Diffüz büyük B hücreli lenfoma hastalarında tanı anındaki klinik ve laboratuvar özelliklerin prognostik değeri; retrospektif çalışma
Küçük Resim Yok
Tarih
2023
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Tekirdağ Namık Kemal Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Her yıl du?nyada yaklaşık 150.000 kişi diffu?z bu?yu?k B hu?creli lenfoma (DBBHL) tanısı almaktadır. Anti-CD20 antikoru olan ritu?ksimabın CHOP (siklofosfamid, doksorubisin, vinkristin, prednizon) kemoterapisine eklenmesiyle hastaların yaklaşık %70'inde tam remisyon sag?lanabilmektedir. Ancak hala hastaların %30 kadarı nu?ks etmektedir. DBBHL'de tedavi yanıtı, ilerlemesiz sag?kalım (PFS) ve genel sag?kalım (OS) u?zerine etkili olan klinik ve laboratuvar parametreler ile yapılan analizler sonucu İnternational Prognostic İndex (IPI) geliştirilmiştir ve hala bu amac?la yaygın olarak kullanılmaktadır. Son yıllarda DBBHL'nin biyolojisinin daha iyi anlaşılması sonucunda prognozda etkili yeni parametreler u?zerine c?alışmalar yapılmaktadır. Bu c?alışmalardan biri de DBBHL'de gen ekspresyonlarına göre belirlenmiş alt tip c?alışmalarıdır. Bu alt tiplerden antijen aktive alt tipinin germinal merkez (GCB) alt tipine göre daha kötu? prognozlu oldug?una dair literatu?rde c?alışmalar mevcuttur. Literatu?rde DBBHL'de prognoz u?zerindeki etkileri araştıran birc?ok retrospektif, prospektif c?alışma ve prognostik indeks mevcut olsa da; farklı cog?rafi ve etnik yapılardaki lenfoma biyolojisi ve hasta ilişkili faktörlerden kaynaklanan deg?işiklikler de prognozda dikkate alınmalıdır. Bu du?şu?nceden yola c?ıkarak c?alışmamızda gerc?ek yaşam verisi olarak; DBBHL hastalarında tanı anındaki klinik, patolojik, demografik ve biyokimyasal özelliklerin remisyon oranı, nu?ks gelişimi, genel sag?kalım ve ilerlemesiz sag?kalım u?zerine etkisini araştırmayı hedefledik. Materyal ve metod: Çalışmamız, 2012-2022 yılları arasında Tekirdag? Namık Kemal Üniversitesi Tıp Faku?ltesi Hematoloji Klinig?i tarafından tanı almış ve tedavi başlanıp takip edilmiş 100 DBBHL hastasının verilerinin retrospektif olarak incelenmesiyle gerc?ekleştirildi. Bu hastaların tanı anındaki yaşı, cinsiyeti, performans skorları, hastalık evresi, B semptom ve ekstranodal tutulum varlıg?ı, IPI ve CNS-IPI risk grupları, splenomegali varlıg?ı, germinal veya non-germinal tip oluşu, hemoglobin, lökosit, kreatinin, trombosit, ferritin, albu?min, LDH, ALT, ALP deg?erleri, aldıkları tedavileri, tedavilere verdikleri yanıtları, nu?ks ve eksitus durumları, zaman parametreleri not edildi. İstatistiksel hesaplamalar IBM SPSS (Statistical Package of Social Science, version 26.0) programı ile yapıldı. Hasta grupları arasında nüks olma ve ölüm riskinin belirlenmesinde Cox regresyon, tedaviye yanıt durumlarının deg?erlendirilmesinde Lojistik regresyon, sag?kalım su?relerinin kıyaslanmasında Kaplan Meier-Log rank yöntemi kullanıldı. Bulgular: Çalışmamıza 50 kadın ve 50 erkek olmak u?zere toplam 100 hasta alındı. 60 yaş ve u?zerinde olan 54, ileri evreye sahip olan 58, ECOG skoru 2 ve u?zeri olan 65, yu?ksek risk IPI'ye sahip olan 23, ekstranodal tutulumu olan 49, yu?ksek risk CNS-IPI'ye sahip olan 28 hasta vardı. Tu?m hastalara birinci basamak tedavi uygulandı. Hastaların %84'u? birinci basamak tedaviye yanıt verdi, %16'sı ise yanıtsız oldu. Takip su?resi boyunca %24 hasta eksitus, %27 hasta ise nu?ks oldu. Du?şu?k lökosite sahip olanların yu?ksek lökosite sahip olanlara göre (HR=0.34, %95 CI:0.12-0.95, p=0.040) ve du?şu?k ferritini olanların yu?ksek ferritini olanlara göre (HR=0.29, %95 CI:0.10-0.81, p=0.018) birinci basamak tedaviye yanıt verme oranı daha fazla saptandı. 60 yaş ve u?zerinde olanlarda, kötu? performans ve ekstranodal tutulum varlıg?ı olanlarda, yu?ksek CNS-IPI ve IPI skoruna sahip olanlarda, yu?ksek kreatinin ve ferritini olanlarda ve du?şu?k albu?mini olanlarda hem ölu?m, hem de nu?ks olma riski daha fazla göru?ldu? (p<0.05). İleri yaş, kötu? performans, yu?ksek IPI, yu?ksek CNS-IPI, ekstranodal tutulum varlıg?ı, du?şu?k hemoglobin ve du?