Amaç: Relaps/refrakter Hodgkin lenfomanýn (HL) otolog hematopoetik kök hücre nakli (OHKHN) sonrasýndaki prognozunu gösterecek belirteçler ve çocukluk çaðýnda yeni bir prognostik skorlama araþtýrýldý.
Gereç ve Yöntem: Bu çalýþmada, Ocak 1990-Aralýk 2014 tarihleri arasýnda OHKHN uygulanan 61 hastanýn OHKHN sonrasý prognozunu etkileyen faktörlerin saðkalým üzerine etkisi araþtýrýldý. Ayný zamanda Yaþa Göre Düzeltilmiþ Uluslararasý Prognostik Ýndeks ve Çocukluk Dönemi Uluslararasý Prognostik Ýndeks’lerinin (ÇDUPÝ) prognoz üzerindeki etkisi deðerlendirildi.
Bulgular: Altmýþ bir hastanýn ortanca yaþý OHKHN sýrasýnda 14,8 yýl (5-20 yýl) idi. Hastalardan, 28 olguda bir relaps, 8 olguda ≥2 relaps ve 25 olguda refrakter hastalýk vardý. Kemosensitivite/kemoterapiye dirençlilik oraný 36/25 idi. Nakil öncesi radyoterapi almamak, nakil öncesi remisyonda olmamak, nakil sonrasý beyaz kan hücresi sayýsýnýn 10x103/μL üzerinde olmasý, nakil sonrasý 100. gün pozitron emisyon tomografisi pozitifliði, tanýda 2,5 g/dL’den düþük serum albümin düzeyi progresyonsuz saðkalým üzerinde etkili belirteçler iken transplantasyon zamaný remisyonda olmamak, tanýda kemik iliði pozitifliði ve OHKHN sonrasý relaps ise genel saðkalým üzerinde etkili parametreler olarak bulundu.
Sonuç: Relaps/refrakter HL’li çocuklarda progresyonsuz ve genel saðkalýmý etkileyen faktörler açýkça gösterildi. Serum laktat dehidrogenaz üst sýnýrýný 500 IU/L olarak kullanan ÇDUPÝ prognozu göstermede etkili bulundu. Relaps hastalarda ilk tam remisyonda OHKHN yapýlmasýný ve taný anýnda yüksek prognostik skoru olan olgularýn da OHKHN açýsýndan
deðerlendirmeye alýnmasýný önermekteyiz.

Objective: The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin’s lymphoma (HL) were evaluated.
Materials and Methods: The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis.
Results: The median age of the 61 patients was 14.8 years (minimummaximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x103/ μL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival.
Conclusion: The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis.

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Amaç: Bu çalýþmada, kemik iliðindeki (KÝ) blast oraný >%30 olan olgularý da içeren akut miyeloid lösemili (AML) yaþlý hastalarda, azasitidinin (AZA) etkinliðinin ve güvenliðinin araþtýrýlmasýný amaçladýk.
Gereç ve Yöntem: Bu geriye dönük, çok merkezli çalýþmaya, yoðun kemoterapi için uygun olmayan ya da konvansiyonel tedavilere raðmen hastalýðý ilerleyen ≥60 yaþtaki 130 hasta dahil edildi.
Bulgular: Ortanca yaþ 73 idi, hastalarýn %61,5’inde KÝ blast oraný >%30 olarak bulundu. Hastalar, ortanca 4 döngü (1-21 aralýðýnda) AZA almýþtý. Baþlangýç genel yanýt oraný [tam yanýtý (TY)/eksik düzelmenin olduðu TY/kýsmi yanýtý içeren] %36,2 idi. Herhangi bir hematolojik düzelme (HD), tüm hastalarýn %36,2’sinde tespit edildi. HD tedaviye yanýtsýz hastalarýn %27,1’inde de saptandý. Ortanca genel saðkalým, yanýt verenlerde 18 ay, yanýt vermeyenlerde 12 ay idi (p=0,005). Tedaviye yanýtsýz hasta grubunda HD’nin, HD olmayanlara kýyasla genel saðkalýmý arttýrdýðý görüldü (ortanca saðkalým 14 aya kýyasla 10 ay, p=0,068). Doðu Kooperatif Onkoloji Grubu performans durumunun <2 olmasý, AZA döngü sayýsýnýn artmasý (≥5 döngü) ve herhangi bir HD olmasý, daha iyi genel saðkalýmý öngörüyordu. Yaþýn, AML tipinin, KÝ blast yüzdesinin etkisi yoktu.
Sonuç: AZA, yaþlý, eþlik eden hastalýklarý olan AML’li hastalarda, KÝ blast sayýsýndan baðýmsýz olarak etkindir ve iyi tolere edilmektedir ve HD’nin, AZA ile tedaviye devam etmek için yeterli bir yanýt olduðu göz önünde bulundurulmalýdýr.

Objective: In this study, we aimed to investigate the efficacy and safety of azacitidine (AZA) in elderly patients with acute myeloid leukemia (AML), including patients with >30% bone marrow (BM) blasts.
Materials and Methods: In this retrospective multicenter study, 130 patients of ≥60 years old who were ineligible for intensive chemotherapy or had progressed despite conventional treatment were included.
Results: The median age was 73 years and 61.5% of patients had >30% BM blasts. Patients received AZA for a median of four cycles (range: 1-21). Initial overall response [including complete remission (CR)/CR with incomplete recovery/partial remission] was 36.2%.
Hematologic improvement (HI) of any kind was documented in 37.7% of all patients. HI was also documented in 27.1% of patients who were unresponsive to treatment.nMedian overall survival (OS) was 18 months for responders and 12 months for nonresponders (p=0.005). In the unresponsive patient group, any HI improved OS compared to patients without any HI (median OS was 14 months versus 10 months, p=0.068). Eastern Cooperative Oncology Group performance status of <2, increasing number of AZA cycles (≥5 courses), and any HI predicted better OS. Age, AML type, and BM blast percentage had no impact.
Conclusion: We conclude that AZA is effective and well tolerated in elderly comorbid AML patients, irrespective of BM blast count, and HI should be considered a sufficient response to continue treatment with AZA.

