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Biomedical subjects

E Roggero

Publications and source records attributed to E Roggero.

At least 37 records · Page 2Linked to original sources

Primary mediastinal large B-cell lymphoma (PMLCL): the need for prospective controlled clinical trials.

Primary mediastinal large-B cell lymphomas (PMLCL) are considered to be a distinct clinicopathologic entity among the diffuse large B-cell lymphomas. This study evaluated the prognostic factors and therapeutic outcome of PMLCL in a single-institution series. Twenty seven patients were reviewed. Nineteen of the 27 had Stage I-II and 8 had Stage III-IV disease. B-symptoms were found in 11 (41%) patients and bulky disease in 10 (37%). All patients were initially given combination chemotherapy (CT): doxorubicin-containing regimens to 23 patients (11 patients had CHOP, 12 more intensive third-generation regimens) and 4 elderly (>70 years) patients received CVP. Eleven responders were consolidated with irradiation (RT) as part of their initial treatment, with a median total dose of 39 Gy. Nineteen patients (70%) achieved clinical remission (15 CR and 4 PR) with their initial therapy. Forty-four percent of patients remained progression-free and 59% are alive at 3 years. The actuarial 10-year TTP and OS were 44% and 50%, respectively. Age >60 years, performance status >1 and IPI intermediate-high to high risk were significantly associated with poorer OS and TTP by univariate analysis (log-rank test). A better outcome was associated with the use of more aggressive chemotherapy regimens or with the inclusion of RT in the first-line treatment. In conclusion our analyses suggest that the application of radiotherapy in combination regimens and the use of more aggressive chemotherapy in the treatment of this particular lymphoma entity should be evaluated in prospective randomized trials.

Adult↗

Immunoglobulin light chain kappa deletion rearrangement as a marker of clonality in mantle cell lymphoma.

Mantle cell lymphoma (MCL) express immunoglobulin light chain lambda (IgL-lambda) more frequently than other non-Hodgkin's lymphomas, and IgL-lambda producing B-cells usually delete one or both alleles of their IgL-kappa genes. This inactivation is mediated by a rearrangement between the kappa deletion element (kappa de) and the Recombinant Signal Sequence (RSS) in the region between the Joining genes and the Constant region, or the RSS at the 3'-site of a Variable (Vkappa) segment. This deletion appears as a feasible tool for detecting monoclonality and minimal residual disease by polymerase chain reaction (PCR). Among twelve MCL patients studied, ten presented IgL-lambda expression, and all but one among these revealed a monoclonal kappa de rearrangement by PCR analysis. Six of the nine cases showed a fusion between the kappa de and the intron RSS, whilst three with a Vkappa segment. Since MCL has the worst prognosis of all B-cell lymphomas and high-dose chemotherapy regimens have been proposed, PCR for the kappa de rearrangement might be a useful molecular tool to evaluate the ability of the different treatment modalities to eradicate the malignant clones.

Biomarkers↗

Clonality assessment in blood of patients with mantle cell lymphoma.

The presence of circulating neoplastic cells at diagnosis was assessed in the blood of patients presenting with mantle cell lymphoma (MCL) to determine the feasibility of a diagnostic molecular assay. Blood samples from 16 patients with pathologically reviewed MCL were analysed for the t(11;14)(q13;q32) translocation by the polymerase chain reaction (PCR): 7 (44%) were found positive. The remaining cases were examined by PCR for the presence of circulating neoplastic B-cells by amplifying the third complementarity region (CDR3) of immunoglobulin heavy chain genes and the immunoglobulin light kappa chain deletion rearrangements. A further 7 (44%) patients showed the presence of clonal lymphoma cells, leaving only 2 (12%) of cases negative for circulating lymphomatous cells. This study suggests that there is a high incidence of lymphoma cells in the blood of patients presenting with MCL. PCR for these clonal cells may be diagnostically useful.

Clone Cells↗

Application of interphase cytogenetics for the detection of t(11;14)(q13;q32) in mantle cell lymphomas.

