Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen-storage-associated mitochondriopathy.

Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose DNA was available, segregated homozygous loss-of-function C2orf69 variants. C2ORF69 bears homology to esterase enzymes, and orthologs can be found in most eukaryotic genomes, including that of unicellular phytoplankton. We found that endogenous C2ORF69 (1) is loosely bound to mitochondria, (2) affects mitochondrial membrane potential and oxidative respiration in cultured neurons, and (3) controls the levels of the glycogen branching enzyme 1 (GBE1) consistent with a glycogen-storage-associated mitochondriopathy. We show that CRISPR-Cas9-mediated inactivation of zebrafish C2orf69 results in lethality by 8 months of age due to spontaneous epileptic seizures, which is preceded by persistent brain inflammation. Collectively, our results delineate an autoinflammatory Mendelian disorder of C2orf69 deficiency that disrupts the development/homeostasis of the immune and central nervous systems.

Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

HEATR3 variants impair nuclear import of uL18 (RPL5) and drive Diamond-Blackfan anemia.

The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report multiple individuals with biallelic HEATR3 variants exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability. These variants destabilize a protein whose yeast homolog is known to synchronize the nuclear import of RPs uL5 (RPL11) and uL18 (RPL5), which are both critical for producing ribosomal subunits and for stabilizing the p53 tumor suppressor when ribosome biogenesis is compromised. Expression of HEATR3 variants or repression of HEATR3 expression in primary cells, cell lines of various origins, and yeast models impairs growth, differentiation, pre-ribosomal RNA processing, and ribosomal subunit formation reminiscent of DBA models of large subunit RP gene variants. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis.

Prognosis of Second Primary Malignancies in Pediatric Acute Lymphoblastic Leukemia Survivors: A Multicenter Study by the Turkish Pediatric Hematology Society.

The improved survival rates of childhood cancers raise the long-term risk of second primary malignancy (SPM) in childhood and adolescent cancer survivors. The intensity of the treatment protocol used, the use of some groups of chemotherapeutics, and radiotherapy were found to be risk factors for the development of second primary malignancies (SPMs). Forty-one patients who developed acute myelocytic leukemia or any solid organ cancer within 25 years of follow-up, after completion of pediatric acute lymphoblastic leukemia (ALL) treatment, were included in the study. The mean duration of initial ALL diagnosis to SPM was 9.3 ± 6.1 years. The 3 most common SPMs were acute myelocytic leukemia, glial tumors, and thyroid cancer. Thirteen (81%) of 16 patients exposed to cranial irradiation had cancer related to the radiation field. In total 13/41 (32%) patients died, and the 5-year overall survival rate was 70 ± 8%. Patients older than 5 years old at ALL diagnosis had significantly worse overall survival than cases younger than 5 years old. In conclusion, children and adolescents who survive ALL have an increased risk of developing SPM compared with healthy populations, and physicians following these patients should screen for SPMs at regular intervals.

Serum interleukin-33 and soluble suppression of tumorigenicity 2 in pediatric leukemia with febrile neutropenia.