şu?k albumin, yu?ksek kreatinin ve yu?ksek ferritin PFS'yi kötu? etkiledi (p<0.05). İleri evre, ileri yaş, kötu? performans, yu?ksek CNS-IPI, yu?ksek IPI, ekstranodal tutulum varlıg?ı, du?şu?k albu?min, yu?ksek kreatinin ve yu?ksek ferritine sahip olan hastaların ise genel sag?kalımının daha kötu? oldug?u göru?ldu? (p<0.05). Literatu?rle uyumlu olarak c?alışmamızdaki hastaların 5 yıllık PFS ve OS oranları sırasıyla %61.9 ve %65.4 saptandı. Sonuç: Literatu?rle uyumlu olarak, c?alışmamızda IPI ve CNS-IPI gibi prognostik indeksler OS ve PFS ile ilişkili bulunmuştur. Aynı zamanda yapılan analizlerde IPI'ye dahil olan yaş, evre, performans ve ekstranodal tutulum varlıg?ı da sag?kalımla ilişkili bulundu; ancak LDH'nin OS, PFS, nu?ks olma ve ölüm riski u?zerine etkisi göru?lmedi. Albu?min du?zeyinin DBBHL prognozuna etkisini araştıran birc?ok c?alışmada c?elişkili sonuc?lar bildirilmiş olmasına rag?men; bizim c?alışmamızda albu?min du?zeyi hastalık sag?kalımı, nu?ks olma ve ölu?m riski ile ilişkili saptanmıştır. Daha önce DBBHL'de tanı anındaki ferritin du?zeyinin birinci basamak tedaviye yanıt u?zerine etkisini araştıran bir c?alışmaya rastlanmamıştır. Bizim c?alışmamızda ise tanı anındaki ferritin du?zeyi ile tedaviye yanıt verme durumu, nu?ks olma ve ölu?m riski, PFS ve OS arasında anlamlı ilişki bulundu. Bu da c?alışmamızı özgu?n kılmakta ve literatu?re katkı sag?lamaktadır. Çalışmamızdaki tu?m sonuc?lara dayanarak, ferritin du?zeyinin bir prognostik parametre oldug?u söylenebilir. Anahtar kelimeler: Lenfoma, Diffu?z Bu?yu?k B Hu?creli Lenfoma, Prognoz, Sag?kalım, Nu?ks, Mortalite
Purpose: Approximately 150.000 people in the world are diagnosed with Diffuse large B cell lymphoma (DLBCL) each year. Complete remission can be achieved in approximately 70% of patients with the addition of rituximab (anti-CD20 antibody) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolon) chemotherapy. However, 30% of patients still relapse. In DLBCL; The International Prognostic Index (IPI) was developed as a result of analyzes made with clinical and laboratory parameters that affect treatment response, progression-free survival (PFS) and overall survival (OS). IPI is still widely used for this purpose. In recent years, as a result of a better understanding of the biology of DLBCL, studies have been carried out on new parameters effective in prognosis. One of these studies is subtypes determined according to gene expressions in DLBCL. There are studies in the literature that the antigen-activated subtype has a worse prognosis than the germinal center subtype (GCB). Although there are retrospective and prospective studies and prognostic indices in the literature investigating the effects on prognosis in DLBCL, variability in the biology of lymphoma and patient-related factors in different geographic and ethnic structures should also be considered. Thus, as real life data in our study; we aimed to investigate the effects of clinical, pathological, demographic and biochemical features at the time of diagnosis on remission rate, recurrence development, overall survival and progression-free survival in DLBCL patients. Material and Method: 100 DLBCL patients diagnosed and treated by Tekirdag? Namık Kemal University Medical Faculty Hematology Clinic between 2012-2022 were included in our study and the data of these patients were analyzed retrospectively. Age, sex, performance scores, stage of the disease, presence of B symptoms and extranodal involvement, risk groups of IPI and CNS-IPI, presence of splenomegaly, germinal or non-germinal type, hemoglobin, leukocyte, creatinine, platelet, ferritin, albumin, LDH, ALT, ALP values, treatments given, responses to treatments, recurrence and ex status, time parameters were noted. Statistical calculations were made with the IBM SPSS (Statistical Package of Social Science, version 26.0) program. Cox regression was used to determine mortality and recurrence risk among patient groups, Logistic regression was used to evaluate