Vincenzo Pitini

Although the clinical outcome of patients with diffuse large B cell lymphoma (DLBCL) has been improved by the addition of rituximab to standard chemotherapy, almost one-third fails or relapses after first line treatment. The presence of monoclonal gammopathy (MG) is a known adverse prognostic factor for DLBCL. Because this subset of patients does not benefit from R-CHOP, new therapeutic options are required. Herein, we report the first case of extranodal DBCL of the lung with a concomitant MG who achieved a long lasting complete remission with lenalidomide. The 73-year-old male patient presented with lateral cervical lymphadenopathy, B symptoms, lactate dehydrogenase and beta2-microglobulin elevation. Computed tomography (CT) showed mediastinal lymphadenopathy and bilateral lung involvement. Biopsy of both disease locations revealed the presence of DLBCL. Successive bone marrow trephine biopsy proved the presence of concordant DLBCL involvement. At the time of diagnosis, a MG was present as well. The patient did not respond to the standard treatments, and subsequently underwent lenalidomide 25 mg/m² days 1–21 q28 plus dexamethasone 40 mg days 1–4, 9–12 e 17–20. This therapeutic regimen was efficacious and safe as salvage therapy in extranodal DBCL with a MG. Furthermore, we observed a close association between DLBCL response to therapy and MG levels, suggesting that the amount of M-protein might be a surrogate marker of disease response. Although DLBCL associated with MG does not respond properly to the standard treatments, it is highly sensitive to lenalidomide, which is why we endorse its role as treatment of choice in this subset of patients. In addition, MG levels appear to correlate with tumor burden, suggesting that it might be a useful marker of disease response. Prospective trials to validate these observations are warranted.

Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months. Ghrelin levels were significantly higher in cancer patients than in healthy subjects (573.31 ± 130 vs 320.20 ± 66.48 ng/ml, p < 0.0001), while obestatin (17.42 ± 7.12 vs 24.89 ± 5.54 ng/ml, p < 0.0001) and leptin (38.4 ± 21.2 vs 76.28 ± 17.48 ng/ml, p < 0.0001) values were lower. At ROC analyses the diagnostic profile of ghrelin (AUC 0.962; sensitivity 83%; specificity 98%), obestatin (AUC 0.798; sensitivity 74.5%; specificity 81.5%) and leptin (AUC 0.828; sensitivity 79%; specificity 73%) was superior to that of albumin (AUC 0.547; sensitivity 63%, specificity 69.4%) for detecting cachexia among cancer patients. On Cox multivariate analyses ghrelin (HR 1.02; 95% CI 1.01 – 1.03; p < 0.0001) and leptin (HR 0.94; 95% CI 0.92 – 0.96; p < 0.0001) were significant predictors of death even after correction for other known risk factors such as presence of metastasis and chronic kidney disease. Ghrelin and leptin are promising biomarkers to diagnose cachexia and to predict survival in cancer patients.

Almost 30% of follicular lymphomas (FL) present with stage I-II disease. Although the standard-of-care consists of involved-field radiotherapy (IFRT), approximately half of patients relapse usually outside the primary irradiation field. Systemic immunotherapy with rituximab (R), with or without IFRT, could reduce distant recurrences leading to a better outcome. Therefore, we compared the efficacy of IFRT-alone or associated with R (R+IFRT) versus R-alone in stage I/II FL (grade 1-3A). From 1995 to September 2012, 108 early-stage FL patients were retrospectively assessed: 36 underwent IFRT, 38 R-alone and 34 R+IFRT. Complete response rate was 84% in the IFRT-group, 87% in the R group and 97% in the R+IFRT-group. Median progression-free survival and time to next treatment were significantly higher in both rituximab arms compared to IFRT-alone. R or R+IFRT have demonstrated a better long-term control of the disease without significant additional toxicities.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity whose prognosis for high-risk patients is poor. Aggressive salvage treatments to improve patient outcome have been unsatisfactory. Therefore, we evaluated the efficacy of yttrium-90-ibritumomab tiuxetan (Zevalin®; (90)Y-IT) consolidation after early salvage chemotherapy with autologous stem cell transplantation. Thirty-seven patients with intermediate-high risk DLBCL not in complete remission (CR) after three cycles of rituximab, cyclophosphomide, doxorubicin, vincristine and prednisone (R-CHOP) were assessed retrospectively. After early salvage treatment, 70% achieved CR and 30% partial remission. Twenty patients underwent additional consolidation with (90)Y-IT. During the 3-year follow-up, 50% in the (90)Y-IT-treated group experienced relapse compared to 82.3% in the other cohort (p=0.002). Progression- and disease-free survival were significantly longer in the (90)Y-IT group. However, probably due to the relatively short follow-up period, no difference in overall survival was observed. (90)Y-IT consolidation after early salvage chemotherapy improves treatment responses and reduces the percentage of relapses without significant additional toxicities.

Occult hepatitis B (OBI) is caused by a persistent low-level replication of HBV. Like overt HBV infection, OBI can be associated with the integration of HBV sequences into the host genome and has a substantial clinical relevance for patients who are severely immunosuppressed for long durations. We present the case of a patient with a diffuse large B-cell non-Hodgkin lymphoma and OBI who developed a hepatocellular carcinoma with a fulminant clinical course following the administration of rituximab plus CHOP.