Impact of Prophylaxis on Bone Mineral Metabolism in Children With Hemophilia.

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.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

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 < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

Relationship Between the Levels of Holotranscobalamin and Vitamin B12 in Children.

The purpose of this study was to evaluate the relationship between the plasma holoTC and serum vitamin B12 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 B12, folate, ferritin and holoTC levels. Children were grouped as with low vitamin B12 level (≤200 pg/mL, group I) and normal vitamin B12 (>200 pg/mL, group II). Serum vitamin B12, and holoTC levels were performed in each patient in the study. In 101 patients with low vitamin B12 (group I) the mean holoTC was 21.74 ± 1.14 pmol/L. In 54 children with normal vitamin B12 (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 B12 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 B12 and holoTC, and defined an optimum cutoff value for vitamin B12 as 165 pg/mL. Further studies using the markers both MMA, tHcy and holoTC to confirm the findings are needed.

Evaluation of endocrine and metabolic dysfunctions after hematopoietic stem cell transplantation in children: a study from Turkey.

BACKGROUND: Endocrine organs are highly susceptible to effects of high-dose chemotherapy. The objective of the study was to evaluate endocrine and metabolic complications after hematopoietic stem cell transplantation (HSCT) in children. METHODS: The patients who underwent HSCT in our center from April 2010 to October 2014 with at least 1 year follow-up were analyzed retrospectively. RESULTS: One-hundred children (M/F:59/41; mean age 8.9±4.8 years, mean follow-up time 3.4±1.2 years) were included in the study. Female hypogonadism was the most common endocrine dysfunction (35.7%), followed by growth impairment (29.4%), malnutrition (27.4%), dyslipidemia (26%), low bone mineral density (BMD) (25%), hypothyroidism (13%) and insulin resistance (12%). Patients who underwent HSCT >10 years of age were significantly at risk for hypogonadism, metabolic syndrome, growth impairment and malnutrition (p<0.05). CONCLUSIONS: Endocrine or metabolic dysfunctions are more prevalent in children who are older than 10 years of age at HSCT. Children who underwent HSCT should be followed-up by a multidisciplinary team during puberty and adolescence.

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

BACKGROUND: The purpose of this study is to determine early myocardial dysfunction in ß-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). METHODS: In this study, we analyzed 60 individuals, 30 of whom were BTM patients and the other 30 of whom were the control group. T2* magnetic resonance imaging (MRI) was used to measure cardiac iron deposition. The myocardial functions were evaluated by conventional echocardiography, TDI and STE. RESULTS: When basal lateral left ventricular and basal septal wall TDI values were compared between the patient group and control group, only isovolumic contraction time values were significantly longer in the patients. The global circumferential strain was significantly lower in the patients. When evaluated as segmental, longitudinal strain values of basal inferoseptum and circumferential strain values of anteroseptum, anterior, and inferolateral segments were significantly lower in the patients. In the patients, global longitudinal and circumferential strains in the group who had pathological T2* values were significantly lower than the group who did not. In addition, circumferential strain values in anteroseptum, anterolateral, inferior, and inferoseptum segments were significantly lower in the patients with T2* values<20 ms than those with T2* values≥20 ms. CONCLUSION: Although T2* MRI is the most sensitive test detecting myocardial iron load, TDI and STE can be used for screening myocardial dysfunction. The abnormal strain values, especially circumferential, may be detected as the first finding of abnormal iron load and related to T2* values.

Effects of stem cell transplantation on bone mineral density and vitamin D status in children with thalassemia major.

HSCT is a curative treatment in TM, but conditioning and immunosuppressive treatment may affect bone metabolism. In this retrospective study, we aimed to compare BMD, vitamin D status, and growth in children with TM who underwent HSCT to those in children with TD TM. Twenty-three children with TM who underwent HSCT (mean age 7.1 years [1.03-14.7]) and 24 children with TD thalassemia (mean age 9.8 years [1.6-14]) were recruited. Lumbar spine BMD of TD thalassemia patients was higher than those in patients who had HSCT at both baseline and second-year assessments (P=.009, P<.001, respectively). However, BMD Z scores or serum 25-OH vitamin D levels were not different in two groups. Being >10 years of age was a significant risk factor for low BMD, height, and weight Z score for both groups. Patients who underwent HSCT with Pesaro risk class II or III had higher risk for low BMD compared to those risk class I patients (P=.044). In conclusion, children with TM who were >10 years at HSCT are at risk for low BMD and growth retardation. HSCT had no effect on BMD deficit in children with TM.

Evaluation of Endocrine Late Complications in Childhood Acute Lymphoblastic Leukemia Survivors: A Report of a Single-Center Experience and Review of the Literature

INTRODUCTION: 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. METHODS: Sixty patients diagnosed with ALL, who were in remission for at least 2 years, were cross-sectionally evaluated for long-term endocrine complications. RESULTS: 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). CONCLUSION: 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.

Total estimated effective doses from radiologic imaging modalities of children with cancer: a single center experience.

