Improvement in liver cirrhosis after treatment of HCV-related mixed cryoglobulinemia with rituximab.

Mixed cryoglobulinemia (MC) is the most strictly virus-related extrahepatic HCV disease. Antiviral therapy is considered the first therapeutic option; however, MC patients are frequently excluded from treatment due to contraindications. The effectiveness of B-cell depletion by anti-CD20 monoclonal antibody (rituximab) has recently been described, but the possibility of an immunodepression- related increase in viral replication and aminotransferase values limits its use in patients with advanced liver disease. Unfortunately, MC patients frequently also have cirrhosis. To our knowledge, no data are available regarding the effect of rituximab therapy in patients with decompensated cirrhosis. We report the successful treatment with rituximab (4 weekly infusions of 375 mg/m 2) of two patients (a 58-year-old man, and a 65-year-old woman) with HCV-related MC syndrome and decompensated liver cirrhosis. These patients underwent at least 6 months of post-treatment follow-up. In both cases a consistent improvement of MC syndrome was evident after treatment. In addition, improvement of liver protidosynthetic activity, increased prothrombin time, impressive reduction or disappearance of ascites and encephalopathy were also observed, in spite of some increase in viral titers or in ALT values. The Child-Pugh score improved from B8 to A6 and from Cll to B7, respectively. Pre- and post-treatment transjugular liver biopsies were available in 1 patient, showing disappearance of lymphocytic infiltration after treatment. These case reports show the effectiveness and safety of rituximab in patients with HCV-related MC and advanced cirrhosis, and strongly suggest that the depletion of CD20+ B-cells induced by rituximab treatment may be responsible for liver function improvement. The mechanisms involved are unknown. Interesting working hypotheses may implicate a role played by B-cell infiltrates in conditioning liver damage. The improvement of Kupffer cell function due to the cryocrit value reduction might also play a role.

Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines.

BACKGROUND: To assess the efficacy and safety of the combination of non-pegylated liposome-encapsulated doxorubicin (Myocet(R)) with cyclophosphamide, vincristine, prednisone and rituximab (R-COMP) in patients with aggressive non-Hodgkin's B-cell lymphomas. METHODS: Twenty-one patients were selected for the presence of negative concurrent clinical features such as cardiac comorbidity and/or previous treatment with anthracycline-based regimens. Liposome-encapsulated doxorubicin at a dose of 50 mg/m(2) was administered in association with cyclophosphamide (750 mg/m(2)), vincristine (1.4 mg/m(2)), prednisone (40 mg/m(2)) and rituximab (375 mg/m(2)) every 21 days for four to six cycles unless progression or unacceptable toxicity occurred. RESULTS: A complete response (CR) was obtained in 16/21 patients (76%), three patients achieved a partial response (14%), with an overall response rate of 90%. Two patients (10%) did not respond to therapy. After a median follow-up of 13 months (range 2-36 months), 2/16 CR patients relapsed, with a disease-free survival (DFS) of 78%. CONCLUSIONS: The replacement of doxorubicin with its non-pegylated liposomal pharmaceutical analogue was well tolerated and highly effective in inducing remission in this group of patients at high risk for cardiac toxicity or previously treated with anthracyclines. Its high tolerability and low incidence of cardiac events (only one patient) warrants further studies to confirm the clinical benefits of liposomal doxorubicin in this subset of patients.

Dose-dense CHOP plus rituximab (R-CHOP14) for the treatment of elderly patients with high-risk diffuse large B cell lymphoma: a pilot study.

BACKGROUND: Aggressive non-Hodgkin's lymphomas (NHL) require intensive therapies which seemed impracticable in elderly patients. Dose reduction and therapy attenuation reduced treatment-related toxicity, but also decreased therapeutic efficacy. In elderly patients too, the achievement of complete remission is the most important prognostic factor affecting outcome. Therefore, we have treated elderly patients with a dose-intensified protocol. Aim of the study was to verify the feasibility of this scheme in a subset of patients with high-risk aggressive lymphomas. METHODS: Between June 2002 and June 2004, 26 patients over the age of 60 years with a diagnosis of aggressive NHL and an intermediate-high or high International Prognostic Index were treated with biweekly CHOP plus rituximab with the support of granulocyte colony-stimulating factors (G-CSF). RESULTS: Seventeen patients (65%) regularly kept the interval between cycles. Haematological and extrahaematological toxicities were moderate in all the patients. Twenty (77%) patients achieved complete remissions, 6 (23%) partial remissions with an overall response rate of 100%. After a median follow-up of 23 months, the overall survival was 79%; after a median follow-up of 17 months, the disease-free survival was 70%. CONCLUSION: These results confirm that a dose-dense CHOP programme can be administered safely and effectively in a subset of elderly patients with high-risk aggressive NHL. The addition of rituximab could increase the response rate without adding toxicity.

