Ekstrakraniyal malign germ hücreli tümör tanılı hastaların klinik özellikleri ve tedavi sonuçları; 20 yıllık tek merkez deneyimi

Introduction: Germ cell tumors account for 2–3% of all pediatric tumors. The aim of this study was to evaluate the clinical features and treatment outcomes of pediatric patients treated and followed up for extragonadal MGCTs in our center. Materials and Methods: A total of 41 patients diagnosed with MGCTs in the pediatric oncology department of Akdeniz University between June 1999 and June 2019 were evaluated retrospectively. Results: Twenty-nine (71%) of the patients were girls and female dominance (p<0.001). The median age was 3.22 (0–18) years. The most patients in the ≤ 5year age group (p<0.001). Nineteen (44%) of the tumors were gonadal and 22 (54%) were extragonadal. The most common histolology of MGCTs were yolk sac tumor (36%), mixed GCTs (29%), immature teratoma (20%), and dysgerminoma (15%). Twenty-five (61%) patients presented with advanced stage disease and 37 patients (90%) were treated with chemotherapy. The patients with stage I testicular and stage I ovarian germ cell tumors underwent complete tumor resection followed by a watch-and-wait approach with alpha fetoprotein monitoring without chemotherapy. Of six patients with relapse/refractory disease, two patients survived. Two patients who underwent autologous stem cell transplantation showed complete response but later died due to infection. The median follow-up period of the patients was 34.9 (4–190.6) months and the 10-year overall and disease-free survival rates were 77.1±6.8% 77.1±6.8%. Two relapsed refractory patients who underwent autologous transplantation survived at a mean of 33.21 months. Conclusions: The clinical features and treatment outcomes of the patients in our study were consistent with the literature. The fact that most of our patients were symptomatic at presentation and had advanced stage disease when diagnosed highlights the importance of detailed evaluation and examination. Although good outcomes are achieved in patients with early stage disease, new treatment approaches are needed for patients with advanced and relapsing diseaseGiriş: Germ hücreli tümör tüm pediatrik tümörlerin %2-3’ünü oluşturur. Özellikle platin bazlı kemoterapi rejimlerinin uygulanmasından sonra sağ kalım oranları %85’lerden fazladır. Malign germ hücreli tümörler (MGHT) çocuklarda oldukça heterojen bir gruptur. Bu çalışma ile ekstrakraniyal MGHT tanılı hastalarımızın klinik özellikleri ve tedavi sonuçlarının değerlendirilmesi amaçlandı. Gereç ve Yöntem: Akdeniz Üniversitesi Çocuk Onkoloji Kliniği’nde 1999 –2019 Haziran tarihleri arasında ekstrakraniyal MGHT tanısı alan 41 hasta geriye dönük olarak değerlendirildi. Bulgular: Hastaların 29 (%71) `i kız olup K/E cinsiyet oranı: 1,75 olup anlamlı olarak kız cinsiyet hakimdi (p<0.001). Ortanca tanı yaşı 3,22 yıl (0-18 yaş) olup hastalar ağırlıklı olarak (%56 hasta) ≤ 5 yaş idi (p<0.001). Tümörlerin 19 (%44) `ü gonadal, 22 (%54) `ü ekstragonadal olup en sık ekstagonadal yerleşim yeri sakrokoksigeal bölge (%22) idi. Histolojik değerlendirmede sırasıyla yolk sak tümörü (%36), mikst GHT (%29), immatür teratom (%20) ve disgerminom (%15) saptandı. Hastaların 25 (%61)`i ileri evre hastalık ile başvurmuştu. Hastaların 37 (%90)’ına kemoterapi verildi. Evre I testis ve evre I over GHT hastalarında tümörün cerrahi olarak tam çıkartılmasının ardından αFP değerleri takip edilerek “bekle ve izle” yaklaşımı ile kemoterapi verilmedi. Tanı sonrası relaps refrakter hastalık ile seyreden 6 hastanın ikisi progresif hastalıktan kaybedildi. Otolog kök hücre nakli yapılan iki hastada nakil sonrası kür sağlanmasına rağmen enfeksiyon nedeni ile kaybedildi. Hastaların ortanca izlem süresi 34.9 ay (4-190,6 ay), 5 ve 10 yıllık genel ve hastalıksız yaşam oranları 81.9±6.3%, 81.9±6.3% ve 77.1±6.8% 77.1±6.8 ve %77,1±6,8 olarak bulundu. Nakil yapılan iki hastanın sağkalım süresi ortalama 33.21 ay olarak hesaplandı. Sonuç: Ekstrakraniyal MGHT`lerin tedavisinde, konservatif cerrahi, evre I hastalar için “bekle ve gör” yaklaşımı ve platin bazlı kemoterapi rejimleri ile başarılı sonuçlar alınmaktadır. İlk başvuruda hastaların yakınmalarının olmasına rağmen çoğu hastanın ileri evre hastalık ile başvurduğunun saptanması hekimlerin ayrıntılı değerlendirme ve muayenelerinin önemine dikkat çekmektedir. Erken evre hastalarda sonuçlar başarılı iken ileri evre ve relaps hastalarda yeni tedavi yaklaşımlarına ihtiyaç vardır

