Gastrik diffüz büyük B hücreli Lenfoma'da immunohistokimyasal risk faktörlerinin prognoz üzerine etkisi
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Tarih
2020
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Diffüz büyük B hücreli lenfoma (DLBCL), Non-Hodgkin Lenfoma (NHL) vakalarının yaklaşık %30-50'sini oluşturan en yaygın Non-Hodgkin lenfoma tipidir. Amerika Birleşik Devletleri (ABD) ve İngiltere'de DLBCL insidansı yılda 7/100.000 vakadır. Bir bütün olarak Avrupa'da, insidans yılda 4,9/100.000'dir. Diğer NHL'lerin çoğu gibi, hafif bir erkek egemenliği vardır. İnsidans yaşla birlikte artar; ortalama başvuru yaşı ortalama olarak 70'tir. Olguların %40'ında ekstranodal tutulum görülür. Mide en sık tutulan ekstranodal lenfoma bölgesidir ve gastrointestinal lenfomaların %68-75'ini oluşturur. DLBCL'nin morfolojik, genetik ve biyolojik davranış açısından oldukça heterojenite gösterdiği bilinmektedir. Floresan instu hibridizasyon (FISH) veya sitogenetik olarak DLBCL'nin %7-%10' unda c-myc, bcl-2 ve / veya bcl-6 rearanjmanı varlığı gösterilmiştir. Önceki çalışmalarda bu birliktelik, DHL (double hit lenfoma) veya THL (triple hit lenfoma) olarak adlandırılmaktadır. WHO (Dünya Sağlık Örgtü) 2016 lenfoma sınıflamasında bu kategori yerine yüksek dereceli B hücreli lenfoma (NOS) tanımı kullanılmaktadır. Bu rearanjmanların olumsuz prognostik anlamı olduğu ve daha yoğun tedaviler ile R-CHOP (Rituksimab, Siklofosfamid, Doksorubisin, Vinkristin, Prednizolon) standart tedavisine göre daha iyi sonuçlar alındığı bilinmektedir. İmmünohistokimyasal olarak birliktelik gösterilir ancak genetik olarak doğrulanamaz ise bu durumda çift ifadeli lenfoma"double ekspresör lenfoma" (DEL) adını almaktadır ve yüksek dereceli lenfomalar kadar olmasa da kötü prognoz göstermektedir. Çalışmamız 2011-2019 tarihleri arasında 49 hasta ile yapılan retrospektif bir çalışmadır. Ege Üniversitesi Hastanesi Hematoloji Kliniği'nde takipli gastrik diffüz büyük B hücreli lenfoma tanısı alan erişkin yaş grubundaki hastalar dahil edilmiştir. Retrospektif olarak, dosya ve hastane sisteminden kayıtlı veriler kullanıldı. Klinik değişkenlerin etkileri (IPI skoru, B semptomları, yaş, cinsiyet, LDH düzeyi, evre, tedavi yöntemi, ECOG viii performans durumu, yanıt oranları ve nükslerin varlığı veya yokluğu) hastalıksız sağkalım ve genel sağkalım üzerine etkileri değerlendirildi. Hematoloji ve Patoloji bölümlerinden hastaların verileri (yaş, cinsiyet, tanı zamanı, tanıdaki belirti ve bulgular, aşamalar, tedaviler, tedavilere yanıtlar, IPI skorlaması ve takip süreleri) temin edildi. Genel ve hastalıksız sağkalım durumları analiz edildi. İmmunohistokimyasal olarak patolojik incelemelerdeki Ki-67,bcl-2,bcl-6,c-myc pozitifliği incelendi. Evrelemede ''Lugano Sınıflaması'' (evreI-IV) kullanıldı. Çalışmamızda kendi merkezimizde DEL sıklığını, immunohistokimyasal risk faktörlerinin sağ kalım üzerine etkilerini araştırmayı amaçladık. Tüm sonuçlar çalışma verilerine kaydedilerek SPPS versiyon 23,0 paket programı ile analiz edildi. İstatiksel olarak p<0,05 anlamlı kabul edildi. Çalışmaya alınan hastaların %59,2'si erkek, %40,8'i kadındı. Hastaların yaş aralığı 40-90 yıl aralığında ve ortalaması 65,7 olarak saptandı. Hastaların genel sağkalım sürelerinin 98,6 ay, hastalıksız sağkalım sürelerinin ise 82,2 ay olduğu gözlemlendi. Hastalığın erken evresinde genel sağkalım süresi 120 ay, ileri evre sağkalım süresi 86 ay olarak hesaplandı. International Prognostik Index (IPI) skor değerleri düşük-düşük orta ve yüksek-yüksek orta olarak iki gruba ayrılmıştır. Düşük-düşük orta IPI skor değeri bakımından genel sağ kalım süresi 101 ay ve yüksek-yüksek orta IPI skor değeri bakımından genel sağ kalım süresi 91 ay olarak hesaplanmıştır. Ayrıca double ekspresör lenfoma'nın genel sağkalım üzerindeki etkileri arasında anlamlı bir fark bulunmazken hastalıksız sağkalım süresi üzerine olumsuz etkileri istatistiksel olarak anlamlı bulunmuştur. (p<0,05)
