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Biomedical subjects

V Zagonel

Publications and source records attributed to V Zagonel.

At least 91 records · Page 5Linked to original sources

Follicular lymphoma of compartmentalized small cleaved center cells and mantle zone lymphocytes. Evidence for a common derivation.

The authors have observed a unique case of follicular lymphoma in which the central zones of neoplastic nodules were composed predominantly of small cleaved cells (SCC) that were surrounded by small lymphoid cells proliferating in wide mantles as in mantle zone (MZ) lymphoma. The central SCC component displayed a follicular SCC lymphoma-like phenotype (IgD-, CD10+, CD5-, CD68-), whereas the neoplastic cells of the peripheral zones had an MZ lymphoma-like phenotypic profile (IgD+, CD10-, CD5+, CD68+). In extranodal involved tissues, either follicular or diffuse (leukemic-like) patterns of lymphoma infiltration were noted. Flow cytometric analyses showed in the bone marrow or the peripheral blood two leukemic B cell populations, one mimicking the phenotypic profile (IgM+, IgD+, CD5+, CD10-, Leu8-) of small lymphoid cells with MZ-like features, and the other with phenotypic features (IgM+, IgD-, CD5+, CD10+, Leu8+) intermediate between those of MZ-like cells and those of the SCC component (follicular center-like) detected in the lymph node. Immunomagnetic sorting and gene rearrangement studies indicated that both CD10+ and CD10- B lymphocytes and lymph node neoplastic B cells shared the same clonal origin. This unusual follicular lymphoma can be viewed as the result of the proliferation of a single follicular progenitor capable of differentiating toward both a germinal center and an MZ phenotype. The simultaneous presence in the same patient of at least three neoplastic B-cell populations at different maturation stages, encompassing follicular center and MZ phenotypes, and showing the same clonal derivation, indicates a close lineage relationship between follicular SCC and MZ lymphomas.

Aged↗

A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin's lymphoma.

PURPOSE: A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken. PATIENTS AND METHODS: Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated. RESULTS: Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy. CONCLUSION: We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.

Age Factors↗

Expression of myelomonocytic antigens is associated with unfavourable clinicoprognostic factors in B-cell chronic lymphocytic leukaemia.

The cross-lineage expression of five myelomonocytic antigens (CD11b, CD11c, CD13, CD14, and CD15) was analysed in neoplastic lymphocytes from 100 consecutive B-cell chronic lymphocytic leukaemia (B-CLL) patients. CD14 antigen was detected on lymphocytes from more than 50% of patients whilst smaller percentages of samples were positive for CD11b (21%), CD11c (26%), CD13 (22%), and CD15 (7%). The presence of the CD13 antigen on neoplastic lymphocytes showed a statistically significant association with the two most important unfavourable clinicoprognostic factors in B-CLL: advanced clinical stage (CD13, P less than 0.01 by the Rai staging system; P less than 0.05 by the Binet staging system) and the diffuse pattern of bone marrow infiltration (CD13, P less than 0.001). A multiple logistic regression analysis showed that the increased risk for CD13-positive patients (13.7-fold higher than CD13-negative cases; P = 0.001) of presenting a diffuse pattern of bone marrow infiltration is independent of all other prognostic factors analysed including sex, age, lymphocyte counts, and clinical stage. A statistically significant association of CD11c (P = 0.002) and CD11b (P = 0.032) expression with the pattern of bone marrow infiltration was also found. Our results indicate for the first time a statistically significant association of CD13, CD11c, and CD11b antigens with unfavourable prognostic factors in B-CLL. They suggest that the cross-lineage expression of myeloid-associated surface peptidase (CD13-aminopeptidase N) and/or cell adhesion molecules (CD11c-LeuCAMc, CD11b-LeuCAMb) may influence the biological and clinical behaviour of chronic lymphoproliferative disorders of B cells.

Age Factors↗

A phase II study of oral idarubicin (4-demethoxidaunorubicin) in previously untreated elderly patients with non-Hodgkin's lymphoma.