The purpose of this study was to evaluate the association between interleukin-33 (IL-33) and its receptor Soluble Suppression of Tumorigenicity-2 (sST2) levels and bacterial infections during febrile neutropenia (FN) in pediatric patients with acute lymphoblastic leukemia (ALL). In this prospective, case-control study, participants were divided into 3 groups: ALL patients with FN (Group A), ALL patients without neutropenia and fever (Group B), and healthy children without infection and chronic disease (Group C). There were 30 cases in each group. Blood samples for IL-33 and sST2 have been drawn from patients in Group A before the initiation of treatment and on days 1 and 5 of treatment, and from patients in Groups B and C at initiation. At admission, mean IL-33 level (39.02 ± 26.40 ng/L) in Group B and mean sST2 level (185.3 ± 371.49 ng/ml) in Group A were significantly higher than the other groups (p = 0.038, p < 0.001, respectively). No difference was observed in the mean IL-33 and sST2 levels in the 5-day follow-up of patients in Group A (p = 0.82, p = 0.86, respectively). IL-33 and sST2 levels were not associated with fever duration, neutropenia duration or length of hospitalization. While C-reactive protein (CRP) was significantly higher in patients with positive blood culture (p = 0.021), IL-33 (p = 0.49) and sST2 (p = 0.21) levels were not associated with culture positivity.  Conclusion: IL-33 and sST2 levels were not found valuable as diagnostic and prognostic markers to predict bacterial sepsis in patients with FN. What is Known: • Neutropenic patients are at high risk of serious bacterial and viral infections, but the admission symptom is often only fever. • Febrile neutropenia has a high mortality rate if not treated effectively. What is New: • Febrile neutropenia is not only caused by bacterial infections. Therefore, new biomarkers should be identified to prevent overuse of antibiotics. • Specific biomarkers are needed to diagnose bacterial sepsis in the early phase of febrile neutropenia.

Does the use of infusion pumps increase hemolysis during blood transfusion in patients with thalassemia?

BACKGROUND: Patients with thalassemia need regular blood transfusions to maintain normal growth and suppression of ineffective erythropoiesis. Packed red blood cell (RBC) units can be delivered by infusion pumps (IPs); however, IPs may cause mechanical stress-induced RBC lysis. This study aimed to investigate the biomarkers of hemolysis related to transfusion techniques in patients with thalassemia. MATERIAL AND METHODS: Eighty-one thalassemia patients compared to those 42 healthy controls in terms of hemolysis markers (hemoglobin, plasma free hemoglobin (Hb), haptoglobin, potassium (K), lactate dehydrogenase (LDH)) before transfusion. Considering the age and peripheral venous diameter of the patient, the physician decided on the caliber of vascular access device (22 G or 24 G) for transfusion and the method to be used (gravitational method [GM] or IP). Hemolysis markers were repeated after transfusion in thalassemia patients. RESULTS: Packed RBC units were transfused to 24 (30 %) patients by IP and 57 (70 %) patients by GM. Plasma free Hb was significantly increased from 4.76 ± 7.92 mg/dL to 9.01 ± 7.66 mg/dL following transfusion (p < 0.001). There was no significant difference between IP and GM in terms of plasma free Hb increase. Post-transfusion plasma free Hb, LDH, and K levels significantly increased in patients who were transfused with 24 G catheters compared to those transfused with 22 G. CONCLUSION: An elevation in LDH levels was detected after transfusion with volumetric IPs; however, plasma free Hb or K levels were not affected by the transfusion method. Studies are needed to determine the factors associated with hemolysis after transfusion.

Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome.

Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.

Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study.

BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.

Analysis of fresh frozen plasma utilization indications in children: An audit of a tertiary care hospital in Turkey.

BACKGROUND: Although indications of fresh frozen plasma (FFP) usage are limited to certain circumstances in children, there is an increasing trend towards inappropriate usage are reported in clinical practice. The aim of this study was to evaluate the appropriateness of pediatric FFP utilization in our tertiary care hospital. METHODS: This prospective observational study was conducted at a tertiary care academic pediatric hospital. All FFP orders were evaluated for appropriateness over a 4-monts period by 2 hematologists. Data collected include demographic information, diagnosis, FFP transfusion indication, pre-transfusion coagulation tests, surgical procedure or bleeding status, and transfusion reactions. RESULTS: Three hundred twenty-four patients (57 % males, 43 % females) were transfused in 987 episodes. The mean age of the patients was 5.4±5.7 years. The majority of the patients (33 %) were under 1 y of age and the products were primarily utilized by pediatric and cardiovascular intensive care units. Pre-transfusion coagulation testing was only available in 674 (68 %) of the transfusion episodes. The rate of appropriate FFP transfusion episodes was 59 % (587/987). Inappropriate usage was mostly related to sepsis and minor coagulation abnormalities without bleeding. The higher rates of inappropriate transfusion orders were observed in pediatric and neonatal intensive care units, and hematology/oncology departments. CONCLUSIONS: Inappropriate use of FFP in children remains a significant challenge. The regular audit and sustainable education programs targeting the efficient use of FFP for health professionals at the national level can improve transfusion practices.

