Pamir Isik

The Role of Prohepcidin in Anemia Due to Helicobacter pylori Infection

Background: Hepcidin, a key regulator of iron homeostasis, increases when inflammation and some infections occur. It plays a critical role in macrophage iron retention, which underlies inflammation/infection caused anemia. It is known that Helicobacter pylori (HP) may lead to iron deficiency (ID) due to occult blood loss or reduced iron absorption. This study investigates the role of prohepcidin, hepcidins precursor, in ID and ID anemia (IDA) with a concurrent HP infection. Methods: In this prospectively designed study, 15 patients with IDA and a concurrent HP infection (group 1), 11 patients with an ID and a concurrent HP infection (group 2), and 18 patients with HP infection (group 3) were observed. All groups received only HP eradication therapy. Twenty-five age- and sex-matched children without ID/IDA and HP infection were included in the study as the control group. In all groups and control group, measurements were taken for pre- and posttreatment hemoglobin, serum prohepcidin, serum ferritin, serum iron (SI), transferrin saturation, erythrocyte sedimentation rate, fibrinogen, and C-reactive protein levels. Results: The pretreatment prohepcidin levels were significantly higher only in group 1 compared to the control group (P < .05). In group 1, a significant increase in hemoglobin and SI levels and a significant reduction in prohepcidin levels were additionally observed following HP eradication treatment (P < .05). However, in groups 2 and 3, significant differences in hemoglobin, iron, and prohepcidin levels between pre- and posttreatment were not observed. Conclusion: Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP.

Venous Thromboembolism after Allogeneic Pediatric Hematopoietic Stem Cell Transplantation: A Single-Center Study.

Objective: Venous thromboembolism (VTE) in children who undergo hematopoietic stem cell transplantation (HSCT) has high morbidity. The aim of this study is to assess the incidence of VTE in allogeneic pediatric HSCT recipients and the contribution of pretransplant prothrombotic risk factors to thrombosis. Materials and Methods: We retrospectively evaluated 92 patients between April 2010 and November 2012 undergoing allogeneic HSCT who had completed 100 days post-HSCT. Before HSCT, coagulation profiles; acquired and inherited prothrombotic risk factors including FV G1691A (factor V Leiden), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T, and MTHFR A1298C mutations; and serum homocysteine and lipoprotein (a), plasma antithrombin III, protein C, and protein S levels were obtained from all patients. Results: In the screening of thrombophilia, 8 patients (9%) were heterozygous for factor V Leiden, 5 (6%) were homozygous for MTHFR 677TT, 12 (14%) were homozygous for MTHFR 1298CC, and 2 (2%) were heterozygous for prothrombin G20210A mutation. We observed VTE in 5 patients (5.4%); a prothrombotic risk factor was found in 3 out of these 5 patients, while 4 out of 5 patients had central venous catheters. It was determined there was no significant relationship between VTE and inherited prothrombotic risk factors. Conclusion: VTE after HSCT seems to be a low-frequency event that may be due to low-dose, low-molecular-weight heparin prophylaxis, and the role of inherited prothrombotic risk factors cannot be entirely excluded without a prospective study.

Endocrinopathies in Turkish children with Beta thalassemia major: results from a single center study.

The endocrinological complications in β-thalassemia major patients do affect the life quality to a large extend. In this study, the endocrinological complications of 47 β-thalassemia patients, who have been followed-up at our hospitals pediatric hematology department, were evaluated. Out of β-thalassemia major cases included to this study, the 55.3% was male and 44.7% was female. The patients’ mean levels of ferritin, whose mean age was 10.0 ± 4.5 years (2–20 years), were 2497 ± 1469 ng/mL (472–8558 ng/mL). At least one endocrinological pathology in 27 out of 47 (57.4%) and more than one endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were observed. The most frequently observed complication in followed-up cases was vitamin D insufficiency and deficiency (78.2%). The other complications in decreasing order were pubertal failure (41.6%), growth retardation (25.5%), decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%), overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired glucose tolerance (2.12%). There was no statistically significant difference between serum mean ferritin level and endocrin complications (P > .05). Four patients (8.5%) had decreased signal intensity in pituitary magnetic resonance imaging (MRI) but this finding was not associated with ferritin levels (P = .87). MRI parameters were similar between patients with and without gonadal dysfunction. Mean height of the pituitary gland was 4.98 ± 1.1 mm (3–9 mm) and this was similar to those normal values in the literature. Ferritin levels were not correlated with pituitary height (P > .05). Beta thalassemia major, having the potential of leading to multisystemic complications, is a chronic disease that should be treated and followed-up by a multidisciplinary approach. Due to frequently encountered endocrinological complications, beta thalassemic patients should be followed-up regularly by hematology and endocrinology departments in coordination.

