Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.

Mutations and long-term outcome of 217 young patients with essential thrombocythemia or early primary myelofibrosis.

We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽ 40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P = 0.04), longer survival (100% versus 96%, P = 0.05) and better combined-EFS (86% versus 71%, P = 0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients.

Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi.

BACKGROUND: Tumor regression after antiviral therapy (AT) is in favor of an etiological role of hepatitis C virus (HCV) in non-Hodgkin's B-cell lymphomas (NHL). PATIENTS AND METHODS: We carried out a cohort study of 704 consecutive HIV-negative, HCV-positive patients with indolent NHL diagnosed and treated from 1993 to 2009 in 39 centers of the Fondazione Italiana Linfomi; 134 patients were managed with AT for lymphoma control. RESULTS: For entire cohort, 5-year overall survival (OS) was 78% [95% confidence interval (CI): 74%-82%] and 5-year progression-free survival (PFS) was 48% (95% CI: 44%-53%). In multivariate analysis, the use of AT during the patients' life had positive impact on OS. Forty-four of the 100 patients treated with first-line AT achieved a complete remission (CR) and 33 a partial response (PR). HCV-RNA clearance was achieved in 80 patients and was related to lymphoma response. At a median follow-up of 3.6 years, 5-year PFS was 63% (95% CI: 50%-73%). CR + PR rate was 85% with AT as second-line treatment. CONCLUSION: AT produces HCV-RNA clearance and consequent tumor regression in most patients with HCV-related indolent NHL. AT used at any time is associated with improved OS. Consequently, AT can be considered an option for patients with indolent lymphomas who do not need immediate cytoreductive treatment.

The prognostic role of post-induction FDG-PET in patients with follicular lymphoma: a subset analysis from the FOLL05 trial of the Fondazione Italiana Linfomi (FIL).

BACKGROUND: [18F]fluorodeoxyglucose-positron emission tomography (PET) is emerging as a strong diagnostic and prognostic tool in follicular lymphoma (FL) patients. PATIENTS AND METHODS: In a subset analysis of the FOLL05 trial (NCT00774826), we investigated the prognostic role of post-induction PET (PI-PET) scan. Patients were eligible to this study if they had a PI-PET scan carried out within 3 months from the end of induction immunochemotherapy. Progression-free survival (PFS) was the primary study end point. RESULTS: A total of 202 patients were eligible and analysed for this study. The median age was 55 years (range 33-75). Overall, PI-PET was defined as positive in 49 (24%) patients. Conventional response assessment with CT scan was substantially modified by PET: 15% (22/145) of patients considered as having a complete response (CR) after CT were considered as having partial response (PR) after PI-PET and 53% (30/57) patients considered as having a PR after CT were considered as a CR after PI-PET. With a median follow-up of 34 months, the 3-year PFS was 66% and 35%, respectively, for patients with negative and positive PI-PET (P<0.001). At multivariate analysis, PI-PET (hazard ratio 2.57, 95% confidence interval 1.52-4.34, P<0.001) was independent of conventional response, FLIPI and treatment arm. Also, the prognostic role of PI-PET was maintained within each FLIPI risk group. CONCLUSIONS: In FL patients, PI-PET substantially modifies response assessment and is strongly predictive for the risk of progression. PET should be considered in further updates of response criteria.

The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi.

BACKGROUND: The role of [¹8F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) in follicular lymphoma (FL) staging is not yet determined. PATIENTS AND METHODS: The aim of the present study was to investigate the role of PET in the initial staging of FL patients enrolled in the FOLL05-phase-III trial that compared first-line regimens (R-CVP, R-CHOP and R-FM). Patients should have undergone conventional staging and have available PET baseline to be included. RESULTS: A total of 142 patients were analysed. PET identified a higher number of nodal areas in 32% (46 of 142) of patients and more extranodal (EN) sites than computed tomography (CT) scan. Also, the Follicular Lymphoma International Prognostic Index (FLIPI) score increased in 18% (26 of 142) and decreased in 6% (9 of 142) of patients. Overall, the impact of PET on modifying the stage was highest in patients with limited stage. Actually, 62% (15 of 24) of cases with limited disease were upstaged with PET. CONCLUSIONS: The inclusion of PET among staging procedures makes the evaluation of patients with FL more accurate and has the potential to modify therapy decision and prognosis in a moderate proportion of patients. Further prospective clinical trials on FL should incorporate PET at different moments, and the therapeutic criteria to start therapy should be re-visited in the views of this new tool.

