Treatment with MRC-12 chemotherapy protocol and 13-year follow-up results in children with acute myeloblastic leukemia

Akut miyeloblastik lösemi (AML) kemik iliğinde olgunlaşmamış hücrelerin klonal çoğalması ile karakterize neoplastik bir hastalıktır. Çocukluk çağı AML'sinde yoğun kemoterapi ve destek tedavisi ile 5 yıllık olaysız yaşam (OS) ve genel yaşam (GS) oranları %60'lara yükselmiştir.Bu çalışmada; Uludağ Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Çocuk Hematoloji Onkoloji Bilimdalında, Ocak 1997- Aralık 2009 tarihleri arasında tanı alan ve tedavi edilen, 50 yeni tanı AML'li olgunun verileri ve tedavi sonuçları değerlendirildi. Bu olguların sonuçlarının incelenmesiyle elde edilen bulgular literatür bilgisiyle karşılaştırıldı.Olguların başvuruları sırasındaki semptomları, öz ve soy geçmişlerine ilişkin öyküleri, fizik bakı bulguları ve laboratuvar verileri kayıt edildi. Olgular Medical Research Council (MRC-12) protokolüne göre tedavi edildi. Bu protokole göre risk grupları, kemoterapi yanıtı, genetik özellikleri, yaş, cinsiyete göre yaşam analizleri değerlendirildi. Nüks ve ölüm oranları ve bu hastaların özellikleri incelendi. Tedaviye ilişkin akut yan etkiler değerlendirildi. İstatistik yöntemi olarak SPSS 13 programı ile Kaplan Meier yaşam analizi ve lojistik regresyon analizleri kullanıldı.Hastaların %40'ı (n:20) kız, %60'ı (n:30) erkek idi. Olguların yaş ortalaması 89±57 ay (4.5 ay-17.5 yıl) olarak saptandı. Ortalama izlem süresi 62±22.5 ay (15 gün ile 13 yıl) olarak bulundu.Beş yıllık olaysız yaşam hızı %52 ve genel yaşam hızı %60 bulundu. Çalışmamızda OS ve GS üzerine en etkili faktörler; kemoterapi yanıtı, risk grubu ve genetik özellikler olduğu bulundu. Yaş, cinsiyet, tanı lökosit sayısının OS ve GS üzerine istatistiksel anlamı olmadığı görüldü.Olguların tümünde her kür sırasında hematolojik, enfeksiyöz ve gastrointestinal yan etkilere rastlandı. Bu yan etkileri; karaciğer ve böbrek fonksiyon bozuklukları izlemiştir. En nadir ise; cilt ve nörolojik yan etkiler gözlenmiştir. Enfeksiyon dışında organ yetmezliğinden ölüm saptanmadı.iiiSerimizde nüks oranı %28 (n=14) bulundu. Tanıdan itibaren 18 aydan önce olan nükslerin yaşam oranları anlamlı olarak daha düşük olarak saptandı (p=0.013). Çalışmamızda 20 (%40) olgumuz öldü. En sık ölüm nedenlerinin nüks lösemi ve nötropenik enfeksiyon olduğu saptandı.Sonuç olarak; kliniğimizde MRC protokolü ile 5 yıllık OS %52 ve GS %60 olarak bulunmuştur. Bu sonuçlar, İngiliz MRC grubun sonuçlarına benzerdir. Ayrıca enfeksiyon önlemlerinin düzenlenmesi ve 2 yaş altı olgularda destek tedavinin güçlendirilmesi ile daha iyi yaşam oranları elde edebileceğimizi düşünmekteyiz.Acute myeloblastic leukemia (AML) is a neoplastic disease characterized by the clonal proliferation of the immature cells in the bone marrow. The 5 years overall (OS) and event free (EFS) survivals have been recently increased to 60% with the intensive chemotherapy protocols and improved supportive care.In the current study, we evaluated the data and treatment results of 50 children diagnosed as de-novo AML in between February 1997 and December 2009 at the Department of Pediatric Hematology in Uludag University. The results were discussed under the knowledge of the other studies in the literature.The symptoms, curriculum vitae, family history, physical and laboratory findings were recorded. The patients were treated according to the Medical Research Council AML (MRC-12) chemotherapy protocol. The informed family consents were taken before starting the treatment. Survival rates were analyzed according to the risk groups, response to chemotherapy, genetic features, age, and gender and white blood cell count (WBC) at diagnosis. Relapse and death rates and the features of these children were separately evaluated. The acute side effects related to the chemotherapy at each course were also analyzed.SPSS-13 program was used for both Kaplan-Meier survival and logistic regression analysis.Twenty patients (40%) were females and the rest (n: 30;60%) were males. Their mean age and follow-up periods were 89±57months (4.5m-17.5y) and 62±22.5months (15d-13years), respectively. The 5 years OS was 60% whereas EFS was found 52%. The most effective factors influencing OS and EFS were determined as chemotherapy response, risk groups and genetic features. The age, gender and WBC count at diagnosis were found insignificant for the survival rates. The most frequent side effects observed in all courses were hematologic, infectious and gastrointestinal of which were then, followed by liver and renal dysfunctions. Skin and neurologic sideveffects were the scarcest ones. None of these side effects excluding neutropenic infection caused mortality.The relapse rate in our data was determined as 28% (n: 14). The survival rate of the children relapsed within 18monts after diagnosis were found significantly lower than the ones relapsed beyond this period (p=0.013). Twenty children (40%) died in our study group. The most frequent reasons for causing death were relapsed /resistant leukemia and neutropenic infections.In conclusion, 5 years OS and EFS in our group treated with MRC-AML-12 protocol were found 60% and 52%, respectively. This result was found similar with the result of English MRC-AML group. However, we can obtain much better survival rates with the improvements in supportive care and infection control, especially in children younger than 2 years old

