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    Central Nervous System Fungal Infections in Children With Leukemia and Undergoing Hematopoietic Stem Cell Transplantation: A Retrospective Multicenter Study
    (Lippincott Williams & Wilkins, 2022) Karaman, Serap; Kebudi, Rejin; Kizilocak, Hande; Karakas, Zeynep; Demirag, Bengu; Evim, Melike S.; Yarali, Nese
    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 combi-nation 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.
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    Central Nervous System Fungal Infections in Children with Leukemia, Risk Factors and Outcome: A Multicentric Study
    (Amer Soc Hematology, 2018) Kebudi, Rejin; Karaman, Serap; Kizilocak, Hande; Karakas, Zeynep; Evim, Melike Sezgin; Demirag, Bengu; Kaya, Zuhre
    [Abstract Not Availabe]
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    Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM)
    (Wiley, 2019) Antmen, Bulent; Karakas, Zeynep; Yesilipek, Mehmet Akif; Kupesiz, Osman Alphan; Sasmaz, Ilgen; Uygun, Vedat; Kurtoglu, Erdal
    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 mu g/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 mu g/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 mu g/L), SCA (1655.5 to 1260 mu g/L), and across age groups of 2-6 years (1971.5 to 1499 mu g/L), 7-12 years (1688.5 to 1159.8 mu g/L), and 13-18 years (1496.5 to 1107 mu g/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.
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    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
    (Wiley, 2019) Karapinar, Deniz Yilmaz; Patiroglu, Turkan; Metin, Ayse; Caliskan, Umran; Celkan, Tiraje; Yilmaz, Baris; Karakas, Zeynep
    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.
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    Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children with Immune Thrombocytopenia in Turkey
    (Galenos Yayincilik, 2020) Yozgat, Ayca Koca; Leblebisatan, Goksel; Akbayram, Sinan; Ozel, Simge Cinar; Karakas, Zeynep; Erduran, Erol; Yilmaz, Sebnem
    Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children. Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia. Results: The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5 +/- 4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of >= 50x109/L was 11.6 +/- 8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8 +/- 9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients. Conclusion: Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.