Pneumatosis cystoides intestinalis: A rare complication after hematopoietic stem cell transplantation.

BACKGROUND: Pneumatosis cystoides intestinalis (PCI) is a disorder in which widespread air sacs are present in mucosa, submucosa, subserosa, and intraabdominal area of the intestinal wall. It has a heterogeneous clinical presentation as a rare complication of intestinal graft-versus-host disease (GVHD). Computed tomography is the preferred imaging method for the diagnosis. Since the air sacs could be ruptured spontaneously, the presence of free air in the peritoneal cavity does not confirm intestinal perforation. The conservative treatment approach is sufficient in cases that do not require urgent surgical intervention, such as perforation or obstruction. CASE: Here, we present a 2.5-year-old patient diagnosed with primary hemophagocytic lymphohistiocytosis (pHLH), who underwent allogeneic hematopoietic stem cell transplantation from a matched unrelated donor (MUD) and developed PCI secondary to intestinal GVHD 14th months after HSCT. CONCLUSIONS: Pneumatosis cystoides intestinalis, which is a rare complication, should be kept in mind, especially in patients with intestinal GVHD and receiving intensive immunosuppressive, octreotide, and steroid treatment after HSCT.

Health-related Quality of Life for Children With Leukemia: Child and Parental Perceptions.

BACKGROUND: The importance of health-related quality of life (HRQoL) in patients with acute lymphoblastic leukemia (ALL) has increased in recent years. This study aimed to assess HRQoL in children with ALL, affecting factors, and the relationship between parent proxy-report and child self-report HRQoL. MATERIALS AND METHODS: A total of 59 children and their parents (both mother and father) were enrolled in this cross-sectional study. Turkish version of the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Modules were used to determine HRQoL. RESULTS: According to subscales of the self-report form, nausea and operational anxiety scores differed significantly by the treatment status; communication score varied considerably by the hospitalization length of stay; pain and hurt, cognitive problems, and perceived physical appearance scores differed significantly by the maternal chronic disease status (P<0.05). The presence of maternal chronic disease was significantly related to the total score of the parent-proxy report (mother) (P<0.05). There was a moderate correlation between total scores of child and mother (P<0.05, r=0.419) but not with the father. CONCLUSION: Children on-treatment had significant problems in nausea and procedural anxiety subscales; however, children who were hospitalized more had fewer issues in the communication subscale. Also, children whose mother had chronic disease had poorer HRQoL regarding pain and hurt cognitive problems and treatment anxiety. Given the importance of assessment and monitoring HRQoL in children with ALL, health professionals should be aware of how parents' chronic disease affects HRQoL. Psychosocial support should be provided to children and their parents, especially for those whose parents have a chronic illness.

Children With Behçet Disease-associated Thrombosis: A Single-Center Experience.

Behçet disease (BD) is a systemic vasculitis that can be complicated with thrombosis, which is an important cause of mortality and morbidity. The course of BD is more severe, and the diagnosis is usually delayed. In children, thrombosis associated with BD is very rare. In this study, we aimed to evaluate the characteristics of children with BD complicated with thrombosis. Forty-six patients with BD who were followed-up at a pediatric rheumatology department between January 2012 and September 2019 were evaluated retrospectively. Thrombosis was detected in 10 patients (21.7%), and it was the first sign of BD in 7 patients. Four patients had cerebral sinus venous thrombosis, 4 patients had deep-vein thrombosis, 1 patient had renal vein thrombosis, 1 had pulmonary artery thrombosis, and 1 had intracardiac thrombosis. None of the patients had arterial thrombosis. All patients had received anticoagulant therapy with immunosuppressive treatment. Any complication due to anticoagulant therapy was not detected. One patient had recurrent thrombosis, and none of the patients died during follow-up. Vasculitic diseases such as BD may cause a predisposition to thrombosis, and thrombosis might be the first sign of BD. Therefore, in children presenting with unprovoked thrombosis, BD should also be investigated.