Typhlitis in acute childhood leukemia.

Objective: To review our experience with typhlitis among children treated for acute leukemia. Material and Methods: The medical records of children with acute leukemia and typhlitis between 2006 and 2009 were reviewed for demographics and symptoms, and for microbiological and imaging findings. Results: In the 75 children with acute leukemia – 54 with acute lymphoblastic leukemia (ALL) and 21 with acute myeloid leukemia (AML) – there were 10 episodes of typhlitis (4.5%) that developed during 221 periods of severe neutropenia. The cumulative risk of typhlitis was 7.4% in patients with ALL and 28.5% in patients with AML. Frequent symptoms were: abdominal pain and tenderness (100% each); fever and nausea (90% each); emesis (80%); diarrhea (50%), and hypotension, peritonitis and abdominal distension (10% each). The median duration of symptoms was 6 days (range: 2–11 days), and that of neutropenia 14 days (range: 3–25 days). All patients were treated medically and none surgically. Two patients died because of typhlitis and sepsis. Conclusions: In our study, the rate of typhlitis among leukemic children was 4.5%; however, the mortality rate was 20%. Thus, rapid identification and timely, aggressive medical intervention are necessary to reduce the morbidity and mortality from typhlitis.

Extramedullary Orbital Granulocytic Sarcoma Without Bone Marrow Involvement: A Report of Two Cases

The authors present herein 2 extramedullary orbital granulocytic sarcoma (GS) cases without bone marrow involvement in view of their rarity and also to reevaluate the treatment approach in this disease. Seven days of high-dose methyl prednisolone (HDMP) treatment (3 days 30 mg/kg/day and 4 days 20 mg/kg/day) was administered initially, and subsequently Acute Myeloid Leukaemia–Berlin Frankfurt Münster (AML-BFM) 2004 treatment protocol was continued for 2 cases. Eye findings of the cases resolved considerably with HDMP treatment. They have still been under systemic chemotherapy without any complication for 1 year. Thus, early diagnosis and AML-targeted intensive chemotherapy improve the prognosis of GS even if there is no bone marrow involvement.

All-transretinoic acid (ATRA) treatment-related pancarditis and severe pulmonary edema in a child with acute promyelocytic leukemia.

Use of all-transretinoic acid (ATRA) with other chemotherapeutic agents in the treatment of acute promyelocytic leukemia (APL) has been shown to cause the differentiation of abnormally granulated specific blast cells into mature granulocytes by acting on the t(15; 17) fusion gene product. The complete remission rate is increased and survival time is prolonged in APL patients who receive chemotherapy plus ATRA, whereas ATRA syndrome and other ATRA-related adverse effects including pseudo tumor cerebri, headache, severe bone pain, mucosal and skin dryness, hypercholesterolemia, and cheilitis may be observed especially during induction phase of the treatment. In this paper, we report a 9-year-old girl with APL who developed pancarditis while receiving the APL-93 treatment protocol. In our patient, endocarditis and myocarditis were initially determined after ATRA treatment during the induction part of the protocol. All findings disappeared after ATRA was discontinued. When ATRA was readministered in the maintenance part of the treatment protocol, she developed pancarditis and severe pulmonary edema. As her symptoms decreased dramatically with the discontinuation of ATRA and the initiation of steroid treatment, the clinical picture strongly suggested the ATRA treatment as the causative factor. To the best of our knowledge, this clinical picture of pancarditis secondary to ATRA treatment has not been reported earlier in the English literature.