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Amaç: Yapýlan birçok çalýþmada Burkitt lenfomanýn seyrinin düzeldiði, hatta kemik iliði nakli ihtiyacýnýn ortadan kalktýðý ileri sürülmektedir. Ancak birkaç ileriye dönük çalýþma haricinde, güncel tedavi yöntemleri altýnda hastalýðýn lösemik formunun seyri hakkýnda araþtýrma yapýlmamýþtýr. Bu çalýþmanýn amacý Burkitt hücreli lösemi (BHL) hastalarýnýn klinik seyrinin, benzer tedavi alan ve transplantasyon uygulanmayan diðer akut lenfoblastik lösemi (ALL) hastalarý ve ilk remisyonlarýnda allojenik kök hücre nakli (AKHN) uygulanan ALL hastalarýyla kýyaslanmasýdýr.
Gereç ve Yöntem: Geriye dönük olarak tasarlanan bu çalýþmaya yaþlarý 16 ile 63 arasýnda deðiþen, 2000 ile 2014 yýllarý arasýnda Hacettepe ve Gazi Üniversitesi Hastaneleri’ne baþvurup kür amacýyla intensif tedavi verilen BHL hastalarý alýnmýþtýr. Transplantasyon haricinde benzer tedavi protokolüyle tedavi edilen tüm ALL hastalarý (NT-ALL) ve ayný dönemde ilk tam remisyonlarýnda AKHN uygulanan hastalar (T-ALL) kontrol gruplarý olarak çalýþmaya alýnmýþlardýr.
Bulgular: Santral sinir sistemi ya da ekstra medüller tutulum hýzlarý, taný anýndaki laktat dehidrogenaz düzeyleri ve beyaz küre sayýsý BHL hastalarýnda NT-ALL hastalarýna göre istatistiksel olarak anlamlý olacak þekilde daha yüksekti. BHL hastalarý T-ALL hastalarýyla benzer hastalýksýz saðkalým (HS) süresine sahip olmakla beraber, NTALL hastalarýnda HS süresi önemli oranda azalmýþtý. Kümülatif nüks insidansý ve kümülatif nüks dýþý ölümler NT-ALL hastalarýnda T-ALL ve BHL hastalarýnda kýyasla daha fazlaydý.
Sonuç: Sonuç olarak, geniþ kabul gören modern bir rejim olan R-HyperCVAD ile tedavi edilen BHL hastalarýnda HS süresi allojenik transplantasyon uygulanmýþ diðer ALL hastalarý ile benzer bulundu. Bizim çalýþmamýzýn sonuçlarý, literatürde ileri dönük dizayn edilmiþ ancak kontrol gruplarý ile karþýlaþtýrma olmadan yapýlmýþ ve BHL’de transplantasyon gerekmediðini öne süren az sayýdaki çalýþma ile örtüþmektedir.

Objective: Many studies reported an improved prognosis in patients with Burkitt’s lymphoma obviating the need of stem cell transplantation. However, prognosis of the advanced disease [i.e. Burkitt’s cell leukemia (BCL)] has not been reported with current treatment modalities except for a few prospective trials. The aim of this study is to compare the prognoses of BCL patients with similarly treated and nontransplanted patients with other types of acute lymphoblastic leukemia (ALL) and with ALL patients that underwent
allogeneic stem cell transplantation (ASCT) in their first remissions.
Materials and Methods: In this retrospective analysis, BCL patients aged between 16 and 63 who were admitted between 2000 and 2014 to the hospitals of Hacettepe or Gazi University and were treated with intensive therapies aimed at cure were included. All ALL patients who were treated with a similar protocol not including transplantation during the same period (NT-ALL group) and all ALL patients who underwent ASCT in the first complete remission during the same period (T-ALL group) served as control groups.
Results: The central nervous system or extramedullary involvement rates, lactate dehydrogenase levels, and white blood cell counts at diagnosis were higher in the BCL group than the NT-ALL group and these differences were significant. BCL patients had disease-free survival (DFS) durations comparable with the T-ALL cohort but NTALL patients had significantly shorter DFS durations. Both cumulative relapse incidence and cumulative nonrelapse mortality were higher in NT-ALL patients compared to the T-ALL group and BCL patients.
Conclusion: DFS in BCL patients treated with a widely accepted modern regimen, R-HyperCVAD, is comparable to results in other ALL patients receiving allogeneic transplantation. Our results are in agreement with a few prospective noncomparative studies suggesting no further need for stem cell transplantation in BCL.

