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In this study, we aimed to investigate changes in calcium (Ca) metabolism in hemophilia patients (PWH). We also aimed to investigate the importance of diagnosis and treatment of factors impairing calcium metabolism and the significance of early diagnosis and prophylaxis with respect to these subjects. For all patients, serum calcium, phosphorus, alkaline phosphatase, 25 hydroxy vitamin D (25-OHD), parathormone (PTH), and calcitonin levels were evaluated. Bone mineral density (BMD) was assessed by dual-energy x-ray absorptiometry. Low BMD scores and 25-OHD deficiency were observed in 29 (74.4%) and 34 (87.2%) patients, respectively. Prophylaxis of PWH did not differ significantly in terms of 25-OHD levels and BMD scores. Patients in the prophylaxis group had significantly higher PTH levels (P=0.042). A negative correlation was found between PTH measurements and Z-score (P=0.008). In summary, our findings, with a small number of PWH in our study group, suggest that biochemical markers of bone turnover may be used to detect bone loss. Follow-up through annual BMD measurements coupled with appropriate exercise programs could be recommended.

Improvement in long-term survival in patients with acute lymphoblastic leukemia (ALL) in childhood has led to the need for monitorization of treatment-related morbidity and mortality. In the current study, we aimed to evaluate endocrine side effects of treatment in ALL survivors who were in remission for at least 2 years.Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications.The median age of the patients at the time of diagnosis, at the time of chemotherapy completion, and at the time of the study was 5 years (minimum-maximum: 1.7-13), 8 years (minimum-maximum: 4.25-16), and 11.7 years (minimum-maximum: 7-22), respectively, and median follow-up time was 4 years (minimum-maximum: 2-10.1). At least one complication was observed in 81.6% of patients. Vitamin D insufficiency/deficiency (46.6%), overweight/obesity (33.3%), and dyslipidemia (23.3%) were the three most frequent endocrine complications. Other complications seen in our patients were hyperparathyroidism secondary to vitamin D deficiency (15%), insulin resistance (11.7%), hypertension (8.3%), short stature (6.7%), thyroid function abnormality (5%), precocious puberty (3.3%), and decreased bone mineral density (1.7%). There were no statistically significant correlations between endocrine complications and age, sex, and radiotherapy, except vitamin D insufficiency/deficiency, which was significantly more frequent in pubertal ALL survivors compared to prepubertal ALL survivors (57.5% and 25%, respectively, p=0.011).A high frequency of endocrine complications was observed in the current study. The high frequency of late effects necessitates long-term surveillance of this population to better understand the incidence of late-occurring events and the defining of high-risk features that can facilitate developing intervention strategies for early detection and prevention.Akut lenfoblastik lösemili (ALL) hastalardaki sağ kalım oranlarının artışı, tedavi sonrası ortaya çıkan morbidite ve mortalite problemlerinin takip edilme ihtiyacını beraberinde getirmiştir. Çalışmamızda, en az iki yıldır remisyonda olan ALL’li hastalarda, tedavi sonrası ortaya çıkabilecek endokrin komplikasyonların değerlendirilmesi amaçlandı.ALL tanısı ile tedavi almış ve tedavisi üzerinden en az iki yıl geçmiş ve remisyonda olan 60 hastada endokrin geç komplikasyonlar kesitsel olarak değerlendirildi.Hastaların tanı aldıkları andaki median yaşları 5 yıl (minimum-maksimum: 1,7-13), kemoterapi sonlandırıldığı andaki median yaşları 8 yıl (minimum-maksimum: 4,25-16), çalışma sırasındaki median yaşları ise 11,7 yıl (minimum-maksimum: 7-22) olarak tespit edildi. Hastaların tedavi sonrası median takip süresi ise 4 yıl (minimum-maksimum: 2-10,1) idi. Hastaların %81,6’sında en az bir endokrin komplikasyon geliştiği görüldü. D vitamini eksikliği/yetersizliği (%46,6), obezite/fazla kiloluluk (%33,3) ve dislipidemi (%23,3) en sık gelişen üç komplikasyon olarak tespit edildi. D vitamini eksikliğine sekonder gelişen hiperparatiroidi (%15), insülin direnci (%11,7), hipertansiyon (%8,3), boy kısalığı (%6,7), tiroid fonksiyon bozukluğu (%5), puberte prekoks (%3,3) ve azalmış kemik mineral yoğunluğu (%1,7) gelişen diğer endokrin komplikasyonlardı. Hastalarda gelişen endokrin komplikasyonlar arasında cinsiyet, yaş, radyoterapi bakımından farklılık saptanmaz iken, D vitamini yetersizliği/eksikliği saptanan hasta sayısı pubertal grupta, prepubertal gruba göre anlamlı derecede fazlaydı (%57,5 ve %25, sırasıyla, p=0,011).Çalışmamızda yüksek oranda endokrin komplikasyon saptandı. Bu komplikasyonlar, geç yan etkilerin ortaya çıkmasına neden olabilecek yüksek risk özellikleri ve sıklığı tanımlayabilmek, erken tanı ve önleyici stratejileri geliştirmek açısından hastaların uzun dönem izlenmelerini gerektirmektedir.