Frequency and clinical characteristics of allergic transfusion reactions in children.

Allergic transfusion reactions (ATRs)are a common form of acute transfusion reaction. It was aimed to determine the clinical characteristics and frequency of ATRs in children. This study included children who were transfused with red cell concentrate (RCC), fresh-frozen plasma (FFP), platelet concentrates(PC), apheresis granulocyte, and cryoprecipitate.The patients' sociodemographic characteristics, the blood product that caused the reaction, the type and timing of the reaction, the patient's age at time of reaction and their diagnosis, follow-up period, and clinical data were recorded. A total of 89703 bags of blood products were transfused to 4193 children.Two hundred eleven acute transfusion-related reactions occurred in 157 (3.74%) patients.Of these, 125 reactions (59%) were allergic. ATR occurred in 125 of 89703 infusions (0.14%).The median age of patients was 9.99 years (IQR:4.67-14.38) and ATRs occurred at a median of 30 minutes into the transfusion. Eighteen (18%) of the patients also had a history of drug reaction.When the blood products that caused ATRs were examined, 43(34.5%) occurred with apheresis and single-donor PC, 37(29.6%) with FFP, 32 (25.6%) with RCC, 10(8%) with pooled PC, 2(1.6%) with cryoprecipitate, 1(0.8%) with apheresis granulocyte.Ninety-nine(79%) of the reactions were minor allergic reactions and 26(21%) were anaphylaxis.Compared to minor allergic reactions, the proportion of PCs was statistically higher in anaphylaxis(p=0.02). Patients receiving PC should be monitored more carefully during the first half hour of transfusion. In addition, approximately one-fifth of the patients who developed ATR also had a history of drug reaction. Patients with previous reactions to drugs may be more likely to have ATR.

Autoimmune atrophic gastritis: The role of Helicobacter pylori infection in children.

BACKGROUND: Autoimmune atrophic gastritis (AIG) is very rare in children. Despite a better understanding of histopathologic changes and serological markers in this disease, underlying etiopathogenic mechanisms and the effect of Helicobacter pylori (H pylori) infection are not well known. We aimed to investigate the relation between AIG and H pylori infection in children. MATERIALS AND METHODS: We evaluated the presence of AIG and H pylori infection in fifty-three patients with positive antiparietal cell antibody (APCA). Demographic data, clinical symptoms, laboratory and endoscopic findings, histopathology, and presence of H pylori were recorded. RESULTS: The children were aged between 5 and 18 years, and 28 (52.8%) of them were male. Mean age was 14.7 ± 2.6 years (median: 15.3; min-max: 5.2-18), and 10 (18.8%) of them had AIG confirmed by histopathology. In the AIG group, the duration of vitamin B12 deficiency was longer (P = .022), hemoglobin levels were lower (P = .018), and APCA (P = .039) and gastrin (P = .002) levels were higher than those in the non-AIG group. Endoscopic findings were similar between the two groups. Intestinal metaplasia was higher (P = .018) in the AIG group. None of the patients in the AIG group had H pylori infection (P = .004). One patient in the AIG group had enterochromaffin-like cell hyperplasia. CONCLUSIONS: Our results show that, in children, H pylori infection may not play a role in AIG. AIG could be associated with vitamin B12 deficiency, iron deficiency, and APCA positivity in children. APCA and gastrin levels should be investigated for the early diagnosis of AIG and intestinal metaplasia.

Evaluation of hypersensitivity reactions to cancer chemotherapeutic agents in pediatric patients.