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Amaç: Multipl miyelom (MM) günümüzde uygulanan yeni MM tedavilerine raðmen, refrakter hastalýðýn relapsý nedeniyle kür edilemeyen bir hastalýktýr. In silico çalýþmalar, MM’nin kronik seyrine karþý verilen klinikopatolojik savaþta alýnan kararlar açýsýndan oldukça önemlidir. Buradaki in silico çalýþmanýn amacý, bortezomib için yapýlmýþ sitotoksisite çalýþmalarýnda ortaya çýkan genlerle eþleþen özgün genleri ortaya koymaktýr.
Gereç ve Yöntem: Biz bu çalýþmada, potansiyel biyobelirteçleri ortaya koymak için araþtýrma konusuna uygun bir þekilde türetilmiþ özetleyici veri seti üreterek in silico literatür taramasý gerçekleþtirdik. “Wellcome Trust Sanger” enstitüsünün 8 miyelom hücre serisi de olmak üzere toplam 789 kanser hücre serisini ilaç tarama verileriyle beraber içeren E-MTAB-783 veri seti ArrayExpress’den elde edilip, GeneSpring v.12.5 kullanýlarak “Robust Multi-array analysis” normalize edildi. Ýlaç toksisite verisi “Genomics of Drug Sensitivity in Cancer” projesinden elde edildi. Biz bu çalýþmada, eþleþen genleri saptamak amacýyla, gen ekspresyon deðerleri ve IC50 verileri arasýndaki istatistiksel açýdan anlamlý korelasyonlarý lineer regresyon temelli yaklaþým uygulayarak araþtýrdýk. Sekiz hücre serisinde gen kesiþimi tespit edildi ve bu hücre serileri ileri analiz için kullanýldý.
Bulgular: Kullandýðýmýz lineer regresyon modeli sayesinde 73 genin ve bazý gen ekspresyon düzeylerinin, bortezomibin IC50 deðeri ile çok yakýn korelasyon gösterdiðini tespit ettik. Tüm 73 geni hiyerarþik küme analizi ile incelediðimizde, iki ana kümede toplanan hücrelerin, görece duyarlý ve dirençli hücreler olduðunu gördük. Bütün önemli genlerin moleküler yolak ve fonksiyon analizi, yolaklara dahil olan genlerle beraber incelenmiþtir.
Sonuç: Gerçekleþtirdiðimiz bu in silico çalýþmada ortaya konan veriler, MM genomiðinin anlaþýlmasý ve bortezomib gibi hedefe yönelik miyelom tedavilerinin daha iyi yönetilebilmesi açýsýndan önemlidir.

Objective: Multiple myeloma (MM) is currently incurable due to refractory disease relapse even under novel anti-myeloma treatment. In silico studies are effective for key decision making during clinicopathological battles against the chronic course of MM. The aim of this present in silico study was to identify individual genes whose expression profiles match that of the one generated by cytotoxicity experiments for bortezomib.
Materials and Methods: We used an in silico literature mining approach to identify potential biomarkers by creating a summarized set of metadata derived from relevant information. The E-MTAB-783 dataset containing expression data from 789 cancer cell lines including 8 myeloma cell lines with drug screening data from the Wellcome Trust Sanger Institute database obtained from ArrayExpress was “Robust Multi-array analysis” normalized using GeneSpring v.12.5. Drug toxicity data were obtained from the Genomics of Drug Sensitivity in Cancer project. In order to identify individual genes whose expression profiles matched that of the one generated by cytotoxicity experiments for bortezomib, we used a linear regressionbased approach, where we searched for statistically significant correlations between gene expression values and IC50 data. The intersections of the genes were identified in 8 cell lines and used for further analysis.
Results: Our linear regression model identified 73 genes and some genes expression levels were found to very closely correlated with bortezomib IC50 values. When all 73 genes were used in a hierarchical cluster analysis, two major clusters of cells representing relatively sensitive and resistant cells could be identified. Pathway and molecular function analysis of all the significant genes was also investigated, as well as the genes involved in pathways.
Conclusion: The findings of our present in silico study could be important not only for the understanding of the genomics of MM but also for the better arrangement of the targeted anti-myeloma therapies, such as bortezomib.

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Amaç: Koagülasyon ve fibrinoliz bozukluklarý primer hiperparatiroidili hastalarda rapor edilmekle beraber bu hasta grubunda trombosit iþlevlerine iliþkin yeterli veri yoktur. Bu nedenle primer ve sekonder hiperparatiroidisi olan hastalarda ve saðlýklý kontrol grubunda
trombosit fonksiyonlarýný deðerlendirmeyi ve gruplar arasýnda farký karþýlaþtýrmayý amaçladýk.
Gereç ve Yöntem: Çalýþmamýza 25 primer hiperparatiroidisi (PHPT) olan hasta, 25 sekonder hiperparatiroidisi (SHPT) olan hasta ve 25 kontrol grubu dahil edildi. Trombosit fonksiyonlarý trombositten zengin plazma ve epinefrin, adenozin difosfat (ADP), kollajen ve ristosetinle trombosit agregasyon testleri yapýlarak deðerlendirildi. Trombosit aktivasyon düzeyini gösteren serum P selektin düzeyleri tüm hastalarda ölçüldü. Kemik mineral dansitometresi tüm hastalarda
deðerlendirildi.
Bulgular: PHPT ve SHPT’li hastalar ve kontrol grubunun trombosit fonksiyon testleri ve serum P selektin düzeyleri arasýnda istatistiksel açýdan anlamlý bir fark saptanmadý. Parathormon düzeyi ile agregasyon parametreleri (ristosetin, epinefrin, kollajen, ve ADP: sýrasýyla p=0,446, 0,537, 0,346 ve 0,302) ve P selektin (p=0,516) düzeyi arasýnda da anlamlý bir korelasyon saptanmadý. Hastalar kalsiyum düzeylerine göre hiperkalsemik ve normokalsemik olarak ayrýldýklarýnda da agregasyon parametreleri ve P selektin düzeyleri arasýnda anlamlý fark saptanmadý. Hasta gruplarýmýzda trombosit fonksiyonlarý, P selektin düzeyi, serum kalsiyum düzeyileri arasýnda istatistiksel açýdan anlamlý fark bulunmadý. Kemik kaybý PHPT’li olan grupta daha belirgindi.
Sonuç: Agregasyon testleri ile deðerlendirildiðinde PHPT veya SHPT ve serum kalsiyum düzeylerinin trombosit fonksiyonlarý üzerine belirgin etkisi yoktur.

