Amaç: Bu çalýþma, TP53’ün klinik önemini ve yaygýn sitogenetik anormallikleri belirlemeyi amaçladý.
Gereç ve Yöntem: 2010 ile 2017 yýllarý arasýnda iþbirliði yapan hastanelerin iki büyük hasta grubundan yeni teþhis edilmiþ multipl miyelom (MM) ve TP53 anormallikleri olan toplam 114 hasta seçildi. Bu hastalarýn özellikleri ve sonuçlarý analiz edildi. MM hastalarýnda TP53 ve diðer yaygýn mutasyonlar, floresan in situ hibridizasyon ile ölçülmüþtür. Hayatta kalma analizi için Kaplan-Meier eðrileri ve logrank testleri uygulandý. Prognostik faktörleri belirlemek amacý ile ortak deðiþken analizi için bir Cox orantýlý tehlike modeli kullanýldý.
Bulgular: Kapsamlý veri analizi ile, TP53 amplifikasyonunun tedaviye tam yanýt (CR) için güçlü bir pozitif öngörücü olduðunu ve hastanýn saðkalýmý ile pozitif korelasyon gösterdiðini bulduk. TP53 mutasyonu ile eþzamanlý genomik anormalliklerin sayýsý, hastanýn saðkalýmý üzerinde sýnýrlý bir etkiye sahiptir. Bu mutasyonlar arasýnda, 1q21 amplifikasyonu, azalmýþ CR (olasýlýk oraný: 4.209) ile iliþkilidir ve FGFR3 seviyeleri, progresyonsuz ve genel saðkalým ile pozitif olarak iliþkilidir.
Sonuç: MM tanýsýndaki TP53 anormallikleri, hastanýn tedaviye yanýtýný ve saðkalýmý öngörmede büyük klinik öneme sahiptir. Ayrýca, 1q21 ve FGFR3 mutasyonlarý, hasta saðkalýmýný daha iyi tahmin etmek ve hasta tedavi stratejilerini geliþtirmek için yüksek riskli hastalarýn seçimine rehberlik etmek amacý ile potansiyel olarak TP53 durumu ile kombine halde kullanýlabilir.

Objective: This study aimed to identify the clinical significance of TP53 and common cytogenetic abnormalities.
Materials and Methods: A total of 114 patients with newly diagnosed multiple myeloma (MM) and TP53 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed. TP53 and other common mutations in MM patients were quantified by fluorescence in situ hybridization. Kaplan-Meier curves and logrank tests were applied for survival analysis. A Cox proportional hazard model for covariate analysis was used to determine the prognostic factors.
Results: By extensive data analysis, we found that TP53 amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with TP53 mutation has a modest impact on patient survival. Among these mutations, 1q21 amplification is associated with decreased CR (odds ratio: 4.209) and FGFR3 levels are positively correlated with progression-free and overall survival.
Conclusion: TP53 abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Furthermore, 1q21 and FGFR3 mutations could potentially be used in combination with TP53 status to better predict patient survival and guide the selection of high-risk patients to advance patient treatment strategies.

