Korelacija kliničkih parametara i bioloških markera apoptoze u prognozi klasičnog Hočkinovog limfoma
Correlation of clinical parameters with apoptotic biological markers in prognosis of classical Hodgkin lymphoma
Author
Jaković, Ljubomir R.Mentor
Bumbaširević, VladimirCommittee members
Mihaljević, Biljana
Trpinac, Dušan
Janković, Gradimir
Bogdanović, Andrija

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Show full item recordAbstract
Hočkinov limfom (HL) je izlečiv tumor, međutim savremeni pristupi lečenju ove
bolesti nisu precizni. Prognozna vrednost bioloških i morfoloških parametara kontroverzna
je, a modeli prognoze nisu široko prihvaćeni.
Cilj studije bio je utvrditi da li varijable zasnovane na karakteristikama tkiva mogu
doprineti prognoznoj vrednosti standardnih kliničkih parametara i da li te varijable mogu
poslužiti za procenu stepena rizika kod bolesnika sa HL.
Prognozna važnost 8 parametara analizirana je u 85 bolesnika sa odmaklim stadijumom
klasičnog HL.
Univarijantna analiza potvrdila je pet indikatora kraćeg ukupnog preživljavanja
(engl. Overall Survival-OS): povećana ekspresija Bcl-2 (>50%Bcl-2+ tumorskih ćelija), povećani
broj CD68 tumor-pridruženih makrofaga (engl. tumor associated macrophages-TAM)
(>25%CD68+TAM); Internacionalni Prognozni Skor (IPS)>2; voluminozna tumorska masa
(engl. Bulky Disease –BD), potpuna zahvaćenost limfnih čvorova tumorskim tkivom (engl.
Total Lymph Node Involvement-TLN...I) (p=0.007, p=0.003 p=0.000, p=0.002, p=0.017, po
redosledu). Nezavisno od TLNI ovi činioci uticali su i na kraće preživljavanja bez znakova
bolesti (engl. Event Free Survival- EFS) (p=0.031, p=0.035, p=0.004, p=0.014, po redosledu).
Multivarijantna analiza utvrdila je pet nezavisnih faktora za OS: >50% Bcl-2+ tumorskih
ćelija; >25% CD68+ TAM; TLNI, IPS>2; BD (p=0.025, p=0.042, p=0.003, p=0.000,
p=0.003, po redosledu). Na EFS uticali su >25% CD68+TAM; IPS>2; BD (p=0.044, p=0.009,
p=0.018, po redosledu).
Dizajnirali smo prognozni model sa 4 grupe rizika (niskog 0-1, srednjeg 2, visokog
3, veoma visokog 4-5 faktora rizika), svaka sa progresivno kraćim OS (100%, 78%, 45%, 0%,
po redosledu, p<0.001).
Naši nalazi ukazuju da se u trenutku postavljanja dijagnoze HL kombinovanjem
tkivnih varijabli i kliničkih parametara mogu otkriti bolesnici sa visokim rizikom loše prognoze.
Although Hodgkin’s lymphoma (HL) is a curable cancer, current treatment strategies
based on risk stratification and response evaluation are not precise enough. The predictive
power of biological and morphological parameters is controversial and prognostic
models have not reached wide acceptance.
The aim of the study was to determine whether tissue-based variables could add
prognostic value to standard clinical parameters and contribute to a better risk stratification
of HL patients. We analyzed the prognostic relevance of 8 parameters in 85 advanced stage
classical HL patients.
Univariate analysis confirmed five indicators of shorter OS: Bcl-2 overexpression
by RS cells (>50%Bcl-2+RS), increased CD68 tumor-associated macrophages
(>25%CD68+TAM); IPS>2, bulky disease, and total involvement of the lymph node by
neoplastic and inflammatory cells (TLNI) (p=0.007, p=0.003 p=0.000, p=0.002, p=0.017,
respectively). These factors also influenced lower EFS (p=0.031, p=0.035, p=0.004, p=0.014,
re...spectively), except of TLNI.
Multivariate analysis identified five separate factors for OS: >50% Bcl-2+RS; >25%
CD68+TAM; TLNI; IPS>2, and bulky disease (p=0.025, p=0.042, p=0.003, p=0.000,
p=0.003, respectively). Furthermore, >25% CD68+TAM, IPS>2, and bulky disease affected
EFS (p=0.044, p=0.009, p=0.018, respectively).
Utilizing the cumulative score of unfavorable prognostic factors for OS, we designed
a prognostic model by stratifying patients into 4 risk groups (low 0-1, intermediate 2, high
3, very high 4-5 risk factors), each with progressively reduced OS (100%, 78%, 45%, 0% respectively,
p<0.001).
Our findings endorse the combining the tissue based variables with clinical parameters,
identifying patients who are at higher risk of poor outcome.