Objective: Coagulation and fibrinolysis defects were reported in primary hyperparathyroid patients. However, there are not enough data regarding platelet functions in this group of patients. Our aim was to evaluate the platelet functions in primary and secondary hyperparathyroid patients and to compare them with healthy subjects.
Materials and Methods: In our study 25 subjects with primary hyperparathyroidism (PHPT), 25 subjects with secondary hyperparathyroidism (SHPT), and 25 healthy controls were included. Platelet functions of the subjects were evaluated by using plateletrich plasma and platelet aggregation tests induced with epinephrine, adenosine diphosphate (ADP), collagen, and ristocetin. Serum P selectin levels, which indicate platelet activation level, were measured in all subjects. Bone mineral densitometry was performed for all patients.
Results: There was no significant difference between the groups with PHPT and SHPT and the control group regarding the platelet aggregation tests and serum P selectin levels. There was also no significant correlation between parathormone levels and aggregation parameters (ristocetin, epinephrine, collagen, and ADP: respectively p=0.446, 0.537, 0.346, and 0.302) and between P selectin (p=0.516) levels. When we separated the patients according to serum calcium levels, there was also no significant difference between aggregation parameters and serum P selectin levels between the patients with hypercalcemia and the patients with normocalcemia. We could not find any significant correlation between aggregation parameters, P selectin levels, and serum calcium levels in this group of patients. Bone loss was greater in patients with PHPT.
Conclusion: There is no significant effect of PHPT or SHPT and serum calcium levels on platelet functions when evaluated by aggregation tests.

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Amaç: Bu çalýþmanýn amacý kontrollerle karþýlaþtýrýldýðýnda hiperkoagülabilite durumlarý olan hastalarda terapötik uluslararasý düzeltme oranýnda (INR) 2 ile 3 aralýðýna ulaþmak için gerekli warfarin doz ve antikoagülan süresindeki farklýlýðý analiz etmektir. Bildiðimiz kadarýyla; bu farklýlýðý tarifleyen literatürdeki ilk çalýþmadýr.
Gereç ve Yöntem: Retrospektif dosya taramasý 3. basamak hastanede yapýldý. Toplam çalýþmaya alýnan hasta sayýsý 622 idi. Venöz tromboembolizmi olan bu hastalardan 125’inin hiperkoagülabilite sendromu olup yaþ, cins ve etnik kökeni ayný 497 kontrol hastasýnda hiperkoagülabilite sendromu yoktu.
Bulgular: Hastalarda terapötik INR’ye ulaþmak için gerekli total warfarin dozu (50,7±17,6 mg) kontrollerin dozu (41,2±17,7 mg) ile karþýlaþtýrýldýðýnda yüksekti. Terapötik INR’ye ulaþmak için gerekli total gün sayýsý hastalarda 8,9±3,5 gün olup kontrollerde 6,8±2,9 gün idi. Her iki karþýlaþtýrmada da istatistiksel farklýlýk anlamlý bulundu (p<0,001).
Sonuç: Hiperkoagülabilite durumlarý olan hastalarda terapötik INR’ye ulaþmak için kontrollere göre yaklaþýk 10 mg ek total warfarin dozu ve ortalama 2 ek gün gereklidir.

Objective: The purpose of this study was to analyze the difference in duration of anticoagulation and dose of warfarin required to reach a therapeutic international normalized ratio [(INR) of 2 to 3] in patients with hypercoagulable conditions as compared to controls. To our knowledge, this study is the first in the literature to delineate such a difference.
Materials and Methods: A retrospective chart review was performed in a tertiary care hospital. The total study population was 622. Cases (n=125) were patients with a diagnosis of a hypercoagulable syndrome who developed venous thromboembolism. Controls (n=497) were patients with a diagnosis of venous thromboembolism in the absence of a hypercoagulable syndrome and were matched for age, sex, and race.
Results: The total dose of warfarin required to reach therapeutic INR in cases was higher (50.7±17.6 mg) as compared to controls (41.2±17.7 mg). The total number of days required to reach therapeutic INR in cases was 8.9±3.5 days as compared to controls (6.8±2.9 days). Both of these differences were statistically significant (p<0.001).
Conclusion: Patients with hypercoagulable conditions require approximately 10 mg of additional total warfarin dose and also
require, on average, 2 extra days to reach therapeutic INR as compared to controls.

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Amaç: Febril nötropenik (FEN) hastalarda mannoz-baðlayýcý lektin (MBL) ve H-fikolin eksikliðinin önemi ve bu belirteçlerin enfeksiyon ataðý sýrasýnda ardýþýk C-reaktif protein (CRP) ve prokalsitonin (PCT) ölçümleri ile korelasyonu araþtýrýlmýþtýr.
Gereç ve Yöntem: Bu tek merkezli prospektif gözlemsel çalýþmaya, hematolojik malignite nedeniyle izlenen ve “mikrobiyolojik olarak doðrulanmýþ enfeksiyon”, “klinik olarak dökümante edilmiþ enfeksiyon” veya “nedeni bilinmeyen ateþ” tanýlarý konulan hastalar dahil edilmiþtir. Serum CRP, PCT, MBL ve H-fikolin düzeyleri; baþlangýçta (hastaneye baþvuru ile kemoterapi baþlangýcý arasýnda), ateþ ataðýnýn baþýnda ve 72. saatinde olmak üzere üç ayrý zamanda ölçülmüþtür.
Bulgular: Kýrk altý (%54 erkek, ortalama yaþ 41,7) hastada geliþen 61 ayrý FEN ataðý deðerlendirildi. Hastalarýn 11’inde (%23,9) “mikrobiyolojik doðrulanmýþ enfeksiyon”, 17’sinde (%37) “klinik dökümante enfeksiyon”, 18’inde (%39,1) ise nedeni bilinmeyen ateþ mevcut idi. Baþlangýç MBL düzeyi (<500 ng/mL) yedi hastada, H-fikolin düzeyi ise (<12,000 ng/mL) 14 hastada düþük bulundu. Bazal MBL ve H-fikolin düzeylerinin ateþin birinci ve üçüncü gününde anlamlý olarak deðiþmediði belirlendi (p=0,076). Baþlangýç MBL düzeyi düþük olan hastalarda gram-negatif bakteremilerin daha sýk ortaya çýktýðý saptandý (p=0,006). PCT düzeyleri “mikrobiyolojik olarak doðrulanmýþ” enfeksiyonu bulunanlarda anlamlý olarak daha yüksekti. Medyan PCT düzeyleri tüm FEN epizodlarýnda anlamlý olarak yükselmiþ bulundu.
Sonuç: Ciddi bakteremilerin ön görülmesi açýsýndan serum H-fikolin düzeylerinin izlenmesinin yararý olmadýðý gösterildi. Düþük bazal MBL düzeyleri ile yüksek gram-negatif bakteremi riski arasýnda iliþkili olduðu belirlenmekle birlikte izlemde anlamlý korelasyon gösterilemedi. Bakteremi olgularýnýn izleminde daha hýzlý ve özgül veriler elde edebilmek için PCT düzeylerinin yakýn izleminin gerekli olduðu sonucuna varýldý.