Childhood Immune Thrombocytopenia: Long-term Follow-up Data Evaluated by the Criteria of the International Working Group on Immune Thrombocytopenic Purpura

OBJECTIVE: Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood, characterized by isolated thrombocytopenia. The International Working Group (IWG) on ITP recently published a consensus report about the standardization of terminology, definitions, and outcome criteria in ITP to overcome the difficulties in these areas. METHODS: The records of patients were retrospectively collected from January 2000 to December 2009 to evaluate the data of children with ITP by using the new definitions of the IWG. RESULTS: The data of 201 children were included in the study. The median follow-up period was 22 months (range: 12-131 months). The median age and platelet count at presentation were 69 months (range: 7-208 months) and 19x109/L (range: 1x109/L to 93x109/L), respectively. We found 2 risk factors for chronic course of ITP: female sex (OR=2.55, CI=1.31-4.95) and age being more than 10 years (OR=3.0, CI=1.5-5.98). Life-threatening bleeding occurred in 5% (n=9) of the patients. Splenectomy was required in 7 (3%) cases. When we excluded 2 splenectomized cases, complete remission at 1 year was achieved in 70% (n=139/199). The disease was resolved in 9 more children between 12 and 90 months. CONCLUSION: Female sex and age above 10 years old significantly influenced chronicity. Therefore, long-term follow-up is necessary in these children

Case Report cerebellar granulocytic sarcoma: a case report

Abstract Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma

Health-Related Quality of Life, Depression, Anxiety, and Self-Image in Acute Lymphocytic Leukemia Survivors

Objective: With increasing survival rates in childhood acute lymphocytic leukemia (ALL), the long-term side effects of treatment have become important. Our aim was to investigate health-related quality of life, depression, anxiety, and self-image among ALL survivors. Materials and Methods: Fifty patients diagnosed with ALL and their siblings were enrolled. The Kovacs Children’s Depression Inventory, State-Trait Anxiety Inventory, Offer Self-Image Questionnaire, and Pediatric Quality of Life InventoryTM were used for collecting data. ANOVA tests were used to determine if there were any significant differences between groups. Results: ALL survivors had higher depression, more anxiety symptoms, lower quality of life, and more negative self-image when compared to their siblings. Conclusion: Continuous diagnostic and interventional mental health services might be necessary for possible emotional side effects of treatment during and after the treatment. Rehabilitation and followup programs should be implemented for children during and after treatment for ALL

Bursa ilinde 1-16 yaş çocuklarda demir eksikliği ve demir eksikliği anemisi prevalansı