Endocrinopathies in Turkish Children with Thalassemia Major

Aim: Endocrinopathies are common in patients with thalassemia major (TM) and affect their life quality. Our aim was to identify the frequency of growth retardation and endocrine complications in these patients. Materials and Methods: Sixty-two patients aged 3-18 years with TM were evaluated retrospectively for height, weight, body mass index (BMI), and pubertal stage. Blood tests for endocrine function, and oral glucose tolerance test (OGTT) results were recorded. Results: The mean age of 62 subjects (33 females/29 males) was 10.4±3.9 years. The frequency of ≤-2 standard deviation scores was 37.1% for height, 33.9% for weight and 11.3% for BMI. Short stature, being underweight, and low BMI were significantly more prevalent in children over 7 years old (p<0.001). Delayed puberty/hypogonadism was present in 37% of 19 adolescents. Thirteen percent of the subjects had vitamin D deficiency (<10 ng/mL), hyperparathyroidism was observed in 29% of the subjects, while subclinical hypothyroidism (thyroid-stimulating hormone 5-10 IU/mL) was determined in 3 (5.5%) of the 55 subjects. In OGTT, impaired fasting glucose was seen in 7 subjects (14.5%), impaired glucose tolerance in 3 (6.3%), diabetes mellitus in 1 (2.1%), and hypoglycemia at 120-min was observed in 5 subjects (10.4%). Overall, 67.7% of the 62 subjects had height standard deviation score ≤-2 and/or at least one endocrinopathy. Conclusion: Growth retardation and endocrine problems are still a serious problem in TM patients, and develop particularly in those older than 7 years. Additionally, attention must be paid to hypoglycemia in these patients as well as diabetes

Paroxysmal nocturnal hemoglobinuria case with thrombosis under eculizumab treatment

43. Ulusal Hematoloji Kongresi’nde sunulmuştur.Paroksismal noktürnal hemoglobinüri (PNH) nadir görülen kronik, ilerleyici ve yaşamı tehdit eden multisistemik bir hastalıktır. Tanı konduktan sonraki ilk beş yıl içerisinde mortalite %35 iken on yıldan sonra % 50’ye ulaşmaktadır. PNH’daki progresif morbidite ve mortalitenin altta yatan nedeni kronik hemoliz iken eşlik eden tromboz ölümlerin % 40-67’sinden sorumlu olabilmektedir. Olguların % 40’ı klinik olarak saptanabilen trombotik olaylar yaşar. Tromboz tedavisinde antikoagülan uygulaması yanı sıra eğer kullanılmıyorsa ekulizumab’ın da başlanması önerilmektedir. Ekulizumab tedavisi altında tromboz gelişmesi nadir bir komplikasyondur. Burada kemik iliği yetmezliği ile başvuran, kök hücre nakli (KHN) hazırlık aşamasında ekulizumab tedavisi altında tromboz gelişen ve hızla ilerleyen bir PNH olgusu literatür eşliğinde bildirilmektedir.Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic, progressive and life-threatening multisystem disease. Within the first five years after diagnosis, mortality is 35%, but after ten years it reaches 50%. The underlying cause of progressive morbidity and mortality in PNH is chronic hemolysis, which is responsible for 40-67% of accompanying thrombotic deaths. 40% of the cases experience clinically detectable thrombotic events. In addition to anticoagulant therapy in the treatment of thrombosis, it is recommended to start ekulizumab if not used. Development of thrombosis under the treatment of equlizumab is a rare complication. It is reported here that a PNH patient who develops thrombosis under equlizumab therapy and progresses rapidly with stem cell transplantation (SCT) preparation with bone marrow failure

