Efficacy and safety of rituximab treatment in patients with progressive transformation of germinal centers after Hodgkin lymphoma in complete remission post-induction chemotherapy and radiotherapy

Because the lymphatic tissue of progressive transformation of germinal centers (PTGC) expresses CD20, rituximab treatment may prevent transformation to lymphoma of this rather atypical entity. We prospectively evaluated the efficacy of immunotherapy with rituximab (375 mg/m2 i.v. weekly for 4 consecutive weeks, followed by a single i.v. infusion of 375 mg/m2 every 3 months for 2 consecutive years) in 48 patients with biopsy-proven PTGC after Hodgkin lymphoma in complete remission post-induction therapy (4-6 courses of anthracycline-containing chemotherapy with radiotherapy). The event-free survival (EFS) of this series was compared with that of a historical cohort of 48 patients with PTGC developing after Hodgkin lymphoma in complete remission post-induction therapy, who underwent observation. At a median follow-up of 40 months, histology showed a malignancy in 27% of patients in the observation group (Hodgkin lymphoma, 13 patients) and in 2% of patients in the rituximab-protected group (non-Hodgkin lymphoma, one patient) (p ∼ 0.001). Rituximab was well tolerated in all treated patients. All relapses in the group not protected by immunotherapy involved the PTGC regions and non-contiguous nodal sites, which suggests that PTGC is a reservoir for malignant transformation and dissemination. The number needed to treat with rituximab to avoid one Hodgkin lymphoma relapse was four. Our study shows that prophylaxis with rituximab helps improve EFS in patients with PTGC and a history of Hodgkin lymphoma

Metabolic tumor volume assessed by 18F-FDG-PET/CT for the prediction of outcome in patients with multiple myeloma

18F-FDG-PET/CT allows the direct measurement of metabolic tumor burden in a variety of different malignancies. Aim. To assess whether metabolic tumor volume (MTV) determined by 18F-FDG-PET/CT can be used in the prediction of progression-free and overall survival in multiple myeloma patients. Methods. Forty-seven patients (18 females, 29 males; mean age 63±11 y) with stage IIIA disease underwent whole-body 18F-FDG-PET/CT. Images were subjected to a 3D region of interest analysis taking into account all focal lesions with an SUVmax>2.5. MTV of each lesion was calculated using an in-house developed SUV-based automated contouring program that uses a threshold of 40% of the SUVmax. The total MTV of each patient was defined as the sum of metabolic volume of all focal lesions. Patients were treated and then subjected to a mean follow-up period of 24 months. Results. In the 47 patients studied, MTV ranged from 1.3 to 316.3 ml with a median value of 23.7 ml. A direct and significant correlation was found between MTV and percentage of infiltrating plasma cells (r=0.46, p=0.006) whereas haemoglobin levels were inversely and significantly correlated with MTV (r=-0.56, p=0.0001). At follow-up, patients who developed progressive disease (n=18) showed a significantly higher MTV (74.7±19.3 ml vs 29.8±5.1 ml, p=0.009) than patients without progression (n=29). Furthermore patients who died of myeloma (n=9) had a significantly higher MTV (123.2±30.6 ml vs 28.9±4.2 ml, p=0.0001) than survivors (n=38). No differences in age, plasma cell infiltration, monoclonal component, albumin, β2-microglobulin, performance status, ISS stage and presence or absence of bone marrow transplant were found between groups. MTV cut-off level was determined by ROC curve analysis and the best discriminative value found for predicting progression-free and overall survival was 42.2 ml and 77.6 ml, respectively. By Kaplan-Meier analysis and log-rank test, progression-free and overall survival at follow-up were significantly better in patients showing MTV lower than the cut-off level as compared to those having MTV higher than the cut-off (χ2=3.9, p=0.04 and χ2=56.3, p<0.0001, respectively). Conclusion. The direct measurement of tumor burden obtained by calculating MTV 1on 18F-FDG-PET/CT images may be used in the prediction of progression-free and overall survival in myeloma patients