Bu çalışmanın amacı Bursa'da yaşayan 1-16 yaş arası çocuklarda demir eksikliği (DE), demir eksikliği anemisi (DEA) prevalansını belirlemek ve beslenme alışkanlıkları ve aile eğitim düzeyinin demir eksikliği anemisi gelişimine etkilerini araştırmaktır. Bu çalışma düşük sosyoekonomik bir bölgede bulunan 3 farklı aile sağlığı merkezine başvuran 1-16 yaş arası 500 sağlıklı çocukta yapılmıştır. Çalışmaya alınan çocuklar sırasıyla 1-1,9, 2-5, 6-10,9 ve 11-16 yaş grubundaki çocuklar olmak üzere dört gruba ayrıldı.Tam kan sayımı, serum demir (µg/dl), demir bağlama kapasitesi (µg/dl), ferritin (ng /ml), transferrin satürasyonu (%) çalışıldı. Araştırmaya alınan çocukların beslenme ve anne-baba eğitim durumlarını araştırmak için anket uygulandı. Bu çalışmada anemi, DE ve DEA National Health and Nutrition Examination Survey (NHANES III) kriterlerine göre araştırıldı. Mentzer indeksi talasemi minör ve DEA'yı ayırt etmek için kullanıldı. Araştırmaya alınan 247 erkek (%49) ve 253 kız (%51)olgularımızın yaş ortalaması 7,4±3,9 yıl idi. NHANES III kriterlerine göre anemi prevalansı %31(n=155) idi. Grup I ve Grup IV'te anemi görülme sıklığı diğer gruplara göre daha yüksekti(p<0.05).Araştırmadaki 500 olgunun %12'sinde (n=61) DE, %7,4'ünde (n=37) DEA bulundu. Serum ferritin seviyesi DEA'nın saptanmasında en yüksek duyarlılık ve özgüllüğe sahipti (p<0,001).Çalışmadaki 500 olgunun 18'inde (%3,6) talasemi minör saptandı. Anemik gruplarda anne eğitim düzeyi anlamlı olarak daha düşüktü(p<0.05).DE ve DEA ülkemiz için halen önemli bir sağlık sorunudur. Annelerin eğitim düzeyi çocuk beslenmesinde önemli role sahiptir. Bu sorunu çözmek için; Ebeveynler, çocuk beslenmesine yönelik eğitim programları ile desteklenmelidir

Factor 8 Gene Mutation Spectrum of 270 Patients with Hemophilia A: Identification of 36 Novel Mutations

Objective: Hemophilia A (HA) is the most severe X-linked inherited bleeding disorder caused by hemizygous mutations in the factor 8 (F8)gene. The aim of this study is to determine the mutation spectrum of the F8 gene in a large HA cohort from Turkey, and then to establish a phenotype-genotype correlation.Materials and Methods: All HA cases (270 patients) analyzed molecularly in the Ege University Pediatric Genetics Molecular Laboratory between March 2017 and March 2018 were included in this study. To identify intron 22 inversion (Inv22), intron 1 inversion (Inv1), small deletion/insertions, and point mutations, molecular analyses of F8 were performed using a sequential application of molecular techniques. Results: The mutation detection success rate was 95.2%. Positive Inv22 was found in 106 patients (39.3%), Inv1 was found in 4 patients (1.5%), and 106 different disease-causing sequence variants were identified in 137 patients (50.6%). In 10 patients (3.7%), amplification failures involving one or more exonic regions, considered to be large intragenic deletions, were identified. Of 106 different F8 mutations, 36 were novel. The relationship between F8 genotype and inhibitor development was considered significant.Conclusion: A high mutation detection rate was achieved via the broad molecular techniques applied in this study, including 36 novel mutations. With regard to mutation types, mutation distribution and their impact on clinical severity and inhibitor development were found to be similar to those previously reported in other hemophilia population studies

Cerebellar Granulocytic Sarcoma: A Case Report

Granulocytic sarcoma is a rare tumor composed of immature granulocytic cells that is usually associated with acute myelogenous leukemia. Intraparenchymal cranial localization without skull, meningeal, or bone marrow invasion is extremely rare. The mechanisms of intraparenchymal cranial localization of GS remains unknown, as only 10 cases with cerebellar granulocytic sarcoma have been previously reported. Herein, we report a four year old boy with cerebellar localization of granulocytic sarcoma