BACKGROUND: Hypersensitivity reactions (HSRs) to chemotherapeutic agents have been increasingly documented. OBJECTIVE: The aim of this study was to investigate HSRs due to chemotherapeutics agents in childhood. METHODS: From January 2007 to June 2019, the patients who were treated for neoplastic diseases in our hospital were evaluated. Patients who developed a HSR to a chemotherapeutic agent were included. RESULTS: Fifty-seven patients with 65 reactions (60% anaphylaxis) were evaluated. Escherichia coli asparaginase was responsible for 38 (58.5%) of these 65 reactions. The other agents were polyethylene glycol (PEG)-asparaginase (n = 11), etoposide (n = 7), methotrexate (n = 4), carboplatin (n = 4), and procarbazine (n = 1). Of the 38 patients who had a reaction to E coli-asparaginase, 33 patients received alternative treatment (PEG-asparaginase or Erwinia asparaginase), 3 patients continued with desensitization, and 2 patients underwent bone marrow transplantation. Five patients who had an initial reaction to PEG-asparaginase continued their treatment with Erwinia asparaginase or E coli asparaginase uneventfully. Of 7 patients who had a reaction to etoposide (4 had anaphylaxis), 3 patients continued with desensitization, and 2 patients used the drug with premedication and prolonged infusion. Two patients had anaphylaxis with methotrexate. Treatment was continued with desensitization in 1 patient and methotrexate treatment was discontinued in the other patient. Of the 4 patients with carboplatin hypersensitivity, 2 had anaphylaxis. Desensitization was performed in 2 patients. One patient had procarbazine HSR, drug was given with premedication. CONCLUSION: Among all chemotherapeutic agents reviewed in our study that caused HSRs, asparaginase was the most common culprit agent in children. Most of reactions are immediate type. Many of the patients can take their treatment by drug replacement or desensitization.

Bone Marrow Necrosis in a Patient Following Blinatumomab Therapy.

Bone marrow necrosis (BMN) is an extremely rare condition characterized by necrosis of the myeloid tissue and medullary stroma leaving an amorphous eosinophilic background and ill-defined necrotic cells in the hematopoietic bone marrow. Several conditions are associated with BMN, including sickle cell disease, metastatic carcinoma, and hematologic malignancies. It is also associated with the use of antineoplastic drugs, such as fludarabine, interferon alpha, and imatinib. Blinatumomab is a CD19/CD3 bispecific T-cell engager antibody which redirects autologous CD3-positive T cells to CD19-positive lymphoblasts creating a cytolytic synapse leading to blastic cells. Cytokine release syndrome, cerebral nervous system toxicities, and febrile neutropenia are the most frequent adverse effects of blinatumomab. Here, we report an adolescent boy with relapse/resistant acute lymphoblastic leukemia developing BMN following blinatumomab therapy. To our knowledge, this is the first case report on BMN following blinatumomab treatment.

Renal function and the oxidative status among children with thalassemia major and healthy controls: A cross-sectional study.

BACKGROUND: Renal dysfunction is an underestimated complication of thalassemia major. OBJECTIVES: The aim of this study is to compare the glomerular and tubular functions in children with ß- Thalassemia major (ß- TM) with healthy controls and assess the oxidative stress caused by high ferritin levels. DESIGN AND SETTING: This prospective cross-sectional study was conducted in tertiary care hospital. METHODS: Complete blood count (CBC), calcium (Ca), urea, creatinine (Cr), serum cystatin C before transfusion and urinary calcium (uCa), creatinine (uCr), protein (UPr) levels were analyzed in fresh samples. Beta-2-microglobulin (uß2-MG), N- acetylglucosaminidase (uNAG), retinol binding protein (uRBP), malonedialdehyde (uMDA) secretion and creatinine levels were analyzed. Serum total antioxidant capacity (sTAC) and total oxidant capacity (sTOC) were measured with colorimetric micro-ELISA method. Last four serum ferritin values were recorded and the mean value was used for statistical analyzes. RESULTS: Data from 47 patients and 32 controls were analyzed. The urinary RBP/Cr, Ca/Cr and Protein/Cr, were significantly higher in ß-TM group. A statistically insignificant increase in urinary ß2MG/Cr, uNAG/Cr, MDA/Cr was also found in the TM group. Proteinuria was present in 46 % (n: 22) and hypercalciuria in 34 % (n: 16) of the patients with ß- TM. Serum total antioxidant capacity and total oxidant status (TOS) levels were significantly elevated in the patient group. Serum ferritin was significantly correlated with proteinuria, cystatin C levels, urinary Protein/Cr and uRBP/Cr. CONCLUSION: Asymptomatic renal dysfunction is prevalent in ß- TM patients that necessitate regular screening. Urinary RBP may be useful for early diagnosis.

