To evaluate in a prospective multicenter trial the feasibility and clinical efficacy of the combination of alemtuzumab (Campath-1H) with the CHOP regimen (CHOP-C) as the primary treatment for patients with peripheral T-cell lymphoma (PTCL), between January 2003 and December 2005, 24 consecutive PTCL patients entered the study and received 8 CHOP courses, Campath was added at 30 mg. s.c. at day -1 initially to the first four courses (four patients), and then to all eight courses (20 patients). CR was achieved in 17 (71%) patients, 1 had partial remission and 6 stable/progressive disease. At a median follow-up of 16 months (5-42), 14 patients are alive, nine had died from progressive disease and one from pneumonia at day +198 while in CR. So far, 13 are disease-free, with an overall median duration of response of 11 months. The most frequent side effect were grade 4 neutropenia and CMV reactivation. Major infections were J-C virus reactivation, pulmonary invasive aspergillosis, Staphylococcus sepsis and pneumonia. This study shows that CHOP-C: (1) is a feasible chemoimmunotherapy regimen; (2) is effective in PTCL with a high rate of CR achievement and (3) is associated with mostly manageable infectious complications. This clinical trial was registered with the Osservatorio Nazionale sulla Sperimentazione cinica as ID# 141202. For personal use only. on October 24, 2017. by guest www.bloodjournal.org From

Prognosis for PTCL patients is poor; the 5-year overall survival rate ranges from 25 to 40%. Despite variable CD52 expression in T-cell malignancies, promising results have been demonstrated with alemtuzumab (Campath ®). We report preliminary results of standard CHOP therapy plus alemtuzumab (CHOP-C) in a cohort of untreated PTCL patients (pts). Beginning Jan 03, 25 consecutive PTCL pts were treated with 8 courses of CHOP. In the first cohort, 4 pts received alemtuzumab 30 mg. sc 1 day prior to the first 4 courses of CHOP, whereas in cohort 2 (N=21) alemtuzumab 30 mg was given one day prior to all 8 CHOP courses administered. The histopathology was centrally reviewed and included 16 patients with PTCL-U, 6 patients with AILD-T, and 3 patients with ALCL Alk. CD52 expression was checked by immunohistochemisty on paraffin-embedded material. Median age of patients was 51.2 years (range: 28–69), 22 (88%) were stage III–IV, 3 (12%) had bulky disease, 11 (44%) had bone marrow involvement, and 13 (52%) had high LDH values. The age-adjusted IPI values were 0 in 5 pts, 1 in 8 pts, 2 in 9 pts, and 3 in 3 pts. All 25 pts completed therapy.

Malignant T-cells show very high CD 52 expression, and promising results have been obtained in T-PLL and in Sezary patients (pts) treated with alentuzumab (Campath ®). Here we report the preliminary results of standard CHOP therapy plus Campath (CHOP-C) in untreated PTCL pts. Starting from January 2003, 20 consecutive PTCL pts were treated by CHOP for 8 courses, preceded on day -1 by Campath 30 mg. s.c. The diagnosis was PTCL-U in 13 pts, AILD-T in 5, and ALCL Alk- in 2. Clinical characteristics of the 20 pts: mean age 53.3 years (28–69), stage III-IV in 18, bulky in 2, B-symptoms in 9, high LDH in 11, bone marrow attainment in 8, aaIPI 2–3 in 10 pts. 15/20 pts are valuable for the analysis. After a median follow-up of 253 days (105–773), 10/15 pts are still alive and 5/15 have died of lymphoma. 8/15 achieved CR 1 PR and 1 MR; 5 pts showed progression; 3/5 pts in Pro,1 pt in RP, and 1 pt in MR have died of lymphoma. 2 pts. relapsed +62 and +119 days after CR. The median OS and DFS were 461 and 264 days, respectively (Fig. 1). No toxic death was recorded. WHO grade 4 neutropenia was seen in 38/90 courses (42%), grade 4 thrombocytopenia in 4/90 (4%), CMV reactivation in 15/90 (17%), local erythema in 2/90, mild fever in 5/90. Major infections were J-C virus reactivation in 1 pt, pulmonary Invasive Aspergillosis in 1, sepsis in 1, pneumonia in 1. The feasibility of CHOP-C in PTCL pts aged up to 70 years has been proven, and the toxicity acceptable; however the efficacy of this regimen should be confirmed on a larger cohort of pts.

