25(OH) vitamin D deficiency in lymphoid malignancies, its prevalence and significance. Are we fully aware of it?

INTRODUCTION: Vitamin D has a role in cellular differentiation, proliferation, apoptosis, and angiogenesis and therefore is studied as a prognostic factor in cancer. The aim of our study was to assess the prevalence and significance of 25(OH)D deficiency in patients with lymphoid malignancies. METHODOLOGY: Between January 2014 and June 2016 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade, the pretreatment serum level of 25(OH)D was determined in 133 (62 women/71 men, median age 58 (18-84) years) previously untreated patients with lymphoid malignancy using a chemiluminescent immunoassay. From their medical records, we noted the age, clinical stage, Eastern Cooperative Oncology Group Performance Scale (ECOG PS), nutritional status using the Nutritional Risk Score 2002 (NRS2002), the time of year, comorbidity index, progression, and progression-free survival (PFS) for a median of 20 (1-32) months. The optimal cutoff point for prediction of outcome was determined using the Maximally Selected Rank Statistics. RESULTS: There were 37 (27.8%) patients with the severe 25(OH)D deficiency ≤ 25 nmol/l, 80 (60.2%) with 25(OH)D deficiency 25-50 nmol/l, and 16 (12%) with 25(OH)D insufficiency 50-75 nmol/l. None of the patients had the desired normal level. There were significant differences between groups in regard to ECOG PS, NRS2002, type of lymphoma, and progression. The severely 25(OH)D-deficient patients had a shorter mean time until progression (P = 0.018). Cox regression analysis showed that 25(OH)D < 19.6 nmol/l remained the only significant parameter for PFS (HR = 2.921; 95% CI 1.307-6.529). CONCLUSION: The prevalence of 25(OH)D deficiency in the analyzed group of patients with lymphoid malignancies is high and greater in malnourished individuals. Patients with pretreatment serum 25(OH)D < 19.6 nmol/l had a significantly shorter PFS.

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.

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.

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.

Unusual presentation of gastric plasmablastic lymphoma in HIV-negative patient.

Plasmablastic lymphoma (PBL) has initially been described as a rapidly progressive and almost invariably fatal diffuse large-cell lymphoma with plasmablastic features, exclusively involving the jaw and oral mucosa in HIV-positive patients. Although its clinical features may help in differential diagnosis, an extra-oral localization in a patient without HIV makes it more difficult to suspect clinically. We describe a very rare case of gastric PBL primarily involving stomach in a middle age man without an HIV infection. A biopsy was performed and its findings revealed a diffuse, monomorphous proliferation of the tumor cells with features of immunoblasts, MUM-1, EMA, and lambda light chains positive. Serology was negative for the human immunodeficiency virus (HIV), HBsAg, and hepatitis C virus infection. The patient started treatment with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but unfortunately died before the second cycle was given. To our knowledge, this is the second case of gastric PBL presented in HIV-negative patients. The findings in this case suggest that PBL should be included in the differential diagnosis of gastrointestinal tumors.

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.