Franco Bernardi

Combined surgery and chemotherapy for the treatment of primary gastrointestinal intermediate- or high-grade non-Hodgkin's lymphomas.

Fifty-five consecutive patients with primary gastrointestinal intermediate or high grade non-Hodgkins lymphoma were analysed to assess the efficacy of chemotherapy following surgical tumour resection. Histological subtypes were high grade (n = 18), intermediate grade (n = 36) and unclassified (n = 1). The majority of patients had gastric presentation (71%) and localised disease (84%). Surgery consisted of radical resection in 25 patients (45%) and partial or palliative excision in the remaining cases (22 and 8 respectively). Four subjects died within 3 months of surgery, two patients refused adjuvant chemotherapy and 49 completed the postoperative chemotherapeutic programme. Chemotherapy included either Fi2/74 (adriamycin + vincristine + bleomycin + cyclophosphamide + prednisone) or Fi3/74 (adriamycin + VM26 + bleomycin + cyclophosphamide + prednisone). Excluding the group who underwent radical tumour resection, postoperative chemotherapy induced complete remission in 81% of the remaining 30 patients. The 10-year cause-specific survival for the 53 treated patients was 76% (median follow-up 58 months) with a stable curve plateau after 80 months. Proportional-hazard multivariate statistics showed that survival was influenced by type of surgical resection (P less than 0.05) and stage (P less than 0.05), whereas age, sex and histological subtype were not influential. Our data indicate that chemotherapy following surgical resection of gastrointestinal lesion induces long-term remission in primary gastrointestinal lymphomas.

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.

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.

A new protocol (MiCEP) for the treatment of intermediate or high-grade non-hodgkin's lymphoma in the elderly

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy. Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.

Combined Surgery and Chemotherapy in Primary Gastric Non-Hodgkin's Lymphoma: a Retrospective Study in Sixty-Six Patients

Sixty-six consecutive patients with primary gastric non-Hodgkins lymphoma are reported. All patients underwent surgery which consisted of radical resection in 23 patients (36%) and partial or palliative excision in the remaining 43 cases (36 and 7 respectively). Three patients died before starting chemotherapy, two refused the treatment and 61 completed the postoperative chemotherapeutic programme. We analysed this group of patients in order to assess the efficacy of chemotherapy following surgery. Chemotherapy included either CVP or the original protocols from our institution. Excluding patients who underwent radical resection, postoperative chemotherapy induced complete remission in 87% of the remaining 39 patients. After a median follow-up of 84 months (range 6-216), the 10-year cause-specific survival was 90% with a stable curve plateau after about 25 months. The survival was only influenced by response to therapy (p < 0.0001). The disease-free survival for patients who were not radically resected was 93%. We encountered only two relapses after 15 and 32 months. One of these was local and the other systemic. Our results indicate that chemotherapy following surgery induces long-term remission and survival in primary gastric lymphoma and in particular improves remission and survival, in stage II. In our opinion, surgery may also be fundamental for the treatment of gastric lymphoma in the majority of cases.

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

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.

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

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.

Primary Conjunctival Lymphoma: Response to Chemotherapy in 4 Cases

Primary Conjunctival Lymphoma: Response to Chemotherapy in 4 Cases G. Bellesi S. di Lollo A. Bosi F. Bernardi G. Campana S. Romagnani P.R. Rossi Ferrini G. Bellesi, S. di Lollo, A. Bosi, F. Bernardi, G. Campana, S. Romagnani, P. Rossi Ferrini, Division of Hematology, Ospedale di Careggi, 50129 Florence (Italy) During the last 10 years few studies have been made concerning primary conjunctival malignant lymphoma. We present a report on 4 cases observed at the Division of Hematology of Florence from May 1970 to May 1980. In all the observed cases the conjunctival lymphoid lesion was painless, lengthening occurred in a large part of the fornix, presenting salmon pink colouring and sharply demarcated borders. The hard elastic tissue of the lesion was covered with uninjured conjunctiva; in 1 case the lesion was bilateral. The histophathologic records were evaluated according to the Rappaport and Kiel classifications. In 1 case, immunologic characterization of the biopsy specimen was also performed [4] and showed B cell proliferation. Staging was based particularly on skull and orbit X-rays, brain and orbit computerized axial tomography (2 patients), lymphography and pyelography or abdominal computerized axial tomography and bone marrow evaluation. All these procedures confirmed the conjunctival involvement alone. Irradiation is generally considered the treatment of choice [2, 5]. Some possible complications are cataract, persistent epiphora and ulceration of the cornea. Furthermore, the generalization of Table I. Characteristics of patients and their responses Observation Sex Age Histology Number of Response Maintenance DiseaseRelapse coursestherapyfree, months