Angiogenesis have implications in leukemia biology. Angiopoietin 1 (Ang 1) is an angiogenic cytokine which is essential in survival and proliferation of endothelial cells. Angiopoietin 2 (Ang 2) promotes dissociation of pericytes and increases vascular permeability and stromal derived factor 1 alpha (SDF 1α) which is a key player in stem cell traffic in the bone marrow (BM), has stimulating effects on angiogenesis as well. Here, we investigated the role of the leukemic BM microenvironment and specifically, the role of SDF 1α-CXCR4 and Ang 1/Ang 2-Tie 2 axes.Here, Ang 1, Ang 2, and SDF 1α levels were measured in the BM plasma and in supernatants of mesenchymal stem/stromal cells (MSCs) of patients with ALL and compared with those of healthy controls.The results showed that at diagnosis, BM plasma levels of Ang 1 and SDF 1α were significantly low and Ang 2 was high when compared to control values. Remission induction was associated with an increase in Ang 1/Ang 2 ratio and SDF levels in BM plasma.The results suggest that BM microenvironment and leukemic cell-stroma interaction influences the secretion of Ang 1, 2 and SDF 1α, thus, may affect both angiogenesis, homing and mobilization of leukemic blasts.

PubMedID: 30300449 Objectives: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. Methods: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (?100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. Results: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P

In this study, we aimed to determine the effect(s) of G-CSF priming on graft and transplantation parameters and compare these findings with those obtained without priming. A total of 64 pediatric patients transplanted from HLA-matched family donors were enrolled in the study. Twenty-nine patients received G-CSF primed marrow (G-BM group) and 35 patients received steady state bone marrow (S-BM group). Number of total nucleated cells (TNC) and CD34(+) cells, CFU-GM colony number, neutrophil and platelet engraftment times, total length of stay in hospital, overall and disease free survival, and occasions of acute and chronic GvHD has been compared between these two groups. Granulocyte colony stimulating factor primed bone marrow (G-BM) yielded higher numbers of CD34(+) cells, TNCs, and CFU-GM colony numbers compared to those obtained in S-BM. The neutrophil engraftment time, platelet engraftment time, length of stay in hospital, overall survival and disease free survival were not different between G-BM and S-BM groups. Also the cumulative incidence of grades II-IV acute and chronic GvHD were similar. It was observed that the use of G-CSF did not increase the risk of acute or chronic GvHD. We concluded that use of G-CSF for stem cell mobilization is an effective and safe method in children.

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.

The study was designed to compare colony forming capacity of granulocyte-colony stimulating factor (G-CSF) stimulated bone marrow (G-BM) with standard unstimulated bone marrow (U-BM) of healthy donors of pediatric patients. CFU-Assay results of 26 healthy donors of pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) were analyzed retrospectively. 13 of donors received 10 μg/kg per day of G-CSF as a single injection for 3 consecutive days and other 13 of donors had unstimulated BM. Colony forming capacity of hematopoietic stem cells evaluated with Colony Forming Unit-Assay (CFU-Assay) with in semi-solid agar culture medium after 14-18 days of culture period. CFU-Assay results of G-BM and U-BM (expressed as means) were; Burst Forming Unit-Erythroid (BFU-E): 15.20 × 10(4)/kg and 8.38 × 10(4)/kg, Colony Forming Unit-Granulocyte Macrophage (CFU-GM): 10.35 × 10(4)/kg and 5.67 × 10(4)/kg, Colony Forming Unit-Erythroid (CFU-E): 0.59 × 10(4)/kg and 0.33 × 10(4)/kg, CFU-Granulocyte Erythroid Macrophage Megakaryocyte (CFU-GEMM): 0.52 × 10(4)/kg and 0.53 × 10(4)/kg respectively. BFU-E and CFU-GM capacity of G-BM was increased and statistically significantly different than standard U-BM (p ⩽ 0.01). In conclusion, increased colony forming capacity of hematopoietic stem cells of G-BM when compared with standard unstimulated BM could be a major advantage for transplantation.