response to treatment and Kaplan Meier-Log rank method was used to compare survival times. Results: A total of 100 patients, 50 women and 50 men, were included in our study. There were 54 patients aged 60 and above, 58 patients with advanced stage, 65 patients with ECOG 2 and above, 23 patients with high risk IPI, 28 patients with high risk CNS-IPI and 49 patients with extranodal involvement. First-line treatment was given to all patients. %84 of the patients responded to the first-line treatment and %16 did not respond. During the follow-up period, mortality occurred in 24% of patients and recurrence in 27%. The rate of responding to first-line treatment was higher in those with low leukocytes than those with high leukocytes (HR=0.34, 95% CI:0.12-0.95, p=0.040). The rate of responding to first-line treatment was higher in those with low ferritin than those with high ferritin (HR=0.29, 95% CI:0.10-0.81, p=0.018). The risk of both mortality and recurrence was higher in those aged 60 and over, poor performance and extranodal involvement, high CNS-IPI and IPI scores, high creatinine and ferritin, and low albumin. İn our study; advanced age, poor performance, high IPI, high CNS-IPI, presence of extranodal involvement, low hemoglobin and low albumin, high creatinine and high ferritin adversely affected PFS. Advanced stage, advanced age, poor performance, high IPI, high CNS-IPI, presence of extranodal involvement, low albumin, high creatinine and high ferritin adversely affected OS. Consistent with the literature; the 5-year PFS and OS rates of the patients in our study were 61.9% and 65.4%, respectively. Conclusion: Consistent with the literature, prognostic indices such as IPI and CNS-IPI were found to be associated with OS and PFS in our study. Age, stage, performance and presence of extranodal involvement included in IPI were also associated with survival. However, there was no effect of LDH on OS, PFS, recurrence and mortality. Conflicting results have been reported in many studies investigating the effect of albumin level on lymphoma prognosis. However; in our study, albumin level was found to be associated with disease survival, recurrence and mortality risk. To date, there has been no study investigating the effect of ferritin level at the time of diagnosis on response to first-line treatment in DLBCL. In our study, a significant correlation was found between ferritin level at the time of diagnosis and response to treatment, recurrence and mortality risk. This makes our study original and contributes to the literature. Based on all the results in our study, it can be said that ferritin level is a prognostic parameter. Keywords: Lymphoma, Diffuse Large B Cell Lymphoma, Prognosis, Survival, Relapse, Mortality
Purpose: Approximately 150.000 people in the world are diagnosed with Diffuse large B cell lymphoma (DLBCL) each year. Complete remission can be achieved in approximately 70% of patients with the addition of rituximab (anti-CD20 antibody) to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolon) chemotherapy. However, 30% of patients still relapse. In DLBCL; The International Prognostic Index (IPI) was developed as a result of analyzes made with clinical and laboratory parameters that affect treatment response, progression-free survival (PFS) and overall survival (OS). IPI is still widely used for this purpose. In recent years, as a result of a better understanding of the biology of DLBCL, studies have been carried out on new parameters effective in prognosis. One of these studies is subtypes determined according to gene expressions in DLBCL. There are studies in the literature that the antigen-activated subtype has a worse prognosis than the germinal center subtype (GCB). Although there are retrospective and prospective studies and prognostic indices in the literature investigating the effects on prognosis in DLBCL, variability in the biology of lymphoma and patient-related factors in different geographic and ethnic structures should also be