Eighteen untreated elderly patients (median age 75 years) with non-Hodgkin's lymphoma (NHL) entered a phase II study with oral Idarubicin (4-demethoxidaunorubicin) at a dosage of 30-35 mg/m2 on day 1 and every 3 weeks thereafter. The medium number of cycles administered was three (range one to nine). We obtained one (6%) complete response and four (25%) partial responses in 16 evaluable patients. Toxicity was mild and no cardiotoxicity was found. At this dosage Idarubicin showed little anticancer activity in NHL.

Administration, Oral↗

Non-Hodgkin's lymphoma in the elderly. I. Pathologic features at presentation.

The pathologic findings of 118 patients aged 70 years or older with non-Hodgkin's lymphoma (NHL) are reported. These patients formed 27.2% of 433 consecutive cases of NHL seen in a single institution over a 5-year period. Thirty-one of 433 NHL cases were histologically not classified, whereas the remaining 402 could be classified according to the International Working Formulation (WF) of NHL for clinical usage. Immunophenotypic analyses were carried out in 112 NHL cases; of this group 28 were NHL in elderly patients. Of the 95 elderly NHL that could be classified in the histologic categories of the WF 28 cases were in the low-grade, 41 in the intermediate-grade, and 26 in the high-grade categories. Eighty-one cases had diffuse histologic types and 14 had follicular/nodular histologic types. Thirty-five cases were of the G (diffuse large cell) + H (large cell, immunoblastic) categories. No significant differences in the prevalence of the different subtypes were observed among patients younger or older than 70 years. Immunohistologically, most NHL cases in the elderly expressed B-cell phenotype. Sixty-two NHL in the elderly were extranodal at presentation. The results of this study indicate that elderly patients form a relevant proportion of patients developing NHL and thereby present a very difficult management problem. The pathologic features of NHL in the elderly does not differ significantly from those of their younger counterparts, although an increase in diffuse versus follicular histologic patterns, and in extranodal versus nodal disease was observed with advancing age.

Aged↗

Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders.

Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of malignant cells from 269 patients with hematologic malignancies showed a heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This marker was expressed by malignant cells of 57 out of 118 patients with myeloid malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand, CD54 was not detected on malignant cells of 16 patients with T-lymphoid malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem cell-derived" malignancies, being detectable on blast cells from almost all patients affected by chronic myelogenous leukemia in blast phase or myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid leukemia (AML). The expression of CD54 did not correlate with any specific myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO) displayed maximal levels of the antigen. The expression of CD54 in AML was significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid malignancies, CD54 expression appears to correlate with the differentiation stage of malignant cells, since B-origin acute lymphoblastic leukemias and conventional B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL, prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non-Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low-grade" ones. This finding in conjunction with the expression of CD54 in all 17 patients with "bright SIg" CLL investigated (characterized by marked organomegaly and poor prognosis) suggest that the differential expression of CD54 in lymphoproliferative disorders may also relate to their degree of malignancy.

Antigens, Surface↗

Report of an unusual small lymphocytic B-cell lymphoma selectively involving the B-zone of lymph node.

Selective involvement of the B-cell compartment of lymph node by B-cell malignant lymphomas is an occasional finding related to early phases of lymph node infiltration. The authors have observed a unique case of diffuse small lymphocytic lymphoma that consisted of immunohistologically and genotypically proven B-clonal population exhibiting a repetitive pattern of infiltration in three lymph node samples obtained from the patient during a 9-year period. This pattern consisted of a selective and complete replacement of the B-areas with disappearance of follicles and widening of the medullary cords, an expanded T-zone showing features consistent with dermatopathic lymphadenitis and well-preserved sinuses. Clinically, multiple involved sites at presentation (lymph nodes, spleen, skin, bone marrow, and peripheral blood) and during the 9-year follow-up (testis) were detected, and the disease was associated with a relative indolent course like other low-grade lymphomas. The phenotypic profile of lymphoma cells studied by immunoperoxidase method, and by single-labeling and double-labeling flow cytometric analyses (SIg+, K+, LN2+, MB1+, MB2+, HLA-DR+, CD 9+, CD19+, CD 20+, CD 21+, CD 22+, CD 24+, Leu 8+, CD 5-, CD 10-, CD 11b-, CD 11c-, CD 25-, CD 38-, PCA-1-, FMC-7-, CD 23-) was consistent with a B-cell proliferation at an intermediate stage of differentiation but distinct from other well-defined B-cell neoplasms. Whether such unique B-zone pattern was due to an intrinsic property of this lymphoma or it is to be related to the coexisting reactive T-zone expansion remains controversial.