Long term results of a randomized study performed by Intergruppo Italiano Linfomi comparing Mini-CEOP vs P-VEBEC in elderly patients with diffuse large B-cell lymphoma.

The Intergruppo Italiano Linfomi started, in 1996, a randomized trial for the initial treatment of elderly patients (older than 65 years) with Diffuse Large B-Cell Lymphoma (B-DLCL) comparing 6 courses of Mini-CEOP vs 8 weeks of P-VEBEC chemotherapy. Study objectives were survival, response and Quality of Life (QoL). Two hundred and thirty-two patients were evaluable for final analysis. Complete Response (CR) and Overall Response Rates (ORR) were 54% vs 66% (p = 0.107) and 90% vs 78% (p = 0.021) for P-VEBEC and Mini-CEOP, respectively. With a median follow-up of 72 months, the 5-year Overall Survival (OS), Relapse Free Survival (RFS), and Failure Free Survival (FFS) were 32%, 52%, and 21%, respectively. Subjects achieving a CR showed improvement of QoL regardless of treatment arm. Both Mini-CEOP and P-VEBEC determined a similar outcome for elderly patients with B-DLCL, with a third of patients alive after more than 6 years of follow-up. Both regimens can be considered equally for combination treatment with anti-CD20 monoclonal antibody.

The role of dose size in a chemotherapy regimen (ProMECE-CytaBOM) for the first-line treatment of large B-cell lymphomas: a randomized trial by the Gruppo Italiano Studio Linfomi (GISL).

BACKGROUND: It is still unclear the actual contribute of dose intensity (DI), dose size (DS) and dose density (DD) in the conventional chemotherapy of large, B-cell non-Hodgkin lymphomas. METHODS: A prospective, randomized trial compared the cyclic schedule of ProMECE-CytaBOM chemotherapy (cyc-PC, 6 cycles) with a modified version of it, which administered the same drugs sequentially (seq-PC), with the same planned cumulative DI and an 83% DD, within the same time frame (113 days), but with three times higher DS of all the drugs except vincristine. RESULTS: Fifty-six patients received cyc-PC and 52 seq-PC. The actual mean cumulative DI was 0.79 +/- 0.15 with cyc-PC, 0.78 +/- 0.17 with seq-PC. Response was complete in 59% and 52%, partial in 20% and 21%, null in 5% and 6%, respectively. There were four toxic deaths (two per arm). Relapses occurred in 36% and 37%, respectively. Toxicity was similar in both arms. Overall, failure-free, progression-free and disease-free survival (median follow-up: 54 months) were statistically indifferent. CONCLUSIONS: The very similar DI actually delivered in both arm seems to be the main common determinant of the indifferent results recorded. Increasing DS--at least within the limits clinically attainable without stem cell rescue--does not improve results.

The role of high-dose therapy and autologous stem cell transplantation in patients with primary refractory Hodgkin's lymphoma: a report from the Gruppo Italiano per lo Studio dei Linfomi (GISL).

GISL recently conducted an exhaustive survey of 1078 patients with Hodgkin's Lymphoma (HL) enrolled between 1988 and 2002 in different prospective trials. Treatment failure was observed in 82 out of 1078 patients; of these 82 patients with refractory HL, complete information was available for 72, who form the evaluable population of the present study. After the initial therapy failure, 51 patients were treated with conventional salvage chemotherapy (CC) (n = 24) or high-dose chemotherapy (HDC) (n = 27); 4-year overall survival (OS) was 81% in the HDC group versus 38% in the CC group (P = 0.019). The remaining 21 patients had rapidly progressive disease and died. After a median follow-up of 2.8 years, the projected OS for all 72 patients is 58 and 49% at 3 and 5 years, respectively. Age <45 years, the absence of systemic symptoms and a PS <1 predicted a significantly longer OS. Interestingly, the majority of patients with two or three negative prognostic factors did not receive potentially curative therapy. In conclusion, HDC seems to be a reasonable option for selected patients with refractory HL, although the majority of them did not receive a transplant. Finally, patients with a high-risk score had little chance of receiving potentially curative treatment.

