PubMed HealthSearch

Biomedical subjects

F Gherlinzoni

Publications and source records attributed to F Gherlinzoni.

At least 19 recordsLinked to original sources

Fludarabine treatment in resistant Waldenstrom's macroglobulinemia.

Fludarabine (FLU) is a fluorinated purine analogue with a promising antineoplastic activity in lymphoproliferative disorders. In this study, we evaluated the efficacy of FLU in 12 previously treated (primary refractory and refractory relapse) patients with Waldenstrom's macroglobulinemia. All patients were treated at a dosage of 25 mg/m2 per day for 5 consecutive days for a total of six courses. Of the 12 patients, 5 (41%) achieved partial response (PR), and the remaining 7 showed no benefit from the treatment. An increased response rate was obtained in the 4 primary refractory patients in which 2 PR were documented. Treatment was well-tolerated and there were no Fludarabine-related fatalities. With a mean follow-up of 10 months, only 1 PR patient has relapsed. Fludarabine is an interesting new salvage agent effective against recurrent/resistant Waldenstrom's macroglobulinemia and should be evaluated in further studies in untreated patients with Fludarabine in monochemotherapy or in combination with other active modalities.

Aged

[Combined treatment of stage I and II gastric lymphoma].

From 1981 to 1991, fifty-three patients with primary gastric lymphoma were referred to our Institute and submitted to a complete pathologic staging followed by gastric resection, i.e., total or partial gastrectomy. According to the Working Formulation criteria, 14 patients (26.4%) were affected with high grade lymphomas, 22 (41.5%) with intermediate lymphomas and 17 (32.1%) with low grade lymphomas. MALT (mucosa associated lymphoid tissue) lymphomas were observed in > 50% of cases. At the pathologic examination of the surgical specimens, infiltration depth was assessed, according to TNM criteria, in the patients whose disease was limited to the muscular gastric wall (T1-T2) and in those whose disease spread to the serosa or beyond it (T3-T4). Twenty-five patients were classified as stage I and 28 as stage II (9 of them in stage II E1 and 19 in stage II E2 according to Musshoff's classification). The treatment protocol of these patients was as follows: stage I patients (T1-T2) with normal surgical resection margins underwent no adjuvant treatment (10 patients); stage I patients (T1-T2) with resection margins infiltrated by the disease were submitted to local irradiation; stage I (T3-T4) and stage II E1 patients underwent large-field postoperative irradiation (14 patients); stage II E2 patients (n = 19) received conventional chemotherapy (CHOP, F-CVP, N-CVP): the ones who failed to reach complete remission or presented with bulky disease at diagnosis completed the treatment with large-field irradiation (10 patients). The disease-free survival (86.5%) and the overall survival (96%) rates of stage I patients exhibited no significant difference relative to stage II patients (DFS: 87% and OS: 90%). The analysis of relapses relative to disease extent demonstrated that this parameter is more significant to prognosis than nodal involvement (T1-T2: 2/39 relapses, 5.1%; T3-T4: 4/14 relapses, 28.6%).

Adult

Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico-pathological study of 69 cases.

Sixty-nine anaplastic large cell lymphomas (ALCLs) were selected from an Italian comparative trial on MACOP-B and F-MACHOP. As no significant difference in effectiveness of the protocols emerged, they were considered homogeneously treated. The ALCLs were divided into two groups according to previously defined criteria: 41 were common type (ALCLs-CT) and 28 Hodgkin-related (ALCLs-HR). T-cell phenotype was most common (58%), while B-cell, null and hybrid forms accounted for 27%, 13% and 2%. Clinically, ALCLs CT and HR differed as to mean age (27 v 34.3 years) and presentation; all ALCLs-HR showed mediastinal involvement, with bulky disease in 57%, and more frequent occurrence in stage II. In contrast, ALCLs-CT showed mediastinal masses in 58.5%, infrequently revealed bulky disease (24%), and were not specifically associated to stage. Among the ALCLs-CT, 68.4% achieved complete remission (CR), 24.4% partial remission (PR), one (2.4%) was resistant to therapy, and two (4.8%) had fatal drug toxicity. Of the ALCLs-HR, 67.8% reached CR, 14.3% PR, and 17.9% did not respond. In CR, ALCLs-CT showed a greater tendency to relapse (32.1% v 14.2%). At present, 65.8% of ALCLs-CT and 67.8% of ALCLs-HR are alive with overall survival/disease-free survival averages of 31/27 and 29/24 months respectively. Our data emphasize that, independently of subtype, ALCLs benefit from the application of third-generation protocols for high-grade non-Hodgkin's lymphomas.

Adolescent

Treatment recommendations for osteosarcoma and adult soft tissue sarcomas.