BACKGROUND: The chromosomal translocation t(11;14)(q13;q32) is the hallmark of mantle cell lymphoma (MCL) in which it can be detected cytogenetically in about 75% of cases. The t(11;14) translocation juxtaposes the bcl-1 locus in chromosome band 11q13 next to the IgH locus in chromosome band 14q32 and, thus, leads to deregulation of the cell cycle regulatory protein cyclin D1, which is encoded by the CCND1 gene localized at the telomeric border of the bcl-1-locus. MCL has the worst prognosis of all low-grade non-Hodgkin's lymphomas (NHL). In some instances, however, histopathologic differentiation between MCL and other low-grade B-cell NHL is difficult. Therefore, detection of the t(11;14) translocation is of essential diagnostic value for the risk-adjusted management of patients with MCL. Unfortunately, chromosome analyses are frequently hampered by the low yield and quality of tumor metaphases. As the 11q13 breakpoints are scattered over a region of more than 120 kb the application of molecular genetic techniques is also limited. PATIENTS AND METHODS: We established an interphase fluorescence in situ hybridization (FISH) approach for the detection of the t(11;14) translocation by use of a cosmid probe hybridizing to the IgH constant region and a YAC spanning the bcl-1 region. Cells containing a t(11;14) translocation show a colocalisation of the signals for IgH and bcl-1. Eight control samples and 15 MCL specimens were investigated. RESULTS: According to our control studies, samples containing more than 10% of cells with this signal constellation can be diagnosed as carrying a clonal t(11;14) translocation. All eleven MCL found to carry the t(11;14) translocation by chromosome analysis were positive in our FISH assay. Additionally, two of four MCL lacking a clonal t(11;14) translocation by chromosome analysis were shown to carry this aberration in 14% and 37% of interphase nuclei. Southern blot data indicate that our FISH assay reliably detects the t(11;14) translocation irrespective of the location of the breakpoints within the bcl-1 region. CONCLUSIONS: The described interphase FISH assay provides a reliable and routinely applicable tool for diagnosis of the t(11;14) translocation.

Aged↗

Management of rare forms of lymphoma.

The recent Revised European-American Classification of Lymphoma (REAL) classification system has been shown to allow easy, accurate, and reproducible identification of several clinically distinctive lymphoma subtypes. Many of these well-recognized lymphoma entities are relatively rare, as shown by a recent large survey of more than 1400 non-Hodgkin's lymphoma (NHL) cases from eight different countries. The purpose of this article is to summarize the present information known about these less common entities. Particular attention will be paid to the management problems of the following subtypes: the marginal-zone B-cell lymphomas of nodal type (or monocytoid lymphoma, comprising 1.8% of total cases in the above-mentioned series), the extranodal marginal-zone B-cell lymphomas (or mucosa-associated lymphoma tissue [MALT] lymphomas, representing 7.6% of the cases), the splenic marginal-zone B-cell lymphomas (< 1% of cases), the mantle cell lymphomas (6% of cases), and the primary mediastinal large B-cell lymphomas (2.4% of cases). Also, the main non-cutaneous peripheral T-cell lymphoma types, which including the natural killer (NK) disorders comprise less than 12% of all lymphoma cases, are discussed.

Humans↗

Macrophage activity, IL-6 levels, antibody response and heart histology in rats undergoing an attenuated Trypanosoma cruzi acute infection upon treatment with recombinant interferon gamma.

Earlier experiments in Trypanosoma cruzi-infected rats showed that recombinant rat (Rr) interferon (IFN)-gamma given shortly after infection ameliorated acute disease without modifying the serum titers of endogenously synthesized IFN-gamma and tumor necrosis factor. To gain some insight into the processes underlying this protective effect, 21-day old 'I' rats that were infected with T. cruzi and the following day started with a 20-day cycle of RrIFN-gamma injections (20000 IU/rat/day) were investigated for the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (day 7 post-infection, pi), antibodies with lytic activity against T. cruzi (days 7, 20, and 28 pi), and serum levels of biologically active interleukin (IL)-6 (days 15 and 30 pi). Therapy with RrIFN-gamma rendered cultured peritoneal macrophages less permissive to infection with T. cruzi. Such an effect was not accompanied by higher amounts of NO in macrophage cultured supernatants, compared with those from T. cruzi-infected rats receiving no RrIFN-gamma, which appeared not to be protected from in vitro infection. Acutely T. cruzi-infected rats had significant amounts of IL-6 in their sera - this not being the case in infected rats given RrIFN-gamma, whose levels appeared decreased as in control rats. The presence of complement-mediated anti-T. cruzi lytic antibodies was not modified by RrIFN-gamma. Likewise, heart histology at day 7 pi revealed that treatment with RrIFN-gamma made no differences as to the amount of acute inflammation, but tended to reduce the myocardial parasite load.

