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To complement the existing treatment guidelines for all tumour types, ESMO organizes consensus conferences to focus on specific issues in each type of tumour. In this setting, a consensus conference on the management of lymphoma was held on 18 June 2011 in Lugano, next to the 11th International Conference on Malignant Lymphoma. The conference convened ∼30 experts from all around Europe, and selected six lymphoma entities to be addressed; for each of them, three to five open questions were to be addressed by the experts. For each question, a recommendation should be given by the panel, referring to the strength of the recommendation based on the level of evidence. This consensus report focuses on the three less common lymphoproliferative malignancies: marginal zone lymphoma, mantle cell lymphoma, and peripheral T-cell lymphomas. A first report had focused on diffuse large B-cell lymphoma, follicular lymphoma, and chronic lymphocytic leukaemia. [ABSTRACT FROM PUBLISHER]

Purpose: Farnesyltransferase (Ftase) was identified by gene-expression profiling and by preclinical evaluation in in vitro and in vivo mantle cell lymphoma (MCL) models as a rational therapeutic target in MCL, one of the most refractory B-cell lymphomas. We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL.Methods: Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-day cycle for 4 cycles, and in case of response for 6 cycles. Study endpoints were objective response at 4 and 6 cycles, progression free survival (PFS), overall survival, and toxicity. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level.Results: Eleven patients (median age, 71 years) were enrolled. Patients received a median number of three prior therapies (range 1-11). Nine patients completed at least 3 cycles of tipifarnib. No grade III-IV hematological toxicities were recorded. One patient presented a complete response (CR) after 4 and a persistent CR at 6 cycles (ORR = 9%). Median PFS was 3 months (range 0.7-14.2). The RASGRP1/APTX gene expression ratio was higher in the responder (n = 1) while the AKAP13 expression was higher in the non-responders (n = 2). This corresponds to the expected result for predicting response to tipifarnib.Conclusion: Treatment with tipifarnib relapsed or refractory MCL is associated with low response rates. Limited gene expression studies suggest that response may be associated with molecular targets. [ABSTRACT FROM AUTHOR]

Since the initial description of splenic marginal zone lymphoma (SMZL) in 1992, an increasing number of publications have dealt with multiple aspects of SMZL diagnosis, molecular pathogenesis and treatment. This process has identified multiple inconsistencies in the diagnostic criteria and lack of clear guidelines for the staging and treatment. The authors of this review have held several meetings and exchanged series of cases with the objective of agreeing on the main diagnostic, staging and therapeutic guidelines for patients with this condition. Specific working groups were created for diagnostic criteria, immunophenotype, staging and treatment. As results of this work, guidelines are proposed for diagnosis, differential diagnosis, staging, prognostic factors, treatment and response criteria. The guidelines proposed here are intended to contribute to the standardization of the diagnosis and treatment of these patients, and should facilitate the future development of clinical trials that could define more precisely predictive markers for histological progression or lack of response, and evaluate new drugs or treatments.Leukemia (2008) 22, 487–495; doi:10.1038/sj.leu.2405068; published online 20 December 2007 [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the classification of hematological malignancies including splenic marginal zone lymphoma.

DNA chips are among the major technological advances in recent years that have led to a more comprehensive and in-depth understanding of tumor biology. This technique, through the hybridization of complementary DNA synthesized from a tumor sample on a surface containing various gene sequences, makes it possible in one step to establish a quantitative assessment of the expression of several thousand genes found in the tumor. Due to their biological and clinical heterogeneity, malignant lymphoma represents an ideal model for the use of this new tool. Complex bioinformatics analyses of several series of samples recently made it possible to described the signaling pathways activated in these lymphoid tumors, which led to recognition of either proximity or individualization of certain histological subtypes, to identification of diagnostic or prognostic biological predictors and, finally, to characterization of new targets for these specific pharmacological agents. By looking at current published studies, we will discuss the impact of this technique on the understanding of the biology and the clinical approach to both Hodgkin’s and non-Hodgkin’s malignant lymphoma. [ABSTRACT FROM AUTHOR]