considered. Thus, as real life data in our study; we aimed to investigate the effects of clinical, pathological, demographic and biochemical features at the time of diagnosis on remission rate, recurrence development, overall survival and progression-free survival in DLBCL patients. Material and Method: 100 DLBCL patients diagnosed and treated by Tekirdag? Namık Kemal University Medical Faculty Hematology Clinic between 2012-2022 were included in our study and the data of these patients were analyzed retrospectively. Age, sex, performance scores, stage of the disease, presence of B symptoms and extranodal involvement, risk groups of IPI and CNS-IPI, presence of splenomegaly, germinal or non-germinal type, hemoglobin, leukocyte, creatinine, platelet, ferritin, albumin, LDH, ALT, ALP values, treatments given, responses to treatments, recurrence and ex status, time parameters were noted. Statistical calculations were made with the IBM SPSS (Statistical Package of Social Science, version 26.0) program. Cox regression was used to determine mortality and recurrence risk among patient groups, Logistic regression was used to evaluate response to treatment and Kaplan Meier-Log rank method was used to compare survival times. Results: A total of 100 patients, 50 women and 50 men, were included in our study. There were 54 patients aged 60 and above, 58 patients with advanced stage, 65 patients with ECOG 2 and above, 23 patients with high risk IPI, 28 patients with high risk CNS-IPI and 49 patients with extranodal involvement. First-line treatment was given to all patients. %84 of the patients responded to the first-line treatment and %16 did not respond. During the follow-up period, mortality occurred in 24% of patients and recurrence in 27%. The rate of responding to first-line treatment was higher in those with low leukocytes than those with high leukocytes (HR=0.34, 95% CI:0.12-0.95, p=0.040). The rate of responding to first-line treatment was higher in those with low ferritin than those with high ferritin (HR=0.29, 95% CI:0.10-0.81, p=0.018). The risk of both mortality and recurrence was higher in those aged 60 and over, poor performance and extranodal involvement, high CNS-IPI and IPI scores, high creatinine and ferritin, and low albumin. İn our study; advanced age, poor performance, high IPI, high CNS-IPI, presence of extranodal involvement, low hemoglobin and low albumin, high creatinine and high ferritin adversely affected PFS. Advanced stage, advanced age, poor performance, high IPI, high CNS-IPI, presence of extranodal involvement, low albumin, high creatinine and high ferritin adversely affected OS. Consistent with the literature; the 5-year PFS and OS rates of the patients in our study were 61.9% and 65.4%, respectively. Conclusion: Consistent with the literature, prognostic indices such as IPI and CNS-IPI were found to be associated with OS and PFS in our study. Age, stage, performance and presence of extranodal involvement included in IPI were also associated with survival. However, there was no effect of LDH on OS, PFS, recurrence and mortality. Conflicting results have been reported in many studies investigating the effect of albumin level on lymphoma prognosis. However; in our study, albumin level was found to be associated with disease survival, recurrence and mortality risk. To date, there has been no study investigating the effect of ferritin level at the time of diagnosis on response to first-line treatment in DLBCL. In our study, a significant correlation was found between ferritin level at the time of diagnosis and response to treatment, recurrence and mortality risk. This makes our study original and contributes to the literature. Based on all the results in our study, it can be said that ferritin level is a prognostic parameter. Keywords: Lymphoma, Diffuse Large B Cell Lymphoma, Prognosis, Survival, Relapse, Mortality
Açıklama
Tıp Fakültesi, İç Hastalıkları Ana Bilim Dalı, İç Hastalıkları Bilim Dalı
Anahtar Kelimeler
Hematoloji, Hematology