Antibodies, Monoclonal↗

Head and neck cancer and ageing: a retrospective study in 438 patients.

To evaluate whether age over 70 years represents a prognostic factor in head and neck cancer, we reviewed all cases observed between 1981 and 1984. Four hundred and thirty-eight (438) patients were considered in relation to three age groups (less than or equal to 59, 60-69, and greater than or equal to 70 years, defined as non-elderly, mid-elderly and elderly respectively). The main parameters analyzed included histological diagnosis (no difference emerged among the three age groups); anatomical site (hypopharyngeal carcinoma was most frequent in non-elderly patients); TNM stage (an higher incidence of early stages was seen in the elderly); performance status (better in the non-elderly); previous illnesses (life-style related diseases were more frequent in the non-elderly); contraindications to surgery (more frequent in the elderly); surgical treatment ('en bloc' resections were more often employed in the non-elderly); post-operative complications and local control (no difference between the three groups); multiple primary malignancies (head and neck, oesophagus and lung were more frequent in non-elderly patients) and survival (no difference). Although age affects several features of head and neck cancer patients, it does not appear from the present study to be an independent prognostic factor for local control and survival. With regard to survival, stage appeared to be the most important prognostic factor.

Age Factors↗

Phase II study of teniposide (VM26) in cutaneous T-cell lymphomas.

A Phase II study of teniposide (VM26) in cutaneous T-cell lymphoma (CTCL) was performed in 15 patients affected by stage III, IV according to TNM (mycosis fungoides or Sézary syndrome). All patients were pretreated, and VM26 was administered at a dose of 100 mg/m2 weekly for at least 3 weeks. Objective responses were observed in 40% of the patients, with two complete responses lasting 26 and 46 months. The drug was well tolerated in elderly patients and deserves further evaluation either for inclusion in first-line combination regimens or for palliative treatment in heavily pretreated or elderly patients.

Adult↗

Combination chemotherapy specifically devised for elderly patients with unfavorable non-Hodgkin's lymphoma.

The results of a prospective trial with a specifically devised chemotherapy regimen in elderly patients with unfavorable non-Hodgkin's lymphoma (NHL) are reported. Between April 1983 and April 1986, 37 consecutive patients 70 years old or more (median age 80) received etoposide and prednimustine (E + P) 100 mg/m2 p.o. for 5 days every 21 days. Thirteen patients were previously treated. Objective response rate in the 35 evaluable patients is 66% with 46% complete response. The objective response rate in the 22 previously untreated patients is nearly 70% with 50% complete response. Median survival is 14 months. The overall toxicity was reasonably acceptable. There were 5% (2 patients) treatment-related deaths, but in an unselected elderly population. We experienced the usefulness of a properly oriented clinical approach to elderly patients with NHL. We suggest that a combination regimen E + P, suitable for oral administration, may be safely employed in elderly patients with unfavorable NHL.

Administration, Oral↗

Persistent generalized lymphadenopathy syndrome vs "AIDS"--unrelated malignant lymphoma: comparison of presenting clinical and laboratory findings in 88 patients. AIDS and Related Syndromes Study Group.

