A diachronic-comparative analysis for the identification of the most powerful prognostic index for localized diffuse large B-cell lymphoma

BACKGROUND: In the rituximab era, the conventional International Prognostic index (IPI) lost at least in part its predictive power, while the National Comprehensive Cancer Network-IPI (NCCN-IPI) seems to be a new and valid prognosticator. However, it has not yet been evaluated in patients with localized disease and it has not been compared with the modified IPI (mIPI) of the pre-rituximab era. In order to evaluate the different prognosticators and to assess the importance of rituximab and radiotherapy (RT), we carried out the so far largest retrospective analysis of patients with localized diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We retrospectively assessed clinical and therapeutical data of 1405 patients treated in from 1987 to 2012 in 10 cancer centers in Italy and 1 in Austria. RESULTS: All patients underwent an anthracycline containing polychemotherapy and 254 additional rituximab. The median follow-up was 5.7 years (range 0.1-23 years). The 5-year overall survival (OS) was 75%, being significantly superior in those who underwent additional rituximab, while RT consolidation did not improve the outcome of those who received immunochemotherapy. Patients with extranodal disease benefited from the addition of rituximab, while RT did not improve OS of the immunochemotherapy subgroup. In the pre-rituximab era, the mIPI showed a better performance than the others. In rituximab-treated patients, the NCCN-IPI had the highest discriminant value and the 5-years OS varied significantly (P < 0.001) between the three risk groups and was 98% in low-risk patients, 82% in those with a low-intermediate risk and 57% among high-intermediate and high-risk cases. CONCLUSIONS: The NCCN-IPI is so far the best prognosticator for patients with localized DLBCL who underwent R-CHOP(-like). The addition of rituximab is indispensable regardless of the risk category and site of involvement, while the addition of RT should be reserved to those cases who are ineligible to rituximab

Italian real life experience with brentuximab vedotin : results of a large observational study on 234 relapsed/refractory Hodgkin&apos;s lymphoma

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity.Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients

Pixantrone for the treatment of adult patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphomas

Stefano Volpetti, Francesco Zaja, Renato FaninDivision of Hematology and Cellular Therapies Unit &ldquo;Carlo Melzi&rdquo;, Department of Experimental and Clinical Sciences, University Hospital &ldquo;Santa Maria della Misericordia&rdquo;, Udine, ItalyAbstract: Treatment of patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphoma remains an unmet clinical need, and the progressive myocardial toxicity related to cumulative, dose-dependent damage induced by anthracyclines represents a tricky issue in the planning of therapy. Pixantrone is a promising aza-anthracenedione with reduced cardiotoxicity and significant antineoplastic activity, and has been investigated in solid and hematologic tumors in several Phase I, II, and III trials. The aim of this review is to summarize the data reported so far on pixantrone as a salvage therapy in relapsed/refractory non-Hodgkin B-cell lymphoma.Keywords: pixantrone, aggressive non-Hodgkin B-cell lymphoma, relapsed/refractor

Pixantrone for the treatment of adult patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphomas.

Treatment of patients with relapsed or refractory aggressive non-Hodgkin B-cell lymphoma remains an unmet clinical need, and the progressive myocardial toxicity related to cumulative, dose-dependent damage induced by anthracyclines represents a tricky issue in the planning of therapy. Pixantrone is a promising aza-anthracenedione with reduced cardiotoxicity and significant antineoplastic activity, and has been investigated in solid and hematologic tumors in several Phase I, II, and III trials. The aim of this review is to summarize the data reported so far on pixantrone as a salvage therapy in relapsed/refractory non-Hodgkin B-cell lymphoma

The role of Rituximab in the therapy of mixed cryoglobulinemia

The chimeric monoclonal antibody (IgG1/\u3ba) rituximab (RTX) is directed against the CD20 antigen, expressed on the surface of normal (from pre-B to mature B lymphocytes) and malignant B lymphocytes. Since mixed cryoglobulinemia is sustained by a low-grade B lymphoproliferation exhibiting autoimmune features, there is a strong rationale for using RTX in the treatment of this disorder. Almost all clinical manifestations of mixed cryoglobulinemia may benefit from RTX treatment, and the antibody is generally well tolerated and safe. Caution should be exerted in patients with high cryoglobulin levels or hyperviscosity at baseline, because of possible flare syndrome. Although RTX can lead to an increase of HCV viremia, hepatitis re-activation is rarely observed. Prospective comparative trials are warranted in order to better evaluate the therapeutic impact of RTX and to define the best treatment approac

