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Two-hundred and 31 patients with a newly diagnosed multiple myeloma first seen and admitted to 17 hospitals located in the North-East of Italy between 1987 and 1992, were registered for a prospective study on the course of the disease. Median age was 68 years (range 41-90). Fifty-one per cent were in stage I, 9% in stage II and 40% in stage III. The presenting features and the survival of the 61 (26%) patients who were first admitted to a division of Hematology of a University Hospital (group HEM) were compared with those of the 170 (74%) patients who were referred to 16 divisions of Internal Medicine at General and County Hospitals (group INT). In the latter group, the patients were older (p = 0.002), had a poorer performance status ( p = 0.0001 ), a higher frequency of renal failure (p = 0.006) and anemia (p = 0.02) and higher beta2 microglobulin levels (p = 0.01). Median survival of group HEM patients did not differ significantly from group INT patients, if all stages were considered, but stage II and III patients of group INT had a significantly shorter median survival than advanced stage patients of group HEM (12 vs. 35 months, p = 0.01). If those older than 65 years or with unfavourable prognostic factors at presentation were excluded, prolonged survival of group INT patients was observed and the curves of the two groups did not differ significantly anymore. These results show that the patients recruited by a specialized centre may represent a selected population with better prognostic factors and younger age and this may affect analysis of clinical trials. Participation of minor centres in clinical trials may considerably contribute in improving interpretation of results of therapy in myeloma and be more representative of the entire population.

Thirty-two patients with multiple myeloma (MM) were autografted in our Centre over a 3-year period. Twenty-three patients had a newly diagnosed MM submitted to one induction regimen and 9 had a refractory or relapsing disease treated with at least two different chemotherapy lines: 15 out of 32 patients were sensitive to conventional treatment. In 2 patients BM was harvested while in the majority PBSC were collected after administration of 7 g/m2 Cyclophosphamide plus G-CSF (in 25 patients) or G-CSF alone at the dose of 16 microg/Kg/daily for 5-7 days (in 5 patients). Conditioning regimen was busulfan 16 mg/Kg plus melphalan 120 mg/m2. One patient died of cerebral hemorrhage after reinfusion of PBSC. Out of 31 evaluable patients, 24 (77%) had a response which was complete in 6 patients (19%) and partial in 18 patients (58%), 5 cases (17%) had no response, and 2 (6%) showed myeloma progression. There was a statistical difference in the outcome between newly diagnosed and pretreated patients (p = 0.003). At a median follow-up of 9 months (range 5-37), two patients had died for progression and 3 out of the 29 alive, relapsed after 17, 18 and 36 months respectively. Although median overall survival was not reached, there was a significant survival benefit for autografted patients in comparison with a matched control group conventionally treated in our Centre before 1994 (p = 0.02).

Background and Objective: Since hepatitis C virus (HCV) infection has been associated with different histotypes of B-cell non-Hodgkin's lymphoma (NHL), with or without concomitant production of cryoglobulins (cryolg), we have investigated the prevalence of the infection among NHL with the aim of defining its relationship with the histotype and with the production of cryolg., Methods: Four-hundred and seventy unselected, consecutive patients with a diagnosis of B-cell NHL were investigated. Anti-HCV antibodies (Ab) and cryolg were sought in all while HCV RNA and rheumatoid factor were detected on HCV-Ab positive samples., Results: Overall, the prevalence of HCV infection was 8.9% (42/470). It was 95.4% (#21) among the 22 patients with, and 4.6% (#21) among the 448 without production of cryoIg. The most common histotype among the HCV-positive, cryoIg-producing cases, was the immunocytoma (16/21, 76%). Among the HCV-positive, non cryoIg-producing cases, the marginal zone and the follicle center lymphomas were the commonest., Interpretation and Conclusions: Close association between HCV infection and cryoIg production, already described in mixed cryoglobulinemia, is confirmed also among B-cell NHL. Nevertheless, 50% of HCV-related lymphomas are non-cryoIg producers. Low-grade lymphomas (in particular the immunocytoma) are the most frequent HCV-related lymphomas. Since new therapeutic strategies might be necessary if the virus is detected, screening for cryoIg and for HCV-Ab among B-cell NHL at diagnosis is mandatory.