DLBCL is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 30-50% of NHL cases. In the United States and England, the incidence of DLBCL is approximately 7 cases per 100,000 persons per year. In Europe as a whole, the incidence is approximately 4.92 cases per 100,000 persons per year. Like most other NHLs, there is a male predominance with approximately 55% of cases occurring in men. Incidence increases with age; the median age at presentation is 70 years for patients as a whole. In up to 40% of cases, the disease arises in extranodal tissues. The stomach is the most common extranodal site of lymphoma and accounts for 68% to 75% of gastrointestinal lymphomas. At the molecular and genetic levels, DLBCL is a heterogeneous disease. Earlier studies using fluorescent in situ hybridization (FISH) reported that 7% to 10% of DLBCL harbored cmyc, bcl-2 and/or bcl-6 translocations, and were called "double hit" lymphoma (DHL), or triple hit lymphoma.(THL) In the 2016 World Health Organization (WHO) revision of lymphoma classification, this category is now recognized as high grade B-cell lymphoma with rearrangements of c-myc and bcl-2 and/or bcl-6 Most retrospective studies suggested that high grade B-cell lymphoma carry a poor prognosis when treated with conventional therapy, such as RCHOP. (Rituksimab, Siklofosfamid, Doksorubisin, Vinkristin, Prednizolon) Other cases of de novo DLBCL are described as double expressor lymphoma (ie, expression of both c-myc and bcl-2 by immunohistochemistry, but without rearrangements of the cmyc and bcl-2 genes). A retrospective analysis of 49 patients with gastric DLBCL who applied to Ege University Medical Faculty Hematology Department between the years of 2011-2019. The data was collected and analyzed retrospectively. Data of the patients (age, sex, time of diagnosis, signs and x symptoms at diagnosis, stages, treatments, responses to treatments, international prognostic index, and follow-up periods) were retrieved from the archives of the Hematology and Pathology departments. The effects of clinical variables (IPI score, B symptoms, age, sex, LDH level, tumor stage, treatment modality, performance status, response rates, and presence or absence of relapses)on disease-free survival and overall survival were assessed Overall and disease-free survival rates were analyzed. Immunohistochemically Ki-67, bcl-2, bcl- 6, c-myc positivity in pathological examinations were evaluated. The Lugano Staging System (stage I–IV) was used for staging of the patients at the time of diagnosis. In our study, we investigated the effects of immunohistochemical risk factorson treatment response and survival. Our aim is to research frequency and clinical feature of double ekspressor lymphoma. All analyses were performed using SPSS 23,0 (SPSS Inc. , Chicago, IL, USA). Statistical significance was defined as. (p< 0,05) 59,2% of the patients included in the study were male and 40,8% were female. The age range of the patients was between 40-90 years and the mean age was 65,7 The overall survival time of the patients was 98,6 months, and the disease-free survival time was 82,2 months. In the early stage of the disease, the overall survival time was 120 months, and the advanced survival time was 86 months. International Prognostic Index (IPI) score values are divided into two groups as low-low medium and high-high medium. Overall survival time for low-low medium IPI score value was 101 months and overall survival time for high-high medium IPI score value was calculated as 91 months. In addition, while there was no significant difference between the effects of double express lymphoma on overall survival, negative effects on disease-free survival time were found statistically significant.( p< 0,05)