The purpose of this report is to document and compare the presenting clinical and laboratory findings of 38 patients, all intravenous drug abusers, with pathologically documented persistent generalized lymphadenopathy (PGL), and of 50 patients with AIDS-unrelated malignant lymphoma (30 with Hodgkin's disease and 20 with non-Hodgkin's lymphoma). All patients, aged 40 years or less, consecutively seen since May 1984 in a single institution in Italy, have prospectively undergone a similar clinico-pathologic approach. In addition to a history of intravenous drug abuse and HIV serology, the results indicate that a history of infection in the previous year, night sweats, weight loss, generalized lymphadenopathy, beta 2 microglobuline, transaminase, T4/T8 ratio less than 1, and polyclonal hypergamma-globulinemia significantly increased among PGL patients compared with patients with AIDS-unrelated malignant lymphoma. In contrast, patients with malignant lymphoma had a significant increase in mediastinal lymph nodes, sedimentation rate, LDH, fibrinogen and anemia. Therefore, at this time of an AIDS epidemic, after histologic diagnosis of reactive lymphadenopathy has been performed in young patients presenting with generalized lymphadenopathy, a request for a second biopsy and other invasive procedures may be avoided if clinical and laboratory data suggest a PGL syndrome. If not already performed, HIV antibody detection should be carried out in this setting.

AIDS-Related Complex↗

Combination chemotherapy with cisplatin and etoposide associated with radiotherapy in the treatment of small-cell lung cancer.

A total of 52 consecutive, previously untreated patients with small-cell lung cancer (SCLC) were scheduled to receive six cycles of a combination of etoposide (75 mg/m2 per day) and cisplatin (20 mg/m2 per day), each cycle given over 5 consecutive days. In all, 28 patients had extensive disease (ED) and 24, limited disease (LD). After three cycles of chemotherapy, all responding patients were given chest radiotherapy (RT) (45 Gy in two split courses and 30 Gy in LD and ED, respectively); only patients with LD who achieved complete remission (CR) after three cycles of chemotherapy were given prophylactic brain irradiation (30 Gy). In the 51 evaluable patients, the overall response rate was 90%, with a 31% CR and a 59% partial remission (PR) rate. In LD and ED patients, 57% and 11% CR rates and 30% and 82% PR rates were noted, respectively. Myelosuppression was the most frequently observed toxicity. The median duration of response was 12 months in LD (range, 3-41 + months) and 7 months (range, 2-12 months) in ED; the median survival was 15 months in LD and 9.3 months in ED, respectively. In all 30% of LD patients are alive and well at a minimal follow-up of 18 months. This trial confirms the activity of the cisplatin-etoposide combination in SCLC.

Aged↗

Intermediate lymphocytic lymphoma encompassing diffuse and mantle zone pattern variants. A distinct entity among low-grade lymphomas?

Intermediate lymphocytic lymphoma has been operationally included among low-grade lymphomas, but few clinical data appeared to support definitely such an inclusion. The clinicopathologic features of 13 out of 14 cases of intermediate lymphocytic lymphoma either encompassing diffuse or mantle-zone pattern variants (ILL or MZL, respectively), diagnosed by conventional histology according to established criteria, are reported. Frozen section immunophenotypic analysis was also performed in 10 cases and enzyme studies were done in five. The 14 cases formed 6.9% of 203 non-Hodgkin's lymphomas (NHL) histologically diagnosed over a 2-year period. Among the 13 cases studied, there were nine males (five with ILL and four with MZL) and four females (one with ILL and three with MZL). Median age was 59 years. Splenomegaly (46%), high stage diseases (100%), involvement of bone marrow (92%) and peripheral blood (38%), and diffusion to and/or involvement of extranodal sites (38%), all were common findings at presentation. The 34 low-grade NHL of the total series classified according to the Working Formulation did not significantly differ from the ILL/MZL group in terms of frequency of involvement of bone marrow (69%) and peripheral blood (56%) as well as diffusion to and/or involvement of extranodal sites (26%). In ILL/MZL, therapy modalities were not uniform and the short follow-up time precluded firm conclusions on prognosis. Immunohistology demonstrated that ILL/MZL diagnosed by adequate morphologic criteria is a fairly homogeneous entity, also sharing most of its consistent immunological features with low-grade NHL. Thus, ILL/MZL is a relatively frequent and consistently recognizable clinical and pathological entity that may deserve a distinct place among NHL according to the Working Formulation. Proper clinical studies are needed to establish on a firmer basis the prognosis and optimal treatment of ILL/MZL.

Adenosine Triphosphatases↗