Abstract | Uvod: B-velikostanični limfom (B-LCL, od engl. B large cells lymphoma) najčešći je ne- Hodgkinov limfom. Prognoza ovisi o kliničkim značajkama, sažetima u tzv. međunarodnom prognostičkom indeksu (IPI, od engl. international prognostic index). Molekulski i imunohistokemijski prognostički bilježi su ili nepouzdani ili njihova cijena i tehnička ograničenja čine rutinsku primjenu nepraktičnom. Stoga je pronalaženje surogatnih biljega, koji mogu poslužiti kao prognostički čimbenik, važan doprinos procjeni individalnog rizika. Cilj istraživanja: odrediti prognostički značaj upalnih prognostičkih bodovnih sustava i širine distribucije eritrocita (RDW, od engl. red blood cell distribution width) u bolesnika s B- LCL-om. Bolesnici i metode: Retrospektivno smo analizirali podatke 81 bolesnika s B-LCL-om koji su dijagnosticirani u razdoblju od 2006. do 2013. godine u KBC-u Osijek. Promatrani su ishodi, ukupno preživljenje (OS, od engl. overall survival) i preživljenje bez događaja (EFS, od engl. event free survival). Korištena je univarijatna i multivarijatna (Coxova regresijska) statistička analiza. Rezultati: Medijan dobi bolesnika bio je 64 godine, 29 ispitanika bili su muškarci (36 %). Vrijednost NLR-a (od engl. neutrophil lymphocyte ratio - omjer neutrofila i limfocita) bila je veća u bolesnika s proširenom bolesti (stadij III i IV) nego u onih s lokaliziranom bolesti (stadij I i II) (medijan [raspon] 3,12 [0,62 - 17,8] vs 2,38 [0,56 - 7,5], P = 0,037) i u onih bolesnika koji nisu odgovorili na terapiju (2,64 [0,56 - 11,29] vs 4 [0,62 - 14,17], P = 0,011). Vrijednost PLR-a (od engl. platelet lymphocyte ratio - omjer trombocita i limfocita) bila je veća u bolesnika s proširenom bolesti (stadij III i IV) nego u onih s lokaliziranom bolesti (stadij I i II) (181,18 [13,05 - 608,93] vs 132,24 [67,44 - 521,37], P = 0,023), a nije bilo statistički značajne razlike u vrijednosti PLR-a između bolesnika koji su odgovorili na terapiju i onih koji nisu (P=0,151). Bolesnici s višim vrijednostima GPS-a bili su lošijeg općeg stanja (P = 0.002), većeg kliničkog stadija po Ann Arboru (P = 0.03) i imali su lošiji odgovor na terapiju (P < 0.001). Veće vrijednosti RDW-a (%) imali su pacijenti s proširenom bolešću (14,94±1,82 vs 13,55 ± 1,54, P = 0,001) i oni s lošim odgovorom na terapiju (14,94± 1,82 vs 13,55 ± 1,54, P = 0,001). Dvogodišnji OS i dvogodišnji EFS bili su značajno lošiji u bolesnika s NLR > 2,63 (rezna vrijednost izračunata ROC, od engl. receiver operating characteristic, analizom) (65,8 % vs 86,6 % za dvogodišnji OS, P = 0,007; 58,2 % vs 86,6 % za dvogodišnji EFS, P = 0,001) i u bolesnika s RDW > 15 % (rezna vrijednost izračunata ROC analizom) (42,2 % vs 91,7 % za dvogodišnji OS, P < 0,001; 42,9 % vs 83,3 % za dvogodišnji EFS, P < 0,001), dok PLR nije bio značajan za preživljenje. Dvogodišnji OS za pacijente s GPS-om (od engl. Glasgow prognostic score - Glasgowski prognostički bodovni sustav) = 0, GPS = 1 i GPS = 2 bila je 89,6 %, 65,8 % i 36,4 % (P = 0,002). Dvogodišnji EFS bio je 81,6 % za pacijente s GPS = 0, 63,2 % za one s GPS = 1 i 36,4 % za pacijente s GPS = 2 (P = 0,014). Multivarijatna analiza utvrdila je da je RDW > 15 % bio neovisan prognostički čimbenik za OS (HR, od engl. hasard ratio - omjer rizika, 8,873, 95 % CI, od engl. confidence interval - interval pouzdanosti, 2,065-38,132, P = 0,003) i EFS (HR 5,755, 95 % CI 1,733-19,11, P = 0.004), dok je NLR bio prognostički značajan samo za EFS (HR 5,973, 95 % CI 1,832-19,481, P = 0,003). Zaključak: U bolesnika s B-LCL-om naše je istraživanje potvrdilo NLR kao koristan prognostički biljeg, dok PLR i GPS nisu pokazali neovisnu prognostičku vrijednost za preživljenje. Visoka početna vrijednost RDW-a bila je povezana s lošijim ishodom. RDW bi mogao biti lako dostupan, jeftin prognostički biljeg za stratifikaciju bolesnika u rizične skupine. |
