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Emanuele Zucca

Publications and source records attributed to Emanuele Zucca.

At least 19 recordsLinked to original sources
PubMed2022

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Advisory Committees↗
PubMed2006

Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years?

Primary gastric (PG) lymphomas are generally non-Hodgkin lymphomas (NHL). They represent 5% of gastric malignancies and show an apparently increasing incidence worldwide. The most common histological subtypes are diffuse large B-cell and marginal zone B-cell NHL of the mucosa-associated lymphoid tissue (MALT)-type. Pathogenesis is often related to Helicobacter pylori infection (HPI). There is still no consensus on the optimal treatment for PG lymphoma. Nowadays surgery is limited to rare cases and radiotherapy--combined or not with chemotherapy--represents an effective therapeutic option ensuring long-term, organ-salvage benefits mainly in aggressive histological subtypes. Additionally, the description of MALT lymphomas has made the situation even more complex, because antibiotics alone can induce lasting remissions in those cases associated with HPI. Consequently, a global therapeutic approach to the cure of PG-NHL has completely changed over the last 10 years: innovative, conservative options to reduce treatment toxicity, thus preventing systemic relapses, have made their appearance and are on the rise.

Helicobacter Infections↗
PubMed2006

Update on the molecular biology of mantle cell lymphoma.

Mantle cell lymphoma (MCL) accounts for 5-10% of non-Hodgkin's lymphomas and it bears the worst prognosis among B cell lymphomas. Even more than in the other lymphomas, new insights in MCL biology are needed. In this review we will discuss the most recent published data. Immunoglobulin sequencing data suggest that the MCL cell of origin is a mature B cell which might have undergone an extra-follicular T-cell independent antigen maturation. The main aberrations that affect cell cycle and DNA repair pathways in MCL are summarized, also discussing the need of the t(11;14)(q13;q32) to make diagnosis of MCL. After the gene expression studies of the last years, now the research focus has moved towards the new opportunities provided by arrayCGH technique for gene discovery and for identification of therapeutic targets. Examples of genes identified because deleted or amplified at DNA level and that might be relevant for MCL pathogenesis are presented.

Cell Cycle↗
PubMed2006

Genomic and expression profiling identifies the B-cell associated tyrosine kinase Syk as a possible therapeutic target in mantle cell lymphoma.

Among B-cell lymphomas mantle cell lymphoma (MCL) has the worst prognosis. By using a combination of genomic and expression profiling (Affymetrix GeneChip Mapping 10k Xba131 and U133 set), we analysed 26 MCL samples to identify genes relevant to MCL pathogenesis and that could represent new therapeutic targets. Recurrent genomic deletions and gains were detected. Genes were identified as overexpressed in regions of DNA gain on 3q, 6p, 8q, 9q, 16p and 18q, including the cancer genes BCL2 and MYC. Among the transcripts with high correlation between DNA and RNA, we identified SYK, a tyrosine kinase involved in B-cell receptor signalling. SYK was amplified at DNA level, as validated by fluorescence in situ hybridisation (FISH) analysis, and overexpressed at both RNA and protein levels in the JeKo-1 cell line. Low-level amplification, with protein overexpression of Syk was demonstrated by FISH in a small subset of clinical samples. After treatment with low doses of the Syk inhibitor piceatannol, cell proliferation arrest and apoptosis were induced in the cell line overexpressing Syk, while cells expressing low levels of Syk were much less sensitive. A combination of genomic and expression profiling suggested Syk inhibition as a new therapeutic strategy to be explored in lymphomas.

Apoptosis↗
PubMed2006

Comparative genome-wide profiling of post-transplant lymphoproliferative disorders and diffuse large B-cell lymphomas.