The role of Rituximab in the therapy of mixed cryoglobulinemia

The chimeric monoclonal antibody (IgG1/\u3ba) rituximab (RTX) is directed against the CD20 antigen, expressed on the surface of normal (from pre-B to mature B lymphocytes) and malignant B lymphocytes. Since mixed cryoglobulinemia is sustained by a low-grade B lymphoproliferation exhibiting autoimmune features, there is a strong rationale for using RTX in the treatment of this disorder. Almost all clinical manifestations of mixed cryoglobulinemia may benefit from RTX treatment, and the antibody is generally well tolerated and safe. Caution should be exerted in patients with high cryoglobulin levels or hyperviscosity at baseline, because of possible flare syndrome. Although RTX can lead to an increase of HCV viremia, hepatitis re-activation is rarely observed. Prospective comparative trials are warranted in order to better evaluate the therapeutic impact of RTX and to define the best treatment approac

Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab

Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP); the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 7 10\u2079/L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count 65 30 7 10\u2079/L) and complete response (CR; platelet count 65 100 7 10\u2079/L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment

Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia

We report the long-term outcome results of 57 consecutive adult patients with immune thrombocytopenia after being treated with rituximab. According to the different period of therapy, patients received either standard dose (SD) rituximab (i.e., 375 mg/m(2) weekly for 4 weeks) or low dose (LD) rituximab (i.e., 100 mg flat dose weekly for 4 weeks). Overall (OR) and complete response (CR) rates were 60 and 40%, respectively. Patients' median follow-up was 52 months, 82 months in the SD, and 44 months in the LD group; 15 out of 34 responsive patients (44%) relapsed, with median response duration of 24 months (range 3-120). The estimated 4-years event-free survival (EFS, considering events the non response status at month 2 or relapses in responders) was 30%. Patients who received SD vs. LD rituximab had better outcome with regard to short term response (OR 66 vs. 52%, CR 50 vs. 28%), relapse rate (38 vs. 54%), probability to achieve and maintain long-term response (41 vs. 24%) and estimated 4-years EFS (35 vs. 23%). Patients with a longer interval between diagnosis and rituximab therapy had worse EFS [HR = 1.005; 95%IC: (1.002-1.009), P = 0.019]. Three patients developed short-term adverse events, two-serum sickness, and one interstitial pneumonia. Four cases of malignancies and two herpes zoster reactivations were registered during long-term follow-up; one patient died for cerebral bleeding. Rituximab SD appears a safe and active agent allowing in nearly 40% of cases to achieve long-term response and splenectomy sparing effect. Am. J. Hematol. 2012. \ua9 2012 Wiley Periodicals, Inc

Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab.

Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP); the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 7 10\u2079/L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count 65 30 7 10\u2079/L) and complete response (CR; platelet count 65 100 7 10\u2079/L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment

Long-term follow-up analysis after rituximab salvage therapy in adult patients with immune thrombocytopenia

We report the long-term outcome results of 57 consecutive adult patients with immune thrombocytopenia after being treated with rituximab. According to the different period of therapy, patients received either standard dose (SD) rituximab (i.e., 375 mg/m(2) weekly for 4 weeks) or low dose (LD) rituximab (i.e., 100 mg flat dose weekly for 4 weeks). Overall (OR) and complete response (CR) rates were 60 and 40%, respectively. Patients' median follow-up was 52 months, 82 months in the SD, and 44 months in the LD group; 15 out of 34 responsive patients (44%) relapsed, with median response duration of 24 months (range 3-120). The estimated 4-years event-free survival (EFS, considering events the non response status at month 2 or relapses in responders) was 30%. Patients who received SD vs. LD rituximab had better outcome with regard to short term response (OR 66 vs. 52%, CR 50 vs. 28%), relapse rate (38 vs. 54%), probability to achieve and maintain long-term response (41 vs. 24%) and estimated 4-years EFS (35 vs. 23%). Patients with a longer interval between diagnosis and rituximab therapy had worse EFS [HR = 1.005; 95%IC: (1.002-1.009), P = 0.019]. Three patients developed short-term adverse events, two-serum sickness, and one interstitial pneumonia. Four cases of malignancies and two herpes zoster reactivations were registered during long-term follow-up; one patient died for cerebral bleeding. Rituximab SD appears a safe and active agent allowing in nearly 40% of cases to achieve long-term response and splenectomy sparing effect. Am. J. Hematol. 2012. \ua9 2012 Wiley Periodicals, Inc