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Amaç: Hastaya özgü uyarýlmýþ pluripotent kök hücreler (uPKH) insan hastalýk modellemesi ve rejeneratif týpta büyük bir potansiyele sahiptir. Hastalýða özgü uPKH’den türetilen hücreler, klinik fenotip ile moleküler veya hücresel patofizyoloji arasýndaki bilgi boþluðunu kapatmak ve ilaç taramasý için yeni stratejiler oluþturmak ve yeni terapötik ajanlar geliþtirmek gibi stratejilerle hastalýk patolojilerini anlamada faydalý olacaktýr. Çalýþmamýzýn amacý multipl myelom (MM) hastalarýndan uPKH üretmektir.
Gereç ve Yöntem: MM hastalarýndan izole edilen MKH’ler Sendai virüs yoluyla uyarýlarak pluripotensi aþamasýna döndürülmüþtür. Çalýþmada fibroblastlar kontrol olarak kullanýlmýþtýr. Her gün mikroskobik analiz yapýlmýþ, koloni seçimi için alkalin fosfataz canlý boyamasý yapýlmýþtýr. Yeniden programlama deneyleri akýþ sitometrisi, immünofloresan (IF) boyama ve gen ekspresyon analizleri ile teyit edilmýþtir. Spontan farklýlaþma potansiyelini doðrulamak için in vitro embriyonik cisimcik (EC) oluþum deneyi yapýlmýþtýr.
Bulgular: Fibroblastlar ve MM hastalarýndan izole edilmiþ MKH’ler; dört Yamanaka faktörü olan Oct3/4, Sox2, Klf4 ve c-Myc ile yeniden programlama vektörleri içeren Sendai virüsü kullanýlarak yeniden programlanmýþtýr. Ýlk olarak, mikroskobik analiz ile üretilen uPKH’lerin klasik embriyonik kök hücre (EKH) benzeri morfolojik özelliklere sahip olduðu ortaya konmuþtur. Ýkinci olarak, her iki hücre hattýnýn da pluripotent aþamaya kadar yeniden programlanabildiði akýþ sitometrisi, IF boyama ve gen ekspresyon analizleri ile teyit edilmiþtir. Ýn vitro embriyonik cisimcik (EC) oluþum deneyleri ile spontan farklýlaþma potansiyeli gösterilmiþtir.
Sonuç: uPKH’ler MM hastalarýndan ilk kez baþarýyla elde edilmiþtir ve bu hücrelerin MM hastalýðýnýn arkasýndaki moleküler mekanizmalarý netleþtirebileceði düþünülmektedir.

Objective: Patient-specific induced pluripotent stem cells (iPSCs) have potential in human disease modeling and regenerative medicine. The in vitro phenotype of disease-specific iPSC-derived cells can be used to bridge the knowledge gap between clinical phenotype and molecular or cellular pathophysiology and to understand the pathology of diseases, along with further applications, such as creating new strategies for drug screening or developing novel therapeutic agents. The aim of our study was to generate iPSCs from multiple myeloma (MM) patients.
Materials and Methods: Mesenchymal stem cells (MSCs) isolated from MM patients were induced for pluripotency via the Sendai virus. Fibroblasts were used as a control. Microscopic analysis was performed daily. For colony selection, live staining was done using alkaline phosphatase staining. Reprogramming experiments were confirmed by flow cytometry, immunofluorescence (IF) staining, and gene expression analyses. To confirm the spontaneous differentiation potential, an in vitro embryonic body (EB) formation assay was performed.
Results: Fibroblasts and MSCs obtained from MM patients were reprogrammed using the Sendai virus, which contains reprogramming vectors with the four Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc. Microscopic analysis revealed that the generated iPSCs possessed classical embryonic stem cell-like morphological characteristics. Reprogramming experiments further showed that both cell lines can be reprogrammed up to the pluripotent stage, which was confirmed by flow cytometry, IF staining, and gene expression analyses. Spontaneous differentiation potential was confirmed by in vitro EB formation assays.
Conclusion: iPSCs have been successfully obtained from MM patients for the first time. These cells could clarify the molecular mechanisms behind this disease.