During the past 20 years, dramatic improvements have been obtained in the treatment of localised osteosarcoma of the extremities, both in the rates of disease-free survival and in quality of life. Twenty years ago 80 to 90% of the patients died, in spite of mutilating surgery, but now about 75% survive and avoid the necessity of amputation. This is due to the introduction of very effective combined treatments, mostly also using preoperative chemotherapy. One of the major issues is that of intensive preoperative chemotherapy, which improves both limb salvage and survival. A multidisciplinary approach is necessary to obtain good results. When the role of adjuvant or neoadjuvant chemotherapy is not accurately defined for soft tissue sarcomas, particular emphasis is given to the staging of the diseases and to the important role of local treatment in the survival of these patients. A combination of radiation therapy and surgery is strongly recommended.

Antineoplastic Agents

Adult Burkitt's lymphoma: clinical and prognostic evaluation of 20 patients.

Burkitt's lymphoma (BL), a rapidly growing lymphoma, is recognized by its aggressive course, brief median survival, and low rates of long-term survival for patients. Several polychemotherapeutic approaches are utilized. Twenty adult patients with BL identified according to the Kiel classification were analysed retrospectively. Therapeutic modifications depended upon the different times of the diagnosis. Eight patients received the LSA2-L2 regimen, 11 patients were treated with third generation polychemotherapeutic regimens for high-grade non-Hodgkin's lymphomas: F-MACHOP and MACOP-B, and 1 elderly patient was given the COP regimen. Of the 11 patients treated with cyclic conventional therapy (7 with F-MACHOP and 4 with MACOP-B), 8 achieved a complete response (CR). Of the 8 patients who were given the LSA2-L2 protocol, 4 obtained a CR. One elderly patient treated with the COP regimen obtained a partial response. Early stage of disease, low levels of LDH, and the absence of bone marrow involvement were characteristics of patients with good prognoses. Effective conventional third-generation polychemotherapy regimens (F-MACHOP and MACOP-B), normally used for high-grade non-Hodgkin's lymphomas, were equally effective for a large fraction of adults with BL. Furthermore, our study confirms the important role of LDH level, stage, and bone marrow involvement as prognostic factors in BL as well as the roles of tumor burden in the CR rate and relapse-free survival.

Adolescent

[Anaplastic large-cell lymphoma. Conceptual and diagnostic assessment].

The authors critically review the concept of anaplastic large cell lymphoma (ALCL). In particular, they provide the guidelines to the morphologic identification of the four main varieties of the tumour: common, giant-cell-rich, lympho-histiocytic, and Hodgkin's-like. The phenotypic and molecular characteristics of the neoplasm are discussed with special emphasis to those which can assist in the differential diagnosis between ALCL and Hodgkin's disease. Finally, the clinical features are presented along with the results obtained in the course of long-term prospective therapeutical trials.

Diagnosis, Differential

Correlations between apoptotic and proliferative indices in malignant non-Hodgkin's lymphomas.

Cell production versus cell loss rates were estimated, across the boundaries of histological classification, in 50 cases of malignant non-Hodgkin's lymphomas by use of mitotic indices, percentage of Ki-67+ cells and percentage of PC10+ cells as proliferative indices, and the relative number of apoptotic bodies (apoptotic indices, AIs) as parameters. Regression analysis revealed significant (P < 0.01) positive correlations between the AIs and the proliferative indices; among the immunohistochemically assessed proliferative indices; and between these, the mitotic indices and the AIs on the one hand and histological malignancy grades on the other hand. The cellular protein BCL-2, which counteracts apoptosis, was significantly (P < 0.01) more often expressed in lymphomas with low than in those with high AIs. Multivariate analysis of data showed that of all parameters tested in this series, only the AIs correlated significantly (P < 0.05) with overall lethality. The correlation between BCL-2 positivity of lymphoma cells and overall survival did not quite attain significance (P = 0.08). Results of the present study suggest that high AIs and lack of BCL-2 expression may be adverse prognostic factors, independent of histological grade.

Apoptosis

Limb sparing versus amputation in osteosarcoma. Correlation between local control, surgical margins and tumor necrosis: Istituto Rizzoli experience.

Three hundred fifty-five patients with osteosarcoma were surgically managed at the Istituto Ortopedico Rizzoli between 1983 and 1988. Three hundred two patients performed two cycles of neoadjuvant chemotherapy according to two different protocols consecutively activated; the remaining 53 patients were immediately operated on without neoadjuvant treatment. Follow-up ranged from 19 to 88 months, with a mean of 51 months. Demolitive surgery was performed in 116 patients (33%), while conservative in 239 patients (67%). A radical margin was achieved only in patients undergoing amputations: no radical surgical margins were achieved by local resection: 174 resected patients (73%) had wide margins, while 34 (14%) had marginal margins; 20 patients had contaminated margins and 11 patients (5%) had intralesional margins. Wide or marginal margins were achieved in 208 (87%) of the patients managed by local resection. Local recurrence was identified in 24 of 355 patients (7%). Incidence of local recurrence is strictly related to surgical margin, but above all, to tumor necrosis induced by neoadjuvant chemotherapy. In fact, neoadjuvant chemotherapy makes limb salvage feasible in the majority of cases without increasing the risk of local recurrence: in the group of patients immediately operated on without neoadjuvant chemotherapy, the incidence of local recurrence is dramatically high even when the surgical margins are adequate.