Successful allogeneic hemopoietic stem cell transplantation in a case of Wiskott-Aldrich syndrome and non-Hodgkin lymphoma.

WAS is a severe X‐linked recessive disorder characterized by microthrombocytopenia, eczema, and immunodeficiency. A six‐yr‐old boy with WAS diagnosed as B‐cell NHL (Stage III) localized in the liver who underwent successful HSCT from HLA‐one antigen mismatch sibling donor has been presented here. His conditioning regimen included ATG, busulfan, and fludarabine. He received 2.3 × 106/kg CD 34(+) stem cells and 11 × 108/kg nucleated cells at day 0. Neutrophil engraftment was achieved at day +14 and platelet engraftment at day +20. He has been in CR for more than two yr after transplantation. Thus, HSCT is an effective treatment for children with WAS even after development of lymphoma.

Assessment of left ventricular functions and myocardial iron load with tissue Doppler and speckle tracking echocardiography and T2* MRI in patients with β‐thalassemia major

The purpose of this study is to determine early myocardial dysfunction in β‐thalassemia major (BTM) patients. Where the myocardial dysfunction cannot be detected by conventional echocardiography, it could be detected by tissue Doppler imaging (TDI) or speckle tracking echocardiography (STE).

Comparison of prophylactic use of intravenous immunoglobulin versus Pentaglobin® in pediatric patients after hematopoietic stem cell transplantation

There are few studies evaluating the use of IgM‐enriched IVIG (Pentaglobin®) in HSCT recipients. This study aimed to compare the efficacy of prophylactic use of IVIG versus prophylactic use of Pentaglobin® within the first 100 days after allogeneic HSCT. We performed a prospective, randomized study of the use of prophylactic IVIG versus prophylactic use of Pentaglobin® in patients after allogeneic HSCT. The first dose of IVIG or Pentaglobin® was given before conditioning regimen and after transplant was given on day +1, +8, +15, and +22. And then, it was given if IgG level was below 400 mg/dL. Twenty‐seven patients in IVIG group and 32 patients in Pentaglobin® group were included in the study. There were no significant differences in the duration of neutropenia, hospitalization, fever, and in the number of pyrexial episode, septicemia, bacteremia, local infection, CMV infection, acute GVHD, VOD, and adverse events between the IVIG group and Pentaglobin® group. Randomized placebo‐controlled trials are needed to conclude that utilization of IVIG or Pentaglobin® has no beneficial effect in HSCT.

Clinical comparison of weight‐ and age‐based strategy of dose administration in children receiving intravenous busulfan for hematopoietic stem cell transplantation

Bu, combined with TDM‐guided dosing, is associated with fewer graft failures/relapses and lower toxicity in pediatric HSCT. We aimed this retrospective study for comparison of weight‐ and age‐based dosing in terms of clinical outcomes such as time to engraftment, early complications, EFS, OS, and toxicity profiles in children receiving iv Bu. Sixty‐one children who underwent HSCT from April 2010 to February 2013 by means of a Bu‐based conditioning regimen and completed 100 days after transplantation at Ankara Children?s Hematology and Oncology Hospital Bone Marrow Transplantation Unit were enrolled in this study. SOS and neutropenic fever occurred more frequently in the weight‐based dosing group. We found a statistically significant correlation between Bu dose and the incidence of SOS (r = 0.26, p = 0.04). Multivariate analysis showed only weight‐based dosing of Bu was a significant predictor of SOS (HR = 9.46; p = 0.009). However, no relationship was found between two groups in terms of hemorrhagic cystitis, engraftment syndrome, acute or chronic GvHD, time to engraftment, chimerism, TRM, OS, and EFS rates. Weight‐based dosing of Bu may cause higher incidence of SOS and early infectious complications at the places where TDM of Bu cannot be performed.