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Amaç: Akut miyeloid lösemi (AML), hematopoietik sistemin bir malinitesidir ve akut lösemilerin yaklaþýk %70’ini oluþturur. Uzun kodlamayan RNA-DUXAP8’in (lncRNA-DUXAP8) çeþitli tümörlerde anormal þekilde ifade edildiði bulunmuþtur. Ancak, AML’deki iþlevi ve mekanizmasý çalýþýlmamýþtýr. AML’nin taný ve tedavisi için yeni bir teorik temel saðlamak amacýyla lncRNA-DUXAP8’in AML ve mekanizmasý üzerindeki etkisini araþtýrdýk.
Gereç ve Yöntem: AML kemik iliði dokularýnda ve THP-1, HL-60, TF-1, AML193 ve U937 hücre dizilerinde lncRNA-DUXAP8 ifadesi qRT-PCR ile tespit edildi. Daha sonra sýrasýyla si-DUXAP8 ve lncRNA-DUXAP8’i aþýrý ifade eden plazmitlerin transfekte edilmesiyle deðiþtirildi. AML hücrelerinin çoðalma yeteneðini deðerlendirmek için CCK8 ve hücre kolonisi testi yapýldý. Ýlaveten, apoptoz sürecini gözlemlemek için akým sitometri kullanýldý. Glukoz tüketimini ve laktat düzeylerini saptamak için glukoz ve laktat kitleri kullanýldý. Son olarak, hücrelerde Wnt/β-katenin sinyal yolu ile ilgili proteinlerin ifadesini saptamak için western blot testi yapýldý.
Bulgular: LncRNA-DUXAP8, hem AML kemik iliði dokularýnda hem de hücre dizilerinde baskýlanmýþtý. AML hücre dizisi THP-1’de lncRNA-DUXAP8’e müdahale edilmesi üzerine, hücre apoptozu inhibe edilirken AML hücre proliferasyonu ve glikoliz kolaylaþtýrýldý. lncRNADUXAP8’ in aþýrý ifadesinden sonra tersi sonuçlar elde edildi. Bu arada, western blot yöntemi, lncRNA-DUXAP8 ile etkileþimin Wnt/β-katenin yolaðýnda Wnt5a, β-katenin, c-Myc ve siklin-D1 proteinlerinin ifadesini stimüle ettiðini doðruladý. Ayrýca, lncRNA-DUXAP8’in aþýrý ifadesi, Wnt/β-katenin yolu proteinlerinin ifadesini inhibe etti. Son olarak, Wnt/β-katenin yolunun bir aktivatörü olan LiCl, DUXAP grubuyla karþýlaþtýrýldýðýnda lncRNA-DUXAP8 upregülasyonu ile AML hücrelerinin regülasyonunu tersine çevirdi.
Sonuç: Bu çalýþma, lncRNA-DUXAP8’in, AML’de glikolizi inhibe etmek ve apoptozu indüklemek için Wnt/β-katenin sinyal yolunu düzenlediðini gösterdi. Bu deney, AML’li hastalarý tedavi etmek için yeni açýlar ve deneysel bir temel saðlamýþtýr.

Objective: Acute myeloid leukemia (AML) is a malignancy of the hematopoietic system, accounting for approximately 70% of acute leukemias. Long noncoding RNA-DUXAP8 (lncRNA-DUXAP8) has been found to be abnormally expressed in a variety of tumors. However, its function and mechanism in AML have not been studied. We investigate the effect of lncRNA-DUXAP8 on AML and its mechanism so as to provide a new theoretical basis for the diagnosis and treatment of AML.
Materials and Methods: The expression of lncRNA-DUXAP8 in AML bone marrow tissues and the THP-1, HL-60, TF-1, AML193, and U937 cell lines was detected by qRT-PCR. It was then altered by transfecting plasmids overexpressing si-DUXAP8 and lncRNA-DUXAP8, respectively. CCK8 and cell colony assay were performed to evaluate the proliferation ability of AML cells. In addition, flow cytometry was used to observe the apoptosis process. Glucose and lactate kits were utilized to detect glucose consumption and lactate levels. Finally, western blotting was performed to detect the expression of proteins related to the Wnt/β-catenin signaling pathway in cells.
Results: LncRNA-DUXAP8 was downregulated in both AML bone marrow tissues and cell lines. Upon interfering with lncRNA-DUXAP8 in AML cell line THP-1, AML cell proliferation and glycolysis were promoted while cell apoptosis was inhibited. The opposite results were obtained after overexpressing lncRNA-DUXAP8. Meanwhile, western blotting confirmed that interference with lncRNA-DUXAP8 stimulated the expression of proteins Wnt5a, β-catenin, c-Myc, and cyclin-D1 in the Wnt/β-catenin pathway. Moreover, overexpression of lncRNA-DUXAP8 inhibited the expression of Wnt/β-catenin pathway proteins. Finally, LiCl, an activator of the Wnt/β-catenin pathway, reversed the regulation of AML cells by lncRNA-DUXAP8 upregulation compared with the DUXAP group.
Conclusion: This study showed that lncRNA-DUXAP8 regulated the Wnt/β-catenin signaling pathway to inhibit glycolysis and induce apoptosis in AML. This experiment has provided new angles and an experimental basis for treating patients with AML.