DLBCL is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 30-50% of NHL cases. In the United States and England, the incidence of DLBCL is approximately 7 cases per 100,000 persons per year. In Europe as a whole, the incidence is approximately 4.92 cases per 100,000 persons per year. Like most other NHLs, there is a male predominance with approximately 55% of cases occurring in men. Incidence increases with age; the median age at presentation is 70 years for patients as a whole. In up to 40% of cases, the disease arises in extranodal tissues. The stomach is the most common extranodal site of lymphoma and accounts for 68% to 75% of gastrointestinal lymphomas. At the molecular and genetic levels, DLBCL is a heterogeneous disease. Earlier studies using fluorescent in situ hybridization (FISH) reported that 7% to 10% of DLBCL harbored cmyc, bcl-2 and/or bcl-6 translocations, and were called "double hit" lymphoma (DHL), or triple hit lymphoma.(THL) In the 2016 World Health Organization (WHO) revision of lymphoma classification, this category is now recognized as high grade B-cell lymphoma with rearrangements of c-myc and bcl-2 and/or bcl-6 Most retrospective studies suggested that high grade B-cell lymphoma carry a poor prognosis when treated with conventional therapy, such as RCHOP. (Rituksimab, Siklofosfamid, Doksorubisin, Vinkristin, Prednizolon) Other cases of de novo DLBCL are described as double expressor lymphoma (ie, expression of both c-myc and bcl-2 by immunohistochemistry, but without rearrangements of the cmyc and bcl-2 genes). A retrospective analysis of 49 patients with gastric DLBCL who applied to Ege University Medical Faculty Hematology Department between the years of 2011-2019. The data was collected and analyzed retrospectively. Data of the patients (age, sex, time of diagnosis, signs and x symptoms at diagnosis, stages, treatments, responses to treatments, international prognostic index, and follow-up periods) were retrieved from the archives of the Hematology and Pathology departments. The effects of clinical variables (IPI score, B symptoms, age, sex, LDH level, tumor stage, treatment modality, performance status, response rates, and presence or absence of relapses)on disease-free survival and overall survival were assessed Overall and disease-free survival rates were analyzed. Immunohistochemically Ki-67, bcl-2, bcl- 6, c-myc positivity in pathological examinations were evaluated. The Lugano Staging System (stage I–IV) was used for staging of the patients at the time of diagnosis. In our study, we investigated the effects of immunohistochemical risk factorson treatment response and survival. Our aim is to research frequency and clinical feature of double ekspressor lymphoma. All analyses were performed using SPSS 23,0 (SPSS Inc. , Chicago, IL, USA). Statistical significance was defined as. (p< 0,05) 59,2% of the patients included in the study were male and 40,8% were female. The age range of the patients was between 40-90 years and the mean age was 65,7 The overall survival time of the patients was 98,6 months, and the disease-free survival time was 82,2 months. In the early stage of the disease, the overall survival time was 120 months, and the advanced survival time was 86 months. International Prognostic Index (IPI) score values are divided into two groups as low-low medium and high-high medium. Overall survival time for low-low medium IPI score value was 101 months and overall survival time for high-high medium IPI score value was calculated as 91 months. In addition, while there was no significant difference between the effects of double express lymphoma on overall survival, negative effects on disease-free survival time were found statistically significant.( p< 0,05)
Açıklama
Anahtar Kelimeler
İmmunohistokimya, Gastrik Diffüz Büyük B Hücreli Lenfoma, Prognoz, Immunohistochemistry, Gastric Diffuse Large B Cell Lymphoma, Prognose