Background Early life-threatening cardiotoxicity and cardiac death have been reported after hematopoietic stem cell transplantation (HSCT). The purpose of the current study was to evaluate cardiac toxicity of conventional chemotherapy followed by HSCT with cardiac markers: heart-type fatty acid binding protein (H-FABP), glycogen phosphorylase BB (GPBB), high sensitive C reactive protein (hsCRP) cardiac troponin I, (cTnI), creatine kinase MB (CK-MB mass) and myoglobin. Methods A total of 20 children who underwent HSCT for malignant and non-malignant diseases were included in this study. Blood samples were collected from all patients in 0th, 7th and 21st day for evaluating these cardiac biomarkers. The patients’ echocardiography was assessment before and after one-month of HSCT. Results Serum 21st H-FABP level was significantly higher when compared with the 0th day H-FABP level (P < 0.05) . 7th day hsCRP level was significantly higher than 0th and 21st day levels (P < 0.05). Interestingly, 7th day GPBB level was significantly lower than 0th and 21st day levels (P < 0.05). Myoglobin, CK-MB mass and cTnI biomarkers remained within the reference range in all patients. Conclusions This study showed that H-FABP and hsCRP both seem to be promising markers for evaluation of cardiotoxicity in HSCT process and probably superior to GPBB, cTnI, CK-MB mass and myoglobin.

Congenital amegakaryocytic thrombocytopenia (CAMT) generally begins at birth with severe thrombocytopenia and progresses to pancytopenia. It is caused by mutations in the thrombopoietin receptor gene, the myeloproliferative leukemia virus oncogene (c-MPL). The association between CAMT and c-MPL mutation type has been reported in the literature. Patients with CAMT have been categorized according to their clinical symptoms caused by different mutations. Missense mutations of c-MPL have been classified as type II and these patients have delayed onset of bone marrow failure compared to type I patients. Here we present a girl with severe clinical course of CAMT II having a missense mutation in exon 4 of the c-MPL gene who was admitted to our hospital with intracranial hemorrhage during the newborn period.Konjenital amegakaryositik trombositopeni (KAMT) genellikle, doğumda ağır trombositopeni ile başlar ve pansitopeniye ilerler. Hastalığın nedeni trombopoetin reseptör geni olan myeloproliferatif lösemi virüs onkogenindeki (c-MPL) mutasyon olup, literatürde KAMT kliniği ile c-MPL mutasyon tipleri arasında ilişki bildirilmiş, hastalar farklı mutasyonların neden olduğu klinik belirtilere göre sınıflandırılmışlardır. c-MPL’nin yanlış anlamlı mutasyonları tip 2 olarak sınıflanmıştır. Bu hastalar tip 1 hastalar ile karşılaştırıldığında kemik iliği yetmezliğinin daha geç başladığı bildirilmiştir. Burada, yenidoğan döneminde intrakranial kanama ile hastanemize başvuran c-MPL geninde ekzon 4’de yanlış anlamlı mutasyonu olan KAMTII tanılı ağır klinik seyirli bir kız sunulmuştur.

Even the life span has prolonged for the last 40 years, increase in frequently seen complications with increasing age negatively affect the life quality of thalassemia patients. In our study, complications encountered in 67 s-thalassemia patients who were followedup at our hospital between 1 January 2004 and 31 May 2009 were retrospectively analyzed. Fifty-six patients were followed up with diagnosis of thalassemia major and 11 with thalassemia intermedia. Totally, 56.7% of patients were male and 43.3% were female. Ages varied between 2-20 years with the mean age of 10.3±4.8 years. Mean ferritin level was 2212±1370 ng/mL (41-6263 ng/mL) for 4.5 years. Complications were increased with increasing age. Complication rates were significantly higher among thalassemia major patients compared to thalassemia intermedia patients. There was no statistically significant relationship between complications and mean ferritin levels. The most common complications were endocrine complications (38.8%). Cardiac complications developed in 22.4% of the patients; gastroenterological complications in 19.4%; allergic complications in 9%; infectious complications in 1.5%; and thrombosis was detected in 1.5%. The endocrine complications were osteoporosis, growth retardation, developmental delay, short stature, hypothyroidism, delayed puberty, hypogonadism, and diabetes mellitus. The cardiac complications were left ventricular wall hypertrophy, diastolic dysfunction, systolic dysfunction, heart failure, pericardial effusion, dilated cardiomyopathy, left ventricular dilatation, left atrial dilatation, and fatal arrhythmias. Mortality occurred in one (1.5%) out of 67 s-thalassemia patient due to dilated cardiomyopathy and fatal arrhythmia.