Post-transplant lymphoproliferative disorders (PTLD) are a major complication of solid organ transplantation, representing a cause of severe morbidity and mortality. Apart from Epstein-Barr virus infection, knowledge of the pathogenesis of monoclonal PTLD is limited. Powerful analysis techniques, such as whole genomic DNA profiling (array comparative genomic hybridisation), can improve our understanding of PTLD pathogenesis. Whole genome profiling using the Affymetrix GeneChip Human Mapping 10 k 2.0 was performed on 20 PTLD cases and 25 cases of diffuse large B-cell lymphoma (DLBCL) from immunocompetent patients as a control group. Recurrent lesions were detected among all the samples. Chromosome 18q, 7q, 3q and 12 were the most common gains in the control group. Chromosomes 5p and 11p were commonly gained in PTLD-DLBCL. The latter had frequent losses of 6q, 17p, 1p and 9p. Chromosome 12p was the most frequent target of deletions among PTLD-DLBCL cases. Loss of heterozygosity (LOH) did not always match DNA loss: chromosome 10 seemed to be targeted by uniparental disomy in PTLD. Small deletions and gains, involving both known (BCL2 and PAX5) and unknown genes (ZDHHC14), were identified. These data suggest that PTLD share, at a lower frequency, common genetic aberrations with DLBCL from immunocompetent patients. The demonstration of 9p13 amplification emphasises the importance of PAX5 in PTLD. The combination of DNA copy number and LOH assessment lead to the hypothesis that uniparental disomy may be a potential mechanism in B-cell lymphomagenesis.

Chromosome Aberrations↗
PubMed2006

Delving deeper into MALT lymphoma biology.

Mucosa-associated lymphoid tissue (MALT) lymphomas can arise in a variety of extranodal sites. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations, all affecting the NF-kappaB pathway, have been implicated in the development and progression of MALT lymphoma. The most common is the translocation t(11;18)(q21;q21), which results in a fusion of the cIAP2 region on chromosome 11q21 with the MALT1 gene on chromosome 18q21 and is present in more than one-third of cases. The frequency of this translocation is site-related: common in the gastrointestinal tract and lung, rare in conjunctiva and orbit, and almost absent in salivary glands, thyroid, liver, and skin. In this issue of the JCI, Hu et al. add to our understanding of the molecular consequences of this translocation, showing that its fusion product, cIAP2-MALT1, may concomitantly contribute to lymphomagenesis both as a tumor suppressor gene and as an oncogene.

Caspases↗
PubMed2005

State-of-the-art therapeutics: marginal-zone lymphoma.

Marginal-zone lymphomas comprise the mucosa-associated lymphoid tissue (MALT) type (extranodal marginal-zone lymphoma [EMZL]), the nodal marginal zone B-cell lymphoma (NMZL) and the splenic MZL (SMZL). EMZL is relatively common, whereas the remaining two entities are relatively rare disorders. EMZL, especially in its gastric localization, is the most studied MZL, and there are many data both on the underlying genetic lesions and on the role of infectious agents. These data have determined unique approach among all other lymphoma subtypes: the possibility of treating a subset of patients with antibiotics alone as first line of treatment. Indeed, there is compelling evidence that histologic regressions can be achieved in most gastric MALT lymphomas by eradicating Helicobacter pylori infection. However, molecular follow-up studies showed the persistence of the malignant clone in half of the cases in histologic remission after antibiotic treatment and transient, either histologic or molecular, relapses have been reported, too. Hence, a careful long-term follow-up is mandatory after antibiotic treatment. Radiotherapy, chemotherapy, anti-CD20 monoclonal antibodies are effective alternative therapies. The precise role of surgical resection should be redefined in view of the encouraging results of conservative approaches. Differently from EMZL, both SMLZ and NMZL often present with disseminated disease at diagnosis. The therapeutic approach comprises splenectomy, for SMZL, and chemotherapy, but with no consensus about the best treatment. This review addresses the current knowledge on the clinical features and therapeutic approaches for the individual MZLs.

Anti-Bacterial Agents↗
PubMed2005

Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma.

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

Central Nervous System Neoplasms↗
PubMed2005

Clinical activity of rituximab in gastric marginal zone non-Hodgkin's lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy.