Childhood mastocytosis: results of a single center

AIM: We aimed to retrospectively evaluate histopathological, demographic and clinical findings of children with mastocytosis diagnosed with mastocytosis in our clinic. MATERIAL AND METHODS: The files of 21 patients diagnosed with mastocytosis between 2000 and 2014 in our clinic were retrospectively analyzed. RESULTS: All patients had cutaneous mastocytosis, 19 patients had urticaria pigmentosa and 2 patients had mastocytoma. The male-female ratio was: 1/1.6. The median age for onset of disease was 12.1 months and the disease occured in the newborn period in 3 patients. While all patients had eruption, 10 patients had pruritis, 1 patient had a bullous formation, 1 patient had abdominal pain and 1 patient had attacks of redness throughout the body and a sense of burning in the chest. Two patients had a positive familial history. The diagnosis was confirmed with skin biopsy in all patients. The median follow up time of the patients were 5 years. The patients were treated with H1, H2 antihistaminics, local moisturizing creams and topical corticosteroid drugs. The lesions resolved completely in 4 patients who reached to puberty and 7 patients had marked improvement in a 5.5 year-follow-up period. Ten patients had stabile lesions in a 3.6 year-follow-up period. CONCLUSIONS: Most cases of childhood mastocytosis are observed in the form of cutaneous mastocytosis. The prognosis is good; the disease limits itself and is prone to regress in the adolescent period

A Translocation Renal Cell Carcinoma with Skeletal Muscle Metastasis in a Child

Renal cell carcinoma is a tumor that is well known for a high rate of metastasis to several locations like the lung, liver and bones. Skeletal muscle is a rare location for dissemination of the disease. Herein, we describe a 7-year-old boy who presented with flank pain. On physical examination, an abdominal mass located on the left kidney as well as a solid palpable lesion on the left upper arm were detected. Total nephrectomy with subsequent excision of the arm mass was performed. Pathology examination revealed presence of translocation renal cell carcinoma. The patient received α-interferon followed by multikinase inhibitor (Sorafenib) treatment but was lost due to progressive disease. This is the first description of a pediatric patient with skeletal muscle metastases of translocation renal cell carcinoma in the literature

Turkey Experience in Molecular Analysis of Hemophilia B: F9 Gene Mutation Spectrum and Genotype-Phenotype Correlation

Amaç: Hemofili B (HB), yaklaşık 30.000 canlı erkek doğumda bir görülen, X’e bağlı kalıtsal kanama bozukluğudur. Klinik bulgular, koagülasyon faktörü 9’un aktivite düzeyine göre değişkenlik gösterir. Bugüne kadar koagülasyon faktörü 9’u kodlayan F9 geninde 1.200’den fazla varyant tanımlanmıştır. Varyantların yaklaşık %70’ini nokta mutasyonları oluşturur. Bu çalışmada, Türkiye’deki HB hastalarında F9 gen varyant dağılımının belirlenmesi ve yeni varyantlar tanımlayarak genotip-fenotip ilişkisine katkıda bulunulması amaçlanmıştır. Gereç ve Yöntemler: Türkiye’deki sekiz farklı merkezde HB tanısı ile takip edilen ve Ege Üniversitesi Tıp Fakültesinde Kasım 2018-Ocak 2020 tarihleri arasında moleküler analizi yapılmış 55 hasta çalışmaya alınmıştır. Olguların klinik ve laboratuvar bulguları hastane kayıtlarından elde edilmiştir. F9 geni dizi analizi, yeni nesil dizi analizi platformu (MiSeq™ Illimuna) kullanılarak yapılmıştır. Saptanan yeni varyantların patojeniteleri ACMG 2015 kriterlerine göre sınıflandırılmıştır. Saptanan varyantlar ile fenotip ilişkisi değerlendirilmiştir. Bulgular: Çalışmaya alınan 55 erkek hastanın 33 (%60)’ünde ağır, 15 (%27,3)’inde orta ve 7 (%12,7)’sinde hafif HB fenotipi vardı. F9 dizi analizi sonucunda 54 (%98,2) olguda 46 farklı varyant saptandı. Bu varyantların 30 (%63,8)’u yanlış anlamlı, 9 (%19,1)’u anlamsız, 3 (%6,4)’ü çerçeve kayması ve 4 (%8,5)’ü kırpılma noktası mutasyonuydu. Belirlenen varyantların 10 tanesi daha önce literatürde tanımlanmamıştı. Sonuç: Bu çalışmada, Türkiye’deki HB hastalarında, moleküler analizin tanı başarısı ve F9 geninde varyant dağılımı literatüre benzer şekilde bulunmuştur. Çalışmanın sonuçları, HB’nin genotipik olarak heterojen bir hastalık olduğunu desteklemektedir. on yeni varyant ilk kez bu çalışma ile tanımlanmış ve hastalığın genotip-fenotip ilişkisine katkıda bulunulmuştur.Objective: Hemophilia B (HB) is an X-linked hereditary bleeding disorder seen in approximately one in 30,000 live male births. Clinical findings vary according to the activity level of the coagulation factor 9. More than 1,200 mutations have been identified in the F9 gene to date. Point mutations make up approximately 70% of the mutations. in this study, we aimed to determine the F9 gene mutation spectrum in HB patients in Turkey and to contribute to the genotype-phenotype relationships identifying novel mutations. Material and Methods: Fifty five patients who were followed with a diagnosis of HB in 8 different centers and molecularly analyzed in Ege University Faculty of Medicine in November 2018 and January 2020 enrolled to the study. Clinical and laboratory findings of patients were obtained from hospital records. F9 gene sequence analysis was performed using a next generation sequencing platform (MiSeq™ Illimuna) Pathogenicity of novel variants were classified according to ACMG 2015. the correlation between mutation distribution and phenotype was evaluated. Results: Among 55 HB patients enrolled in the study, severe HB phenotype were determined in 33 (60%), moderate in 15 (27.3%) and mild in 7 (12.7%). Molecular analysis was revealed 46 different variants in 54 patients (98.2%) of these variants, 30 were missense (63.8%), nine nonsense (19.1%), three frameshift (6.4%), and four splice site (8.5%) mutations. Ten of 46 variants identified has not previously been reported. in one patient no mutation was dertected by sequencing. Conclusion: in this study, the molecular diagnostic success rate and F9 gene mutation spectrum in Turkish HB patients was in accordance with the literature. the results of the study support that HB is a genotypically heterogeneous disease. Ten novel mutations were identified for the first time with this study and contributed to the genotype-phenotype relationship sof the disease