Objective: The significance of mannose-binding lectin (MBL) and H-ficolin deficiency in febrile neutropenic (FN) patients and the correlation of these markers along with consecutive C-reactive protein (CRP) and procalcitonin (PCT) levels during the infectious process are investigated.
Materials and Methods: Patients with any hematological malignancies who were defined to have “microbiologically confirmed infection”, “clinically documented infection”, or “fever of unknown origin” were included in this single-center prospective observational study. Serum levels of CRP, PCT, MBL, and H-ficolin were determined on 3 separate occasions: at baseline (between hospital admission and chemotherapy), at the onset of fever, and at the 72nd hour of fever.
Results: Forty-six patients (54% male, mean age 41.7 years) with 61 separate episodes of FN were evaluated. Eleven patients (23.9%) had “microbiologically confirmed infection”, 17 (37%) had “clinically documented infection”, and 18 (39.1%) had “fever of unknown origin”. Fourteen (30.4%) patients had low (<500 ng/mL) initial MBL levels and 7 (15.21%) had low (<12,000 ng/mL) H-ficolin levels. Baseline MBL and H-ficolin levels did not significantly change on the first and third days of fever (p=0.076). Gram-negative bacteremia more frequently occurred in those with low initial MBL levels (p=0.006). PCT levels were significantly higher in those with microbiologically documented infections. Mean and median PCT levels were significantly higher in cases with bacteremia. There was no significant difference between hemoculture-positive and-negative patients in terms of CRP levels.
Conclusion: Monitoring serum H-ficolin levels was shown to be of no benefit in terms of predicting severe infection. Low baseline MBL levels were correlated with high risk of gram-negative bacteremia; however, no significant correlation was shown in the follow-up. Close monitoring of PCT levels is warranted to provide more accurate and specific data while monitoring cases of bacteremia.

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Amaç: Enfeksiyonlar, kanser hastalarýnda önde gelen morbidite ve mortaliteleri nedeni olmuþlardýr. Bu çalýþmada hastanede yatan kanser hastalarýnda enfeksiyonlarýn sýklýðýný, tiplerini, etiyolojilerini ve enfeksiyon geliþimi ve mortalite için risk faktörlerini belirlemeyi amaçladýk.
Gereç ve Yöntem: Üçüncü basamak bir üniversite hastanesinin iç hastalýklarý servislerinde Ocak-Aðustos 2004 tarihleri arasýnda izlenmiþ olan eriþkin kanser hastalarý dahil edildi. Yatýþ süreleri boyunca nötropeni, enfeksiyonlar, kültür sonuçlarý ve mortalite açýsýndan prospektif olarak izlendiler.
Bulgular: Toplam 473 kanser hastasýnýn 818 hastaneye yatýþ ataðý izlendi. Toplam 818 yatýþ ataðý sýrasýnda 384 (%46) enfeksiyon ataðý gözlendi- %79’u nozokomiyaldi. Febril nötropeni (FN) tüm ataklarýn 196’sýnda (%51) görüldü. Bakteremi, FN ataklarýnýn %29’unda ve nötropenik olmayan hastalarýn %8’inde görüldü. Gram-pozitifler hem nötropenik olan hem de olmayan hastalardaki bakteremilerin önde gelen etkeni olarak görüldü (%70 ve %58, sýrasýyla). Santral kateter varlýðýnýn bakteremi riskini 3 kat artýrdýðý görüldü. Toplam mortalite %17 iken bakteremisi olan hastalarda mortalite %34 saptandý. Bakteremi varlýðý ve ileri evre hastalýk toplam mortaliteyi, sýrasýyla, 6,1
ve 3,7 kat artýrmaktaydý.
Sonuç: Hastanede yatan kanser hastalarýnýn neredeyse yarýsýnda en azýndan bir enfeksiyon geliþmektedir ve bu enfeksiyonlarda grampozitifler hakimdir. Bu bilgiler, 2004 yýlýna kadar kanser hastalarýnda en sýk görülen mikroorganizmalarýn gram-negatif mikroorganizmalar olduðu göz önüne alýndýðýnda, enfeksiyonlarda deðiþen eðilimler olduðunu göstermektedir.

