José Carlos Morais

Lack of association of tumor-associated macrophages with clinical outcome in patients with classical Hodgkin's lymphoma

BACKGROUND A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkins lymphoma (cHL). PATIENTS AND METHODS The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.BACKGROUND A recent study demonstrated that an increased number of CD68+ macrophages were correlated with primary treatment failure, shortened progression-free survival (PFS) and disease-specific survival (DSS) in patients with classical Hodgkins lymphoma (cHL). PATIENTS AND METHODS The aim of the present study was to verify the relationship between the number of CD68+ and CD163+ macrophages with clinical outcomes in a cohort of 265 well-characterized patients with cHL treated uniformly with the standard doxorubicin, bleomycin, vinblastine and dacarbazine chemotherapy regimen. Two pairs of hematopathologists carried out independent pathological evaluations of tissue microarray slides. RESULTS There were no associations between clinical characteristics and the expression of CD68 or CD163. However, higher levels of CD68 and CD163 expression were correlated with the presence of Epstein-Barr virus-positive Hodgkin tumor cells (P = 0.01 and 0.037, respectively). The expression of CD68 or CD163 was not associated with either the PFS or the DSS. CONCLUSION CD68 and CD163 expression require further evaluation before their use can be recommended for prognostic stratification of patients with cHL.

CD10 and Bcl-2 expression combined with the International Prognostic Index can identify subgroups of patients with diffuse large-cell lymphoma with very good or very poor prognoses

Aims : Diffuse large B‐cell lymphoma (DLBCL) is characterized by marked biological heterogeneity. The identification of reproducible parameters that can be combined with the International Prognostic Index (IPI) to better predict outcome could lead to the development of effective risk‐adaptive strategies.

CD137 Is Expressed in Follicular Dendritic Cell Tumors and in Classical Hodgkin and T-Cell Lymphomas: Diagnostic and Therapeutic Implications

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.

Socioeconomic inequality and short-term outcome in Hodgkin's lymphoma.

Socioeconomic status (SES) is a determinant of outcome in various types of cancer. The aim of this study is to analyze the impact of the SES in Hodgkins lymphoma (HL). From 2001 to 2005, 194 consecutive patients were prospectively followed in 5 institutions. Patients answered a questionnaire with a set of items used to determine the SES, and were then divided in 2 groups according to their SES score. There were 151 patients (78%) with a higher SES and 43 patients (22%) with a lower SES. The complete remission (CR) rate was 82%. Patients with a higher SES had a higher CR rate than those with a lower SES (85 vs. 72%, crude odds ratio = 2.27, p = 0.046). A lower SES and the performance status >1 were independently associated with a trend towards a lower CR, even when controlled for the other covariables of interest. Ten patients (5%) died during treatment. Death during treatment was associated with a lower SES (16 vs. 2%, p = 0.001), a performance status >1 (p < 0.0001), a lower lymphocyte count (p = 0.012) and weakly with a lower albumin level (p = 0.065). With a median follow‐up of 1.7 years, a higher SES was associated with a better 2‐year overall survival (93 vs. 79%, p = 0.01). In underprivileged countries, patients with a lower SES require a more careful monitoring during treatment, possibly with specific support measures. Regimens more intense than doxorubicin, bleomycin, vinblastine and dacarbazine could pose a prohibitive risk of complications in this group of patients.

The prognostic value of the expression of Bcl-2, p53 and LMP-1 in patients with Hodgkin's lymphoma.

This study was undertaken to evaluate the clinical significance of the expression of Bcl-2, p53 and LMP-1 in Hodgkin and Reed - Sternberg cells of patients with Hodgkins lymphoma. The expression of these proteins in pre-treatment tissue biopsy specimens was correlated with presenting clinical features, failure-free survival (FFS) and overall survival (OS) in 83 patients with a confirmed Hodgkins lymphoma treated in a single institution. HIV-positive patients were excluded. Patients were classified according to the International Prognostic Score (IPS) in low-risk (0 - 2 factors) and high-risk groups. The median age was 41 years (15 - 84), 41% were women, and 93% had advanced-stage disease (IIB - IVB). The expression of Bcl-2, p53 and LMP-1 was not associated with the complete remission rate, FFS or OS. The IPS risk group was the only factor significantly associated with OS. Patients with a high IPS had a lower 5 year OS (43% vs. 79%, P = 0.003). The expression of Bcl-2, p53 and LMP-1 did not add prognostic information to the IPS.