Clinical activity and safety of combination immunotherapy with IFN-alpha 2a and Rituximab in patients with relapsed low grade non-Hodgkin's lymphoma.

BACKGROUND AND OBJECTIVES: To determine the clinical activity and safety of the combination immunotherapy of the chimeric anti-CD20 antibody, Rituximab, and Interferon (IFN)- alpha 2a DESIGN AND METHODS: Sixty-four patients with relapsed low-grade or follicular B-cell non Hodgkin's lymphoma received 4 infusion of Rituximab (375 mg/m(2) x dose) after priming and simultaneous treatment with IFN- alpha 2a. RESULTS: The overall response rate was 70% with 33% complete responses. Median for duration of response is 19 months, after a median follow-up of 22 months. By univariate analysis none of the most common prognostic factors predicted for response to therapy. After treatment 10 patients become bcl-2 negative in the bone marrow, but no correlation between molecular and clinical response was found. Fifty-three patients (83%) had drug related or unknown origin adverse events. The number of adverse events per patient varied from 1 to 21. Considering all 272 events, 231 (85%) were grade 1 or 2, 36 (13%) grade 3 and 5 (2%) grade 4. Twenty-three patients required reduction in the dose and/or short discontinuation of IFN treatment, either during priming or subsequent treatment. The most frequent adverse events were leukopenia, fever, neutropenia, hypotension and thrombocytopenia. INTERPRETATION AND CONCLUSIONS: this report shows that combination immunotherapy Rituximab + IFN- alpha 2a is active and relatively well tolerated. The overall response rate of 70% and the median duration remission of 19 months compare favorable with the results obtained with Rituximab alone in similar subset of patients. Randomized trials, investigating Rituximab versus combination immunotherapy are needed.

Erythema nodosum and Hodgkin's disease.

A 27-year-old woman with a 5-month history of recurrent erythema nodosum was found to have Hodgkin's disease. A temporal relationship between the two disorders suggested a causative role of the lymphoma. A review of the literature yielded 15 cases of this association, suggesting that the diagnosis of Hodgkin's disease should be considered in patients with unexplained erythema nodosum.

Comparison of prognostic models in patients with advanced Hodgkin disease. Promising results from integration of the best three systems.

BACKGROUND: Several prognostic systems have been elaborated for patients with Hodgkin disease (HD) over the last 12 years, but early identification of a reasonably large group of both low and high risk, advanced stage patients remains unsatisfactory. METHODS: Seven well known models were applied to 516 patients with advanced HD, with 315 patients used for the study sample and 201 patients used for the test sample. Individual performances as well as joint performances were analyzed univariately and multivariately in relation to overall survival, recurrence free survival, and time to treatment failure by means of a proportional hazards model. RESULTS: None of the models identified a group containing > 10% of patients from the total population who had a failure risk of either < or = 10% or > or = 50%. The systems of the International Database on Hodgkin Disease, the Memorial Sloan-Kettering Cancer Center, and the International Prognostic Factor Project showed the best prognostic power; only these three, when analyzed together, predicted clinical outcome with a statistically significant fit to the clinical data. Integration of the three systems in a linear model dramatically improved their individual discriminatory capacity by identifying patients with 10% and 50% failure risks, respectively, in 23% and 24% of the study patient population and in 19% and 25% of the test population, respectively. CONCLUSIONS: As powerful and simple new prognostic factors are awaited that may improve our predictive ability, this integrated index is probably the best way to exploit the significance of those presently available. The program required for the calculations can be downloaded from the Internet at the web site http://www.unimo.it/gisl/default.htm.