Objective: We aimed to determine the frequency, type, and etiology of infections and the risk factors for infections and mortality in hospitalized cancer patients.
Materials and Methods: We prospectively enrolled adult cancer patients hospitalized in the internal medicine wards of a tertiary care academic center between January and August 2004. Patients were followed during their hospitalization periods for neutropenia, infections, culture results, and mortality.
Results: We followed 473 cancer patients with 818 hospitalization episodes and 384 infection episodes in total. Seventy-nine percent of the infections were nosocomial, and febrile neutropenia (FN) was observed in 196 (51%) of the infection episodes. Bacteremia was found in 29% of FN episodes and in 8% of nonneutropenic patients. Gram-positive bacteria were the leading cause of bacteremia in both
neutropenic and nonneutropenic cases (70% and 58%, respectively). Presence of an indwelling central catheter increased bacteremia risk
by 3-fold. The overall mortality rate was 17%, whereas 34% of the patients with bloodstream infections died. Presence of bacteremia and advanced disease stage increased overall mortality by 6.1-fold and 3.7-fold, respectively.
Conclusion: Nearly half of the cancer patients developed an infection during their hospital stays, with gram-positive bacteria being the
predominant etiologic microorganisms. This demonstrates the changing trends in infections considering that, until 2004, gramnegative bacteria were the most predominant microorganisms among cancer patients in our institute.

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Amaç: Hemokromatozis, demir birikiminin önemli nedenlerinden biri olan otozomal resesif bir hastalýktýr. Orak hücreli anemi, hemoglobin genindeki homozigot mutasyon sonucu ortaya çýkan bir hemoglobinopatidir. Eritrosit transfüzyonu, bu hastalýðýn tedavisinde sýklýkla kullanýlmaktadýr. Transfüzyonun yarattýðý demir yükü diðer hemoglobinopatilerde olduðu gibi orak hücreli anemi hastalarýnýn mortalite ve morbiditesinde önem kazanmaktadýr. Bu çalýþmada hemokromatozis geni (HFE) p.H63D ve p.C282Y mutasyonlarýnýn, homozigot hemoglobin S mutasyonu taþýyan orak hücreli anemi hastalarýnda, kalp ve karaciðerde transfüzyonla iliþkili demir yüklenmesine olan etkisi araþtýrýlmýþtýr.
Gereç ve Yöntem: Bu çalýþma, homozigot hemoglobin S mutasyonu olan hastalarda 2008-2013 yýllarýný kapsayan prospektif, tek merkezli kesitsel bir çalýþmadýr. Hastalar þelasyon tedavisi alan (n=31) ve almayan (n=13) olarak iki gruba ayrýldý. Hastalarda direk ve endirekt demir yükü sýrasýyla manyetik rezonans görüntüleme ve biyokimyasal olarak analiz edildi. HFE geni mutasyon analizi polimeraz zincir reaksiyonu-restriksiyon fragment uzunluk polimorfizmi yöntemleri ile gerçekleþtirildi. Ýstatistik analizi Independent samples t-testi uygulanarak gerçekleþtirildi.
Bulgular: p.H63D mutasyonu grup A’da 10 hastada (%32,3), grup B’de ise sadece 1 (%7,7) hastada saptandý. Demir birikimi açýsýndan gruplar karþýlaþtýrýldýðýnda karaciðerde demir birikiminin grup B’de istatistiksel olarak anlamlý derecede yüksek olduðu görülmüþtür (p<0,05). Grup A’da, mutasyonu olan bireylerde olmayanlara göre karaciðerdeki demir birikiminin istatistiksel olarak anlamlý derecede yüksek olduðu görülmüþtür (p=0,05).
Sonuç: Bu çalýþmanýn sonucu HFE genindeki mutasyonlarýn, orak hücreli anemi hastalarýnda karaciðerde demir birikimi üzerinde etkili olduðunu göstermektedir.

Objective: Hemochromatosis is an autosomal recessive disease that is one of the most important reasons for iron overload. Sickle cell disease is a hemoglobinopathy that occurs as a result of a homozygous mutation in the hemoglobin gene. Erythrocyte transfusion is frequently used in the treatment of this disease. Iron overload as a result of transfusion is important in the mortality and morbidity of sickle cell anemia patients as well as in other hemoglobinopathies. In this study, the effect of hemochromatosis gene (HFE) p.H63D and p.C282Y mutations on transfusion-related cardiac and liver iron overload in sickle cell disease patients who carry homozygous hemoglobin S mutation has been investigated.
Materials and Methods: This is a prospective single-center crosssectional study in patients with homozygous hemoglobin S mutation between the years 2008 and 2013. The patients were divided into two groups. The first group (group A, n=31) was receiving chelation therapy and the second group (group B, n=13) was not. Direct and indirect iron loads were analyzed by magnetic resonance imaging and biochemically, respectively. HFE gene mutations were analyzed by polymerase chain reaction-restriction fragment length polymorphism method. Statistical analyses were performed by independent samples t-test.
Results: p.H63D mutation was detected in 10 (32.3%) patients in group A and in only 1 patient (7.7%) in group B. When the 2 groups were compared for iron overload, iron deposition in the liver was significantly higher in group B (p=0.046). In addition, in group A, iron deposition was significantly higher in HFE mutation carriers compared to patients without the mutation (p=0.05).
Conclusion: Results of this study showed that HFE gene mutations are important in iron deposition in the liver in patients with sickle cell disease.

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Amaç: Akut lenfoblastik lösemide (ALL) saðkalým oranlarýnýn artmasýyla tedavinin uzun süreli yan etkileri önemli hale gelmiþtir. Bu çalýþmanýn amacý da ALL saðkalanlarýnda, saðlýkla iliþkili yaþam kalitesi, depresyon, anksiyete ve kendilik imajýný incelemektir.
Gereç ve Yöntem: ALL tanýsý almýþ 50 çocuk ile onlarýn ayný sayýdaki saðlýklý kardeþleri çalýþmaya dahil edilmiþtir. Verileri toplamak için, Kovaks Çocuklar için Depresyon Anketi, Durumluluk-Sürekli Kaygý Envanteri, Offer Kendilik Ýmajý anketi ve Pediatric Quality of Life InventoryTM kullanýlmýþtýr. Gruplar arasý farklar ANOVA yöntemi kullanýlarak araþtýrýlmýþtýr.
Bulgular: ALL saðkalanlarýnýn, kardeþlerine göre, depresyon ve anksiyete puanlarý anlamlý olarak fazladýr. Ayrýca, benlik imajlarýnýn daha olumsuz, yaþam kalitelerinin daha düþük idi.
Sonuç: ALL tedavisi sýrasýnda ve sonrasýnda olasý duygusal yan etkiler için sürekli tanýsal ve giriþimsel mental saðlýk servisleri gerekli olabilir. Tedavi sýrasýnda ve sonrasýnda ALL’li çocuklar için rehabilitasyon ve izlem programlarý uygulanmalýdýr.