Efficacy and safety of granulocyte transfusion in children: A single-center experience.

BACKGROUND: Granulocyte suspension transfusion (GTx) can be used in severely neutropenic patients with infections that cannot be controlled despite appropriate antibiotic therapy. OBJECTIVE: We aimed to evaluate the effectiveness and safety of GTx for the treatment of febrile neutropenia (FEN) in the pediatric age group. METHODS: Patients who underwent GTx in the Hematology Clinic of Ankara Child Health and Diseases Hematology Oncology Training and Research Hospital between 2013 and 2017 were evaluated retrospectively. Hematologic and clinical response rates, effects on survival, and adverse effects were investigated. Clinical response was defined at two time points: clinical response I was evaluated after each transfusion, while clinical response II was evaluated after the final GTx in a FEN episode. RESULTS: During the study period, 343 GTx were given 107 FEN episodes of 74 patients. The mean number of granulocyte suspensions administered per patient and per FEN episode was 4.6 units and 3.2 units. The mean GTx volume administered was 237 ± 40 mL, and the mean granulocyte count was 2.8 ± 1.3 x 1010 /unit. Hematologic response was attained in 163 (47.6%) of 343 transfusions. Clinical response I was obtained in 88 (25.7%) of the GTx, and clinical response II was attained in 83 (78.5%) of 107 episodes. Life-threatening adverse event was not observed. The cumulative 1-month and 3-month survival rates were 87.8% and 76.5%, respectively. CONCLUSION: High hematologic response and clinical recovery rates were achieved with GTx, with no limiting adverse effects. Granulocyte transfusion appears to be a safe and effective treatment in pediatric patients with FEN.

The effect of deferasirox on endocrine complications in children with thalassemia.

Endocrine system dysfunctions are the significant complications of excessive iron overload in beta thalassemia patients. The aim of this study was to evaluate the long-term effect of chelation with deferasirox on endocrine complications. The study group consisted of children with beta thalassemia who had been evaluated for the growth and pubertal development, bone metabolism, thyroid/parathyroid functions, glucose metabolism dysfunctions in the department of pediatric hematology of Ankara Diskapi Child Health and Diseases Hematology Oncology Training And Research Hospital between 2009-2011 and reevaluated after deferasirox chelation therapy in 2018. Thirty-one transfusion dependent beta-thalassemia patients were enrolled for the study. Seventeen (54.8%) patients were male and the mean age was 16.9 ± 3.8 (9-23) years. Splenectomy was performed in 11 patients (35.5%). In the initial evaluation, 26 patients (84%) received deferoxamine and/or deferiprone and five (17%) patients received deferasirox as a chelator; in the final evaluation all patients were receiving deferasirox. The mean duration of deferasirox treatment was 5.9 ± 2.02 years (1-10 years). Of the 26 patients who had endocrine complications between 2009-2011, 18 were recovered. In the final evaluation, eight patients (25%) developed new endocrinopathies. The frequency of endocrine complications seen before the deferasirox treatment (83%) was higher than the frequency of complications while receiving deferasirox treatment (25.8%) (p < 0,05). In this study, it was determined that both existing endocrine abnormalities were reduced and recent developed problems were less likely with long-term deferasirox treatment in thalassemia patients.