Clinical Factors Predictive of Bone Marrow Involvement in Hodgkin's Disease

The role of bone marrow biopsy in the staging of Hodgkins disease is undergoing reevaluation. We have studied the relationship of clinical factors to the presence of bone marrow involvement in 130 previously untreated patients with Hodgkins disease. The presence of fever, spleen enlargement, anemia, leukopenia, poor performance status and poor histologic subgroups were positively correlated with the presence of bone marrow involvement in the univariate analysis. In the multivariate analysis, only fever, spleen involvement, leukopenia and poor histologic subgroups were significant. The predictive value of the absence of fever in regard to the absence of bone marrow involvement was 98%. The likelihood of bone marrow involvement in the absence of all four significant factors was only 0.05%. Patients without these clinical factors should probably not be submitted to a bone marrow biopsy as part of the staging procedures performed in Hodgkins disease.

Spinal cord compression due to extramedullary hematopoiesis in the proliferative phase of polycythemia vera

Extramedullary hematopoiesis is a common accompaniment of a variety of hematologic diseases such as hereditary spherocytosis, thalassemia and myelofibrosis. The association of extramedullary hematopoiesis with polycythemia vera in the proliferative phase is much less usual. We report a patient who presented with paraplegia due to spinal cord compression; clinical investigation revealed a paravertebral hematopoietic tumor, and the diagnosis of polycythemia vera was then established.

Association of social network and social support with health-related quality of life and fatigue in long-term survivors of Hodgkin lymphoma

PurposeAs the number of survivors of Hodgkin’s lymphoma (HL) increases, there has been a growing interest in long-term treatment-related side effects and their impact on the quality of life (QoL). The aim of this study was to assess the association of social network and social support with the QoL and fatigue among long-term HL survivors.MethodsA total of 200 HL survivors were included. The generic Short Form-12 (SF-12) questionnaire, the QoL cancer survivor’s questionnaire (QOL-CS), and the Multidimensional Fatigue Inventory were used to assess QoL and fatigue. Social network and social support were evaluated with the Social Support Survey.ResultsSocial network and all social support measures were favorably associated with two or more SF-12 scales, mainly with physical functioning and the mental health scales. Social network and social support dimensions were also associated with better QOL-CS scores. Affective support, informational support, positive interaction, and emotional support were associated with less fatigue.ConclusionsBoth social network and social support are associated with better QoL and lower levels of fatigue in HL survivors. This information may be useful to health professionals and community organizations in implementing effective interventions to improve these patients’ quality of life.

PKC-beta II expression has prognostic impact in nodal diffuse large B-cell lymphoma.

Recent studies of gene expression and immunohistochemistry have shown that protein kinase C-beta II (PKC-beta II) might have prognostic significance in patients with diffuse large B-cell lymphoma (DLBCL). We sought to determine the prognostic significance of the expression of PKC-beta II in patients with nodal DLBCL. Formalin-fixed, paraffin-embedded tissues were stained with a monoclonal antibody to PKC-beta II protein. A total of 125 patients were studied; 83 patients (66%) were in the low-risk International Prognostic Index (IPI) group. Forty-eight patients (38%) were positive for PKC-beta II. Complete remission was obtained in 70%, and was not influenced by the PKC-beta II status (67 vs 71%). The 5-year event-free survival (EFS) was worse in high-risk patients (14 vs 58%, P<0.001) and in those with PKC-beta II positivity (36 vs 49%, P=0.054). In low-risk IPI patients, PKC-beta II expression was related to a worse 5-year overall survival (OS) (60 vs 76%, P=0.033) and a worse 5-year EFS (48 vs 66%, P=0.014). In a Cox regression analysis for EFS, both PKC-beta II expression (hazard ratio=1.68, P=0.037) and the IPI (HR=3.07, P<0.001) were independent poor prognostic factors. PKC-beta II (HR=1.72, P=0.046) and the IPI (HR=5.16, P<0.001) were also independent poor prognostic factors for the OS. PKC-beta II expression, along with the IPI, were associated with a worse EFS and OS in patients with nodal DLBCL specially in low-risk IPI patients.

Detection of free circulating Epstein-Barr virus DNA in plasma of patients with Hodgkin's disease

CONTEXT AND OBJECTIVE Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of Hodgkins disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS A cohort of 30 patients with newly diagnosed Hodgkins disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43% versus 8%, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100% versus 29%, p = 0.0007) and those with advanced disease (63% versus 9%, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION EBV DNA was present in 91% of patients with EBV-associated Hodgkins disease, and in all patients with HIV-associated Hodgkins disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.