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B-12 in children and to identify a cutoff cobalamin values according to holoTC. One hundred and fifty-five children were enrolled into the study. All children were evaluated for hemoglobin, vitamin B-12, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B-12 level ( 200 pg/mL, group II). Serum vitamin B-12, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B-12 (group I) the mean holoTC was 21.74 +/- 1.14 pmol/L. In 54 children with normal vitamin B-12 (group II) mean holoTC was 44.0 +/- 2.7 pmol/L (p < 0.01). A ROC curve analysis was performed to delineate the optimum cut-off point for vitamin B-12 level and it was found to be 165 pg/mL with a sensitivity of 70% and specificity of 74%; the area under curve was 0.783 (p < 0.01). Our study displayed a positive correlation between vitamin B-12 and holoTC, and defined an optimum cutoff value for vitamin B-12 as 165 pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed.

Background and Objectives Candida-associated bloodstream infections are frequent and potentially life-threatening conditions in hematology patients. The aim of this study is to evaluate the characteristics, risk factors, and outcome of Candida-associated bloodstream infections in children with hematological diseases. Methods The medical records of the patients with hematological diseases and hematopoietic stem cell transplantation (HSCT) recipients who were diagnosed as Candida-associated bloodstream infection between February 2010 and February 2014 were reviewed retrospectively. Results Thirty episodes of candidemia involving 26 patients (38% female, and 62% male) with a median age of 7-year (range; 1 to 17) were noted. The incidence of candidemia in our study was 5.2 per 1000 hospital admissions. Infections with non-albicans Candida spp. occurred more frequently (63%) and C. krusei was the predominant microorganism among non-albicans Candida spp. (37%). Candida albicans was isolated from 11 of the 30 episodes (37%). Twenty-six of the episodes (88%) patients had a central venous catheter (CVC) prior to candidemia, and they were removed in 16 (62%). Thirty-day mortality rate was 20%. Isolated Candida spp, underlying disease and its status, presence of mucositis, neutropenia, using of broad spectrum antibiotics, corticosteroids or total parenteral nutrition were not identified as predictors of outcome. Multivariate analysis revealed that CVCs kept in place was the only significant factor associated with mortality (OR, 0.07; 95% CI, 0.006–0.716). Conclusions Candida-associated bloodstream infections were common in children with hematological diseases and HSCT recipients, particularly in patients with CVCs. In addition to appropriate antifungal therapy, CVC removal improves the outcome of candidemia in children with hematological disease.

Thirty-nine children with Fanconi aplastic anemia (FAA) have been followed up in our center between January 2008 and November 2010. Eight of these children (20%) with a transfusional iron overload had been undergoing deferasirox treatment during the study period. In the English literature, transfusional iron overload and the use of an iron chelator in children with FAA has not yet been evaluated. Here, we have presented the effectivity and tolerability of deferasirox in children with FAA and a transfusional iron overload. Before the deferasirox treatment, the mean serum ferritin level was 3377 ± 2200 ng/mL. After a mean 13.6-month treatment duration, the mean ferritin level decreased to 2274 ± 1300 ng/mL (P

Asparaginase, an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL), has become an important component of most childhood ALL regimens during the remission induction or intensification phases of treatment. The incidence range of asparaginase-associated lipid abnormalities that are seen in children is 67-72%. Lipemia causes erroneous results, which uses photometric methods to analyze blood samples. We describe a case of l-asparaginase-associated severe hyperlipidemia with complete blood count abnormalities. Complete blood count analysis was performed with Beckman COULTER(®) GEN·S™ system, which uses the Coulter Volume, Conductivity, Scatter technology to probe hydrodynamically focused cells. Although an expected significant inaccuracy in hemoglobin determination occurred starting from a lipid value of 3450 mg/dl, we observed that triglyceride level was 1466 mg/dl. Complete blood count analysis revealed that exceptionally high hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration levels vs. discordant with red blood cell count, mean corpuscular volume, and hematocrit levels. Total leukocyte count altered spontaneously in a wide range, and was checked with blood smear. Platelet count was in expected range (Table 1). Thus, we thought it was a laboratory error, and the patient's follow-up especially for red cell parameters was made by red blood cell and hematocrit values.

Pyomyositis is a primary infection of the skeletal muscles, usually present as single or multiple abscess formation. Early diagnosis is frequently difficult in nontropical countries because of the ...