Image-aided estimate of tumor burden in Hodgkin's disease: evidence of its primary prognostic importance.

PURPOSE: To explore a more direct method for evaluating tumor burden (TB) in Hodgkin's disease (HD) and to verify its prognostic importance. PATIENTS AND METHODS: The volume of TB at diagnosis was directly and retrospectively measured in 121 HD patients through images of the lesions recorded by computed tomographic (CT) scan of the thorax, abdomen, and pelvis for all deep sites of involvement and many superficial ones, and by ultrasonography (US) for the remaining superficial lesions. RESULTS: The TB, which was obtained from the sum of the volumes of all the lesions measured on CT scans and US and normalized to body-surface area (relative TB [rTB]), showed a median value of 102.6 cm(3)/m(2) (range, 2.2 to 582.8). At multivariate analysis for prognostic value, rTB was the parameter that statistically correlated best with time to treatment failure (P = 2.2 x 10(-6)), followed by erythrocyte sedimentation rate (ESR) (P =.0003), and serum fibrinogen (P =.0112). The prognostic discrimination allowed by rTB alone proved to be clearly superior to that obtained with the score of the International Prognostic Factor Project. The rTB was found to be correlated with many clinical staging parameters (bulky disease, number of involved lymph node regions, serum lactate dehydrogenase, ESR, hemoglobin, Karnofsky index), but its predictability from these variables was low (R(2) =.668). CONCLUSION: Relative TB is emerging as a strong prognostic factor in HD, more powerful than and largely independent of those hitherto known and used. Further studies are needed to confirm these results and exploit their clinical value, particularly the relationship among rTB, drug doses, and response.

Validation of the international prognostic index in working formulation group A low-grade non-Hodgkin's lymphoma: retrospective analysis of 137 patients from the Gruppo Italiano per lo Studio dei Linfomi registry.

BACKGROUND AND OBJECTIVE: The subset of non-follicular non-Hodgkin's lymphoma (NHL) includes patients with varied prognoses, thus suitable for different therapeutic approaches. The International Prognostic Index (IPI), originally proposed for aggressive NHL, has been demonstrated to be of prognostic relevance also in follicular NHL. The main aim of the study was to validate the IPI in this histologic category; in addition, the specific prognostic classification, currently employed in the Gruppo Italiano per lo Studio dei Linfomi (GISL) prospective therapeutic trials and based on different features, more similar to those applied to chronic lymphocytic leukemia, was analyzed. DESIGN AND METHODS: The present series consists of 137 evaluable patients affected by Working Formulation group A NHL out of 256 cases referred to the GISL Registry. The retrospective prognostic study included the evaluation by both univariate and multivariate analyses of overall survival, response to therapy and response duration. The IPI was applied as originally proposed. The GISL definition of indolent and aggressive disease at diagnosis was based on the presence of B symptoms, bulky disease, anemia and thrombocytopenia. RESULTS: The distribution of patients in IPI risk groups was rather unbalanced with 18%, 47%, 28% and 7% of cases classified as low (L), intermediate-low (IL), intermediate-high (IH) and high (H) risk, respectively. The median overall survival was not reached in either L or IL risk groups, and was 84.1 and 7.4 months for IH and H risk groups, respectively (p=0. 0005). A simplified IPI model was designed merging patients in both intermediate risk groups and the statistical difference of survival retained its significance. GISL prognostic stratification was demonstrated to have a significant association with survival, with a median survival of 71.3 months in aggressive disease and a median survival not reached at 152 months in indolent disease. Both the simplified IPI model and the GISL risk definition retained their significance in multivariate analysis for overall survival, while for response to therapy only the simplified IPI model resulted to be of statistical significance. In addition, the GISL prognostic stratification identified patients with different outcomes within the IPI intermediate risk group, with a median survival of 70.2 months for patients with aggressive disease wheras the median survival for those with indolent disease was not reached. Finally, a prognostic score resulting from the integration of the simplified IPI and the GISL system was statistically validated. INTERPRETATION AND CONCLUSIONS: The retrospective analysis of this series demonstrates the validity of the IPI in non-follicular indolent NHL and the usefulness of integrating the IPI parameters with disease specific prognostic variables.