BACKGROUND. The activation of the clotting-fibrinolytic system in cancer patients is common and represents an unfavorable clinical sign. D-dimer (DD) is a sensitive marker of fibrinolysis.METHODS. The current study comprised 826 new lung carcinoma patients seen consecutively in a single institution over a 10-year period (1992-2001). For each patient, 31 variables, including DD and survival duration, were available for analysis.RESULTS. Only weak relationships between DD and the other variables were found. The DD variable correlated best with the level of lactate dehydrogenase, performance status, tissue polypeptide antigen, stage of disease, and the number of metastases (rho 0.33, -0.25, 0.18, 0.18, and 0.15, respectively). The D-dimer distinguished patients with different prognoses. The median survival periods were 154 days (95% confidence interval [CI], 122-189 days) and 308 days (95% Cl, 227-409 days; log rank statistic, 26.56; P < 0.01), respectively, for abnormally elevated and normal values. The difference was greater in patients with adenocarcinoma and in patients presenting with a less advanced disease, especially in patients with pathologic Stage la disease. The best multivariate survival model selected 10 significant covariates, including DD.CONCLUSIONS. The authors recommend measuring the plasma level of DD in all new lung carcinoma patients. This measurement may help to formulate individual prognoses and can be used to indicate adjuvant treatment for surgical patients. (C) 2003 American Cancer Society.

PURPOSEThe purpose of this study was to assess the relationship of alcohol consumption and intake of 15 selected micronutrients with risk of liver cirrhosis.METHODSData from a case-control study performed in 1989-1990 in central Italy involving 115 incident cases and 167 hospital controls were used.RESULTSCases and controls did not differ for mean daily intake of calories, carbohydrates, lipids, and proteins. Significant direct dose-response relationships between the intakes of vitamin A and iron and the risk cirrhosis were observed, while significant protective effects were obtained for the intakes of vitamins B2 (riboflavin) and B12. Different patterns of the joint effect of nutrients and alcohol were also observed. The intakes of vitamin A and iron were significantly associated with the risk of cirrhosis in lifetime teetotalers (odds ratios (OR) and 95% coincidence intervals (CI) of 33.6 (1.2-979.9) and 37.9 (1.8-819.4) for higher intake of vitamin A and iron, respectively) and in consumers of < 50 g/day of alcohol (vitamin A: OR 45.0; 95% CI, (2.6-774.6); iron: OR, 73.6; 95% CI, 4.3-999). The OR associated with intakes of vitamins B2 (riboflavin) and B12 were not significant for the first two categories of alcohol use, while a higher intake of these two vitamins reduced the risk of cirrhosis associated with alcohol consumption above 50 g/day; the ORs (95% CI) were 23.0 (2.7-198.9) and 104.4 (7.2-999), respectively, for higher and lower intakes of riboflavin and 12.8 (1.8-88.1) and 138.4 (14.0-999), respectively, for higher and lower intake of vitamin B12.CONCLUSIONThese findings might explain at least a portion of the individual susceptibility to alcohol-induced liver damage.

The aim of this pilot study was to investigate if chemotherapy (CT) followed by the combination of interferon-beta (IFN-beta), retinoids, and tamoxifen could be effective in the treatment of metastatic breast cancer (MBC). Thirty-six patients with stage IV carcinoma of the breast were treated with six courses of cyclophosphamide, 5-fluorouracil, 4-epidoxorubicin, vincristine, and prednisone every 3 weeks (FECPV), followed by two courses of non-cross-resistant drugs, methotrexate, mitomycin C, and mitoxantrone (MMM). Treatment was continued, in responders, with low dose IFN-beta, retinyl palmitate, and tamoxifen until relapse of the disease occurred. Among 36 evaluable patients, 23 achieved a clinical response (64 %) (95 % confidence interval [c.i.] 46 %-79 %), 7 had stable disease (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in 6, and anemia in 11. Sixteen patients had nausea/vomiting, stomatitis was observed in 9, and diarrhea occurred in 3. Toxicity from maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-107). Median overall survival was 32 months (9-108). Our study shows that this combined approach for the treatment of MBC is feasible, with an acceptable toxicity.