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Amaç: Kronik lenfositik lösemi hastalarýnda tek ajan ibrutinib tedavisinin etkinliðini, güvenliðini ve saðkalým sonuçlarýný geriye dönük olarak deðerlendirmek.
Gereç ve Yöntem: Otuz üç merkezde yapýlan bu retrospektif, çok merkezli, giriþimsel olmayan hastane kayýt çalýþmasýna en az bir doz ibrutinib uygulanan 136 hasta (ortalama ± standart sapma yaþ 64,6 10,3, % 66,9’u erkek) dahil edildi. Hastalarýn demografik verileri, bazal karakteristikleri, laboratuvar bulgularý, lösemi hücre sitogenetiði ile ilgili veriler kaydedildi. Tedavi yanýtý, genel saðkalým (OS), progresyonsuz saðkalým (PFS) ve güvenlik verileri analiz edildi.
Bulgular: Hastalarýn %36,7’sinde ECOG 2-3, % 44,9’u Rai evre 4 idi. FISH ile hastalarýn %39,8’inde del(17p) varlýðýný gösterdi. Hastalar medyan 2 (0 ila 7 arasýnda) sýra pre-ibrutinib tedavisi aldý. Medyan tedavi süresi 8,8 aydý (0,4-58 ay). Bir yýllýk PFS ve OS oranlarý sýrasýyla %82,2 ve %84,6, medyan (SE, %95 güven aralýðý) PFS süresi 30 (5,1, 20-40) ay ve OS süresi 37,9 (3,2, 31,5-44,2) aydý. Tedavi yanýtý (CR veya PR), PFS ve OS süreleri; ibrutinib öncesi 3-7 basamak tedaviye karþý 0-2 basamak tedavi alanlarda (p<0,001, p=0,001 ve p<0,001, sýrayla), ECOG 2-3’e göre ECOG 0-2 olanlarda (p=0,006, p=0,011 ve p=0,001, sýrasýyla), Rai evre 0-2 olanlarda Rai evre 3-4 olanlara göre (p=0,002, p=0,001 and p=0,002, sýrasýyla) daha iyiydi. Komorbidite, hacimli hastalýk veya del(17p) varlýðýna göre tedaviye yanýt oranlarýnda veya saðkalým sonuçlarýnda önemli bir fark kaydedilmedi. 74 hastada (%54,4) 176 advers olay (AE) saptandý; 176 AE’nin 46’sý derece 3-4 idi. Bunlar; pnömoni (n=12), nötropeni (n=11), anemi (n=5), trombositopeni (n=5) ve ateþ (n=5) idi.
Sonuç: Bu gerçek hayat analizi, uzun vadeli ibrutinib tedavisinin olumlu etkililiðini ve güvenlik profilini doðrularken, kötü ECOG performans durumunun, ibrutinib’den önce aðýr þekilde tedavi verilmiþ olmasýnýn ve ileri evre hastalýðýn, hasta uyumu, tedavi yanýtý ve saðkalým üzerindeki potansiyel olumsuz etkilerini ortaya koymuþtur.

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients.
Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed.
Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5).
Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