Prognostic Significance of Notch1 and Fbxw7 Mutations in Pediatric T-All

The NOTCH signaling pathway plays important role in the development of multicellular organisms, as it regulates cell proliferation, survival, and differentiation. In adults, it is essential for the T- or B-lymphocyte lineage commitment. NOTCH1 and FBXW7 mutations both lead the activation of the NOTCH1 pathway and are found in the majority of T- ALL patients. In this study, the mutation analysis of NOTCH1 and FBXW7 genes was performed in 87 pediatric T-ALLs who were treated on the ALL-BFM protocols. In 19 patients (22%), activating NOTCH1 mutations were observed either in the heterodimerization domain or in the PEST domain and 7 cases (10%) demonstrated FBXW7 mutations (2 cases had both NOTCH1 and FBXW7 mutations). We also analyzed the relationship of the mutation data between the clinical and biological data of the patients. NOTCH1 and FBXW7, NOTCH1 alone were found correlated with lower initial leucocyte counts which was independent from the sex and T- cell immunophenotype. However, NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of pediatric T-ALLs.Wo

Türkiye´de hematologların transfüzyon tıbbı uzmanlık eğitim hedeflerine ulaşımının öz yeterlilik anketi ile değerlendirilmesi

Background: Proper clinical use of blood andblood products requires competent theoreticaland practical knowledge of transfusion medicine.The Curriculum Development and StandardDetermination System Medical SpecializationBoard is prepared Hematology SpecialistEducation Core Curriculum in Turkey. In thisstudy, we aimed to determine the access ofhematologists to the learning objectives definedby curriculum for the transfusion medicine andthe factors affecting it.Methods: Hematologists who have beenmembers of Turkish Hematology Society since2013 have been included in the study, Thesurvey questions were prepared based on thecurriculum for transfusion medicine. The studywas applied to hematologists with “surveymonkey” application. The questionnaireconsisted of a competence self-assessment withLikert scale and theoretical multiple-choiceknowledge questions.Results: Of the 213 hematologists, 54 (25%)were included in the study. Hematologists ratedtheir competences in the clinical competenceareas as 3,65 ± 0,73 (median 3,60) as “I knowbut not t a sufficient level”. The participants‘perception of competence was “I know, butnot at a sufficient level’” with an average of3.31 ± 0.84 (median3.5) in the blood bankingfield, while the average in hemapheresis andtransfusion medicine was 4.04 ± 0.63 (median4) as “enough”. In interventional procedures,hematologists stated that their vocationalcompetences were 2,79± 0,92 (median 2,93)on average as “I have an idea- I know, but notenough”. The correct answer to 13 theoreticalquestions was an average of 6,96 ± 1,89(median 7). Hematologists performing bloodrotation felt significantly more competent thanthe physicians who could not do the rotation inthe blood bank, blood banking t(52) = -3.9, p <.001 , transfusion medicine and interventionalcompetence t(52) = -2.2, p = .04 . Physicianswho believed that they are sufficient in theblood banking area, were more confident intransfusion medicine r(54) = .67, p <.001 andmanaging interventional procedures r(54) =.85, p <.001.Conclusion: In this study, hematologistsgenerally felt more competent in subjects suchas transfusion and therapeutic apheresis,which