A population-based epidemiological study that concerns the estimate of incidence rates of Hodgkin's Disease (HD) and Non Hodgkin's Lymphoma (NHL) in a Central Italy area was performed. All the new cases of HD and NHL diagnosed from 1982 till 1994 in the target population were collected by multiple information sources. The temporal trend of incidence rates and their relation with age, gender and histological variant were analyzed. In the considered period 95 cases of HD and 297 cases of NHL were collected. Constant age-adjusted incidence rates of HD were observed, while an increasing trend of NHL incidence rates was observed especially for cases at presentation in stage III and IV and for histotypes G, H and I. The investigations carried out on patients with HD have shown that this condition prevails in women in the younger age groups, while in men presentation occurs more frequently at an advanced age. Moreover the authors have confirmed previous reports of a distinctly increased incidence of nodular sclerosis in contrast to the other three histological variants which do not show a juvenile peak but a gradual increase in incidence with advancing age. The epidemiological features of NHL's observed correspond to the standard incidence rates obtained in Europe and throughout the world. NHL's appear to be a pathological entity typical of elderly patients: however high-grade NHL's, in contrast to low-grade NHL's, was present with increased frequency also in childhood and in patients under the age of 30.

The heterogeneity in the results of observational studies that investigated the association between alcohol consumption and risk of liver cirrhosis was analysed by means of a meta-analysis that included 15 articles published from 1978 to 1997. Relative risks associated with low levels of alcohol intake (25 g/day) ranged from 1.5 [95% confidence interval (CI): 1.4-1.5] for a linear model fitting the results of the six studies performed in Mediterranean areas, to 3.6 (95% CI 3.1-4.3) for a quadratic model fitting the results of the nine studies performed in other areas. A strong indication of heterogeneity was observed when combining all studies. Quadratic term of alcohol intake, quality of the study and area in which the study was performed explained most of this heterogeneity. Efforts should be made to explain the strong heterogeneity in the trend estimates. Reproducible methods to collect relevant and valid information on alcohol intake should be developed and the role of drinking patterns and viral and nutritional factors in modifying the effect of alcohol on the risk of liver cirrhosis should be investigated.

Backgrounds/Aims: Knowledge of the proportion of liver cirrhosis attributable to the main risk factors is largely based on methodologically questionable clinical reports.Methods: The proportion of newly diagnosed cases of symptomatic liver cirrhosis attributable to known risk factors was estimated by a case-control study performed during 1989-1996 in 23 medical divisions of several hospitals distributed throughout Italy. Cases were 462 inpatients with cirrhosis admitted for the first time for liver decompensation. Controls were 651 patients admitted during the same period and to the same hospitals as the cases, for acute diseases unrelated to alcohol and virus infection, The proportion of symptomatic liver cirrhosis cases due to alcohol intake and hepatitis B and C viruses and the combination of these was expressed as the population attributable risk.Results: Attributable risks were 67.9% (95% confidence interval (CI): 53.8-79.4) for alcohol, 40.1% (95% CI: 35.3-45.2) for hepatitis C virus and 4.4% (95% CI: 2.5-7.6) for hepatitis B virus, The three factors together explained 98.1% (95% CI: 81.6-99.6) of cases in men and 67.0% (95% CI: 50.4-85.8) in women.Conclusions: Alcohol is the risk factor with the highest impact on symptomatic liver cirrhosis risk in Italy. From a public health viewpoint, with the elimination of the web-known risk factors (particularly alcohol and hepatitis C virus), liver cirrhosis should become a rare disease.