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Amaç: Hasarlý hücrelerden salýnan bilinen bir tehlike sinyali olan ürik asit (ÜA), önemli bir enflamasyon belirtecidir. Bu çalýþmayý hazýrlama rejimine baþlamadan önce bakýlan serum ürik asit seviyesi ile hematopoetik kök hücre transplantasyonu (HKHT) sonrasý hepatik sinüzoidal obstrüksiyon sendromu (SOS) geliþimi riski arasýndaki iliþkiyi deðerlendirmeyi amaçladýk.
Gereç ve Yöntem: Bu retrospektif çalýþmaya Hacettepe Üniversitesi Pediatrik KÝT Ünitesi’nde 2000-2014 yýllarý arasýnda allojenik HKHT uygulanan 222 çocuk hasta dahil edildi. Serum ÜA seviyeleri, hastalarýn transplantasyon öncesi enflamatuvar durumunun bir göstergesi olarak hazýrlama rejimi öncesi ölçülmüþtür. SOS tanýsý olan ve olmayan hastalar, birincil taný, SOS için daha önce tanýmlanan risk faktörleri ve rejim öncesi serum ÜA açýsýndan karþýlaþtýrýldý.
Bulgular: SOS tanýsý alan 42 hastada rejim öncesi ÜA düzeyleri olmayan hastalara göre daha yüksek saptandý. Nakil öncesi bakýlan serum kreatinin, gama-glutamil transferaz, bilirubin, ferritin ve C-reaktif protein parametreler açýsýndan daha düþük olan serum albümini dýþýnda, SOS geliþen hastalar ile geliþmeyen hastalar arasýnda anlamlý farklýlýk gözlenmedi. ROC analizi, 3,32 mg/dL’den yüksek rejim öncesi ÜA düzeyinin SOS geliþimini öngördüðünü ortaya koydu. Çok deðiþkenli bir modele uygulandýðýnda, yalnýzca rejim öncesi ÜA ve albümin seviyeleri SOS için önemli risk faktörleri belirlendi (ÜA; odds ratio (OR), 2,54; %95 güven aralýðý (GA), 1,26 ila 5,12; p=0,009 ve albumin; OR, 0,45; %95 GA, 0,22 ila 0,95; p=0,037).
Sonuç: Sonuçlarýmýz, rejim öncesi serum ÜA düzeyinin SOS için baðýmsýz bir risk faktörü olduðunu ve önceden tanýmlanmýþ klinik/ laboratuvar parametreleriyle birlikte hepatik SOS’nin geliþimi açýsýndan erken bir belirteç olarak kullanýlabileceðini göstermektedir.

Objective: Uric acid (UA), a known danger signal released from injured cells, is a valuable sign of inflammation. We aimed to evaluate the association of serum UA levels before the start of conditioning regimens with the risk of hepatic sinusoidal obstruction syndrome (SOS) development after hematopoietic stem cell transplantation (HSCT).
Materials and Methods: Two hundred and twenty-two children who underwent allogeneic HSCT at the Pediatric BMT Unit of Hacettepe University between 2000 and 2014 were included in this retrospective study. Serum UA levels were measured before conditioning as an indicator of the pre-transplant inflammatory status of the patients. Patients with and without a diagnosis of SOS were compared regarding primary diagnosis, previously described risk factors for SOS, and preconditioning serum UA.
Results: SOS was diagnosed in 42 patients who had higher pre-conditioning serum UA levels compared to those who did not. Pre-transplant serum creatinine, gamma-glutamyl transferase, bilirubin, ferritin, and C-reactive protein levels did not differ significantly among patients with and without SOS; however, serum albumin was lower in the patients who developed SOS. Receiver operating characteristic analysis revealed that a pre-conditioning UA level higher than 3.32 mg/dL was predictive of SOS. When applied to a multivariate model, only pre-conditioning UA and albumin levels remained significant risk factors for SOS (UA: odds ratio [OR], 2.54; 95% confidence interval [CI], 1.26-5.12, p=0.009; albumin: OR, 0.45, 95% CI, 0.22-0.95, p=0.037).
Conclusion: Our results suggest that pre-conditioning serum UA is an independent risk factor for SOS, and it might be used as an early predictor of hepatic SOS together with previously described clinical and laboratory parameters.