PURPOSE: Preliminary results using rituximab in extranodal marginal zone (MALT) non-Hodgkin's lymphoma (NHL) patients seem to indicate a relevant clinical activity. Aim of the present study is to investigate the efficacy of conventional weekly treatment using rituximab in gastric MALT NHL patients resistant/refractory or not suitable for eradication treatment, and to evaluate the relevance of the t(11; 18)(q21; q21) translocation and its possible role as a predictive criteria of response. PATIENTS AND METHODS: Twenty-seven patients presenting with gastric MALT NHL at any stage, relapsed/refractory to initial treatment or not suitable for eradication were treated with rituximab in a weekly conventional schedule and evaluated for response and relapse. Flourescence in situ hybridization (FISH) analysis for the presence of 18q21 translocation was performed in 21 patients and was evaluated with clinical outcome. RESULTS: Among the 26 evaluated patients, 20 (77%) achieved an objective response. Twelve patients (46%) had a pathological and clinical complete remission, and eight (31%) had a partial response. With a median follow-up of 33 months, only two patients relapsed at 26 and 14 months, respectively. No correlation was founded between FISH analysis and response or relapse. CONCLUSION: Our experience seems to confirm the clinical activity of rituximab in gastric MALT NHL patients resistant/refractory to antibiotics treatment or not presenting with clinical evidence of Helicobacter pylori infection. The t(11; 18)(q21; q21) translocation seems not to be a predictive marker to response or to subsequent relapse.

Adult↗
PubMed2005

Understanding the group of peripheral T-cell lymphomas, unspecified.

Presumably diverse cases are at present lumped under the heading peripheral T-cell lymphoma, not otherwise categorized, or unspecified (PTCL-U), which comprise the largest group of T-cell neoplasms in Western countries. Although a variety of morphologic subtypes have been described, no consistent immunophenotypic, genetic, or clinical features have been associated with most of them. Hopefully, some progress can be expected from the novel sophisticated and powerful genomic and proteomics technologies, which may uncover the group of T-cell neoplasms, and perhaps identify some specific disease entities. An improved understanding of their biology may improve our ability to develop better treatments for these disorders. Indeed, these disorders are among the most aggressive lymphomas, representing a wide variety of infrequent clinicopathologic syndromes that share a dismal prognosis. The treatments used for diffuse large B-cell lymphoma have produced disappointing results in peripheral T-cell lymphoma. Clinical trials focusing specifically on these subtypes are therefore warranted. Novel strategies need to be developed and specific regimens including active agents in peripheral T-cell lymphoma should be investigated. This effort will be successful only if a large international collaboration can be set up because of the rarity of most subtypes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs < or = 60 years), Ann Arbor stage (III-IV vs I-II), hemoglobin level (< 120 g/L vs > or = 120 g/L), number of nodal areas (> 4 vs < or = 4), and serum LDH level (above normal vs normal or below). Three risk groups were defined: low risk (0-1 adverse factor, 36% of patients), intermediate risk (2 factors, 37% of patients, hazard ratio [HR] of 2.3), and poor risk (> or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments.

Adult↗
PubMed2004

Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule.

The potential benefits of extended rituximab treatment have been investigated in a randomized trial comparing the standard schedule with prolonged treatment in 202 patients with newly diagnosed or refractory/relapsed follicular lymphoma (FL). All patients received standard treatment (rituximab 375 mg/m(2) weekly x 4). In 185 evaluable patients, the overall response rate was 67% in chemotherapy-naive patients and 46% in pretreated cases (P <.01). Patients responding or with stable disease at week 12 (n = 151) were randomized to no further treatment or prolonged rituximab administration (375 mg/m(2) every 2 months for 4 times). At a median follow-up of 35 months, the median event-free survival (EFS) was 12 months in the no further treatment versus 23 months in the prolonged treatment arm (P =.02), the difference being particularly notable in chemotherapy-naive patients (19 vs 36 months; P =.009) and in patients responding to induction treatment (16 vs 36 months; P =.004). The number of t(14;18)-positive cells in peripheral blood (P =.0035) and in bone marrow (P =.0052) at baseline was predictive for clinical response. Circulating normal B lymphocytes and immunoglobulin M (IgM) plasma levels decreased for a significantly longer time after prolonged treatment, but the incidence of adverse events was not increased. In patients with FL, the administration of 4 additional doses of rituximab at 8-week intervals significantly improves the EFS.

