Bernard-Soulier Syndrome: A Review of Epidemiology, Molecular Pathology, Clinical Features, Laboratory Diagnosis, and Therapeutic Management.

Bernard-Soulier syndrome (BSS) is an inherited platelet function disorder caused by mutations in the genes that encode the glycoprotein (GP) Ibα and GPIbß subunits, as well as the GPIX subunit in the GPIbIX complex, which is located on the platelet surface and has roles in platelet adhesion and activation. Patients with autosomal recessively inherited biallelic BSS have a homozygous or compound heterozygous expression in the GPIbα, GPIbß, and GPIX subunits of the GPIbIX complex. Patients with autosomal dominantly inherited monoallelic BSS have a heterozygous expression in only the GPIbα and GPIbß subunits of the GPIbIX complex. To date, no BSS mutations in the GP5 gene have been reported. Patients with biallelic form are usually diagnosed at a young age, typically with mucocutaneous bleeding, whereas monoallelic forms are generally identified later in life and are frequently misdiagnosed with immune thrombocytopenic purpura (ITP). In biallelic BSS, giant platelets in the peripheral blood smear, absence of ristocetin-induced platelet aggregation (RIPA) using light transmission aggregometry (LTA), and complete loss of GPIbIX complex in flow cytometry are observed, whereas in monoallelic forms, genetic diagnosis is recommended due to the presence of large platelets in the peripheral blood smear, decreased or normal RIPA response in LTA, and partial loss or normal GPIbIX complex in flow cytometry. Platelet transfusion is the main therapy but recombinant factor VIIa is advised in alloimmunized patients, and allogeneic stem cell transplantation is suggested in refractory cases. Antifibrinolytics and oral contraceptives are utilized as supplementary treatments. Finally, differentiation from ITP is critical due to differences in management. Thus, BSS should be kept in mind in the presence of individuals with chronic persistent thrombocytopenia, positive family history, unresponsive ITP treatment, macrothrombocytopenia, and absence of RIPA response.

Concurrent Osteonecrosis of the Jaw and Hip in a Child With Severe Aplastic Anemia Undergoing Transplant.

We present the first case of concomitant hip and jaw osteonecrosis in a 10-year-old child with aplastic anemia undergoing a transplant. Biphosphonate treatment may be beneficial for hip osteonecrosis but harmful for jaw osteonecrosis. Our experience suggests that clinicians should be cautious when prescribing bisphosphonate to children with simultaneous hip and jaw osteonecrosis. They should be aware of the osteonecrosis locations and treatment choices.

The Role of Monocyte Distribution Width in the Early Prediction of Sepsis in Patients Undergoing Cardiovascular Surgery: A Cross-Sectional Study.

Background and Objectives: This is the first study to examine the role of monocyte distribution width (MDW) in predicting sepsis after cardiovascular surgery. Methods: This study included 43 consecutive patients who had undergone cardiovascular surgery between July 2021 and July 2022. All patients were examined at the following three time points (TPs): preoperative period (TP1), postoperative at 24 h (TP2), and discharge (TP3). SOFA score, leukocyte count, neutrophil-to-lymphocyte ratio (NLR), MDW, C-reactive protein (CRP), and procalcitonin (PCT) levels were tested at each TPs. The Sepsis-3 criteria were used to diagnose patients with sepsis. Results: The mean values of all variables (leukocyte count, NLR, MDW, CRP, and PCT levels) were significantly higher at TP2 and TP3 than at TP1 (p < 0.05). All these values were significantly higher at TP2 than at TP3 (p < 0.05). Patients with sepsis had significantly higher mean values for leukocyte count, NLR, MDW, CRP, and PCT levels than those without sepsis (p < 0.05). There was a significant correlation between MDW and inflammatory markers (CRP, PCT, and NLR) during the three time periods (p < 0.05). According to the ROC analysis, the optimal MDW cutoff value with the highest sensitivity and specificity for predicting sepsis in the postoperative period was 20.5. Conclusions: Our findings indicate that elevated MDW levels may be a valuable predictor of sepsis in patients following cardiovascular surgery.

