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V Zagonel

Publications and source records attributed to V Zagonel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients.

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.

Adult↗
PubMed1998

Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia.

Thirty-eight patients with primary resistant or relapsing acute myeloid leukemia (AML) were treated with fludarabine, cytarabine and granulocyte colony-stimulating factor (FLAG). Median age was 41 (range 11-70). Sixteen patients had AML that was primary resistant to induction treatment, while 22 were relapsed, 11 after autologous bone marrow transplant (AuBMT), 8 less than 6 months from complete remission (CR) achievement, and 3 were second relapse from chemotherapy alone. Overall, 21 of 38 patients (55%) obtained CR. Age, sex, length of CR, and interval between autoBMT and FLAG administration did not significantly influence the CR rate. On the contrary, a normal karyotype at diagnosis was significantly related to a better outcome. There were 4 induction deaths (10%), due to fungal infection in 2 patients and hemorrhagic complications in the remaining two. All patients experienced profound cytopenia. Median time to neutrophil (>500/microl) recovery was 21 days, while a platelet count >20,000/microl was reached after 23 days. The median period of hospitalization was 31 days. The nonhematological toxicity was mild, mainly consisting of mucositis. There were 17 documented infections and 17 episodes of fever of unknown origin. Following CR achievement, 6 patients received autoBMT, 3 alloBMT, 2 high-dose arabinosil-cytosine, and 2 are on a waiting list for transplantation procedure. We conclude that FLAG is an effective and well-tolerated regimen for refractory or recurrent AML, mainly useful for patients to be admitted to bone marrow transplantation.

Acute Disease↗
PubMed1998

Treatment of non-Hodgkin's lymphoma in the elderly: an update.

Recent studies specifically directed toward assessing the outcome of older patients with non-Hodgkin's lymphoma (NHL) indicate that age per se is an important and independent prognostic factor for response and survival. We report a review of the clinical trials of the literature and the Aviano Group experience in the treatment of NHL in the elderly. Prospective studies have addressed therapeutic approaches in these patients. Direct comparison of trial results is difficult since different age limits were set for the inclusion of patients under study. These studies suggest that older patients with aggressive NHL should be treated with curative intent.

Aged↗
PubMed1998

Hodgkin's disease: a disorder of dysregulated cellular cross-talk.

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.

Cell Communication↗
PubMed1998

Differential expression of the RET gene in human acute myeloid leukemia.

The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multi-subunit membrane receptor complex for at least two different types of transforming growth factor (TGF)-beta-related neurotrophic factors. We have previously shown that RET gene expression in acute myeloid leukemia (AML) occurs more frequently in AMLs displaying either a monocytic (FAB M4/M5) or intermediate-mature myeloid phenotype (FAB M2/M3) than in leukemias reflecting an earlier stage of myeloid differentiation (FAB M0/M1). To further verify the association between RET expression and the relative maturation stage of AML cells, we have performed a quantitative estimation of relative abundances of RET transcripts among various FAB subtypes of AMLs. By analyzing 13 AML samples and normal hematopoietic cells through a competitive-quantitative RT-PCR approach, we were able to show that the relative levels of RET-specific mRNAs continuously increase with blast cell maturation in human AML, i.e., the amounts of RET gene-specific transcripts differ among RET-expressing AMLs, being higher in the more differentiated FAB phenotypes. In addition, we provide evidence that the relative amounts of RET transcripts increase upon in vitro and in vivo differentiation of leukemic promyelocytes from FAB M3 AML patients, becoming overall comparable to those found in normal granulocytes. These results indicate that RET expression in human AMLs is maturation-associated, probably mirroring the developmental regulation of this gene during differentiation of normal hematopoietic cells.

Acute Disease↗
PubMed1998

Lymphomas.

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Age Factors↗
PubMed1998

Multiple myeloma.

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Age Factors↗
PubMed1998

Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients.