BACKGROUND: Recently, awareness of the cumulative radiation exposure for pediatric oncology patients has been increasing, together with increased survival rates and longer life expectancy. The aim of our study was to quantify the amount of ionising radiation from imaging modalities of pediatric oncology patients. METHODS: Eighty-eight patients who were diagnosed with childhood cancer and followed up for 5 years between 2004-2014 in our center were included in the study. Patients' medical files were reviewed retrospectively for imaging history in the first 5 years after diagnosis. Total estimated effective doses from radiologic imaging modalities were determined. Also, the basic demographic data, histologic type, stage, and outcomes of disease were collected for all patients. RESULTS: The individual total estimated effective doses ranged from 8.73 to 167 mSv, with a median of 62.92 mSv. Computed tomography was the greatest contributor of total effective doses. The doses ranged 21.45-113.20 mSv (median: 62.92 mSv) in Hodgkin lymphoma, 12.53-167.10 mSv (median: 52 mSv) in non-Hodgkin lymphoma, 4.13-172.98 mSv (median: 52 mSv) in neuroblastoma, 31-149.89 mSv (median: 63.10 mSv) in Wilms' tumor, 11.50-73.72 mSv (median: 36.90 mSv) in germ cell tumor, 26.46-125.86 mSv (median: 80.90 mSv) in other solid tumor and 0.02-13.31 mSv (5.25 mSv) in brain tumor subgroup. Twenty-two children (25%) died with progressive disease during the 5-year follow-up period. CONCLUSIONS: Similar to previous studies, the total estimated effective doses in children with cancer have been found various according to diagnosis, stage and clinical course. To clarify the harmfull effects of radiation burden, prospective studies should be conducted in children with cancer.

Beneficial Effect of the Nutritional Support in Children Who Underwent Hematopoietic Stem Cell Transplant.

OBJECTIVES: The aim of this study was to evaluate nutritional status in children who underwent hematopoietic stem cell transplant compared with a healthy control group. A secondary aim was to utilize mid-upper arm circumference as a measure of nutritional status in these groups of children. MATERIALS AND METHODS: Our study group included 40 children (18 girls, 22 boys) with mean age of 9.2 ± 4.6 years (range, 2-17 y) who underwent hematopoietic stem cell transplant. Our control group consisted of 20 healthy children (9 girls, 11 boys). The children were evaluated at admission to the hospital and followed regularly 3, 6, 9, and 12 months after discharge from the hospital. RESULTS: In the study group, 27 of 40 patients (67.5%) received nutritional support during hematopoietic stem cell transplant, with 15 patients (56%) receiving enteral nutrition, 6 (22%) receiving total parenteral nutrition, and 6 (22%) receiving enteral and total parenteral nutrition. Chronic malnutrition rate in the study group was 47.5% on admission to the hospital, with the control group having a rate of 20%. One year after transplant, the rate decreased to 20% in the study group and 5% in the control group. The mid-upper arm circumference was lower in children in the study group versus the control group at the beginning of the study (P < .05). However, there were no significant differences in mid-upper arm circumference measurements between groups at follow-up examinations (P > .05). During follow-up, all anthropometric measurements increased significantly in both groups. CONCLUSIONS: Monitoring nutritional status and initiating appropriate nutritional support improved the success of hematopoietic stem cell transplant and provided a more comfortable process during the transplant period. Furthermore, mid-upper arm circumference is a more sensitive, useful, and safer parameter that can be used to measure nutritional status of children who undergo hematopoietic stem cell transplant.

Factors associated with bone marrow stem cell yield for pediatric allogeneic stem cell transplantation: The impact of donor characteristics.

The aim of this study was to investigate the effects of donor characteristics on CD34+ cell yield in BM harvest. Between April 2010 and November 2013, consecutive donors who underwent BM harvesting in our BM transplantation unit were retrospectively investigated. Donors were classified into two groups: those who donated BM without mobilization (steady-state BM donors) and those who received G-CSF for stem cell mobilization (G-CSF-primed BM donors). Donor characteristics (age, gender, race, body weight, BMI, and laboratory factors including donor's leukocyte, platelet, and monocyte) and their relationship with total nuclear cell and CD34+ cell numbers has been evaluated. A total of 64 healthy related donors (29 males/35 females, median age 11.2 years; 49 [76.6%] younger than 18 and 36 [56.3%] younger than 12 years) were included in the study. The median CD34+ cell yield in the harvest was 0.12×106 /L (0.02-0.21) in SS-BM donors and 0.18×106 /L (0.09-0.67) in GP-BM donors (P=.03). Median of CD34+ cell count given to recipients was 2.6×106 /recipient body weight (1.3-19.3) in SS-BM yields and 3.8×106 /recipient body weight (1.1-10.2) in GP-BM yields, respectively. Multiple regression analysis showed that donor height and pre-G-CSF platelet were the most important parameters to obtain a sufficient BM harvest. Our data suggest that the shorter donors and the donors with higher thrombocyte counts may offer more hematopoietic stem cell. The height and thrombocyte count of the donors should be taken into consideration before planning the targeted CD34+ cell count especially for pediatric donors.

