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Biomedical subjects

F Merli

Publications and source records attributed to F Merli.

At least 19 recordsLinked to original sources
PubMed2006

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.

Adult↗
PubMed2006

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.

Adolescent↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Adolescent↗
PubMed2001

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2000

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.

Lymphoma, Non-Hodgkin↗
PubMed1998

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.

Adolescent↗
PubMed1998

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.

Aged↗
PubMed1995

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.

Adult↗
PubMed1989

T-cell receptor genes expression in B-cell leukaemias.

Using Northern-blot analysis we have studied the expression of T-cell receptor (TCR) alpha, beta and gamma chain genes in primary cells obtained from 36 leukaemic patients. Fifteen patients had myeloid leukaemias, two had T-cell leukaemias, and 19 leukaemias corresponding to various stages of B-lymphocyte differentiation. We observed that truncated TCR beta mRNAs were produced in B-cells at relatively high levels even in the absence of detectable gene rearrangements. Ti alpha mRNAs of abnormal size were also frequently found. Such transcripts were not detectable in total RNA extracted from leukaemic myeloid cells. Factors allowing Ti alpha and beta gene transcription must be active in leukaemic pre-B and B cells but not in myeloid cells. Neither B-lineage nor myeloid leukaemias expressed TCR gamma gene at detectable levels.

B-Lymphocytes↗
PubMed1989

Heavy metals: sources and environmental presence.

The Istituto Superiore di Sanità has for many years been involved in the problem of environmental pollution caused by heavy metals. A brief review of the sources of this pollution is first presented which also includes the presence in nature of some heavy metals which are among the most dangerous. Data gathered by the authors is then presented from sampling of the emissions of urban solid waste (USW) incinerators and from environmental monitoring programs in different areas in Italy according to four categories: urban, industrial, rural and mixed.

Environmental Pollutants↗
PubMed1988

Myeloperoxidase gene expression in blast cells with a lymphoid phenotype in cases of acute lymphoblastic leukemia.

By using a cDNA clone of the myeloperoxidase (MPO) gene, we have studied, by Northern blot analysis, the level of MPO mRNA in eight cases of acute lymphoblastic leukemia (ALL). The blast cell populations studied were characterized by morphologic, cytochemical, immunochemical, and molecular criteria. With all the methods used the populations were found to be highly homogeneous and showed a typical lymphoid phenotype. In particular, the Ig heavy-chain gene rearrangement was largely prevalent, and the germ line configuration was almost absent. However, in three of eight cases, high levels of MPO mRNA were detected. The remarkable homogeneity of the cell populations examined suggests that the MPO mRNA observed was present in cellular elements certainly identified as lymphoid. The absence of contamination by myeloid cells was confirmed by the results of Western blot analysis of the proteins of the cell population studied: no MPO protein was detectable. The levels of mRNA observed were high enough to be comparable to those observed in a promyelocytic cell population.

Cell Transformation, Neoplastic↗
PubMed1986

Analytical procedures to detect 2,3,7,8-TCDD at Seveso after the industrial accident of July 10, 1976.

The analytical procedures used at Seveso (Milan, Italy) for the determination of 2,3,7,8-TCDD, and some isomers, in biological and environmental samples are reviewed in this paper. During the emergency period, up until the first 10 days of August, the extracts, mostly from soil or vegetation samples, were evaporated to dryness and then mixed with less than or equal to 10-ml solvent. Of these solutions, aliquots up to 10 microliter were injected into a low-resolution gas chromatograph (GC) combined with a low-resolution mass spectrometer (MS). Analytical sensitivity for vegetation and soil was less than 10 ppb and approximately 100 ppt, respectively--sufficient for the early mapping of the most heavily contaminated territory. After the emergency period, the greatest improvement in environmental sample analysis was the introduction of cleanup procedure which greatly reduced the presence of unwanted material in samples. Cleanup was followed by the complete removal of the solvent. Dry samples could be taken up with rather small volumes (greater than or equal to 0.1 ml) of solvent, of which an aliquot was used for GC-MS analysis. The instrumental setup was kept as above. For animal samples, extraction entailed preliminary alkaline digestion followed by a number of cleanup steps. The final dry sample was taken to desired volume by adding solvent (greater than or equal to 0.1 ml), of which a few microliters were injected in GC-MS apparatuses. Detection thresholds improved markedly and were less than 10 ppt for agricultural soil and sediment, less than or equal to 0.05 ppt for water, in the range of 60 to 200 ppt for air dust, less than 10 ng/m2 and 10 ppt for wipe and scrape tests, respectively, less than 50 ppt for vegetation, and 250 ppt for biological substrata. Major later improvements in TCDD assay were the use of high-resolution gas chromatography (hrGC-MS), in some cases combined with high-resolution mass spectrometry (hrGC-hrMS). This provided greater specificity, sometimes accompanied by a very marked increase in detection sensitivity.

Accidents, Occupational↗
PubMed1978

Gas-liquid-chromatography of trimethylsilyl derivatives from whole cell methanolysates of Leptospira : preliminary evaluation of its applicability to the taxonomy of the genus.

Gas-liquid-chromatography of trimethylsilyl derivatives from whole cell methanolysates was investigated as a supplmentary means for taxonomical classification within the genus Leptospira. Reproducibility of this technique was assessed through the peak height variations occurring in chromatograms of strain Patoc 1, serotype patoc, when samples either from the same or different batches of culture were used. From each chromatogram seven peaks were selected. Their heights were measured and calculated as percent values of the seven peaks total height. The values of relative standard deviation reported show that the reproducibility of this technique lies within the usual limits of biological methods. Four out of seven different serotypes analyzed gave elution patterns dissimilar enough to allow a clear distinction among them by the simple visual examination. Differentiation of the other three had to be done comparing the relative heights of the seven selected peaks. One not yet classified new strain was submitted to this technique; results seemed to confirm available serological information about it. Data reported encourage further research in order to evaluate the potential of GLC as an useful aid in the taxonomy of genus Leptospira.

Chromatography, Gas↗