Prognostic significance of Bcl-2, tumor-associated macrophages, and total neoplastic and inflammatory lymph node involvement in advanced stage classical Hodgkin's lymphoma.

BACKGROUND: Although Hodgkin's lymphoma (HL) is a curable cancer, current treatment strategies based on risk stratification and response modulation are not precise enough. The predictive power of biological and morphological parameters is controversial, with prognostic models not reaching wide acceptance. PATIENTS AND METHODS: We analyzed the prognostic relevance of 8 parameters in 85 advanced stage classical HL patients, in order to determine whether tissue-based variables could add prognostic value to standard clinical parameters, thus contributing to better risk stratification at presentation. RESULTS: Univariate analysis confirmed 5 indicators of shorter overall survival (OS): Bcl-2 overexpression; increased CD68+ tumor-associated macrophages (TAM); international prognostic score (IPS) > 2; bulky disease; and total lymph node involvement (TLNI) with regard to neoplastic and inflammatory cells. Apart from TLNI, these parameters influenced lower event-free survival (EFS). Multivariate analysis identified 5 independent factors for OS: Bcl-2 overexpression; increased CD68+ TAM; TLNI; IPS > 2; and bulky disease. Increased CD68+ TAM, IPS > 2, and bulky disease affected the EFS. Utilizing the cumulative score of unfavorable prognostic factors for OS, we designed a prognostic model stratifying patients into 4 risk groups (with 0-1, 2, 3, or 4-5 factors), each with progressively reduced OS (p < 0.001). CONCLUSION: Our findings support the combination of tissue-based variables with clinical parameters at diagnosis, identifying patients who are at higher risk of poor outcome.

Hodgkin's lymphoma relapse in the uterine cervix 15 years after the initial cure.

Uterine cervix is an uncommon site for the presentation of Hodgkin's lymphoma. We describe a 62-year-old woman who developed an unusual relapse of classical Hodgkin's lymphoma, a nodular sclerosis subtype, in the uterine cervix, with propagation to the vaginal wall. She relapsed 15 years after achieving a complete remission of Hodgkin's lymphoma, initially in clinical stage IVB. This late relapse of the Hodgkin's lymphoma was in the clinical stage IEB and the treatment was initiated according to ABVD regimen. After the second course, lethal outcome ensued due to progression of the renal failure, which ensued in the meantime, probably as an adverse effect of the previous therapy.

The expression of Ki-67 and Bcl-2 in Hodgkin's lymphoma: correlation with the International Prognostic Score and bulky disease: a study by the Serbian Lymphoma Study Group (SLG).

The prognosis of Hodgkin's lymphoma has been improved over last 10 yr due to identification of prognostic parameters. These factors may predict the clinical outcome and therefore may have influence on the selection of appropriate treatment. In a cohort of 40 patients with Hodgkin's lymphoma of nodular sclerosis subtype, treated with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) regimen, we analyzed prognostic relevance of the expression of Ki-67 and Bcl-2 at diagnosis as well as other clinical parameters: International Prognostic Score, bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate. Significance was tested according to response rate and overall survival. Patients with a high proliferative fraction (Ki-67 > 50%) had worse overall survival compared with those with low proliferation, 56% vs 91%. There was a correlation between Ki-67 positivity and the achievement of complete remission. Cox's multivariate model revealed that Ki-67 positivity at threshold of 50% was a significant independent prognostic factor. The Bcl-2 expression in less than 50% of tumor cells was detected in 65.5% of patients, and in a majority of cases it was associated with complete remission. Patients with high IPS had more progressive disease and shorter survival. Bulky disease, tissue eosinophilia, and high erythrocyte sedimentation rate had no significant influence on complete remission and survival. However, there was a marked divergence in survival curves after 4 yr follow-up for each of these parameters. Patients with high Ki-67, IPS > 3, bulky disease, tissue eosinophilia, and high sedimentation rate are at a higher risk of treatment failure and relapse and therefore might be eligible for other aggressive therapeutic approach.

Prognostic value of lymphocyte/monocyte ratio in advanced Hodgkin lymphoma: correlation with International Prognostic Score and tumor associated macrophages.

We studied the prognostic significance of the absolute lymphocyte/monocyte count ratio (ALC/AMC), its contribution to the prognostic value of the International Prognostic Score (IPS), and evaluated if ALC/AMC could serve as a proxy for the frequency of CD68 + tumor-associated macrophages (TAMs) in 101 patients with advanced Hodgkin lymphoma (HL). The receiver operating characteristic (ROC) curve identified best cut-off values of 2.0 for ALC/AMC and 25% for CD68 + TAM. Patients with ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM had an inferior overall survival (OS) and event-free survival (EFS). Spearman's test also uncovered a significant correlation between the ALC/AMC and TAM. Multivariate analysis identified ALC/AMC < 2, IPS > 2 and > 25% CD68 + TAM as poor prognostic factors of OS and EFS. After evaluating ALC/AMC and IPS, we stratified patients into three progressively-worse-outcome groups (low-risk: 0 risk factors; intermediate: 1 risk factor; high: 2 risk factors). Our study encourages the combination of ALC/AMC with IPS, for refining risk prediction in advanced HL patients.

ABVD as the treatment option in advanced Hodgkin's lymphoma patients older than 45 years.

Advanced age is considered an unfavourable prognostic factor for Hodgkin's lymphoma (HL). The optimal treatment for these patients is not yet defined, especially for the advanced stages. We analysed the outcome and prognostic relevance of patient and disease characteristics in 46 advanced stage HL patients who were older than 45 years, treated with ABVD. Elderly patients (>60 year) had a significantly higher rate of comorbidities (p < 0.05). The complete remission rate was significantly lower in elderly patients and in patients with an IPS ≥ 3 (p < 0.05, p < 0.05, respectively). Elderly patients had significantly shorter event-free survival (p < 0.01) and overall survival (p < 0.01) compared to patients of 45-60 year. Extranodal disease, an IPS ≥ 3, bulky disease, an ESR > 50 and the presence of a large mediastinal tumour mass didn't have an influence on survival (p > 0.05). The multivariate Cox regression analysis identified the age of >60 year as an independent prognostic factor. The prospective clinical trials seem to be needed for defining the optimal therapeutic approach in elderly patients.

The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma.

Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.