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Amaç: Geriye dönük çok merkezli bir çalýþma düzenleyerek, çocuk hematoloji uzmanlarýnýn sistemik rekombinant doku plazminojen aktivatörü (rtPA) kullanýmý ile ilgili deneyimlerinin ortaya konmasý amaçlandý
Gereç ve Yöntem: Türkiye’deki 13 pediatrik hematoloji merkezinden geriye dönük veriler toplandý. rtPA tedavisinin dozu ve süresi, eþzamanlý antikoagülan tedavi, tam pýhtý erimesi (TPE), kýsmi pýhtý erimesi (KPE) ve kanama komplikasyonlarý deðerlendirildi. Düþük doz (DD) rtPA tedavisi 0,01-0,06 mg/kg/saat ve yüksek doz (YD) 0,1-0,5 mg/kg/saat olarak tanýmlandý.
Bulgular: 2005-2019 yýllarý arasýnda ortanca yaþý 5 yýl (1 gün-17,75 yýl) olan 54 hastanýn 55 trombotik epizodu deðerlendirildi. Hastalarýn tanýlarý; intrakardiyak tromboz (n=16), derin ven trombozu (DVT) (n=15), inme dýþý arteriyel tromboz (n=14), pulmoner tromboemboli (PE) (n=6) ve inme (n=4) idi. Trombüs saptanmasýndan rtPA baþlangýcýna kadar geçen süre medyan 12 saat (2 sa-504 sa) idi ve inme, inme olmayan arteriyel tromboz ve intrakardiyak tromboza kýyasla DVT ve PE için anlamlý olarak daha uzundu (p=0,024). Ataklarýn %63,6’sýnda rtPA tedavisinden önce heparin baþlandý. Ataklarýn 22’sine DD ve 33’üne YD rtPA uygulandý. DD ve YD rtPA ataklarýnýn sýrasýyla %90’ýnda ve %36’sýnda eþ zamanlý antikoagülasyon kullanýldý (p=0,0001). DD ve YD rtPA infüzyonlarýnýn medyan toplam süresi sýrasýyla 30 sa (2 sa- 120 sa) ve 18 sa (2 sa-120 sa) idi (p=0,044). Ölümcül olmayan majör ve minör kanama oranlarý DD için sýrasýyla %12,5, %16,7 ve YD rtPA için %3,2, %25,8 idi. rtPA infüzyonlarýnýn sonunda, ataklarýn sýrasýyla %32,7’sinde TPE ve %49’unda KPE elde edildi. Tromboliz için en baþarýlý bölge intrakardiyak trombozdu. YD’ye karþý DD rtPA uygulamasý, TPE/ KPE veya kanama ile korele deðildi (p>0,05).
Sonuç: Yüksek riskli trombozlu çocuklarda sistemik trombolitik tedavi, deneyimli hematologlar tarafýndan rekanalizasyon ve kanamanýn yakýn takibi altýnda doðru endikasyon ve doðru zamanda kullanýldýðýnda etkin bir þekilde hayat ve organ kurtarabilir.

Objective: This study aimed to evaluate systemic thrombolysis experiences with recombinant tissue plasminogen activator (rtPA).
Materials and Methods: Retrospective data were collected from 13 Turkish pediatric hematology centers. The dose and duration of rtPA treatment, concomitant anticoagulant treatment, complete clot resolution (CCR), partial clot resolution (PCR), and bleeding complications were evaluated. Low-dose (LD) rtPA treatment was defined as 0.01-0.06 mg/kg/h and high-dose (HD) rtPA as 0.1-0.5 mg/kg/h.
Results: Between 2005 and 2019, 55 thrombotic episodes of 54 pediatric patients with a median age of 5 years (range: 1 day to 17.75 years) were evaluated. These patients had intracardiac thrombosis (n=16), deep vein thrombosis (DVT) (n=15), non-stroke arterial thrombosis (n=14), pulmonary thromboembolism (PE) (n=6), and stroke (n=4). The duration from thrombus detection to rtPA initiation was a median of 12 h (range: 2-504 h) and it was significantly longer in cases of DVT and PE compared to stroke, non-stroke arterial thrombosis, and intracardiac thrombosis (p=0.024). In 63.6% of the episodes, heparin was initiated before rtPA treatment. LD and HD rtPA were administered in 22 and 33 of the episodes, respectively. Concomitant anticoagulation was used in 90% and 36% of the episodes with LD and HD rtPA, respectively (p=0.0001). Median total duration of LD and HD rtPA infusions was 30 h (range: 2-120 h) and 18 h (2-120 h), respectively (p=0.044). Non-fatal major and minor bleeding rates were 12.5% and 16.7% for LD and 3.2% and 25.8% for HD rtPA, respectively. At the end of the rtPA infusions, CCR and PCR were achieved in 32.7% and 49.0% of the episodes, respectively. The most successful site for thrombolysis was intracardiac thrombosis. HD versus LD rtPA administration was not correlated with CCR/PCR or bleeding (p>0.05).
Conclusion: Systemic thrombolytic therapy may save lives and organs effectively if it is used at the right indications and the right times in children with high-risk thrombosis by experienced hematologists with close monitoring of recanalization and bleeding.