All-trans-retinoic acid (ATRA), which is used in acute promyelocytic leukemia, is usually well tolerated, but some side effects can be observed. Retinoic acid syndrome is the most severe side effect. Triazole derivatives such as fluconazole inhibit the NADPH-dependent cytochrome P-450-mediated catabolism of ATRA and are increased plasma levels of ATRA. Here, the authors report a case of APL who developed acute renal failure during ATRA and concurrent use of fluconazole.

Direct antiglobulin test positivity had been reported in the course of some lymphoproliferative neoplasms. However, there are a few case reports describing direct antiglobulin test (DAT) positivity in children with acute lymphoblastic leukemia (ALL). We herein report 8 patients who had positive DAT among 95 newly diagnosed children with ALL. None of these patients had evidence of hemolysis during the follow-up. An antibody was detected in 2 of 8 patients with positive DAT. These 2 children also had positive indirect antiglobulin test (IAT); an autoantibody that was reactive at 4°C, and an alloantibody (anti E) that was reactive at 37°C was detected. We believe DAT positivity in ALL without significant hemolysis is not a rare disorder, and a need for further prospective studies is apparent.

Invasive fungal infections have turned out to be a significant cause of morbidity and mortality in pediatric patients with malignant disorders. Massive hemoptysis, a rare complication of invasive pulmonary aspergillosis, may threaten the lives of patients, usually during the resolution of neutropenia. In this report, we describe a patient with massive hemoptysis due to invasive pulmonary aspergillosis whose bleeding was controlled successfully with off-label use of recombinant factor VIIa and subsequent coil embolization of the right pulmonary artery.İnvaziv fungal enfeksiyonlar pediatrik malin hastalıklarda morbidite ve mortalitenin önemli bir nedenidir. Masif hemoptizi de sıklıkla nötropenin düzelme aşamasında görülen, invaziv pulmoner aspergillozisin hayatı tehdit edici nadir bir komplikasyonudur. Bu yazıda invaziv pulmoner aspergillozise bağlı masif hemoptizi gelişen bir hastada endikasyon dışı recombinant FVIIa kullanımı ardından sağ pulmoner artere coil embolizasyon uygulanarak kanama kontrolu sağlanan bir olgu sunulmuştur.

Granulocyte colony stimulating factor (G-CSF) is sometimes administered to donors before bone marrow (BM) harvest. G-CSF–primed (G-BM) and unprimed BM (U-BM)–derived mesenchymal stem cells (MSC) were obtained from 16 healthy donors and were expanded in vitro. Their proliferative characteristics, morphology, and differentiation capacity were examined. Supernatants of the second passage of MSCs were evaluated for transforming growth factor β1, hepatocyte growth factor, and prostaglandin E2 (PGE2) levels and compared with controls. The analyses of cytokines in the G-BM– and U-BM–derived MSCs supernatants revealed that PGE2 levels were significantly lower in the G-CSF–primed samples. These cytokines were also measured in BM plasma. The level of hepatocyte growth factor in G-BM plasma was significantly increased. The current study is the first to show the effects of G-CSF on the BM microenvironment of healthy human donors. The preliminary data suggest that G-BM– and U-BM–derived MSCs have similar morphologic/phenotypic properties and differentiation capacity but differ in their secretory capacity. Significant changes in cytokine levels of BM plasma in G-CSF–primed donors were also demonstrated. These findings suggest that BM MSCs and changes in the BM microenvironment may contribute to the effects of G-CSF on inflammation and immunomodulation.

Thrombocytopenia and absent radii (TAR) syndrome is a rare disorder. It may be associated with, for example, as cardiovascular, genitourinary, gastrointestinal, skeletal, neurological, ophthalmic, and facial anomalies. Esophageal atresia is also a rare anomaly associated with genitourinary, skeletal, and cardiovascular anomalies, among others. Here, the authors present a child with TAR syndrome and esophageal atresia with tracheoesophageal fistula. This association has been reported in only one other case in literature.