Adolescent

Primary chemotherapy and delayed surgery for osteosarcoma of the extremities with synchronous metastases.

From September 1986 to September 1989 11 patients affected by osteosarcoma of the extremities with synchronous metastases were treated with two cycles of high-dose methotrexate i.v., cisplatin i.a. and adriamycin i.v. followed by simultaneous resection of the primary and metastatic tumor. A complete histological examination of the resected specimens was always performed to evaluate the percentage of necrosis produced by chemotherapy on both the primary and metastatic tumor. After surgery the patients received 3 more cycles of the same drugs as used preoperatively plus ifosfamide. The histological response of the primary tumor was 'good' (90% or more tumor necrosis) in 4 patients and 'poor' (less than 90% of tumor necrosis) in 7, while in the 34 metastatic nodules the resulting necrosis was good in 8 and poor in 26. A good correlation between the histological response in the primary and metastatic tumor was observed, particularly for poor responders (91% of poor responses also in metastatic nodules). At an average follow-up of 42 months, only 3 patients are alive, 2 disease-free, and one with uncontrolled disease. These data suggest that the prognosis of osteosarcoma of the extremities with synchronous metastases remains poor, even with a very aggressive treatment. Our results also seem to confirm the validity of the present strategy in the treatment of non-metastatic osteosarcoma: introducing new drugs post-operatively in poor responding patients can allow a better treatment of microscopic disease and can improve the prognosis for these patients.

Adolescent

Radiation therapy and conservative surgery for soft tissue sarcomas of the extremities, torso and head and neck.

Between May 1985 and July 1990, 45 patients (pts.) with primary (39) or recurrent (6) soft tissue sarcomas of the extremities (82%), torso (11%) and head and neck (7%) were treated with radiation therapy and conservative surgery. Seven pts. not amenable to conservative surgery underwent preoperative radiation therapy whereas 38 pts. underwent local excision and post-operative radiation therapy. Out of the 38 pts. managed by postoperative radiation, 24 (63%) showed negative surgical margins and 14 (37%) positive margins, their tumor being adjacent to vital structures. Preoperative radiation allowed conservative surgery in all 7 pts. with initially inoperable tumor; surgical margins were negative in 5 and positive in 2 pts. Twenty-six pts. (58%) had tumor greater than or equal to 5 cm (5-24) and 19 (42%) less than 5 cm (2.5-4.5) in diameter. High grade tumors (G2-G3) were reported in 41 pts. (90%). In pts. treated postoperatively the radiation dose was 64-66 Gy/32-33 fractions and the pts. treated preoperatively received a dose of 50 Gy/25 fractions. Median follow-up was 33 months and all pts. had a minimum follow-up of 12 months (12-72). Three pts. (6.5%) had local failure and 9 (20%) developed distant metastases with local tumor control. All distant metastases occurred in AJC stage IIIB, 9/18 (50%), with an increased frequency by tumor size. Overall local control and disease free survival rates at 5 years (product-limit method) were 93% and 73%, respectively. An evident decrease in disease-free survival rate (33%) was noted for stage IIIB pts.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Expression of MDR1 and GST-pi in human soft tissue sarcomas: relation to drug resistance and biological aggressiveness.

Human soft tissue sarcomas (HSTS) in adults are a family of mesenchymal tumors characterized by high biological aggressiveness and general refractoriness to chemotherapy. A series of 36 HSTS, 24 untreated and 12 homogeneously treated with a presurgical chemotherapeutic regimen consisting of doxorubicin (intra-arterial) and iphosphamide (intra-vein), was analyzed for expression of MDR1 and the glutathione-S-transferase-pi (GST-pi) gene in order to identify molecular phenomena which may be implicated in the chemoresistance displayed by these tumors. The MDR1 gene was expressed in a greater percentage of drug-treated tumors and at higher levels than in untreated ones. By contrast, chemotherapeutic treatment has no effect on GST-pi mRNA expression. The GST-pi expression level (EL) was much higher in the HSTS with biologically aggressive features. In fact, significant correlations were observed between GST-pi and histologic grade (p = 0.01); aneuploidy (p less than 0.01); and histone H3 EL (p = 0.01), suggesting a possible causal relationship between GST-pi activity and biological aggressiveness in HSTS.