18FDG-positron emission tomography in post treatment evaluation of residual mass in Hodgkin's lymphoma: long-term results.

In patients with Hodgkin's lymphoma (HL) at the end of first line therapy an accurate imaging technique with high prognostic value is needed to assess response to treatment and predict those patients who will suffer disease relapse. This technique and its results permit the quick initiation of a second line therapy in patients suffering from a progressive disease or those unresponsive to treatment avoid over-treatment of patients in complete remission or those having a non-active residual disease. We included a (18)FDG-positron emission tomography (PET) scan to the diagnostic set-up to investigate 28 patients following the end of their treatment. Fifteen patients out of the 28 (54%) had positive CT scans while 13 (46%) had negative ones. Eleven patients out of the 15 CT positive (73%) had negative PET scans and no relapse. The remaining four patients (27%) had positive PET scans with only one relapse (25%). With respect to the 13 patients who had negative CT scans, 9 patients (69%) had negative PET scans and no relapse. The remaining 4 patients (31%) had positive PET scans with 3 relapse cases (75%). In our final assessment after a median follow-up period of 45 months, starting from PET execution to the last follow-up, overall sensitivity of the CT and the PET were 25 and 100% respectively, specificity 42 and 83% respectively, positive predictive value (PPV) 7 and 50% respectively, negative predictive value (NPV) 77 and 100% respectively, and accuracy 39 and 86% respectively. In our experience, FDG-PET performed in patients after induction therapy appears to offer important additional information: FDG-PET results are predictors of prognosis giving 100% DFS in PET negative patients and 54% DSF in PET positive patients.

Combined chemotherapy with carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor for the treatment of aggressive non-Hodgkin lymphoma: a long-term follow-up study.

BACKGROUND: The standard treatment for patients with aggressive non-Hodgkin lymphoma (NHL) is cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Since 1989, the authors have used a new chemotherapy regimen with combined carmustine, doxorubicin, etoposide, vincristine, and cyclophosphamide plus mitoxantrone, cytarabine and methotrexate with citrovorum factor called BAVEC-MiMA. The objective of the current study was to explore, after a long follow-up period, the impact of this third-generation regimen for the treatment of aggressive NHL. METHODS: One hundred and one consecutive patients (median age, 41 years) with either B-cell (n=94 patients) or non-B-cell (n=7 patients), aggressive lymphoma were diagnosed and treated between 1989 and 1999 with the BAVEC-MiMA regimen. RESULTS: The complete response rate was 74%, and the overall response rate was 89%. Eleven patients with refractory disease died rapidly after a median period of 5 months. The major toxicity was Grade 4 neutropenia (according to World Health Organization criteria), which was observed in 15 patients (15%). There were four toxicity-related deaths. The overall survival rate was 63% at 9 years. In multivariate analysis, factors that were associated with advantage in overall survival were response to induction therapy, bulky disease, and high score on the International Prognostic Index (IPI). The disease-free survival rate was 77% at 9 years. In multivariate analysis, the IPI was the most important variable for the definition of disease-free survival. CONCLUSIONS: The BAVEC-MiMA regimen was feasible on an outpatient basis, it was tolerated well, and it showed a low toxicity-related mortality. The long follow-up in patients with NHL, which is a rapidly fatal disease, led the authors to observe that, with this regimen, a cure was obtained in > 50% of patients who had low-risk or low-to-intermediate-risk, aggressive NHL.

Treatment of large cell lymphoma in elderly patients with a mitoxantrone, cyclophosphamide, etoposide, and prednisone regimen: long-term follow-up results.

BACKGROUND: Patients with aggressive non-Hodgkin lymphoma (NHL) require intensive and extensive therapy, which seems impracticable in elderly patients due to hematologic and extrahematologic toxicity. Consequent dose reduction and therapy attenuation can reduce treatment-related toxicity but also decreases therapeutic efficacy. Thus, age represents a fundamental prognostic factor that has a profound influence on both therapeutic decisions and patient outcome. METHODS: Between January, 1990 and June, 1997, 145 patients age > 64 years (median age, 72.3 years) with a diagnosis of aggressive NHL were treated on a chemotherapy regimen that consisted of mitoxantrone, cyclophosphamide, etoposide, and prednisone. RESULTS: Ninety-one patients (63%) achieved complete remission, and 48 patients (33%) achieved partial remission, for an overall response rate of 96%. Six patients (4%) were resistant to therapy. The overall survival rate, with a median follow-up of 66 months, was 44%, and the failure free survival rate was 42%. The disease free survival rate was 63.5%, with a median follow-up of 60 months. Multivariate survival analysis showed that the achievement of complete remission was the single most important prognostic factor, which was associated significantly with longer survival (P < 0.0001). Toxicity was moderate, with 5 deaths (3%) due to complications related to therapy. CONCLUSIONS: The current results confirm that a protocol devised specifically for elderly patients may reduce toxicity and allow longer overall survival in this particular subset of patients.