Eight-year event-free survival (EFS) was evaluated in 205 patients with acute lymphoblastic leukemia (ALL), to consider the efficacy of high-dose methylprednisolone (HDMP) given during remission induction chemotherapy between 1 and 29 days. The St Jude Total XI Study protocol was used after some minor modifications in this trial. Patients were randomized into two groups. Group A (n = 108) received conventional dose (60 mg/m(2)/day orally) prednisolone and group B (n = 97) received HDMP (Prednol-L, 900-600 mg/m(2) orally) during remission induction chemotherapy. Complete remission was obtained in 95% of the 205 patients who were followed-up for 11 years; median follow-up was 72 months (range 60-129) and 8-year EFS rate was 60% overall (53% in group A, 66% in group 13). The EFS rate of group B was significantly higher than of group A (P = 0.05). The 8-year EFS rate of groups A and B in the high-risk groups was 39% vs 63% (P = 0.002). When we compared 8-year EFS rate in groups A and B in the high-risk subgroup for both ages together less than or equal to2 or greater than or equal to10 years, it was 44% vs 74%, respectively. Among patients in the high-risk subgroup with a WBC count greater than or equal to50 x 10(9)/l, the 8-year EFS was 38% in group A vs 58% in group B. During the 11-year follow-up period, a total of 64 relapses occurred in 205 patients. In group A relapses were higher (39%) than in group B (23%) (P = 0.05). These results suggest that HDMP during remission-induction chemotherapy improves the EFS rate significantly for high-risk patients in terms of the chances of cure.

In English literature, there are only 2 specific series of pandemic H1N1 influenza infection in children with leukemia. To increase knowledge about pandemic influenza in children with leukemia and better understand the risk factors for severe disease, we have presented the clinical characteristics of 8 children with acute leukemia and pandemic influenza treated at our center. The mean age of the children (4 girls and 4 boys) was 6.7±2.0 years (range, 4 to 10 y). All these children [3 acute lymphoblastic leukemia and 5 acute myeloid leukemia (AML) cases] were receiving chemotherapy during the course of infection, except 1 who was found to be H1N1 positive at the same time that she was diagnosed with AML. Among the other 7 patients undergoing chemotherapy, 4 were receiving induction, 1 was receiving consolidation, and 2 were undergoing maintenance chemotherapy. In our series, 1 patient with AML had a fatal course. She had recently received a chemotherapy bloc. Her neutrophil count was 0 during the course of H1N1 infection. She developed acute respiratory distress syndrome within a short time after the symptoms commenced and she died within 4 days. In conclusion, the clinical course of H1N1 infection may be fatal in rare cases of leukemic children receiving chemotherapy. Thus, vaccination is advisable for all leukemic children, especially for those under maintenance chemotherapy, as it might be life saving during such pandemics.

Invasive fungal infections (IFIs) constitute a leading cause of morbidity and infection-related mortality among hematopoietic stem cell transplant (HSCT) recipients. With the use of secondary prophylaxis, a history of IFI is not an absolute contraindication to allo-HSCT. However, still, IFI recurrence remains a risk factor for transplant-related mortality. In this study, of the 105 children undergoing HSCT between April 2010 and February 2013, 10 patients who had IFI history before transplantation and had undergone allo-HSCT were evaluated retrospectively to investigate results of secondary prophylaxis. In conclusion, our study shows that amphotericin B and caspofungin was successful as secondary antifungal prophylaxis agents with no relapse of IFI. In addition, after engraftment, secondary prophylaxis was continued with voriconazole orally in 4 patients that yielded good results.

Massive splenic infarction and portal vein thrombosis (PVT) due to chronic myeloid leukemia (CML) is extremely rare. We describe 2 children who were presented with massive splenic infarction and PVT in the course of CML. Massive splenic infarction and PVT treated with splenectomy in one and with medical treatment in another in whom PVT resolved by cytoreductive treatment, led to downsizing of spleen or splenectomy. Splenic infarct and PVT should be considered in CML patients with long-lasting severe abdominal pain despite appropriate medical attempts. Splenectomy should be spared for persistent symptoms and complications.

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 hospital's 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.

The effect of single high-dose methylprednisolone (HDMP) on eosinophil and lymphocyte phenotype in two siblings with marked hypereosinophilia was investigated. Since conventional dose steroids failed to produce a haematological and clinical response in case one, both children were given HDMP (20 mg/kg/day). Eosinophils and lymphocytes showed an activated state before treatment, characterized by marked expression of CD11b, CD18, CD45RO on eosinophils and increased HLA-DR, CD95, CD18, CD38 on lymphocytes. Twenty-four hours after administration of HDMP a dramatic reduction in peripheral blood eosinophil count was observed in both patients associated with phenotypic changes characterized by decreased expression of CD11b, CD18, CD13 and increased CD95 expression in one. Furthermore, HDMP treatment induced a drop in the expression of CD95 and CD18 on lymphocytes. These changes may suggest a suppressive role for HDMP on eosinophil and lymphocyte activation which may have contributed to the haematological and clinical response.

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.