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Amaç: Radyoaktif iyot (RAÝ) tedavisi hematolojik anormalliklere yol açabilir. Bu çalýþmada, diferansiye tiroid kanserli (DTC) hastalarda RAÝ tedavisi sonrasý uzun dönemli hematolojik etkilerin deðerlendirilmesi amaçlanmýþtýr.
Gereç ve Yöntem: Bin üç yüz seksen dokuz RAÝ ile tedavi edilmiþ DTC’li hasta retrospektif olarak deðerlendirildi. Tedavi öncesi, son takip ve hematolojik malignite geliþtikten sonra ölçülen tam kan sayýmlarý elektronik kayýtlardan elde edildi.
Bulgular: Uzun dönemli analizde trombositopeni ve lenfopeni özellikle 60 yaþ üstü bireylerde gözlendi. Trombositopeni erkek hastalarda daha sýktý. Lökopeni, trombositopeni ve lenfopeni >175 mCi dozlarda anlamlý oranda artmýþtý. Trombositopeni ve lenfopeni çoklu doz uygulamasý olanlarda anlamlý oranda izlendi. Anemi, trombositopeni, lökopeni, nötropeni ve lenfopeni, ileri evre hastalýklý hastalarda daha sýktý. Ancak ileri evre hastalýða sahip hastalar, erken evrelilere göre hem daha yüksek doz hem de çoklu doz tedavi almýþlardý. Hematolojik malignite oraný genel popülasyondan daha yüksek oranda idi.
Sonuç: Özellikle 60 yaþ üstü hastalar sitopeniler açýsýndan daha yakýn izlenmelidir. RAÝ tedavi sonrasý en önemli risk faktörü erkek cinsiyettir. Klinik olarak sitopeniler için en önemli belirleyici ileri evre hastalýktýr, ki bu da, daha yüksek doz ve çoklu doz tedavi uygulanmýþ olmasýnýn ve daha fazla tümör yükünün kombine etkisi ile iliþkilidir.

Objective: Radioactive iodine (RAI) therapy may cause hematologic abnormalities. The aim of this study is to evaluate long-term hematologic effects in differentiated thyroid cancer (DTC) patients after RAI therapy.
Materials and Methods: A total of 1389 patients with DTC who were treated with RAI were retrospectively evaluated. Complete blood cell counts before RAI therapy and at last follow-up and hematologic malignancy development were obtained from the electronic records.
Results: In the long-term analysis, thrombocytopenia and lymphopenia were observed significantly in patients over 60 years of age. Thrombocytopenia was observed more frequently in men. Leukopenia, thrombocytopenia, and lymphopenia were observed significantly with doses of >175 mCi. Thrombocytopenia and lymphopenia were observed significantly with multiple dose administration. Higher frequencies of anemia, thrombocytopenia, leukopenia, neutropenia, and lymphopenia were found in patients with advanced-stage disease. However, patients with advanced-stage disease had higher doses and more multiple doses than patients with early-stage disease. The rate of hematologic malignancy was found to be higher than in the general population.
Conclusion: We suggest that cytopenia be surveyed more carefully in patients older than 60 years of age. The most important risk factor for lower platelets after RAI therapy is male gender. Clinically, the most important predictor for cytopenia is advanced disease stage, which is related to the combined effects of applied high dose activity, multiple dose applications, and high tumor burden.

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Castleman hastalýðý, anjiyofolliküler lenf nodu hiperplazisi olarak da bilinen nadir bir lenfoproliferatif hastalýktýr. Histolojik olarak hiyalin vasküler ve plazmasitik varyant olarak sýnýflandýrýlýr ancak nadiren iki tipe ait özellikler bir arada bulunabilir. Unisentrik hastalýðý olan olgularýn çoðu hiyalin vasküler, multisentrik hastalýðý olan olgularýn çoðu ise plazma hücreli histolojik tipindedir. Patogenezi tam olarak anlaþýlmamýþtýr fakat unisentrik hastalýkta interlökin (IL)-6’nýn, multisentrik hastalýkta IL-6 ve human herpes virüs-8’in rolü iyi tanýmlanmýþtýr. Unisentrik hastalýk tipik olarak lokalizedir, semptomlar minimaldir ve tek baþýna lokal tedavi uygulanýr. Multisentrik hastalýk sistemik bir hastalýktýr ve klinik olarak yaygýn lenfadenopati, splenomegali, anemi ve sistemik inflamatuar semptomlarla karakterizedir. Baþlýca sistemik tedaviler uygulanýr. Lenfomalar, POEMS sendromu, folliküler dendritik hücreli sarkomlar, paraneoplastik pemphigus, Kaposi sarkomu, amiloidoz Castleman hastalýðý ile iliþkili olabilir. Bu yazýda nadir bir hastalýk olan Castleman hastalýðý ile ilgili güncel bilgiler özetlenmiþtir.