Occurrence of familial Mediterranean fever in haemophilia patients.

INTRODUCTION: This is the first study of simultaneous occurrences of Familial Mediterranean Fever (FMF) in patients with haemophilia. AIM: The aim was to investigate the frequency and clinical characteristics of FMF in patients with severe haemophilia. METHODS: Our study included 30 patients with severe haemophilia (26 haemophilia A and four haemophilia B). All 30 patients are screened for MEFV genotypes in FMF according to the new Eurofever/PRINTO diagnostic criteria. All cohorts were genetically tested for FMF and thrombophilia. RESULTS: Eight (26%) of 30 haemophilic patients were diagnosed with FMF. Six different heterozygous FMF mutations including M694V (n = 2), E148Q (n = 2), V726A(n = 1), P369S (n = 1), E148Q/K695R (n = 1) and E148Q/M694I (n = 1) were identified. Seven had haemophilia A and only one had haemophilia B. Four (50%) patients had a positive family history and three of them had extraarticular findings specific to FMF. Only one haemophilia B patient received colchicine. Target joints in the knee, ankle, and elbow were identified in three FMF patients. The number of target joints in eight patients with FMF was significantly lower than in twenty-two patients without FMF (p < .05). The annual number of suspected joint bleedings in FMF patients admitted to the hospital was 40; however, 15 (37.5%) were documented bleedings in ultrasounds. Hereditary thrombophilia was detected in seven of eight patients. CONCLUSION: Our data indicate that screening for FMF may be useful in patients with haemophilia who develop arthritis without prominent bleeding and have a positive family history in many Mediterranean countries, including Turkey.

Central nervous system thrombosis in pediatric acute lymphoblastic leukemia in Turkey: A multicenter study.

BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.

Polycythemia as an Uncommon Finding in 2 Children, One With Systemic Capillary Leak Syndrome and the Other With Protein-losing Enteropathy Caused by CD55 Deficiency.

We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. There is only a single case series about polycythemia in children with SCLS, but none on polycythemia in children with PLE. We present a 10-year-old girl with hypoalbuminemia, polycythemia, and edema who died as a result of an SCLS attack and a 1-year-old girl with PLE who was successfully treated with eculizumab. Our experience suggests that hematologists should be alert for SCLS and PLE in children with relative polycythemia.

Persistent Rhinovirus Infection in a Child With Leukemia.

Human Rhinovirus (HRV) is one of the most common pathogens causing acute respiratory tract infections in infants and children. Several reports suggest that HRV has the potential to cause chronic infection after an acute viral infection in an immunosuppressed patient. Although chronic HRV infection has been reported in lung transplant recipients, patients with hypogammaglobulinemia and cystic fibrosis, the duration and severity of HRV infection remain unclear. In this study, we present a case of persistent HRV infection in a stem cell transplanted leukemia patient. This report raises several questions regarding the risk factors, duration, and severity of persistent HRV infection in acute leukemia patients, which warrants prospective and longitudinal studies.

Prognostic role of serum cytokines and soluble HLA-G levels in children with leukemia who undergo allogeneic stem cell transplantation.

This is the first study to have investigated the prognostic role of cytokines and soluble human leukocyte antigen-G (sHLA-G) levels in pediatric leukemia patients who have undergone allogeneic stem cell transplantation (allo-SCT). Forty-one patients with acute leukemia (n = 28, acute lymphoblastic leukemia (ALL) and n = 13, acute myeloblastic leukemia) were recruited. Patients were examined at diagnosis (n = 26), in the pre-transplantation period (PreTx) (n = 26), on the day of transplantation (Tx0) (n = 41), and on post-transplantation Days 14 (PostTx14) (n = 41) and 28 (PostTx28) (n = 41). Serum levels of pro-inflammatory cytokines (interleukin [IL]-1, IL-2, IL-6, Tumor necrosis factor [TNF]-α), anti-inflammatory cytokines (IL-4, IL-10), and sHLA-G were measured by Enzyme-Linked ImmunoSorbent Assay. Median levels of all cytokines tested and sHLA-G were significantly higher at diagnosis and at the post-transplant time points than at PreTx (all p < 0.05). At the time of diagnosis (specifically ALL) and at PostTx14, elevated IL-4, IL-10, and/or sHLA-G were associated with higher post-transplant relapse rates (all p < 0.05). Elevated IL-2 and TNF-α at Tx0 were associated with lower survival rates (both p < 0.05). Levels of serum cytokines and sHLA-G may be useful predictors of survival and relapse in pediatric leukemia patients who undergo allo-SCT.