Celiac disease (CD) is one of the most common chronic disorders in childhood. Autoimmune and nonauto-immune disorders including dermatitis herpetiformis, type 1 diabetes mellitus, and autoimmune thyroiditis can be encountered associated with CD. Common hematologic manifestations of CD include anemia owing to iron, folate, or vitamin B-12 deficiency. We report a case with CD associated with Evans syndrome of whom to our knowledge, is the first child to be reported in the literature.

Background Peripheral blood stem cell mobilization is usually performed following chemotherapy plus G-CSF in children. This standard approach may not be successful in some heavily pretreated patients undergoing mobilization. Plerixafor (AMD3100) has been used in adults as a second line mobilizing agent. Our aim is to analyze our experiences with plerixafor in children. Methods We retrospectively evaluated three children who received plerixafor as a second line stem cell mobilizing agent in our department in the 2010–2012 period. Data including age, sex, diagnosis, previous chemotherapy, radiotherapy details, previous harvest attempts, adverse reaction, and harvest outcome were analyzed. Results We used plerixafor in combination with G-CSF and chemotherapy or with only G-CSF seven times in three patients. All three patients were treated with different multiple chemotherapy regimens prior to stem cell harvest and failed earlier mobilization with chemotherapy plus G-CSF. The diagnoses were relapsed Hodgkin lymphoma in two and recurrent Ewing’s sarcoma in one patient. We used plerixafor in combination with G-CSF and chemotherapy or with only G-CSF seven times in three patients. The harvest was successful in four of seven attempts. No adverse reaction was observed in the patients. Conclusion The success rate is four out of seven attempts (57%) in our group. Although the data regarding the use of plerixafor in children is scarce, our experience also supports its use in poor mobilizer children. The use of plerixafor in children results in effective increases in peripheral stem cell counts and reduces the risk of mobilization failure.

One of the most important morbidity causes of aplastic anemia is invasive fungal infections. It could not be possible to take control of infection without neutrophils despite the recent developments in the antifungals. In this presented case, a patient with severe aplastic anemia, granulocyte transfusion were administered as 46 times because of the presence of widely invasive aspergillosis and resistance. Only fever reaction was observed as a complication of transfusion amongst the other complications such as acute lung damage, alloimmunisation, and graft-versus-host disease. Granulosit transfusions should not be avoided in patients who had an indication for.

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, hepcidin's precursor, in ID and ID anemia (IDA) with a concurrent HP infection.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.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.Elevated serum prohepcidin might indicate the role of inflammation in the etiology of anemia concurrent with HP.

The primary objective was to evaluate the response rate of rituximab therapy for children with chronic immune thrombocytopenic purpura (ITP) and Evans syndrome (ES) and immune reconstitution of these children after rituximab therapy. Eleven patients with chronic ITP and 2 with ES between 6 and 18 years of age and platelet count less than 20 × 109/L received rituximab. Overall response (OR) was defined as an increase in platelet count above 50 × 109/L. The mean age of 13 children (9 girls, 4 boys) was 11.2 ± 3.8 years (6-18). One of the patients with ES had been splenectomized; others were not. The patients mean follow-up time was 10.3 ± 9.3 months after rituximab therapy. Two patients achieved complete response, 4 patients achieved partial response, and OR rate was 46% (6 of 13) after therapy. Seven patients have no response. In conclusion, rituximab may be considered prior to splenectomy in children with chronic ITP and ES with an acceptable toxicity profile.

Candida infections are the most frequent infections in neutropenic patients. Hepatosplenic candidiasis (HSC) is a part of disseminated Candida infection that occurs most commonly in patients with hematologic malignancies treated with chemotherapy and requires protracted antifungal therapy. During invasive mycosis with rapid resolution of immunosuppression, immune reconstitution inflammatory syndrome (IRIS) which mimics treatment failure, drug toxicity or breakthrough infections may occur. Manifestation period, histopathologic findings and favorable effect of steroids to its inflammatory symptoms strongly suggest that HSC belongs to the invasive fungal infection induced IRIS. We present a child with B cell-acute lymphoblastic leukemia who developed HSC and addition of corticosteroid therapy to antifungal treatment achieved rapid resolution of the clinical symptoms and laboratory findings.

