfusion was performed when he was 3 months old. At a visit 3 months after the last transfusion, his blood count was as follows: Hb of 9.5 g/dL, hematocrit of 28.2%, MCV of 68.2 fL, and RDW of 30.5%. Erythrocyte osmotic fragility was found to be normal and Hb electrophoresis revealed Hb F of 6.6% and Hb A2 of 1.7%. Upon physical examination he had mild jaundice and no splenomegaly. The parents’ blood counts were within normal ranges. Peripheral blood smear revealed prominent elliptocytes and occasional microcytic and fragmented erythrocytes with poikilocytosis (Figure 1). The clinical findings and laboratory results were diagnostic for the hereditary pyropoikilocytosis (HPP) type of hereditary elliptocytosis (HE), but in vitro fragmentation testing was not performed. Figure 1 The peripheral blood smear of the patient: prominent elliptocytic erythrocytes, in addition to microcytic erythrocytes (arrows) and fragmented erythrocytes (circles). HE is a common hemolytic red cell membrane disease with variant clinical presentations [1]. Common mutations that cause HE are found in the α-spectrin, β-spectrin, and protein 4.1 genes [2]. The majority of patients with HE are asymptomatic, but HPP is a severe form of HE that presents with hemolytic anemia and jaundice during the infantile period. Erythrocyte morphology in HPP resembles that of blood smears in thermal burns with poikilocytes, red blood cell fragments, microspherocytes, and elliptocytes [3]. Low MCV (25 to 75 fL) due to fragmented red blood cells is characteristic and osmotic fragility is commonly normal [1,3].