Thoracic Air Leak Syndrome, Pulmonary Aspergillosis, and COVID-19 Pneumonia After Allogeneic Stem Cell Transplantation in a Child With Myelodysplastic Syndrome.

Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.

Assessment of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia: A Multicenter Study From Turkey.

Assestment of minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL) is of utmost importance both for risk classification and tailoring of the therapy. The data of pediatric ALL patients that received treatment with Berlin-Frankfurt-Münster (BFM) protocols were retrospectively collected from 5 university hospitals in Turkey. Of the 1388 patients enrolled in the study 390 were treated according to MRD-based protocols. MRD assestment was with real time quantitative polymerase chain reaction (qPCR) in 283 patients and with multiparametric flow cytometry (MFC)-MRD in 107 patients. MRD monitoring had upstaged a total of 8 patients (2%) from intermediate risk group to high-risk group. Univariate analysis revealed age 10 years or above, prednisone poor response, PCR-MRD ≥10-3 on day 33 and on day 78 as poor prognostic factors affecting event-free survival (EFS). Detection of >10% blasts on day 15 with MFC (MFC-high-risk group) was not shown to affect EFS and/or overall survival (log-rank P=0.339). Multiple logistic regression analysis revealed PCR-MRD ≥10-3 on day 78 as the only poor prognostic factor affecting EFS (odds ratio: 8.03; 95% confidence interval: 2.5-25; P=0.000). It is very important to establish the infrastructure and ensure necessary standardization for both MRD methods for optimal management of children with ALL.

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.

Impact of peri-transplant RBC transfusion and ABO incompatibility on acute graft-versus-host disease in pediatric hematopoietic stem cell transplant patients.

It is well known that stem cell transplantation is curative for many diseases; however, graft versus host disease (GVHD), which is a common posttransplant complication, has still a substantial place among the causes of transplant-related morbidity and mortality. The association between ABO incompatibility and GVHD is controversial. There is also limited available data about the association between blood component transfusions during the peritransplant period and GVHD development in the pediatric setting. Hence, we retrospectively evaluated both the impact of ABO-mismatch and transfusions of RBC and platelets between day -7 pre-transplant and +30 post-transplant to the development of acute GVHD (aGVHD). We analyzed 139 allotransplants in 133 patients who were transplanted by myeloablative conditioning. Fifty-one patients out of 133 (36.7 %) were found to have aGVHD within +100 days post-transplantation. Of them 40 patients had grade I-II and 11 patients had grade III-IV aGVHD. Increased risk of aGVHD is associated with ABO minor mismatch (p: 0.030). Nevertheless, there was no association between ABO mismatch and severity of aGVHD. The median number of RBC transfusions in aGVHD patients was higher than the number of transfusions in patients without aGVHD; however, the difference was not statistically significant (p: 0.11). Platelet transfusion numbers were statistically similar between aGVHD patients and the patients without aGVHD (p: 0.79). In conclusion, major and bi-directional ABO-incompatibility between donors and recipients, and RBC and platelet transfusions between day -7 pretransplant and day +30 post-transplant do not contribute to aGVHD development in children undergoing HSCT by myeloablative conditioning, while ABO minor mismatch is associated with the development of aGVHD.

Identification of subclinical iron deficiency using new erythrocytes, leukocytes, and reticulocytes parameters during nonsevere acute infection in pediatric outpatients.