Abstract (english) | Background: B-large cell lymphoma (B-LCL) is the most common non-Hodgkin's lymphoma. The prognosis depends primarily on clinical features, summarized in the so-called International Prognostic Index (IPI). There are certain molecular and immunohistochemical prognostic markers in patients with B-LCL, but their cost and technical constraints make such an application in routine impractical and expensive. Therefore, finding surrogate markers that may serve as a prognostic factor is an important contribution to the establishment of individual risk assessment. Objectives: The aim of this study was to analyze the prognostic significance of inflammation based prognostic scores and red blood cell distribution width (RDW) in B-LCL patients. Patients and methods: We retrospectively analyzed data from 81 B-LCL patients diagnosed from 2006 to 2013 at the University Hospital Center Osijek, Osijek, Croatia. We evaluated disease outcome, overall survival (OS) and event-free survival (EFS), and demographic, clinical and laboratory factors affecting outcome. Univariate analysis and Cox regression analysis were used. Results: The median age of patients was 64 years, 29 were men (35.8 %). Higher neutrophil to lymphocyte ratio (NLR) was found in patients with an advanced disase (median [range] 3.12 [0.62 - 17.8] vs 2.38 [0.56 - 7.5], P = 0.037 and a poorer response to therapy (median [range] 2.64 [0.56 - 11.29] vs 4 [0.62 - 14.17], P = 0.011). Higher platelet to lymphocyte ratio (PLR) was found in patients with an advanced disase (median [range] 181,18 [13,05 - 608,93] vs 132,24 [67,44 - 521,37], P = 0,023), values of PLR were not significant for response to treatment. Patients with higher GPS were in poorer general condition (P = 0.002), advanced disease stage (P = 0.03), and a poorer response to therapy (P < 0.001). Higher RDW levels (%) were found in patients with advanced Ann Arbor clinical stage (14.94±1.82 vs 13.55± 1.54, P = 0.001) and in those with poor response to therapy (14.94±1.82 vs 13.55± 1.54, P = 0.001). Patients with NLR values of > 2.63 (cutoff value calculated by receiver-operating characteristic) had a significantly worse two-year OS (65.8 % vs 86.6 %, P = 0.007) and two-year EFS (58.2 % vs 86.6 %, P = 0.001). PLR values were not significant for survival. The two-year OS rates for patients with Glasgow prognostic score (GPS) = 0, GPS = 1, and GPS = 2 were 89.6 %, 65.8 % and 36.4 % (P = 0.002) and EFS rates were 81.6 %, 63.2 %, and 36.4 %, respectively (P = 0.014). Patients with RDW>15 % (cut-off was calculated by receiver operating characteristics) had a significantly worse two-year OS (42.2 % vs 91.7 %, P < 0.001) and two-year EFS (42.9 % vs 83.3 %, P < 0.001). Cox regression analysis showed that RDW > 15 % was an independent prognostic factor for OS (hazard ratio [HR] 8.873, 95 % confidence interval [CI] 2.065-38.132, P = 0.003) and EFS (HR 5.755, 95 % CI 1.733-19.11, P = 0.004) while NLR values of > 2.63 were an independent prognostic factor only for EFS (HR 5.973, 95 % CI 1.832-19.481, P = 0.003) Conclusion: Our research confirmed NLR as a useful independent prognostic marker for survival. PLR and GPS did not show an independent prognostic value. High baseline RDW is an independent prognostic marker of poor outcome in patients with DLBCL. RDW could be an easily available and inexpensive marker for the risk stratification in patients with B-LCL. |