Background: Since July 1991 we have employed the F-MACHOP regimen for the treatment of aggressive non-Hodgkin's lymphomas (NHL). The aim of the present study was to evaluate the response rate and the toxicity of this chemotherapy program., Patients and Methods: Seventy-two consecutive patients entered the study and were treated with the F-MACHOP regimen for 6 planned courses, given every 21 days. G- or GM-CSF were administered whenever required., Results: Sixty-six patients (92%) obtained a response: 38 (53%) a complete remission (CR) and 28 (39%) a partial remission (PR); 4 (6%) proved to be resistant and 2 (3%) died of chemotherapy-related toxicity. Fifty-seven patients with a good performance status were subsequently selected to undergo autologous stem cell transplantation (ASCT). During chemotherapy, grade III-IV neutropenia was observed in 59% of the patients; a significant drop in hemoglobin levels was detected, with blood transfusions being required in 21% of the cases; platelet counts were unaffected. The main extrahematological toxic events were: alopecia (100% of the patients), osteoarthromyalgias (58%), grade I-II neuropathy (53%) and grade I-II hepatic toxicity (43%)., Conclusions: Our study confirms the efficacy of the F-MACHOP regimen in obtaining a high rate of response (CR + PR) in most aggressive NHL cases, with an acceptable toxicity and a low rate of toxic deaths. This regimen enables the majority of patients to be selected for ASCT as consolidation therapy without significant toxicity.

Background: Vincristine and anthracyclines are first-line agents for the treatment of multiple myeloma (MM). P170-related multidrug resistance (MDR) may influence the response to these drugs., Materials and Methods: P170 expression of bone marrow plasma cells was assayed by immunocytochemistry (alkaline phosphatase anti-alkaline phosphatase technique) with the MRK-16 monoclonal antibody. A case was considered positive if one per cent or more of plasma cells stained as strongly as positive controls., Results: Six of 17 (35%) cases in relapse and 18/72 (25%) at diagnosis were MDR positive. MDR positivity was not found in micromolecular MM and was significantly associated with the serum beta 2-microglobulin level. Response to treatments including dexamethasone, vincristine and doxorubicin, or idarubicin, or mitoxantrone was independent of MDR positivity (50% in positive cases vs. 56% in negative ones)., Conclusions: The detection of P170 in bone marrow plasma cells with the currently available methodology is not likely to predict response to treatments that include vincristine, anthracyclines or mitoxantrone. Further studies are required to evaluate the relevance of P170-related MDR to the development of MM therapy.

Coagulation disorders are frequently detected in patients affected by different tumours even though clinical symptoms occur in a very small percentage of such subjects. Coagulation processes are probably involved in the mechanism of metastatic spread. We assayed the plasma levels of thrombin-antithrombin III (TAT) complexes in a group of 276 patients with several tumours in different stages in order to achieve a better understanding of the complex interactions between coagulation disorders and either tumour growth or metastatic spread. High levels of TAT complexes were found in 51% of localized, 66.3% of metastatic and 58.3% of patients with no evidence of disease; a statistically significant difference was observed comparing metastatic cancer either with localized (p < 0.00015) or with free-of-disease (p < 0.004) groups. Gastrointestinal tract neoplasms showed higher levels of TAT complexes in the metastatic than in the localized group. No difference was seen between small-cell and non-small-cell lung-localized cancer. Our results confirm the frequent coexistence of cancer and subclinical blood coagulation disorders. The evidence of higher levels of TAT complexes in metastatic cancer than in the other groups could be related to the mechanisms involved in tumour spread.

The relationship between cancer and coagulation disorders is widely accepted. Such disorders can contribute to the metastatic spreading of the primary tumor. Aim of our study was to evaluate the alterations of thrombin-antithrombin III complex (TAT) measured by an ELISA plasma assay in a population of 78 patients suffering from various gastrointestinal tumors. We found high levels of TAT in 68.6% of the patients. Our data show that assay of TAT plasma levels may be a useful test in detecting early coagulation disorders in cancer patients.