Adult↗
PubMed2004

Immunoglobulin heavy chain genes somatic hypermutations and chromosome 11q22-23 deletion in classic mantle cell lymphoma: a study of the Swiss Group for Clinical Cancer Research.

Mantle cell lymphoma (MCL) shares immunophenotypic and karyotypic features with chronic lymphocytic leukaemia. The latter comprises two distinct entities with prognosis dependent upon immunoglobulin heavy chain (IgH) gene mutational status and the presence of 11q deletion. We evaluated the relevance of IgH gene mutational status, IgV gene family usage and presence of 11q deletion in a series of 42 histologically reviewed classical MCL cases to determine the prognostic impact. VH3 was the most common VH family, with VH3-21 being the most frequent individual VH gene. Approximately 30% of the cases had a IgH somatic mutation rate higher than 2%, but was only higher than 4% in <10% of cases. Half of the cases had deletion of chromosome 11q21-telomere (11q21->ter), with two minimal deleted regions, at 11q22.2 and 11q23.2. There was no association between 11q loss and IgH gene somatic mutation rate; the use of VH3-21 gene could be associated with a better prognosis.

Aged↗
PubMed2004

Mantle cell lymphoma.

PURPOSE OF REVIEW: Mantle cell lymphoma is the B-cell lymphoma with the worst prognosis. Until now, no standard treatment has resulted in cure. Improvements in understanding of the disease are needed to advance therapeutic efforts. RECENT FINDINGS: Pathology and immunohistochemistry can identify the subset of patients with the worse prognosis. New data suggest that at least a subset of mantle cell lymphoma cases have undergone some form of antigene selection, and particular types of Ig gene rearrangement seem to give a better prognosis. The cell cycle, the ATM, gene and the nuclear factor kappaB pathways are the main targets of the genetic abnormalities occurring in mantle cell lymphoma: new genomic and expression data have been recently published. Unfortunately, this progress has not yet brought any major improvements in therapeutic approaches, which still remain highly unsatisfactory. Autologous and allogenic bone marrow transplantations appear to be the only current treatments that might improve the outcome of patients with PMCL. New additional treatment modalities are currently under investigation. SUMMARY: This review summarizes all the most recent data published on the biology and treatment of mantle cell lymphoma.

Chromosome Deletion↗
PubMed2004

Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'.

Despite its recognition as a distinct, extremely rare entity, no large studies of intravascular lymphoma (IVL) have been reported. The clinico-pathological characteristics of 38 human immunodeficiency virus-negative patients with IVL diagnosed in Western countries were reviewed to better delineate clinical presentation, clinical variants, natural history and optimal therapy. The IVL is an aggressive and usually disseminated disease (Ann Arbor stage IV in 68% of cases) that predominantly affects elderly patients (median age 70 years, range: 34-90; male:female ratio 0.9), resulting in poor Eastern Cooperative Oncology Group Performance Status (ECOG-PS >1 in 61%), B symptoms (55%), anaemia (63%) and high serum lactate dehydrogenase level (86%). The brain and skin are the most common sites of disease. In contrast to previous reports, hepatosplenic involvement (26%) and bone marrow infiltration (32%) were found to be common features in IVL, while nodal disease was confirmed as rare (11% of cases). Patients with disease limited to the skin ('cutaneous variant'; 26% of cases) were invariably females with a normal platelet count, and exhibited a significantly better outcome than the remaining patients, which deserves further investigation. Overall survival was usually poor; however, the early use of intensive therapies could improve outcome in young patients with unfavourable features. ECOG-PS >1, 'cutaneous variant', stage I and chemotherapy use were independently associated with improved survival.

Adult↗