they often think of as not having enoughknowledge in the area of blood banking.Hematologists have been more confident inthe field of transfusion medicine as their yearsof expertise increased, but they did not feelbetter equipped in the fields of blood bankingand interventional competence. The currentresults suggested that hematologists who areexpected to be the blood bank supervisors do notinternalize the area of blood banking, are notstrong in their competence, and do not want towork in this area unless they are required.In hematology education curriculum, positiverevisions in education can be achieved byrevising blood banking curriculum and learningobjectives, standardizing blood center rotationswith content and duration, and support fromonline distance education programs.Giriş: Kan ve kan ürünlerinin uygun klinik kullanımı, transfüzyon tıbbı konusunda teorik ve pratik bilgi birikimini gerektirir. Türkiye’de Müfredat Geliştirme ve Standart Belirleme Sistemi Tıbbi Uzmanlık Kurulu tarafından, Hematoloji Uzmanlık Eğitimi Temel Müfredatı hazırlanmıştır. Bu çalışmada hematologların transfüzyon tıbbı müfredatı ile belirlenen öğrenme hedeflerine ulaşımını ve bu durumu etkileyen faktörleri belirlemeyi amaçladık. Metot: 2013 yılından bu yana Türk Hematoloji Derneği üyesi olan hematologlara transfüzyon tıbbı için müfredatı esas alınarak hazırlanan anket “Survey Monkey” uygulaması ile uygulandı. Anket, Likert ölçeği ve teorik çoktan seçmeli bilgi soruları ile öz yeterlilik değerlendirmelerinden oluşuyordu. Sonuçlar: 213 hematologdan 54’ü (%25) çalışmaya katılmıştır. Hematologların yeterlilik algıları klinik yetkinlik alanlarında ortalama 3,65 ± 0,73 (ortanca 3,60) olarak “Biliyorum ama yeterli düzeyde değil”; kan bankacılığı alanında ortalama 3.31 ± 0.84 (ortanca 3.5) puan ile “biliyorum ama yeterli düzeyde değil”; hemaferez ve transfüzyon tıbbı alanında ise ortalama 4.04 ± 0.63 (ortanca 4) “yeterli” olarak ölçüldü. Girişimsel işlemlerde hematologlar mesleki yeterliliklerinin ortalama 2,79± 0,92 (ortanca 2,93) “Bir fikrim var, biliyorum ama yeterli değil” olarak ifade ettiler. 13 teorik sorunun doğru cevabı ortalama 6,96 ± 1,89 idi (ortanca 7). Kan bankası rotasyonu yapan hematologlar yapamayanlara göre kan bankacılığı t(52) = -3.9, p < .001, transfüzyon tıbbı ve girişimsel alanlarda t(52) = -2.2, p = .04 kendilerini çok daha yetkin hissediyordu. Kan bankacılığı alanında yeterli olduğuna inanan hekimler, transfüzyon tıbbında r(54) = .67, p <.001 ve girişimsel işlemlerin r(54) = .85, p <.001yönetiminde de kendilerinden daha eminlerdi. Tartışma: Bu çalışmada, hematologlar genellikle kan bankacılığı alanında yeterli bilgiye sahip olmadığını düşünürken transfüzyon tıbbı ve terapötik aferez gibi konularda kendilerini daha yetkin hissetmistirler. Hematologlar, uzmanlık yılları arttıkça transfüzyon tıbbı alanında kendilerine daha fazla güvenmeye başlarken, kan bankacılığı ve girişimsel yeterlilik alanlarında kendilerini hala yeterli donanımda hissetmiyorlardı. Mevcut sonuçlar, hematologların kan bankacılığı alanını içselleştirmediklerini, yetkinliklerinde güçlü olmadıklarını ve gerekli olmadıkça bu alanda çalışmak istemediklerini göstermiştir. Transfüzyon tıbbı müfredatının ve öğrenme hedeflerinin gözden geçirilmesi, kan merkezi rotasyonlarının içerik ve süresinin standartlaştırılması ve çevrimiçi uzaktan eğitim programları ile desteklenmesi hematoloji eğitimine olumlu katkılar sağlayabilir