Adult

Massive mediastinal involvement in stage I-II Hodgkin's disease: response to combined modality treatment.

Thirty-seven patients with stage I-II Hodgkin's disease and massive mediastinal involvement, observed between June 1981 and November 1989, underwent combined modality treatment. This treatment included: 3 cycles of mechlorethamine, vincristine, procarbazine, and prednisone followed by mantle-field irradiation, and subsequently by 3 additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Thirty-five (95%) patients achieved complete responses and only 2 (5%) had partial responses. All the complete responders are living and relapse-free at a median follow-up of 62 months; no major toxic reactions were recorded. These data suggest, as did those of other studies, that combined modality therapy is superior to either radiotherapy or chemotherapy alone for patients in stage I-II with bulky disease, especially in the mediastinum. In fact, in these particular patients, if adequately treated with a combination of chemotherapy and radiotherapy, the role of massive mediastinal involvement as a poor prognostic factor appears to be less significant.

Adolescent

Eosinophilic pustular folliculitis (Ofuji's disease) and non-Hodgkin lymphoma.

The authors report the third case of eosinophilic pustular folliculitis (EPF) associated with a non-Hodgkin lymphoma. The dermatosis occurred after an autologous bone marrow transplantation performed as treatment for the lymphoproliferative disorder. Although EPF was initially described as an idiopathic disease, the association of some cases with immunologic alterations or diseases, such as immunodeficiencies, suggests a possible immunopathologic event in the pathogenesis of EPF.

Adult

Immunohistochemical detection of the multidrug transport protein P170 in human normal tissues and malignant lymphomas.

Two monoclonal antibodies, MRK16 and C219, both directed at the 170 kDa P-glycoprotein multidrug resistance agent, were applied to frozen sections or cytospin preparations from normal human tissues and 60 non-Hodgkin's malignant lymphomas. Adrenal gland, kidney, liver and pancreas were always stained by the reagents, albeit with slightly different patterns. Brain capillaries as well as macrophages and some elements of the bone marrow, peripheral blood, ovarian stroma and colonic, gastric and jejunal mucosa were positive in all examined preparations. There were differences in the staining patterns with the two antibodies. Among the 60 non-Hodgkin's lymphomas, 25 contained a number of positive cells, which ranged from 2% to 100%. No correlation was seen between the expression of P170 and histological type, stage, clinical symptoms or growth fraction. A close relationship was shown between the presence of P170 positive elements and the clinical course of the disease (P less than 0.001).

ATP Binding Cassette Transporter, Subfamily B, Mem

MACOP-B vs F-MACHOP in the treatment of high-grade non-Hodgkin's lymphomas.

From September 1988 two hundred-sixty-seven (267) untreated patients (pts) with stage II to IV high grade non Hodgkin's lymphoma (NHL) have been enrolled in a multicenter, randomized, still ongoing study, comparing two third-generation combination chemotherapy regimens, MACOP-B versus F-MACHOP. At the present time, 177 pts have completed the treatment program and are evaluable, with a median follow-up of 13 months. Clinical, histologic and laboratory characteristics are equally distributed in both groups. Among the 92 pts treated with MACOP-B, 58 (63%) achieved a complete remission (CR), 17 complete responders have relapsed (29%), and 21 have died (23%), including 3 treatment-related deaths. Among the 85 pts who received F-MACHOP, 65 (76%) achieved a CR, 9 complete responders have relapsed (14%), and 11 pts have died (13%), including 3 treatment related deaths. 30 months-projected survival is 64% for MACOP-B treated pts compared to 84% for F-MACHOP treated pts; 30 months-projected relapse- free survival is 80% and 84%, respectively. F-MACHOP seems to be superior in immunoblastic lymphoma (overall survival, OS, 82% vs. 54%) and in Burkitt-type lymphoblastic lymphoma (OS 100% vs, 42%). The degree of hematological and non-hematological toxicity was similar in both regimens. More reliable conclusions will be drawn after a longer follow-up.

Adult

CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report.

Between March 1987 and December 1988, 30 previously untreated patients with low-grade non-Hodgkin's lymphomas (NHL), according to the Kiel classification, were treated by a combination of therapy including cyclophosphamide, epirubicin, vincristine, and prednisone (CEOP). Eighteen patients (60%) achieved a complete pathologic remission, and 8 patients (26.6%) had a partial response with a reduction of more than 50% of tumor-related manifestations. Four patients (13.4%) were primary resistant to CEOP. The overall survival was 96.6% with a median follow-up of 25 months from the diagnosis; none of the patients who achieved complete response relapsed at a median follow-up of 21 months from the completion of treatment. Clinical and hematologic toxicities were irrelevant. This regimen was effective in inducing a good remission rate of low-grade NHL, but a longer follow-up for definitive conclusions is warranted.

Adult