Browsing by Author "Dalva, Klara"

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    Hematopoietik kök hücre nakli için toplanan aferez ürünlerinde CD34+ hücrelerin mutlak sayımında "single platform" ISHAGE Protokolü ile volümetrik ölçümlerin karşılaştırılması
    (Sağlık Bilimleri Enstitüsü, 2019) Topcu, Nazlı Kozan; Dalva, Klara; Sağlık Bilimleri
    Kök hücreler kendini yenileyebilme ve birden fazla dokuya farklılaşma özelliği gösteren hücrelerdir. Hematopoietik kök hücreler (HKH) farklılaşabilme yeteneklerine göre multipotent olarak sınıflandırılan ve tüm olgun kan hücrelerine farklılaşabilen kök hücrelerdir. Hematopoietik Kök Hücre Nakli (HKHN), hematopoietik sistemin yeniden yapılanmasını sağlamak için kişinin kendisinden veya doku grubu uyumlu kişilerden kök hücreleri toplandıktan sonra uygun koşullarda alıcıya nakledilmesidir. Bu amaçla uygun koşullarda dolaşımdan toplanan kök hücreler "aferez ürünü" olarak adlandırılmaktadır. HKHN başarılı olabilmesi için aferez ürünlerinin belirli bir kök hücre sayısına sahip olması gerekmektedir ve bu sayı, klinik uygulamaların başarısında önemli bir etkiye sahiptir. HKH sayısının belirlenmesi için çeşitli analiz yöntemleri geliştirilmiştir. Bu amaçla akan hücre ölçer kullanarak hücrelerin yüzey antijenlerinin immünfenotipleme ile ortaya konması en sık kullanılan yöntemdir. Yapılan birçok çalışma sonucu HKH yüzey antijenleri Lin- CD34+ CD38- CD90+ olarak kabul edilmekle birlikte klinik uygulamalarda yamanmayla ilişkisi gösterilmiş olan CD34 hücre yüzey antijeninin saptanması yeterli kabul edilmektedir. Günümüzde CD34+ hücre sayımı için doğru ve hızlı sonuç veren standardize edilmiş yöntemler kullanılmaktadır. Bu yöntemler ile CD34+ hücreler, floresan boncuk kullanarak (single platform) ya da kullanmadan tam kan sayımı (TKS) sonuçları üzerinden (dual platform) sayılmaktadır. Bu çalışmada tavsiye edilen yöntem olan ve boncuklar ile yapılan "single platform" sayımlarda preanalitik hata riskleri bulunması sebebiyle boncuk kullanımı veya TKS gerektirmeyen alternatif bir yöntem olan "volümetrik" sayım arasındaki performansın karşılaştırılması ve volümetrik ölçüm güvenilirliğinin değerlendirilerek doğrulanması hedeflenmiştir. Çalışma sonuçlarına göre her iki yöntem ile elde edilen mutlak CD34+ hücre sayıları arasında uyum olduğu gözlenmiştir.
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    Impact of "killer immunoglobulin-like receptor/ligand" genotypes on outcome following surgery among patients with colorectal cancer: activating KIRS are associated with long-term disease free survival
    (2015) Dalva, Klara; Beksaç, Meral; Kök Hücre Enstitüsü; Tıp Fakültesi
    Approximately 30% of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations. We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI =0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/one/two KIR : 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.
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    Impact of“Killer Immunoglobulin-LikeReceptor /Ligand”Genotypes on Outcomefollowing Surgery among Patients withColorectal Cancer: Activating KIRs AreAssociated with Long-Term Disease FreeSurvival
    (2015) Beksaç, Meral; Dalva, Klara; Tıp Fakültesi
    Approximately 30%of patients with stage II/III colorectal cancer develop recurrence following surgery. How individual regulation of host mediated anti-tumor cytotoxicity is modified by the killer-cell immunoglobulin-like receptor (KIRs) genotype is essential for prediction of outcome. We analyzed the frequency of KIR and KIR ligand Human Leukocyte Antigen Class I genotypes, and their effects on recurrence and disease-free survival (DFS). Out of randomly selected 87 colorectal cancer patients who underwent R0 resection operations between 2005 and 2008, 29 patients whose cancers progressed within a median five-year follow-up period were compared with 58 patients with no recurrence within the same time period. Recurrent cases shared similar tumor stages with non-recurrent cases, but had different localizations.We used DNA isolated from pathological archival lymphoid and tumor tissues for KIR and KIR ligand (HLA-C, group C1, group C2, and HLA-A-Bw4) genotyping. Among cases with recurrence, KIR2DL1 (inhibitory KIR) and A-Bw4 (ligand for inhibitory KIR3DL1) were observed more frequently (p=0.017 and p=0.024); and KIR2DS2 and KIR2DS3 (both activating KIRs) were observed less frequently (p=0.005 and p=0.043). Similarly, in the non-recurrent group, inhibitory KIR-ligand combinations 2DL1-C2 and 2DL3-C1 were less frequent, while the activating combination 2DS2-C1 was more frequent. The lack of KIR2DL1, 2DL1-C2, and 2DL3-C1 improved disease-free survival (DFS) (100% vs. 62.3%, p=0.05; 93.8% vs. 60.0%, p=0.035; 73.6% vs. 55.9%, p=0.07). The presence of KIR2DS2, 2DS3, and 2DS2-C1 improved DFS (77.8% vs. 48.5%, p=0.01; 79.4% vs. 58.5%, p=0.003; 76.9% vs. 51.4%, p=0.023). KIR2DS3 reduced the risk of recurrence (HR=0.263, 95% CI = 0.080-0.863, p=0.028). The number of activating KIRs are correlated strongly with DFS, none/ one/ two KIR: 54/77/98 months (p=0.004). In conclusion the inheritance of increasing numbers of activating KIRs and lack of inhibitory KIRs, independent of tumor localization or stage, is associated with long-term DFS.
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    Report from the European myeloma network on interphase FISH in multiple myeloma and related disorders
    (2017) Dalva, Klara; Fen Fakültesi
    The European Myeloma Network has organized two workshops on fluorescence in situ hybridization in multiple myeloma. The first aimed to identify specific indications and consensus technical approaches of current practice. A second workshop followed a quality control exercise in which 21 laboratories analyzed diagnostic cases of purified plasma cells for recurrent abnormalities. The summary report was discussed at the EHA Myeloma Scientific Working Group Meeting 2010. During the quality control exercise, there was acceptable agreement on more than 1,000 tests. The conclusions from the exercise were that the primary clinical applications for FISH analysis were for newly diagnosed cases of MM or frank relapse cases. A range of technical recommendations included: 1) material should be part of the first draw of the aspirate; 2) samples should be sent at suitable times to allow for the lengthy processing procedure; 3) most importantly, PCs must be purified or specifically identified; 4) positive cut-off levels should be relatively conservative: 10% for fusion or breakapart probes, 20% for numerical abnormalities; 5) informative probes should be combined to best effect; 6) in specialist laboratories, a single experienced analyst is considered adequate; 7) at least 100 PC should be scored; 8) essential abnormalities to test for are t(4;14), t(14;16) and 17p13 deletions; 9) suitable commercial probes should be available for clinically relevant abnormalities; 10) the clinical report should be expressed clearly and must state the percentage of PC involved and the method used for identification; 11) a retrospective European based FISH data bank linked to clinical data should be generated; and 12) prospective analysis should be centralized for upcoming trials based on the recommendations made. The European Myeloma Network aims to build on these recommendations to establish standards for a common European data base to define subgroups with prognostic significance. © 2012 Ferrata Storti Foundation.
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