Genotype/allele distributions of leptin promoter G-2548A polymorphism, serum leptin and insulin levels and body weight were not significantly different between 72 children (39 male/33 female; age range 1.08-16, median 6 years) with acute leukemia (56 acute lymphoblastic leukemia [ALL]/16 acute non-lymphoblastic leukemia [ANLL]) at diagnosis and 70 age- and sex-matched controls (p0.05). The - 2548GG genotype was associated with the highest leptin levels in controls and patients with acute leukemia after 7-day high-dose methylprednisolone (HDMP) therapy (p0.05), while no significant association of genotype with leptin levels was detected in patients at diagnosis (p0.05). One-week HDMP therapy in patients carrying the - 2548G allele caused a significant increase in leptin levels and body weight (p0.001), whereas increases in those carrying the - 2548AA genotype were insignificant (p0.05). Decreases in white blood cell counts of patients after therapy were insignificant in - 2548GG (p0.05) yet significant in - 2548GA and - 2548AA (p0.05) genotypes. These results revealed no association of leptin genotype with the etiology of childhood acute leukemia but a possible association with leptin levels and effects of HDMP therapy.

Hb Adana (HBA1: c.179GA) is a very rare, unstable form of α-globin variant that results from deficient synthesis of functional α chains. We present a 2-month-old boy with hypochromic microcytic anemia, and remarkable anisocytosis, target cells and basophilic stippling on his peripheral blood smear. α-Globin gene analysis of the patient determined homozygosity for HBA1: c.179GA, a mutation known as Hb Adana. On his follow-up visit, hemoglobin (Hb) levels were stable at 9.0-9.5 g/dL and mean corpuscular volume (MCV) was 62.2-62.5 fL without the need for a blood transfusion. Clinical and hematological findings of our case were comparable to Hb H (β4) or β-thalassemia intermedia (β-TI)-like phenotypes, despite the fact that he carried an α1 gene mutation. Heterozygosity for the HBA1: c.179GA mutation may also lead to microcytosis only as seen in his parents. According to our current knowledge, this is the first described case with homozygosity for the Hb Adana mutation, carried on the α1 gene. The relatively mild presentation of the case highlights the milder phenotypic consequences of nondeletional α mutations in the α1 vs. the α2 gene.

The aim of this study was to interpret the antibody response to hepatitis B (HB) vaccination following a two booster dose schedule in 94 acute lymphoblastic leukemia (ALL) patients. All patients were between 1-16 years of age with negative hepatitis B virus (HBV) serology and normal hepatic function. Fifty patients were vaccinated with Engerix B vaccine, and 44 patients were vaccinated with GenHevac B vaccine, with a schedule of 0, 1, 6 and 0, 1, 2, as well as booster doses, in 12 and 6 months respectively. A second booster was given as a fifth dose to 16 unresponsive patients in each vaccine group, 3 and 6 months after the first booster for Engerix B and GenHevac B vaccines respectively. Dosage was 20 microg HbsAg for all patients. Seroconversion rates with protective level antibody were 35.1% (n=33/94). The figures were 32.1% (n=16/50) and 38.6% (n=17/44) for Engerix B and GenHevac B vaccines, respectively. Seroconversion rate in patients younger than 10 years old was found to be higher (39.11%) than older patients (24%), but this was not statistically significant. This study indicates that one third of the leukemic children undergoing maintenence chemotherapy responded to HB vaccine with protective titers of anti-HBs. We recommend HB vaccination especially in developing countries.

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 Munster (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.

The presence of central cyanosis that is unrelated to cardiopulmonary causes alerts clinicians to a possible diagnosis of methemoglobinemia. Congenital methemoglobinemia due to deficiency of nicotinamide-adenine dinucleotide (NADH)-cytochrome b5 reductase (cb(5)r) is an autosomal recessive disorder characterized by life long cyanosis. Here we report a six-year old boy who presented with central cyanosis and upon examination revealed a methemoglobin level of 19.0%. Sequencing the CYB5R3 gene identified a homozygous T-->C transition at base c.653, which changed codon 218 from leucine to proline (L218P) in cb(5)r protein. Treatment with ascorbic acid relieved the cyanosis and returned methemoglobin levels to normal.

Since the equipment of therapeutic apheresis is prepared for adults, the use of it in children may lead to higher complication risks and there are little data in children undergoing therapeutic apheresis. Methods In this study the complications experienced during therapeutic apheresis in children between April 2010 and May 2012 at our center are analyzed retrospectively. There were 14 patients who had undergone a total of 50 sessions of therapeutic apheresis. The ages of patients’ ages ranged from 20 months to 16 years. The procedures were plasma exchange and leukodepletion. Results Complications were observed in four patients. One of them was vascular access complication because of insufficient flow. Urticeria was observed in two patients. Abdominal pain and chilling were other complications. Our patients, who underwent TA, did not experience major complications. Minimal or mild allergic reactions were observed and treated by medications. For extracorporeal volume erythrocyte prime is useful. TA will be performed more successfully with correct planning and close examination of the patient with an experienced team.