BACKGROUND: B-diffuse large-cell lymphomas (DLCL) have been associated with some molecular lesions, but the role of such lesions as prognostic markers is still controversial. This report concerns an investigation of the frequency and clinical correlation of bcl-6, bcl-2, c-myc rearrangements and 6(q) deletions in B-DLCL. PATIENTS AND METHODS: The presence of these genetic lesions was analyzed in samples of lymph nodes or bone marrow collected at diagnosis in 71 patients with B-DLCL, all treated with an anthracycline-containing chemotherapy regimen. RESULTS: Rearrangement of bcl-6 was found in 11 patients (15%), rearranged bcl-2 in 12 (17%), 6(q) deletions in 10 patients (14%) and c-myc rearrangement in four (6%). Patients with rearranged bcl-6 tended to have a more aggressive disease than patients with germ-line bcl-6 (intermediate-high/high risk according to IPI criteria: 73% vs. 43%), but there were no differences in three-year survival rates (62% vs. 42%) between the two groups. The numbers of involved extranodal sites were similar in patients with rearranged and those with germ-line bcl-6. Patients with bcl-2 rearrangement appeared to have a less aggressive disease than those with germ-line bcl-2 (low/ low-intermediate risk 75% vs. 47%) and a slightly better three-year survival rate (70% vs. 41%) but again the difference was not significant. Both groups with or without 6(q) deletion had similar clinical characteristics and outcomes. The four patients with c-myc rearrangement had aggressive disease and did poorly. CONCLUSIONS: The analysis of molecular lesions in B-DLCL may be useful for a better diagnostic definition; however, in this study we were unable to show that the evaluated genetic lesions had a significant impact on clinical outcome.

Adolescent↗
PubMed1998

Hepatitis C virus, non-Hodgkin's lymphomas and hepatocellular carcinoma.

In a case-control study in northeastern Italy hepatitis C virus infection seemed to increase by about 50-fold the risk of non-Hodgkin's lymphoma involving the liver and major salivary glands (i.e. larger than that for hepatocellular carcinoma) and by about fourfold the risk of lymphomas at other sites.

Adult↗
PubMed1998

CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group.

PURPOSE: We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Patients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm. RESULTS: Overall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP. CONCLUSION: CHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.

Aged↗
PubMed1998

Acute myeloid leukemia in the elderly: a critical review of therapeutic approaches and appraisal of results of therapy.

In the elderly, acute myeloid leukemia (AML) is characterized by a poorer prognosis than in younger patients, due to either host related factors (poor performance status, co-morbid diseases, organ function impairment) or the biology of leukemia itself (high incidence of adverse cytogenetic abnormalities, high frequency of preceding myelodysplastic syndromes, intrinsic resistance to cytotoxic drugs). Current therapeutic results are mostly unsatisfactory and studies reporting high rates of complete remission are probably influenced by selection biases as suggested by the low rate of elderly patients inclusion into cooperative trials. Availability of intensive support including hematopoietic growth factors could stimulate clinicians to manage an increasing number of elderly patients with AML with aggressive programs. However, chemotherapy in the elderly is difficult, costly and usually associated with high morbidity and mortality rate. Therefore, all efforts should be made to identify those subset of elderly patients in whom aggressive treatment may result in a true improvement of disease free and overall survival. The critical analysis of our five years experience, as reported here, seems to suggest that older AML patients displaying unfavourable prognostic factors at diagnosis (i.e., adverse karyotype and high serum LDH levels), but clinically eligible for intensive chemotherapy, do not actually benefit from an aggressive approach. A blind attempt to treat these patients aggressively may be associated with a life threatening toxicity not counterbalanced by an actual survival advantage. We suggest therefore that aggressive treatment should be reserved for elderly AML cases in whom the presence of good prognostic factors at diagnosis predicts that the loss of some patients due to toxicity may be balanced by the achievement of a substantial proportion of long term survivors. Finally, given the biological and clinical heterogeneity of elderly AML patients, a more precise prognostic categorization of these patients would be particularly useful in interpreting future therapeutic results.

Acute Disease↗
PubMed1997

Characterization of overt B-cell lymphomas in patients with hepatitis C virus infection.