Acute Disease↗

Clinical relevance of bcl-2(MBR)/J(H) rearrangement detected by polymerase chain reaction in the peripheral blood of patients with follicular lymphoma.

We evaluated the prognostic role of peripheral blood polymerase chain reaction (PCR) assay for detection of the bcl-2(MBR)/J(H) rearrangement in 59 patients with follicular lymphoma (FL) treated at our centre since 1989. Thirty-five (59%) patients were bcl-2/J(H) positive and 24 (41%) were negative in the peripheral blood at diagnosis. Peripheral blood bcl-2/J(H) rearrangement detection at diagnosis had no relation to overall survival (OS) and time to progression (TTP). Peripheral blood PCR assay was performed post treatment in 17 patients who were bcl-2/J(H) positive at diagnosis. Fourteen of the patients (82%, 95% CI 56-96%) became bcl-2/J(H) negative. Nine of these patients were further analysed during follow-up and, after several months, circulating cells carrying the bcl-2/J(H) rearrangement reappeared in five of the nine patients. Peripheral blood clearance of bcl-2/J(H)-positive cells was correlated with better overall survival (log-rank P < 0.05) but not with TTP. Our data confirmed that bcl-2(MBR)/J(H) rearrangement detection by PCR at diagnosis is not a prognostic factor in follicular lymphoma. In our series, clearance of circulating bcl-2/J(H)-positive cells appeared to correlate with better overall survival. Post-treatment examination of the peripheral blood by PCR may have clinical relevance for prediction of the survival pattern of the patients.

Genes, bcl-2↗

Immunoglobulin heavy chain diversity genes rearrangement pattern indicates that MALT-type gastric lymphoma B cells have undergone an antigen selection process.

Gastric MALT lymphoma usually develops from chronic gastritis, the vast majority of which (>90%) is associated with Helicobacter pylori infection. We sequenced the third complementarity determining region (CDR3) of immunoglobulin heavy chain genes in 19 gastric MALT lymphoma clones to determine the pattern of variable (V), diversity (D) and joining (J) gene utilization during immunoglobulin gene rearrangement. DNA was extracted from paraffin-embedded sections and the rearranged CDR3 regions were amplified using a semi-nested polymerase chain reaction (with primers complementary to the conserved framework-three segment of the variable region [FR3A] and J regions). The DNA used for cloning and sequencing was obtained after purification of monoclonal bands excised from polyacrylamide gels. The N-D-N region specific to each clone was compared with known germline D sequences. Similarly to that observed in normal and leukaemic B cells, our series of gastric MALT lymphomas showed apparent preferential utilization of genes from the DXP family. In two cases no similarity between the CDR3 nucleotide sequences of the neoplastic clones and the known germline D sequences could be found. In 10/19 analysed alleles the lymphoma B-cell clones appeared to contain two D gene segments (D-D recombination), a rare occurrence in normal individuals but one which has been described as a significant event in the determination of idiotype expression and antigen-binding affinity. Remarkably, despite the use of different D and J segments, the resultant amino acid sequences matched in two patients, suggesting the presence of a common selecting antigen. The observed pattern of D gene rearrangement suggests that MALT lymphoma B-cell clones have undergone antigen selection, which seems to indicate that the antigen stimulation plays a pivotal role in the development of the lymphoma.

Amino Acid Sequence↗

Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma.