Weekly administration of vincristine, cyclophosphamide, mitoxantrone and bleomycin (VEMB) in the treatment of elderly aggressive non Hodgkin's lymphoma. Gruppo Italiano per lo Studio dei Linfomi.

BACKGROUND AND OBJECTIVE: Aim of the study was to assess the efficacy of VEMB, a short-lasting therapeutic regimen (50 days) which alternates two myelotoxic drugs (cyclophosphamide and mitoxantrone) every week with two less hematologically toxic drugs (vincristine and bleomycin) in the treatment of aggressive NHL in the elderly (over 70). DESIGN AND METHODS: Between November 1994 and March 1996, 37 patients aged more than 70 years, with highly or moderately malignant NHL (according to the Working Formulation) have been enrolled into the study. The stage of the disease ranged between II and IV according to Ann Arbor. Mean age was 77 years; 14 patients (38%) had stage IV; 19 patients (51%) had LDH higher than normal; 26 patients (70%) had extranodal and 9 patients (24%) had bulky disease at time of diagnosis. RESULTS: Sixty-two percent of patients achieved a complete and 22% a partial remission. Non-responders amounted to 5%. Four patients (11%) died during the therapy. Nine patients (24%) experienced grade III-IV neutropenia. The most frequently observed event was mild neurotoxicity (43% of cases). The overall survival rate at 30 months was 55%. DFS at 24 months was 66%. INTERPRETATION AND CONCLUSIONS: VEMB is a therapeutic regimen whose efficacy is comparable to that of the other derived MACOP-B therapeutic regimens used in the elderly NHL. It has proved to have a good feasibility, though the number of toxic deaths should not be neglected.

Long-term results from MOPPEBVCAD chemotherapy with optional limited radiotherapy in advanced Hodgkin's disease.

The purpose was to verify the 5-year results of the MOPPEBVCAD chemotherapy regimen with limited radiotherapy in relation to the promising preliminary data. Mechlorethamine, vincristine, procarbazine, prednisone, epidoxorubicin, bleomycin, vinblastine, lomustine, melphalan, and vindesine were delivered according to a schedule derived through hybridization, intensification, and shortening of the corresponding alternating CAD/MOPP/ABV regimen. Radiotherapy was restricted to sites of bulky involvement or to areas that responded incompletely to chemotherapy. This multicenter, controlled, nonrandomized trial involved 145 eligible patients. Radiotherapy was administered to 47 patients, 46 of whom were in complete remission after chemotherapy. Remissions were complete in 137 patients (94%), partial in 4 (3%), and null in the remaining 4. Tumor-specific, overall, relapse-free, and failure-free survival at 5 years were 0.89, 0.86, 0.82, and 0.78, respectively. Hematologic toxicity was considerable, whereas nonhematologic side effects were fully acceptable. Most of the unfavorable prognostic factors lost their clinical weight. Only age and lymphocyte depletion histologic type were statistically correlated with major follow-up endpoints; performance status and bone marrow involvement were subordinate to age. Seven patients developed a second cancer (including 3 myelodysplasias). MOPPEBVCAD with selected radiotherapy is a highly effective regimen in advanced Hodgkin's disease. Early and late toxicity are no more severe than what would be expected with other alternating or hybrid regimens. A comparison with ABVD, which is currently considered the standard regimen for advanced Hodgkin's disease, is needed.

CCNU, vinblastine, procarbazine and prednisone (CVPP) with extended-field radiotherapy in the treatment of early unfavorable Hodgkin's disease. A prospective study on behalf of the Gruppo Italiano per lo Studio dei Linfomi (GISL).