BACKGROUND: This study aims to investigate the diagnostic utility of new erythrocytes, leukocytes, and reticulocytes parameters for the identification of subclinical iron deficiency (ID) in children under 6 years with nonsevere acute infection in pediatric outpatients. METHODS: The study included 102 children with acute infections and 31 true ID. Traditional and new hematology parameters were measured in a Sysmex-XN®, along with C-reactive protein level, and iron parameters. Participants' ID were categorized as: the ferritin < 100 ng/mL, transferrin saturation < 20% was defined as "subclinical or functional ID (FID) in Group 1"; ferritin < 30 ng/mL, transferrin saturation < 20%, as "absolute-ID (AID)" in Group 2; ferritin < 12 ng/mL without anemia and infection, as "true ID" in Group 3. RESULTS: The frequencies of FID and AID among the 102 children with acute infection were 24% and 76%, respectively. Compared with the Group 2 patients, Group 1 had a significantly higher mean percentage of hypochromic erythrocytes (Hypo-He), and significantly lower levels of hemoglobin (Hb) and Hb content of reticulocytes (RET-He) (p < 0.05 for all). Compared with Group 2 and Group 3 patients, Group 1 had a significantly higher mean percentage of immature reticulocyte fraction (IRF) and immature granulocyte (IG) values (p < 0.05 for all). The RET-He, IRF%, Hypo-He%, and IG% cut-off values for predicting FID during infection were 27.0 pg, 10.6%, 2.5%, and 0.35% respectively. DISCUSSION: The RET-He, Hypo-He, IRF, and IG may be useful parameters for identifying subclinical ID in small children with nonsevere acute infection in pediatric outpatients.

Expanded circulating hematopoietic stem/progenitor cells as novel cell source for the treatment of TCIRG1 osteopetrosis.

Allogeneic hematopoietic stem cell transplantation is the treatment of choice for autosomal recessive osteopetrosis caused by defects in the TCIRG1 gene. Despite recent progress in conditioning, a relevant number of patients are not eligible for allogeneic stem cell transplantation because of the severity of the disease and significant transplant-related morbidity. We exploited peripheral CD34+ cells, known to circulate at high frequency in the peripheral blood of TCIRG1-deficient patients, as a novel cell source for autologous transplantation of gene corrected cells. Detailed phenotypical analysis showed that circulating CD34+ cells have a cellular composition that resembles bone marrow, supporting their use in gene therapy protocols. Transcriptomic profile revealed enrichment in genes expressed by hematopoietic stem and progenitor cells (HSPCs). To overcome the limit of bone marrow harvest/ HSPC mobilization and serial blood drawings in TCIRG1 patients, we applied UM171-based ex-vivo expansion of HSPCs coupled with lentiviral gene transfer. Circulating CD34+ cells from TCIRG1-defective patients were transduced with a clinically-optimized lentiviral vector (LV) expressing TCIRG1 under the control of phosphoglycerate promoter and expanded ex vivo. Expanded cells maintained long-term engraftment capacity and multi-lineage repopulating potential when transplanted in vivo both in primary and secondary NSG recipients. Moreover, when CD34+ cells were differentiated in vitro, genetically corrected osteoclasts resorbed the bone efficiently. Overall, we provide evidence that expansion of circulating HSPCs coupled to gene therapy can overcome the limit of stem cell harvest in osteopetrotic patients, thus opening the way to future gene-based treatment of skeletal diseases caused by bone marrow fibrosis.

The contribution of neurocognitive situation, physical capacity and daily life activities to quality of life in childhood acute lymphoblastic leukemia survivors