The purpose of this paper is to report the clinical characteristics and treatment outcome following different therapeutic approaches in a large series of patients with primary low-grade MALT lymphoma of the stomach. A total of ninety-three patients (median age 63 years) were reviewed. The patients were treated by different modalities (local treatment alone, combined treatment, chemotherapy, antibiotics alone); seven patients refused any treatment. The antibiotic-treated group of patients was prospectively followed with regular endoscopic biopsies, and their responses were histologically evaluated. The 5-years projected overall survival is 82% (95% C.I.; 67%-91%) in the series as a whole. Second tumors were observed in 21.5% of the patients in this series (95% CI 14%v to 31%). There was no apparent difference in overall survival and event-free survival between patients who received different treatments. In the antibiotic-treated group histologic regression of MALT lymphoma was documented in 67% of patients (95% CI 51% to 80%). In conclusion the indolent nature of the disease justifies a conservative approach. The use of antibiotics as first-line therapy may avert or at least postpone the indication for surgical resection in the majority of patients.

Adult↗

The last 3 months of life of cancer patients: medical aspects and role of home-care services in southern Switzerland.

The clinical data on terminal cancer patients who have died since the establishment of a program of collaboration between community services and the cancer center of Canton of Ticino, southern Switzerland, were retrospectively analyzed to describe the characteristics of patients seen and the effect on them of a home-care program coordinated by the cancer center. The home-care program is based on five geographically grouped community-based domiciliary services, with the addition of one nurse responsible for coordination and one physician from the oncology center. Selection criteria for participation in the home-care program are defined. The main outcome measures were: number of hospitalizations and median hospital stay during the last 3 months of life; reasons for and median length of last hospitalization; place of death of patients who had home care and those who did not. In the group of 993 patients analyzed, the median contact time with the cancer center was 9.5 months (10th percentile: 1 month, 90th percentile: 71 months); the most frequent neoplasm was lung cancer (22%) with the briefest contact time (7.5 months; 10th percentile: 1 month; 90th percentile: 21 months); 13.5% of patients were never hospitalized; half of the patients had a total hospital stay of 24 days or longer and 23% died at home. The sociodemographic and medical characteristics of home-care users were similar to those of the home-care non-users and to those of the overall group. In the group of home-care users (32% of the total) 22% were never hospitalized, half of the patients had a total hospital stay of 17 days or longer, and 43.5% of them died at home. These values were significantly different (P > 0.001) from those reported in the group of home-care non-users. Palliative care, provided at home through community-based domiciliary services, is associated with less frequent and shorter hospitalizations in the last 3 months of life. Medical oncology and palliative treatments should be mutually complementary to improve patients care. Cancer centers should be involved in the planning and coordination of supportive-care domiciliary services.

Aged↗

Clinical significance of bcl-2 (MBR)/JH rearrangement in the peripheral blood of patients with diffuse large B-cell lymphomas.

BACKGROUND: Approximately one-fourth of diffuse large B-cell lymphomas (DLCL) carry the bcl-2(MBR)/JH rearrangement caused by the t(14;18) translocation. The clinical significance of this rearrangement in patients with DLCL remains controversial. By polymerase chain reaction (PCR) we prospectively evaluated the prognostic relevance of the bcl-2 (MBR)/JH rearrangement present in circulating B-cells at the time of diagnosis. MATERIALS AND METHODS: The bcl-2 (MBR)/JH rearrangement was analysed by a nested-PCR method in peripheral blood samples of 51 HIV-negative patients with previously untreated DLCL. RESULTS: The bcl-2 (MBR)/JH rearrangement was detected in 16 cases (31%). Peripheral blood bcl-2 (MBR)/JH rearrangement detection by PCR at diagnosis was correlated with poor overall survival, lymphoma-specific survival and time to progression (log-rank P < 0.05). There was no statistically significant difference between the clinical characteristics at presentation of bcl-2/JH-positive and negative patients. CONCLUSIONS: The peripheral blood is a readily accessible tissue for this type of analysis, and this study indicates that detection of the t(14;18) translocation at presentation in the blood of patients with DLCL may presage a poor prognosis.

Chromosomes, Human, Pair 14↗