PURPOSE: The purpose of this study was to assess the relationship of alcohol consumption and intake of 15 selected micronutrients with risk of liver cirrhosis.METHODS: Data from a case-control study performed in 1989-1990 in central Italy involving 115 incident cases and 167 hospital controls were used.RESULTS: Cases and controls did not differ for mean daily intake of calories, carbohydrates, lipids, and proteins. Significant direct dose-response relationships between the intakes of vitamin A and iron and the risk cirrhosis were observed, while significant protective effects of nutrients and alcohol were also observed. The intakes of vitamin A and iron were significantly associated with the risk of cirrhosis in lifetime teetotalers (odds ratios (OR) and 95% confidence intervals (CI) of 33.6 (1.2-979.9) and 37.9 (1.8-819.4) for higher intake of vitamin A and iron, respectively) and in consumers of <50 g/day of alcohol (vitamin A: OR 45.0; 95% CI, (2.6-774.6); iron: OR, 73.6; 95% CI, 4.3-999). The OR associated with intakes of vitamins B-2 (riboflavin) and B-12 were not significant for the first two categories of alcohol use, while a higher intake of these two vitamins reduced the risk of cirrhosis associated with alcohol consumption above 50 g/day; the ORs (95% CI) were 23.0 (2.7-198.9) and 14.0-999, respectively, for higher and lower intake of vitamin B-12.CONCLUSION: These findings might explain at least a portion of the individual susceptibility to alcohol-induced damage. (C) 1998 Elsevier Science Inc.

BACKGROUND:Evidence on gender-related differences in susceptibility to alcohol-induced liver diseases is questionable with regard to both methodologic and clinical aspects. With the aim to assess the role of gender in the risk of liver cirrhosis, independently and in combination with known risk factors, data from three case-control studies performed in various Italian areas were analysed.METHODS:The cases were 462 cirrhotic patients (300 men and 162 women) admitted for the first time to hospital for liver decompensation. Controls were 651 patients (355 men and 296 women) admitted to the same hospitals during the same period as the cases, for acute diseases unrelated to alcohol. Alcohol consumption was expressed as lifetime daily alcohol intake.RESULTS:A significant and independent associations between alcohol intake, chronic hepatitis B and C virus infections, and the risk of liver cirrhosis was observed. The effect of alcohol intake was multiplicatively increased in women. The odds ratio (OR) increased from 1.0 (reference category: men, lifetime abstainers) to 31.4 (95% confidence interval (CI), 10.3-95.8) in men drinking more than 100 g/day of alcohol, and from 2.2 (95% CI, 1.0-7.1) in abstaining women to 44.8 (95% CI, 8.2-224.0) in women drinking more than 100 g/day of alcohol. An increased risk of liver cirrhosis associated with female gender independently of alcohol consumption and virus infection was also observed.CONCLUSIONS:A higher susceptibility to alcohol-induced liver diseases was confirmed for women, and an independent effect of female sex on the risk of cirrhosis was observed. Besides alcohol and viruses, some unknown gender-related factor might then be involved in the occurrence of the disease.

The prognosis for patients with metastatic breast cancer, progressing after anthracycline-based cytotoxic therapy, is poor, and new treatment strategies are needed. Carboplatin (CBDCA), etoposide (VP-16), and cyclophosphamide (CTX) combination therapy has proved activity against a wide variety of tumors. This study was undertaken to evaluate the activity and toxicity of standard doses of CBDCA, VP-16, and CTX administered as salvage chemotherapy in a group of patients with metastatic breast cancer previously treated with two chemotherapy regimens, including anthracyclines. Thirty patients received an average 3.5 courses of the following treatment: CBDCA, 300 mg/m2, and CTX, 500 mg/m2, on day 1; VP-16, 60 mg/m2, on days 2, 3, and 4. Thirteen patients (43%) achieved an objective response, seven (23%) stabilized, while 10 (34%) progressed. The median response duration was 11.5 months (range, 1-19); the median overall survival from protocol entry was 9.1 months (range, 1.5-26). Gastrointestinal toxicity was noted in six patients, and hematologic toxicity of grade 3-4 was found in 11 patients. The combination of CTX, CBDCA, and VP-16 at this dose and schedule is active as salvage treatment of patients with breast cancer. Even when the toxicity was severe, responders had good symptom palliation with a substantial improvement in performance status.