Stepwise diet management in pediatric gastrointestinal graft versus host disease.

Gastrointestinal tract is one of the major systems affected by graft-versus-host disease (GVHD). Injury to the gut during conditioning therapy before stem-cell transplantation (SCT) plays a pivotal role in the initiation of inflammatory stimuli. We reviewed medical records of the patients who underwent SCT between April 2010 and June 2013 in our center. A stepwise upgrade diet was given to the children with acute GI-GVHD (Gastrointestinal GVHD) including parenteral and enteral nutrition. A total of 105 patients underwent SCT and seven patients developed grade III-IV acute GI-GVHD. Total parenteral nutrition (TPN) was initiated to all patients after the diagnosis of GI-GVHD and minimal enteral nutrition (1-2 ml/kg/day standard pediatric enteral formula/special meat soup) was given to the patients. GI-GVHD improved in all patients with no change in body weight, and recovery to a normal diet took 10-30 days. Stepwise diet management of oral nutrition contributed to rapid improvement of grades III-IV acute GI-GVHD.

Risk factors, complications and outcome of cholelithiasis in children: A retrospective, single-centre review.

AIM: The aim of this study was to evaluate the clinical presentation, risk factors, complications, treatment and outcomes of cholelithiasis in children. METHODS: Children with cholelithiasis were reviewed for demographic information, predisposing factors, presenting symptoms, laboratory findings, complications, treatment and outcome, retrospectively. RESULTS: A total of 254 children with cholelithiasis (mean age: 8.9 ± 5.2 years) were recruited to the study. Girls (52.8%) were significantly older than boys (P < 0.001). Symptomatic patients (59%) were significantly older than asymptomatic patients (P = 0.002). Abdominal pain was the most frequent symptom. No risk factors were identified in 56.6% of the patients. Ceftriaxone (20%) was the most commonly associated risk factor. At presentation, at least one of the following complications was seen in 14.1% of patients: cholecystitis (10.9%), obstructive jaundice (2.7%), pancreatitis (1.96%) and cholangitis (1.2%). There was no relationship between gallstone size and symptoms, aetiological factors and complications. The cholelithiasis dissolution rate was higher in younger children (P = 0.032), in those with biliary sludge (P < 0.0001) and ceftriaxone-related cholelithiasis (P < 0.001). Haemolytic anaemia (P = 0.001) and older age (P = 0.002) were associated with stable stones. Ursodeoxycholic acid was administered to 94.4% of patients at presentation. Twenty-nine patients underwent cholecystectomy, and seven patients underwent endoscopic retrograde cholangiopancreotography. Patients who were symptomatic at presentation had significantly more frequent symptoms at follow-up (P < 0.001) CONCLUSIONS: Dissolution rate of cholelithiasis was higher in younger children, biliary sludge formation and ceftriaxone-related cholelithiasis but lower in older children and haemolytic anaemia-related cholelithiasis.

Candida Associated Bloodstream Infections in Pediatric Hematology Patients: A Single Center Experience.

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.

The successful non-invasive management of pulmonary thromboembolism in a child with acute lymphoblastic leukemia.

In childhood, pulmonary thromboembolism (PTE) is an uncommonbut potentially life-threatening disease. The greater numbers of venous thromboembolism (VTE) are complications of underlying risk factors such as malignancies, chemotherapy (L-asparaginase), and central venous catheter. We report a patient with acute lymphoblastic leukemia and PTE, who presented with near-syncope, and was successfully treated with low molecular weight heparin and calcium channel blockers.

Angiopoietins in the bone marrow microenvironment of acute lymphoblastic leukemia.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Éxito en el manejo no invasivo de la tromboembolia pulmonar en un niño con leucemia linfocítica aguda / The successful non-invasive management of pulmonary thromboembolism in a child with acute lymphoblastic leukemia

Durante la niñez, la tromboembolia pulmonar (TEP) es una afección poco frecuente, aunque potencialmente mortal. El mayor número de episodios de tromboemblia venosa (TEV) es resultado de complicaciones de factores de riesgo subyacentes, tales como tumores malignos, quimioterapia (L-asparaginasa) y colocación de un catéter venoso central. Presentamos el caso de un paciente con leucemia linfocítica aguda y TEP que tuvo un presíncope y fue tratado satisfactoriamente con heparina de bajo peso molecular y antagonistas del calcio.

In childhood, pulmonary thromboembolism (PTE) is an uncommonbut potentially life-threatening disease. The greater numbers of venous thromboembolism (VTE) are complications of underlying risk factors such as malignancies, chemotherapy (L-asparaginase), and central venous catheter. We report a patient with acute lymphoblastic leukemia and PTE, who presented with near-syncope, and was successfully treated with low molecular weight heparin and calcium channel blockers.

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.