Background/aim: There are no extensive studies on the QL in children who completed acute lymphoblastic leukemia (ALL) treatment and currently living without any disease in Turkey. Our study aimed to analyze both the QL and the effects of physical, neurocognitive capacities on QL in childhood ALL survivors aged 7­12 years at the time of recruitment. Materials and methods: PedsQL cancer module 3.0 child and proxy report, for ages 5­7 and 8­12 years, WeeFIM scale, BOTMP Short Form, RPM, reading, writing, and mathematics assessment tools, sociodemographic information form were carried out to the children and their family. Results: There was no effect of the months since the completion of therapy on pain, anxiety, cognitive problems, perceived physical appearance, and the total QL scores of children and proxy reports (p > 0.05). Children's physical capacities were significantly worse than healthy controls and have not reached the level of healthy children even after a long time since completion of ALL therapy. There was a significant association between physical capacity and daily independent living status (p < 0.001). Reading, writing, and mathematical skills were significantly associated with the mean time off-treatment (p < 0.001), and the total score of RPM and PedsQL of those with mathematical difficulties were significantly lower than those without any difficulty (p < 0.05). Conclusion: The months after the treatment (off-treatment time) have not affected total and subunit QL scores. As motor skills difficulties will lead to low academic achievement, early recognition direct the parents for immediate intervention. lead to low academic achievement, early recognition could direct the parents for immediate intervention. Planning psychosocial support programs for physical activity and age-appropriate development of patients from the initiation of treatment will increase the QL in childhood ALL with a survival rate of 80% or more.

Inherited coagulation disorders in Turkish children: A retrospective, single-center cohort study.

OBJECTIVE: This study aims to investigate the distribution, clinical characteristics and outcome of inherited coagulation disorders (ICD) in Turkish children. SUBJECTS AND METHODS: Data from all children (age<18 years) with ICD examined in our center were retrospectively reviewed. RESULTS: There were 403 children with ICD (233 males and 170 females) with a median age of four years at diagnosis. The percentages of von Willebrand disease (vWd), hemophilia and rare bleeding disorders (RBD) were 40 %, 34 % and 26 %, type-1, type-2 and type-3 vWd were 63 % 17 % and 20 %, hemophilia A and B were 84 % and 16 %, and severe, moderate and mild hemophilia were 48 %, 30 % and 22 %, respectively. Factor VII and FXI deficiencies were the most prevalent, comprising 56 % and 22 % of all children with RBD, respectively. Parental consanguinity rates were 72 % in type-3 vWd and 61 % in severe RBD. The overall prevalence of gastrointestinal bleedings was 4.5 % (18/403), intracranial bleeding (ICB) was 4.96 % (20/403), mortality from ICB was 30 % (6/20) and the overall mortality rate was 1.49 % (6/403). No life-threatening bleeding was seen during regular prophylaxis. Chronic arthropathy prevalence in severe hemophilia was 8 % with primary prophylaxis and 53 % with demand therap. Inhibitor prevalence was 14 % in hemophilia-A and 5 % in hemophilia-B. CONCLUSIONS: These data show that vWd is the most common ICD, type-3 vWd and RBD are prevalent due to frequent consanguineous marriages and diagnosis of ICD is substantially delayed in Turkish children. Prophylactic replacement therapy prevents occurrence of life-threatening bleedings and reduces the development of hemophilic arthropathy.

Risks and outcomes of invasive fungal infections in pediatric allogeneic hematopoietic stem cell transplant recipients receiving fluconazole prophylaxis: a multicenter cohort study by the Turkish Pediatric Bone Marrow Transplantation Study Group.

Invasive fungal infections (IFIs) are a major cause of infection-related morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Data from pediatric settings are scarce. To determine the incidence, risk factors and outcomes of IFIs in a 180-day period post-transplantation, 408 pediatric patients who underwent allogeneic HSCT were retrospectively analyzed. The study included only proven and probable IFIs. The cumulative incidences of IFI were 2.7%, 5.0%, and 6.5% at 30, 100, and 180 days post-transplantation, respectively. According to the multivariate analysis, the factors associated with increased IFI risk in the 180-day period post-HSCT were previous HSCT history (hazard ratio [HR], 4.57; 95% confidence interval [CI] 1.42-14.71; P = .011), use of anti-thymocyte globulin (ATG) (HR, 2.94; 95% CI 1.27-6.80; P = .012), grade III-IV acute graft-versus-host-disease (GVHD) (HR, 2.91; 95% CI 1.24-6.80; P = .014) and late or no lymphocyte engraftment (HR, 2.71; 95% CI 1.30-5.62; P = .007). CMV reactivation was marginally associated with an increased risk of IFI development (HR, 1.91; 95% CI 0.97-3.74; P = .063). IFI-related mortality was 1.5%, and case fatality rate was 27.0%.The close monitoring of IFIs in pediatric patients with severe acute GVHD who receive ATG during conditioning is critical to reduce morbidity and mortality after allogeneic HSCT, particularly among those with prior HSCT and no or late lymphocyte engraftment.