A pathogenetic role of the hepatitis C virus (HCV) has been hypothesized for a subset of B-cell non-Hodgkin's lymphomas (NHLs). However, the preliminary characterization of B-cell NHLs in HCV-infected individuals has been poorly addressed. In the present study, we report detailed information on 35 consecutive patients with overt B-cell NHL of recent onset and HCV infection; all patients referred to a single oncological center in Northeast Italy. Histopathologic evaluation was performed by a single reference hemopathologist, and the link with the two relevant autoimmune diseases predisposing to B-cell NHL and in which HCV has been implied, ie, "essential" mixed cryoglobulinemia (EMC) and Sjogren's syndrome, was investigated. Control groups included 122 consecutive HCV-negative patients with B-cell NHL and 464 consecutive histopathologic cases of B-cell NHL referred to the same center, as well as 127 consecutive patients with HCV infection and without lymphoma referred to a different center in the same geographical area. B-cell NHLs in HCV-infected patients frequently presented at onset (1) an extranodal localization with peculiar target organs of HCV infection (ie, the liver and major salivary glands) being significantly overrepresented; (2) a diffuse large cell histotype without any prior history of low-grade B-cell malignancy or bone marrow involvement; and (3) a weak association with a full-blown predisposing autoimmune disease, although serum autoimmune features were common and cryoglobulins were always present. Therefore, the HCV-related B-cell NHLs in this oncological series presented distinctive features compared with B-cell NHLs in HCV-negative patients, and they differed from bone marrow low-grade NHLs frequently diagnosed in HCV-positive patients with EMC. Such novel information may be relevant for future research aimed at clarifying the possible link between HCV infection, autoimmunity, nonmalignant B-cell lymphoproliferation, and overt B-cell malignancy.

Aged↗
PubMed1997

Reed-Sternberg cells of classical Hodgkin's disease react with the plasma cell-specific monoclonal antibody B-B4 and express human syndecan-1.

Although the cellular origin of Reed-Sternberg (RS) cells of classical Hodgkin's disease (HD) has been a controversial issue for many years, recent immunophenotypic and molecular studies have suggested that RS cells of a subset of classical HD cases may be related to B cells. To further define the immunophenotypic features and the differentiation stage of RS cells, a series of 56 HD samples, including both nodular lymphocyte predominance (LP) (eight cases) and classical HD (nodular sclerosis [NS], 32 cases; mixed cellularity [MC], 16 cases) with a non-T-cell phenotype, were evaluated for the immunohistochemical expression of the B-B4 antigen, a specific marker for terminally differentiated B cells. Because the cDNA of the B-B4 antigen encodes syndecan-1, a member of a family of transmembrane heparan sulfate proteoglycans thought to be involved in binding cells of the B lineage to the interstitial matrix, the B-B4 immunoreactivity was correlated with the expression of syndecan-1 in HD-derived cell lines (L428, KM-H2), as detected by both reverse transcriptase polymerase chain reaction (RT-PCR) studies and Western blotting. Our results show that B-B4 reacts with RS cells and their morphological variants of all cases of classical HD, irrespective of their antigenic phenotype (B, undetermined), albeit at a varying degree of cellular expression. Notably, a high reactivity and staining intensity for the B-B4 monoclonal antibody (MoAb) was restricted to tumor cells from NS HD. In cases of the latter subtype, B-B4 positivity was also found in sclerosis-trapped spindle cells (fibrocytes/fibroblasts). Conversely, the putative tumor cells of nodular LP HD were consistently unreactive with the B-B4 MoAb. Finally, we have demonstrated by RT-PCR, flow cytometry, and Western blotting that cultured RS cells, of B and undetermined phenotype, express syndecan-1 mRNA and produce a form of syndecan-1, recognized by the B-B4 MoAb, which is predominantly associated with glycosaminoglycans and is present at the cell surface. Our detection of the plasma cell-specific antigen B-B4 (syndecan-1) on tumor cells of classical HD further supports that RS cell progenitors may be related to germinal/postgerminal center mature B cells and suggests that expression of syndecan-1 may contribute to some of the typical biologic and histopathologic features of classical HD, with a special regard to the NS subtype.

Antibodies, Monoclonal↗
PubMed1997

Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment.