BACKGROUND Since the mid 1970s, a striking reduction in alcohol-related problems has been observed in many Western countries. Liver cirrhosis mortality is considered to be a major indicator of alcohol-related problems in the general population. The aim of the present study is to describe liver cirrhosis mortality trends in European countries between 1970 and 1989. METHODS This is a descriptive study on liver cirrhosis mortality in 25 European countries, and in four grouped European regions. A Poisson log-linear age-period-cohort model is used to clarify whether the recent trend in mortality represents a short-term fluctuation or an emerging long-term trend. In addition, a descriptive comparison between trends in per capital alcohol consumption and liver cirrhosis mortality is conducted. RESULTS In the whole European population and in that of Western and Southern Europe increasing period effects were observed until the second half of the 1970s followed by a decline in the next periods. In Eastern Europe the decline in period effects started in the first half of the 1980s, whereas in Northern Europe an increasing period effect was observed until the second half of the 1970s, followed by a stabilization. Similar trends were observed for per capita alcohol consumption. The age effect analysis showed a continuously rising effect in Eastern Europe, whereas an attenuation of the effect at around age 65 years was observed in Western Europe. Intermediate patterns were observed in Southern and Northern Europe. The birth cohort effect suggested that in the Western and Southern populations mortality could continue to decrease over the next decade, while in Eastern and Northern mortality is still rising and this will probably continue for the next decade. CONCLUSIONS The age-period-cohort analysis allows targeting of health care and prevention programmes based on future trends. Aetiological and prognostic factors act differently in Europe. A better understanding of the trends would require more detailed information on alcoholism treatment rates, alcohol habits, viral hepatitic infections and other factors involved in the aetiopathogenesis of the disease.

BACKGROUND This work followed a group of patients living in a psychiatric hospital in Central Italy in 1978 at the time of enforcement of the Italian reform law (No. 180) for closing down mental hospitals. The study had the following aims: a) to compare in terms of mortality patients discharged into the community with patients who did not experience deinstitutionalization; b) to determine the survival of the cohort of patients and to analyse prognostic risk factors for death; c) to analyse differences in mortality rates between psychiatric patients and the general population. METHODS The study was designed as an historical follow-up investigation. Univariate (product limit) and multivariate (proportional hazards model) methods were used to estimate prognostic variables and related death risks. Mortality was assessed using standardized mortality ratios (SMR) on the entire cohort as well as after stratification according to age, sex, cause of death and discharge status, assuming the Abruzzo Region's population as standard. RESULTS Length of hospitalization and discharge from hospital are prognostic variables for death risk, with relative risks respectively of 4.22 (95% confidence interval [CI]: 2.41-7.40) for a length of hospitalization of 10-25 years, and 8.13 (95% CI: 4.73-13.88) for non-discharge. The global SMR of the cohort was 2.68 (95% CI: 2.42-3.07). Non-discharged patients showed higher SMR than discharged. Excess mortality was found both in males and females for circulatory, respiratory and undefined diseases. A significantly lower mortality for cancer was observed in male patients. A strong excess mortality was observed in younger patients (20-29 years: SMRmales = 43.57; SMRfemales = 97.52). CONCLUSIONS Longer periods of hospitalization and non-discharge from hospital are the main risk factors for death in psychiatric patients, who globally experience higher death rates than the general population for a wide spectrum of causes of death, whatever their diagnosis or gender. These findings strongly suggest positive actions in order to overcome the effects of institutionalization.

OBJECTIVE:A striking reduction of alcohol-related problems, such as liver cirrhosis death rates, has been observed in many western countries in recent years. It might be expected that these declines are accompanied by a lagged reduction in per capita alcohol consumption, since many years of intake are required for cirrhosis of the liver to develop (lag theory). The main aim of this study is to verify the validity of the lag theory, taking as target populations those resident in European countries.METHOD:Changes in liver cirrhosis death rates in 22 European countries between 1970 and 1089 were regressed onto changes in per capita alcohol consumption (1961-89) to evaluate the latency period between trends of these variables.RESULTS:Eastern countries had a latency period between trends in alcohol consumption and in mortality rates of many years, whereas in northern, western and southern Europe cirrhosis mortality rates were explained by their relationship with per capita alcohol consumption, which lagged a few years. In some countries, an immediate contemporary appearance of the two phenomena was observed.CONCLUSIONS:These results suggest that the lag theory cannot fully explain the relationship between changing alcohol consumption and cirrhosis mortality and that other factors, such as alcoholism treatment rates, are involved in the wide geographical variability of the latency periods.