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry.

BACKGROUND: Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. METHOD: Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. RESULTS: The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow-up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. CONCLUSION: In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.

Comparison of FDG PET/MRI and FDG PET/CT in Pediatric Oncology in Terms of Anatomic Correlation of FDG-positive Lesions.

The aims of our study were to compare F-18 fluorodeoxyglucose (FDG) positron-emission tomography/magnetic resonance imaging (PET/MRI) and PET/computed tomography (CT) in pediatric oncology patients in terms of anatomic correlation of FDG-positive lesions, and also to compare diffusion-weighted imaging (DWI) with PET to assess the correlation between apparent diffusion coefficient (ADC) values and standardized uptake value (SUV). Sequential PET/CT and PET/MRI images and/or whole-body DWI and ADC mapping in 34 pediatric patients were retrospectively analyzed. FDG-positive lesions were visually scored for CT, T1-weighted, T2-weighted, and DWI images separately in terms of anatomic correlation of FDG-avid lesions. Correlation analysis was performed for SUV parameters and ADC values. Among 47 FDG-positive lesions identified concurrently on PET/CT and PET/MRI, 37 were positive on CT and 46 were positive on at least one MRI sequence (P=0.012). Among 32 FDG-positive lesions for which DWI were available, 31 could be clearly depicted on DWI, resulting in significant difference compared with CT alone in the detection of FDG-positive lesions. No correlation was found between ADC and SUV. FDG PET/MRI exhibits better performance than PET/CT in terms of anatomic correlation of FDG-avid lesions. Therefore, PET/MRI may be more advantageous than PET/CT, not only due to reduced ionizing radiation dose but also for a better depiction of FDG-avid lesions in pediatric PET imaging.

The Role of Human Parvovirus B19 in the Pediatric Patients with Pancytopenia?

BACKGROUND: Parvoviruses are small DNA viruses causing erythema infectiosum, which is known as the fifth disease. The aim of this study was to investigate the presence of Parvovirus B19 DNA by Real-Time-PCR retrospectively in clinical samples of children diagnosed as acute leukemia and aplastic anemia when investigating the cause of pancytopenia and to investigate its relationship with the clinical manifestations. METHODS: The study samples were collected between March 2014 and March 2018 in Gazi University, Faculty of Medicine, Department of Pediatric Hematology. Sixty pediatric patients; 37 males and 23 females, were included in the study. Nucleic acid isolation was performed by using MagNA-Pure Compact Nucleic Acid Isolation Kit (Roche, Germany). Extracted DNA was studied with LightCycler® 2.0 using the Real-Time PCR method and LightCycler® Parvovirus B19 Quantification Kit (Roche, Germany), and the results were evaluated quantitatively. Parvovirus B19 DNA detection interval of the kit was 101 - 106 copies/mL. RESULTS: Sixty serum samples were investigated and 8.3% (5/60) Parvovirus B19 DNA positivity was determined. Of the five patients with Parvovirus B19 DNA positivity, three had acute lymphoblastic leukemia and two were diagnosed as aplastic anemia. Regarding viral load; 2/5, 1/5, 1/5, and 1/5 of the samples had a viral load of 102, 103, 104, and 105 copies/mL, respectively. Parvovirus B19 DNA positivity was detected in samples from March (2/5), April (2/5), and August (1/5). CONCLUSIONS: Patients with acute leukemia and aplastic anemia in childhood using immunosuppressive drugs, blood, and blood products during chemotherapy, encounter Parvovirus B19 infections in the follow-up period and are diagnosed by serological and molecular methods. As a result of the study, we suggest that the detection of Parvovirus B19 DNA by Real-Time PCR method in children being admitted with pancytopenia and diagnosed as acute leukemia and aplastic anemia is useful in the follow-up and treatment.