The RET proto-oncogene product is a receptor tyrosine kinase representing the signal-transducing molecule of a multisubunit surface receptor complex for the glial cell line-derived neurotrophic factor (GDNF), in which a novel glycosyl-phosphatidylinositol (PI)-linked protein (termed GDNFR-alpha) acts as the ligand-binding component. We have analyzed expression of RET and GDNFR-alpha in purified normal hematolymphopoietic cells, leukemia/lymphoma cell lines, and 154 primary samples from patients with hematopoietic malignancies encompassing different lineages and differentiation stages. Relatively low amounts of RET mRNA were found in early CD34+ hematopoietic progenitors, but RET transcripts appeared to increase after myelomonocytic maturation. No expression of RET was found in peripheral blood and tissue B and T lymphocytes. Analysis of human myelomonocytic cell lines was overall consistent with results obtained on purified normal cells. Accordingly, RET expression was mainly confined to acute myeloid leukemias (AMLs) displaying either monocytic (French-American-British M4 and M5) or intermediate-mature myeloid (M2 and M3) phenotypes, being less frequently detected in early myeloid (M0 and M1) AMLs. In contrast, RET mRNA was sporadically detected in B-cell tumors, whereas, among T-cell malignancies, RET transcripts were mainly detected in cells of postthymic and mature T-cell phenotype. RET broad detection in primary tumors was not paralleled by the mutual expression of GDNFR-alpha, which was detected only in 2 isolated primary samples and in 3 leukemia/lymphoma cell lines. However, GDNFR-alpha transcripts, in the absence of RET mRNA, were found in normal bone marrow stromal cells (BMSC), in BM fibroblasts, and in two osteoblast cell lines previously described to support normal hematopoiesis. In the presence of GDNF-receptors derived from BMSC by PI-specific phospholipase C cleavage, GDNF efficiently bound RET-expressing AML blasts and was functionally active by reducing their clonogenic growth and triggering the monocytic maturation of leukemic cells.

Adipose Tissue↗
PubMed1997

CD30 ligand is frequently expressed in human hematopoietic malignancies of myeloid and lymphoid origin.

CD30 ligand (CD30L) is a type-II membrane glycoprotein capable of transducing signals leading to either cell death or proliferation through its specific counterstructure CD30. Although several lines of evidence indicate that CD30L plays a key role as a paracrine- or autocrine-acting surface molecule in the deregulated cytokine cascade of Hodgkin's disease, little is known regarding its distribution and biologic significance in other human hematopoietic malignancies. By analyzing tumor cells from 181 patients with RNA studies and immunostaining by the anti-CD30L monoclonal antibody M80, we were able to show that human hematopoietic malignancies of different lineage and maturation stage display a frequent and broad expression of the ligand. CD30L mRNA and surface protein were detected in 60% of acute myeloid leukemias (AMLs), 54% of B-lineage acute lymphoblastic leukemias (ALLs), and in a consistent fraction (68%) of B-cell lymphoproliferative disorders. In this latter group, hairy cell leukemia and high-grade B-cell non-Hodgkin's lymphoma (B-NHL) expressed a higher surface density of CD30L as compared with B-cell chronic lymphocytic leukemia and low-grade B-NHL. Purified plasmacells from a fraction of multiple myeloma patients also displayed CD30L mRNA and protein. A more restricted expression of CD30L was found in T-cell tumors that was mainly confined to neoplasms with an activated peripheral T-cell phenotype, such as T-cell prolymphocytic leukemia, peripheral T-NHL, and adult T-cell leukemia/lymphoma. In contrast, none of the T-lineage ALLs analyzed expressed the ligand. In AML, a high cellular density of CD30L was detected in French-American-British M3, M4, and M5 phenotypes, which are directly associated with the presence on tumor cells of certain surface structures, including the p55 interleukin-2 receptor alpha-chain, the alpha(M) (CD11b) chain of beta2 integrins, and the intercellular adhesion molecule-1 (CD54). Analysis of normal hematopoietic cells evidenced that, in addition to circulating and tonsil B cells, a fraction of bone marrow myeloid precursors, erythroblasts, and subsets of megakaryocytes also express CD30L. Finally, we have shown that native CD30L expressed on primary leukemic cells is functionally active by triggering both mitogenic and antiproliferative signals on CD30+ target cells. As opposed to CD30L, only 10 of 181 primary tumors expressed CD30 mRNA or protein, rendering therefore unlikely a CD30-CD30L autocrine loop in human hematopoietic neoplasms. Taken together, our data indicate that CD30L is widely expressed from early to late stages of human hematopoiesis and suggest a regulatory role for this molecule in the interactions of normal and malignant hematopoietic cells with CD30+ immune effectors and/or microenvironmental accessory cells.

Acute Disease↗