Alvaro J. Alencar

Primary bone lymphoma the university of miami experience

Primary bone lymphoma (PBL) is a rare disease. There has been paucity of studies addressing its therapy and prognosis. We retrospectively examined PBL cases seen at the University of Miami from June 2000 to August 2007 to describe our single institution experience and review the literature. Fifty-three patients were identified with a median age of 52 (18–87) and a median follow-up of 40 months (0–106). The most common histologic type was diffuse large B-cell lymphoma (83%). Forty-one patients (77%) presented with localized disease and 48 were treated at our institution. Forty-six patients underwent chemotherapy (40 patients) and/or radiation (36 patients). Forty-four patients achieved a complete response and all patients were alive at last follow-up. The progression-free survival (PFS) was 83% at 4 years. No difference in PFS was observed between patients treated with chemotherapy or combined chemotherapy plus radiation. There was a trend toward improvement in PFS (p = 0.062) of patients with DLBCL treated with rituximab plus chemotherapy. Our single institutional experience demonstrates that the outcome of patients with PBL is excellent. Although the current data support the use of combined modality treatment for localized PBL, randomized controlled trials are needed especially now, when rituximab is routinely added to chemotherapy regimens.

Rituximab for treatment of chemoimmunotherapy naive marginal zone lymphoma

Marginal zone lymphomas (MZL) represent a group of lymphomas originating from B lymphocytes normally residing in the marginal zone of secondary lymphoid follicles. These lymphomas are classified into nodal MZL, splenic MZL, or extranodal MZL of the mucosa associated lymphoid tissue (MALT) type according to the primary involvement site [1]. In the Non-Hodgkin’s Lymphoma Classification Project, MZLs constituted approximately 9% of the lymphomas [2], mainly accounted by MALT lymphomas. Although eradication of Helicobacter pylori (H. pylori) is considered the initial therapy of choice for patients with localized H. pylori-positive gastric MALT and radiation is frequently used to treat other localized MALT or nodal MZL, there is no uniformly established therapy for patients with other presentations. Following the report on efficient control of MALT lymphomas with a single agent rituximab by Conconi et al. [3], starting October 2003 our lymphoma program decided to use this therapeutic regimen in all the newly diagnosed patients with chemoimmunotherapy naı̈ve MZL, who were older than 18 years of age, had biopsy-proven MZL according to the World Health Organization classification criteria, and were not eligible or refused to receive radiation therapy as a single modality therapy for stage I disease or splenectomy for splenic marginal zone lymphoma. Previous radiation therapy and antibiotics for Helicobacter pylori did not preclude use of rituximab. Until December 2005, when we changed our program guidelines, a total of 16 patients, representing all the patients with MZL eligible for this treatment based on our guidelines, were treated with rituximab and represent the basis of this report. Rituximab was administered weekly for four consecutive weeks at a dose of 375 mg/m by slow intravenous infusion following standard guidelines. Response to the therapy was evaluated 6 – 8 weeks after completion of the fourth dose of rituximab by standard criteria. In the case of gastric MALT lymphomas, endoscopies with biopsies from abnormally appearing mucosa or from at least four random normally appearing gastric mucosa sites were performed to assess the response to treatment. The primary end points of this report were overall response rate including complete response (CR) and partial response (PR) and time to treatment failure (TTF), defined as the time from initiation of rituximab therapy to disease progression, administration of additional therapy because of failure to achieve at least PR or death. The median age of the 16 treated patients (Table I) was 55 years (range 30 – 82). There were three patients with nodal MZL, one patient with splenic MZL, and 12 patients with extranodal MALT, including three with gastric and nine with nongastric presentation. All cases underwent central histologic review by an expert lymphoma pathologist confirming MZL diagnosis. Three patients received radiation therapy for localized disease at 2, 6, and 36 months prior to rituximab. Two of the three patients with gastric MALT lymphoma were H. pylori-positive but failed to respond to a course of antibiotic therapy.

MiR-181 family-specific behavior in different cancers: a meta-analysis view

The involvement of microRNAs in malignant transformation and cancer progression was previously grounded. The observations made by multiple published studies led to the conclusion that some of these small sequences could be eventually used as biomarkers for diagnosis/prognosis. This meta-analysis investigated whether microRNA-181 family members could predict the outcome of patients carrying different types of cancer. We searched the PubMed and Embase databases for studies evaluating the expression levels of miR-181a/b/c/d in patients with cancer, selecting the publications that assessed the relation between low and high levels of one of these four microRNAs and patients’ outcome. Hazard ratios (HRs) or risk ratios (RRs) were extracted from the studies, and random-effect model was performed to investigate the role of miR-181 in the outcome of these patients. The meta-analysis comprised 26 studies including 2653 cancer patients from 6 countries. The results showed significant association between the expression of miR-181 family members and colorectal cancer. Considering the heterogeneity of the pathologies, the analysis, including all types of cancer and the expression of all the miR-181 family members together, showed no association with distinct outcome (HR = 1.099, p = 0.435). When the analysis was performed on each microRNA separately, the expression of miR-181c was significantly associated with the outcome of patients with cancer (HR = 2.356, p = 0.011) and miR-181a expression levels significantly correlated with survival in patients with non-small-cell lung cancer (HR = 0.177, p < 0.05). This meta-analysis revealed evidence regarding the involvement of miR-181 family members in the outcome of patients with some types of cancer, according to their expression level.

Abstract PR5: Prediction of survival in diffuse large B-cell lymphoma based on the expression of two genes integrating tumor and microenvironment

Several gene expression signatures are predictive of prognosis in diffuse large B cell lymphoma (DLBCL), but the lack of practical methods for a genome scale analysis has restricted their clinical applicability. Towards construction of a molecular predictor amenable to rapid testing on routinely obtained diagnostic clinical specimens, we studied genes previously reported to be associated with survival in DLBCL, testing and validating risk scoring models with robust survival associations in the current therapeutic era. We identified LMO2 expression as a robust univariate predictor of survival and cell of origin classification of DLBCL, with independent prognostic value. We examined bivariate models combining expression of LMO2 with other genes, and identified TNFRSF9 as a tumor microenvironment gene with independent prognostic influence. A combined model integrating both LMO2 and TNFRSF9 expression was independent of “cell of origin” classification, “stromal signatures,” International Prognostic Index (IPI), and added to the predictive power of IPI. A composite model was validated in multiple independent patient cohorts using public microarray data. Using routinely obtained formalin fixed, paraffin embedded diagnostic specimens from an independent cohort, we developed a simple assay validating the clinical utility of this 2-gene model, as well as a composite model integrating the IPI. In conclusion, measurement of a single gene expressed by tumor cells and a single gene expressed by the immune microenvironment is sufficient to predict overall survival in patients with DLBCL treated with R-CHOP. A combined model serves as a robust clinical risk assessment tool. This talk is also presented as Poster A27. Citation Information: Clin Cancer Res 2010;16(14 Suppl):PR5.