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.

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Down sendromu (DS) olmayan çocuklarda akut megakaryoblastik löseminin (AMKL) prognozu çok kötü ve 3 yýllýk saðkalým %40’ýn altýnda iken, DS’li çocuklarda AMKL’nin saðkalým oraný mükemmeldir. Yakýn zamanda, DS olmayan AMKL’li çocuklarýn yaklaþýk %30’unda CBFA2T3 ve GLIS2’yi içeren yeni bir tekrarlayan translokasyon tanýmlandý ve füzyon geninin pediatrik AMKL olgularýnda kötü prognoz ile iliþkili güçlü bir prognostik belirteç olduðu bildirildi. CBFA2T3-GLIS2 füzyon genini taþýyan AMKL tanýlý pediatrik hastalarda sorunlu klinik seyri bildiriyoruz.

Acute megakaryoblastic leukemia (AMKL) in children without Down syndrome (DS) has an extremely poor outcome with 3-year survival of less than 40%, whereas AMKL in children with DS has an excellent survival rate. Recently, a novel recurrent translocation involving CBFA2T3 and GLIS2 was identified in about 30% of children with non-DS AMKL, and the fusion gene was reported as a strong poor prognostic factor in pediatric AMKL. We report the difficult clinical courses of pediatric patients with AMKL harboring the CBFA2T3-GLIS2 fusion gene.

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Amaç: Kronik lenfositik lösemi (KLL) olgun görünümlü B lenfositlerin hastalýðýdýr. Ýnsülin-benzeri büyüme faktörü-1 (IGF-1), mitojenik ve antiapoptotik etkili küçük peptid hormondur ve insülin-benzeri büyüme faktörü baðlayýcý protein-3 (IGFBP-3) ise hücre üzerinde antiproliferative etki gösterir. Çalýþmamýzda, KLL hasta grubu ve kontrol grubunda plazma IGF-1 ve IGFBP-3 düzeylerini ve prognostik faktörlerle iliþkisini karþýlaþtýrdýk.
Gereç ve Yöntemler: Haseki Eðitim ve Araþtýrma Hastanesi, Hematoloji Bölümü’nde takip edilen yeni taný almýþ KLL hastalarý ile kontrol grubu çalýþmaya dahil edilmiþtir. Hastalar Rai sistemine göre evrelendirilmiþtir. Ýstatistiksel analiz SPSS for Windows version 17.0 kullanýlarak yapýlmýþtýr.
Bulgular: Kýrk üç hasta [16 kadýn (%37) ve 27 erkek (%63)] çalýþmaya alýnmýþtýr. Kontrol grubu 21 kiþiden (11 kadýn, 10 erkek) oluþmuþtur. Hasta grubunda ortanca yaþ 65±9 (18-63), kontrol grubunda 68±8’dir (18-63). Kontrol grubu ile karþýlaþtýrýldýðýnda; çalýþma grubunda plazma IGF-1 düzeyi yüksek; IGFBP-3 düzeyi düþük, IGF-I/IGFBP-3 oraný ise yüksek olarak bulunmasýna raðmen istatistiksel yönden anlamlý deðildi (p>0,05). Çalýþma grubunda plazma IGF-1 düzeyi yüksekliði ile Rai ileri evresi paralellik gösteriyordu. Diðer gruplarla istatistiksel yönden anlamlý farklýlýk yoktu (p=0,105).
Sonuç: Çalýþma grubunda, plazma IGF-1 düzeyi kontrol grubundan daha yüksek, IGFBP-3 düzeyi ise düþük bulundu, bununla beraber istatistiksel yönden anlamlý farklýlýk yoktu. Plazma IGF-1 düzeyi yüksekliði ile Rai ileri evresi uyumlu idi. Bu sonuçlar bize, IGF-1 düzeyinin KLL hastalarýnda tümor yükü ve Rai evresi ile iliþkili olduðunu ve prognostik faktör olarak deðerli olabileceðini düþündürmüþtür. Bu sonuçlarý destekleyebilmek için daha geniþ kapsamlý çalýþmalara ihtiyaç vardýr.

Objective: Chronic lymphocytic leukemia (CLL) is a disease of nonproliferating and mature-appearing B lymphocytes. Insulin-like growth factor-1 (IGF-1) is a small peptide hormone and has mitogenic and antiapoptotic effects, and insulin-like growth factor binding protein-3 (IGFBP-3) has antiproliferative effects on cells. In this study, we investigated plasma levels of both IGF-1 and IGFBP-3 in patients with CLL compared with controls, and we compared these plasma levels according to prognostic factors. Materials and Methods: Patients with newly diagnosed CLL who were being followed at the Haseki Training and Research Hospital, Ýstanbul, Turkey, and volunteers were included in this study. Patients were stratified according to the Rai staging system. Statistical analysis was conducted using SPSS 17.0 for Windows. Results: Forty-three patients [16 women (37%) and 27 men (63%)] were enrolled in this study. Twenty-one volunteers (11 women, 10 men) were included in the control group. The median age of the patients was 65±9 years (range: 18-63 years), and subjects in the control group were 68±8 years old (range: 18-63 years). Even though the plasma levels of IGF-1 were higher and those of IGFBP-3 were lower and the ratio of IGF-I/IGFBP-3 was higher in comparison with the control group, these differences were not statistically significant (p>0.05). In the study group, IGF-1 levels appeared to be increased in parallel to more advanced Rai stages. There were no significant differences between the other groups (p=0.105). Conclusion: Plasma IGF-I levels were found higher in patients than in the control group and plasma IGFBP-3 levels were lower; however, neither result was statistically significant. Plasma IGF level increment was observed in concordance with Rai staging. These results prompted us to think that plasma IGF-1 levels in CLL patients are correlated with tumor burden and Rai staging and therefore could be a valuable prognostic factor. Further comprehensive studies are required to support our results.

