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    Central nervous system fungal infections in children with leukemia and undergoing hematopoietic stem cell transplantation: A retrospective multicenter study
    (2022) Karaman, Serap; Kebudi, Rejin; Kızılocak, Hande; Karakaş, Zeynep; Demirağ, Bengü; Evim, Melike Sezgin; Yaralı, Neşe; Kaya, Zühre; Karagün, Barbaros Şahin; Aydoğdu, Selime; Çalışkan, Ümran; Ayhan, Aylin Canbolat; Bahadır, Ayşenur; Çakır, Betül; Güner, Burçak T.; Albayrak, Canan; Karapınar, Deniz Yılmaz; Kazancı, Elif Güner; Ünal, Ekrem; Türkkan, Emine; Akıcı, Ferhan; Bor, Özcan; Vural, Sema; Yılmaz, Şebnem; Apak, Hilmi; Baytan, Birol; Tahta, Neryal Müminoğlu; Güzelküçük, Zeliha; Koçak, Ülker; Antmen, Bülent; Tokgöz, Hüseyin; Fışgın, Tunç; Özdemir, Nihal; Güneş, Adalet Meral; Vergin, Canan; Ünüvar, Ayşegül; Özbek, Namık; Tuğcu, Deniz; Bay, Sema Büyükkapu; Tanyıldız, Hikmet Gülşah; Celkan, Tiraje
    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.
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    COVID-19 infection in children with cancer and stem cell transplant recipients in Turkey: A nationwide study
    (Wiley, 2021) Kebudi, Rejin; Kurucu, Nilgün; Tuğcu, Deniz; Hacısalihoğlu, Sadan; Fışgın, Tunç; Ocak, Süheyla; Kara, Ateş; Bozkurt, Ceyhun; Ince, Dilek; Aras, Seda; Aycicek, Ali; Aksoy, Basak Adakli; Karadas, Nihal; Ozturk, Gulyuz; Orhan, Mehmet Fatih; Ataseven, Eda; Akbayram, Sinan; Yilmaz, Ebru; Tufekci, Ozlem; Vural, Sema; Akyay, Arzu; Ayhan, Aylin Canbolat; Kilic, Suar; Uzel, Veysiye Hulya; Duzenli, Yeter; Acipayam, Can; Elli, Murat; Tanyeli, Atilla; Karakas, Zeynep; Somer, Ayper; Kara, Ates
    Adults with cancer are reported to have a higher risk for coronavirus disease (COVID-19) infection and more severe disease and mortality than the general population.1,2 Although children seem to be at a lower risk for COVID-19 than adults,3–5 data specifically addressing children with cancer are limited.6–12 We conducted a retrospective, multicenter, cross-sectional study on behalf of the Turkish Pediatric Hematology Society (TPHD) and Turkish Pediatric Oncology Group (TPOG) Society to analyze the characteristics of COVID-19 in all patients with cancer and stem cell transplant (SCT) recipients in all centers in Turkey, during March 11-May 31, 2020. Approval for the study was obtained by Turkish Ministry of Health (MoH), Istanbul University COVID Scientific Research Committee, and Istanbul University Ethics Committee. The study was carried out through the analysis of a questionnaire with 62 questions, which was sent to all members of the TPOG and TPHD Societies working in all 66 pediatric hematology/oncology departments in university, state, and private hospitals in Turkey. All replied and 53 patients were reported from the 24 centers.
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    Lymphoma predisposing gene in an extended family: CD70 signaling defect
    (Springer/Plenum Publishers, 2020) Khodzhaev, Khusan; Bay, Sema Buyukkapu; Kebudi, Rejin; Altindirek, Didem; Kaya, Ayşenur; Erbilgin, Yücel; Sayitoğlu, Müge; Aksoy, Başak Adaklı; Zengin, Feride Şen
    Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missenseCD70variation was detected (NM_001252.5:c332C>T) in concordance withCD70phenotype and familial segregation was confirmed.CD70variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missenseCD70variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.
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    Tandem high-dose chemotherapy followed by autologous stem cell transplantation: An infant with trilateral retinoblastoma
    (2023) Töret, Ersin; Özdemir, Zeynep Canan; Zengin Ersoy, Gizem; Öztunalı, Çiğdem; Bozkurt, Ceyhun; Kebudi, Rejin
    Background: Retinoblastoma (RB) is the most common intraocular malignancy in childhood. Advanced RB, associated with exceedingly poor prognosis, requires more intensive multiagent chemotherapy than conventional regimens. Rescue of the bone marrow after intensive chemotherapy is achieved with stem cell transplantation. The sequential courses (tandem transplantation) of high-dose chemotherapy followed by autologous stem cell transplantation allow for even greater dose intensity in consolidation with the potential to use different active chemotherapeutics at each transplant and have proven feasible and successful in treating children with recurrent/refractory solid tumors. Case description: We report an infant with trilateral high-risk RB who received tandem high-dose chemotherapy (HDC) followed by autologous stem cell transplantation after the conventional chemotherapy. A 5-month-old female patient presented with strabismus, and the ophthalmoscopic examination showed intraocular tumoral lesions in both eyes. Magnetic resonance imaging (MRI) concluded the trilateral retinoblastoma diagnosis due to a tumoral mass in the optic chiasm. The follow-up ophthalmologic examinations and the MRI detected stable disease after six cycles of multiagent chemotherapy. Conclusions: Rescue with autologous stem cell transplantation after HDC allows for an increase in chemotherapy intensity. Tandem transplantation provides the chance to perform different chemotherapeutics at each transplant and enables an increase in the chemotherapy intensity, thus providing a positive effect on disease-free survival.