Castleman disease is a rare lymphoproliferative disease also known as angiofollicular lymph node hyperplasia. It is classified as hyaline vascular and plasmacytic variants histologically but characteristics of both types can coexist. Most unicentric cases of the disease are hyaline vascular while most multicentric cases are of the plasmacytic type. Although the pathogenesis is not completely understood, the role of interleukin (IL)-6 in unicentric disease and the roles of IL-6 and human herpes virus-8 in multicentric disease are well defined. Unicentric disease is typically localized and symptoms are minimal and treated locally. Multicentric disease is systemic and clinically characterized by generalized lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. Systemic therapies are primarily given. Several malignant diseases including lymphomas, POEMS syndrome, follicular dendritic cell sarcomas, paraneoplastic pemphigus, Kaposi sarcoma, and amyloidosis can be associated with Castleman disease. In this paper, recent information about Castleman disease, which is a rare disease, is summarized.

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Amaç: Çalýþmanýn amacý tedavi sürecinde standart tedavilere ek olarak konvalesan plazma (KP) tedavisi uygulanan COVID-19 hastalarýnda takipte oluþan COVID-19 antikor düzeylerini incelemektir.
Gereç ve Yöntemler: Yatarak tedavi alan COVID-19 hastalarý içinde standart tedavilere ek olarak KP tedavisi alanlar retrospektif olarak incelenmiþtir ve takipte COVID-19 antikor düzeyleri bakýlmýþ olanlar çalýþmaya dahil edilmiþtir. Ayný zaman zarfýnda yatarak takip edilen, standart tedavi alan ve takipte COVID-19 antikor düzeyi bakýlmýþ olan COVID-19 hastalarý arasýndan yaþ, cinsiyet ve komorbidite sýklýðý eþleþtirilmiþ bir kontrol grubu oluþturulmuþtur. Ýki grup arasýnda COVID-19 antikor düzeyleri karþýlaþtýrýlmýþtýr.
Bulgular: KP tedavisi alan ve takipte antikor düzeyleri bakýlmýþ olan 33 COVID-19 hastasý çalýþmaya dahil edildi. Kontrol grubunda 34 hasta mevcuttu. Median total COVID-19 antikor indeks düzeyleri standart yaklaþýma ek olarak KP alan grupta anlamlý olarak düþük saptandý.
Sonuç: KP tedavisinin COVID-19 hastalarýnda sonuçlar üzerine olumlu etkileri görülmekle beraber hastalýk sonrasýnda azalmýþ antikor yanýtý, uzun dönem baðýþýklýk üzerine olumsuz etkilerin bir göstergesi olabilir.

Objective: The aim of this study is to investigate post-COVID-19 antibody titers in patients who received convalescent plasma (CP) in addition to standard-of-care treatment.
Materials and Methods: Hospitalized COVID-19 patients who received CP in addition to standard care were retrospectively investigated. Patients who received CP with a recorded total COVID-19 antibody test result after treatment were included. From among hospitalized COVID-19 patients who received only standard care with a recorded total COVID-19 antibody test result, a control group matched for age, gender, and comorbidities was formed. Total COVID-19 antibody index levels were compared.
Results: Thirty-three CP recipients were enrolled in the study. The control group consisted of 34 age-, gender-, and comorbiditymatched standard-care patients. Median total COVID-19 antibody index levels were significantly reduced in the CP group.
Conclusion: Although CP therapy may have benefits for disease outcome, its potential ability to hamper long-term immunity may be a problem.

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