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Bu çalýþmada akut lenfoblastik lösemili (ALL) hastalarda insan lökosit antijeni alellerinin (A, B, ve DRB1) Türk toplumundaki daðýlýmýný araþtýrdýk. Çalýþmaya 90 ALL hastasý ve 126 saðlýklý kontrol dahil edildi. Kontrollerle karþýlaþtýrdýðýmýzda ALL hastalarýnda A*03, DRB1*03, DRB1*04 alellerinin, A*02/B*35/DRB1*13 haplotipinin ve homozigot olarak A*02 alelinin daha sýk olarak (sýrasý ile p=0,006, p=0,003, p=0,002, p=0,01 ve p=0,02) daðýldýðýný gözlemledik. Aksine A*23, B*13, B*40 ve DRB1*13 alelleri (sýrasý ile p=0,002, p=0,07, p=0,002 ve p=0,003) ise kontrol grubunda daha fazla olarak saptandý. Ayrýca DRB1*04 ve DRB1*07 alelleri (sýrasý ile p=0,009 ve p=0,007) risk gruplarýna göre yapýlan karþýlaþtýrmada sýrasý ile yüksek ve standart riskli hastalarda daha fazla bulundu. Bu çalýþma ile ALL hastalarýnda Türk toplumu için A*03, DRB1*03, DRB1*04 alelleri, A*02/B*35/DRB1*13 haplotipi ve homozigot formdaki A*02 alelinin bir risk faktörü olabileceði gözlemlendi. Ayrýca DRB1*04 ve DRB1*07 alellerinin risk gruplarýnýn oluþmasýnda sýrasý ile yüksek ve standart risk gruplarýnda daha fazla bulunabileceði tespit edildi.

We studied the frequencies of human leukocyte antigen alleles (A, B, and DRB1) in 90 patients with acute lymphoblastic leukemia (ALL) and then compared them with 126 controls in this study. Although the frequencies of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and homozygosity of A*02 were higher in patients (p=0.006, p=0.003, p=0.002, p=0.01, and p=0.02, respectively), the frequencies of the A*23, B*13, B*40, and DRB1*13 alleles were lower (p=0.002, p=0.07, p=0.002, and p=0.003, respectively) in patients than controls. The frequencies of the DRB1*04 and DRB1*07 alleles were higher in patients in the high-risk group and standard-risk group, respectively (p=0.009 and p=0.007, respectively). This study indicated that the frequency of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and A*02 homozygosity may play a predisposing role in patients with ALL in the Turkish population. The frequency of the DRB1*04 and DRB1*07 alleles may also be associated with high risk and standard risk in patients with ALL, respectively.

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Primer varisella zoster virüs (VZV) enfeksiyonu benign, kendi kendini sýnýrlayan bir hastalýktýr. Bu çalýþmada pediatrik malignitesi olan hastalarda VZV enfeksiyonu ve tedavisine odaklý tecrübelerimizi gözden geçirmeyi amaçladýk. Çalýþma süresi boyunca; VZV enfeksiyonu tanýsý alan pediatrik maligniteli toplam 41 hasta hastaneye yatýrýldý. Tüm hastalar ortalama 7 gün (5 ila 21 gün arasýnda deðiþen) intravenöz asiklovir ile tedavi edildi. VZV enfeksiyonlarýna baðlý olarak hesaplanan atfedilebilir kemoterapi gecikmesi ortalama 8 gündü (2 ile 60 gün arasýnda deðiþen). VZV enfeksiyonuna baðlý komplikasyonlar 41 hastadan 3’ünde (%7) akut solunum distres sendromu olarak görüldü ve bu hastalardan hemofagositik lenfohistiyositozu olan bir tanesi asiklovir, geniþ spektrumlu antibiyotik ve destekleyici tedaviye raðmen solunum yetmezliði nedeniyle kaybedildi. VZV enfeksiyonlarý, pediatrik malignite hastalarýnda hala önemli bulaþýcý hastalýklardan biridir, çünkü sadece ciddi mortaliteye sebep olmakla kalmayýp kemoterapi baþlangýcýný da geciktirmektedir.

Primary varicella-zoster virus (VZV) infection is a benign self-limited disease. In this study, we review our experience in focusing on the outcome and treatment of VZV infection in pediatric malignancy patients. During the study period, a total of 41 patients with pediatric malignancy had been hospitalized with the diagnosis of VZV infection. All the patients were treated with intravenous acyclovir for a median of 7 days (ranging from 5 to 21 days). The calculated attributable delay of chemotherapy due to VZV infections was 8 days (ranging from 2 to 60 days). VZV-related complications were observed in 3 of 41 patients (7%) who suffered from acute respiratory distress syndrome, and one of them with hemophagocytic lymphohistiocytosis died due to respiratory failure despite acyclovir and broad-spectrum antimicrobial treatment plus supportive treatment. VZV infections are still important contagious diseases in pediatric cancer patients, because they cause not only significant mortality but also a delay in chemotherapy.

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