PURPOSE: To test the adequacy of the CVPP four-drug regimen as ancillary chemotherapy associated with extended-field radiotherapy in the treatment of early, unfavorable, clinically staged Hodgkin's disease. PATIENTS AND METHODS: The population of this prospective, multicenter study consisted of 49 patients with stage I-II disease, associated with bulky involvement or unfavorable histology (lymphocyte-depleted nodular sclerosis or lymphocyte depletion), systemic symptoms or extranodal involvement, or presenting with stage III A favorable-histology disease, with or without extranodal involvement. RESULTS: Complete remission was achieved in 39 patients, partial remission in 2, while 8 patients did not respond. Four patients have relapsed so far (median follow-up: 43 months), all of whom were subsequently rescued with different salvage treatments. Dose intensity (mean +/- SD: 0.83 +/- 0.12) and hematological toxicity (including 2 deaths from infection) were higher when RT followed CT than when it was interposed in the middle of the 6 cycles. No growth factors were used. Nonhematological toxicity was very low and fully tolerable. CONCLUSIONS: Results confirmed the mild neurological and gastroenteric side effects of CVPP that make it an interesting MOPP-variant regimen. This combination seems most indicated when a regimen devoid of cardiac and pulmonary toxicity is required for association with full-dosage mediastinal radiotherapy, as is often the case in early, unfavorable Hodgkin's disease. The optimal sequence consists of radiotherapy administered after completion of the chemotherapy program. The use of growth factors for correction (or prevention) of marked leukopenia seems appropriate.

Autoimmune thyroid dysfunctions in hematologic malignancies treated with alpha-interferon.

The widespread use of alpha-interferon (IFN-alpha) therapy in different diseases draws attention to its side effects, such as autoimmune-related diseases, especially thyroid autoimmune dysfunctions. Data about hepatitis and nonhematologic neoplasia are available, while data about hematologic malignancies are fragmentary. We studied the incidence of autoimmune-related disturbances and thyroid dysfunctions in 54 consecutive patients suffering from hematologic malignancies, treated with recombinant human IFN-alpha for a mean time of 15.9 +/- 8.9 months. Our results minimize the incidence of autoimmune dysfunctions in hematologic malignancies as side effects of IFN-alpha therapy. We registered the appearance of autoantibodies in only 3 females (5% of total): 2 patients (1 affected with essential thrombocythemia and one with multiple myeloma) presented antithyroglobulin antibodies with no clinical symptoms; 1 patient, affected with essential thrombocythemia, developed antinuclear antibodies with arthralgia and myalgia. ARA criteria for systemic lupus erythematosus were not fulfilled but the therapy had to be interrupted. No patient developed thyroid dysfunction. In patients with hematologic malignancies, the dosage and the duration of IFN-alpha treatment do not seem to influence the appearance of autoantibodies, while female sex appears to be a risk factor.

[Ovarian hyperstimulation syndrome with bilateral hydrothorax and ascites]. / Sindrome da iperstimolazione ovarica con idrotorace bilaterale ed ascite.

Ovarian hyperstimulation syndrome (OHSS) is an unusual complication of ovarian stimulation with exogenous gonadotrophins. We describe a case of severe OHSS with bilateral hydrothorax and ascites. We discuss the different pathogenetic hypothesis and the differential diagnostic possibility.

Polycyclic aromatic hydrocarbons in olive oils on the Italian market.

The six olive oils and seven virgin olive oils which are most consumed in Italy were analysed for 28 polycyclic aromatic hydrocarbons (PAHs). The aim was to evaluate whether a carcinogenic hazard for the general population can derive from the dietary intake of this food, which is consumed particularly highly in the Mediterranean area. The analytical method involved extraction by liquid-liquid partition, filtration on silica gel, clean-up by thin-layer chromatography on silica gel, and analysis by high-resolution gas chromatography with a flame ionization detector. The 3- and 4-ring PAHs which are most abundant in the environment were found in all samples, at individual levels up to ca. 40 micrograms/kg (for phenanthrene); no important difference was observed between olive oils and virgin olive oils. PAHs which are most suspected of being carcinogenic for humans were not detected (limit of detection, ca. 3 micrograms/kg). The average yearly intake of the detected PAHs through this food was estimated at ca. 0.56 mg per capita.