Aims : To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. Methods and results : The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). Conclusion : NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to document the frequency and distribution of karyotypic changes present at diagnosis in 103 non-MALT marginal zone cell lymphoma (MZL) patients. This cytogenetic analysis of a large cohort extends previous observations and allows the identification of new cytogenetic features. Abnormalities identified in more than 15% of patients included +3/+3q (37%), 7q deletions (31%), +18/+18q (28%), 6q deletions (19%), +12/+12q (15%) and 8p deletions (15%). Trisomy 3/3q, 7q deletions, +18 and +12 were seen in different combinations in more than 30% of patients in comparison to 2% in lymphocytic lymphomas/chronic lymphocytic leukemias, 1% in mantle cell lymphomas and 7% in follicular lymphomas. The marked propensity of these abnormalities to be recurrently associated with the same tumoral clone of individual karyotypes allowed the delineation of a cytogenetic profile that may help to distinguish non-MALT MZL among other mature B-cell neoplasms. If +3/3q, +12/+12q, and 6q, 7q and 8p deletions were significantly associated with clinical prognostic factors previously reported to influence survival and time to progression, patients displaying these abnormalities did not experience a significantly shorter time to progression.Leukemia (2005) 19, 1818–1823. doi:10.1038/sj.leu.2403909; published online 11 August 2005 [ABSTRACT FROM AUTHOR]

Summary:The pathogenesis of thrombocytopenia occurring after autologous stem cell transplantation (ASCT) remains unclear. Six cases of classical peripheral thrombocytopenia that developed after ASCT for non-Hodgkin's lymphoma (NHL) are presented. Resolution of this complication was obtained by usual treatment such as steroids, splenectomy or progressively resolved without specific treatment. Five out of six patients have been followed for more than 5 years after hematopoietic transplantation and are still alive in complete remission despite poor prognostic factors at diagnosis. Several arguments suggest that this phenomenon represents autoimmune thrombocytopenia and may be the consequence of an altered immune balance. Consequently, development of autoimmune reactions after bone marrow transplantation might be associated with an antitumoral effect (graft-versus-lymphoma effect).Bone Marrow Transplantation (2003) 32, 89-95. doi:10.1038/sj.bmt.1704073 [ABSTRACT FROM AUTHOR]

High-dose melphalan (HDM) has been adopted as standard therapy in the treatment of multiple myeloma. This treatment is associated with non-selective cytotoxicity, causing oral mucositis as the major non-hematological side-effect. Amifostine is a cytoprotector which prevents toxicity induced by anticancer therapy. We prospectively compared two groups of patients who either received (group A, n = 21) or did not receive (group B, n = 20) amifostine (740 mg/m2) before HDM (200 mg/m2) followed by autologous peripheral blood progenitor cell transplantation. The occurrence of severe oral mucositis was significantly decreased in group A in comparison to group B (33% vs 65%, P < 0.05). Six patients in group A required opioid analgesic therapy during a mean period of 4.8 days as compared to eight patients for 6.5 days in group B (P = NS). Delayed vomiting was less frequent in group A (43% vs 70%, P = 0.07) and significantly less severe in group A (grade 2–4) vomiting: two patients vs nine patients, P < 0.02). No difference was observed between the two groups in either hematological toxicity after HDM or in response rate. Grade I emesis was the only immediate side-effect observed after amifostine administration. We conclude that amifostine can reduce mucositis induced by HDM.Bone Marrow Transplantation (2002) 30, 769–775. doi:10.1038/sj.bmt.1703757 [ABSTRACT FROM AUTHOR]

Presents updates on bone marrow transplantation as of March 2002. Information on the potential pathogenicity of human parainfluenza virus type 4 in post-hematopoietic stem cell transplants; Details on the possible role of defibrotide in treating thrombotic thrombocytopenic purpura in patients undergoing bone marrow transplantation; Discussion on acute toxicities associated with autologous peripheral progenitor cell infusion in patients receiving high-dose chemotherapy.

Serum lactic dehydrogenase (LDH) is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). We have examined the LDH isoenzyme content in serum and CSF of patients with NHL, at diagnosis and at relapse. In patients with increased serum LDH at diagnosis, the percentage of isoenzyme 2 was increased in 52% of patients and the absolute value of isoenzyme 3 was increased in 64% of patients. In relapsing patients these values were respectively 69% and 65%. Conversely in patients with increased serum LDH due to myeloid regeneration after chemotherapy, isoenzymes 4 and 5, but not isoenzymes 2 or 3, were increased. High absolute values of isoenzyme 3 were correlated with an altered performance status, advanced tumor stage, and aggressive histology whereas high isoenzyme 2 percentages were correlated with altered performance status only. Among patients with high total serum LDH, a high content of isoenzyme 2 and a high absolute value of isoenzyme 3 were correlated with high serum levels of TNFalpha and TNF receptor p75. Analysis of total LDH and LDH isoenzyme profiles in CSF did not reveal any correlation with meningeal involvement by lymphoma. High isoenzyme 2 percentages and high absolute values of isoenzyme 3 in serum were both significantly associated with a shorter freedom-from-progression and overall survival. Isoenzyme 3 remained a prognostic factor for survival even when considering only patients with high total serum LDH at diagnosis. We conclude that there are some characteristic serum LDH isoenzyme profiles in patients with NHL and that some of these specific alterations may help refine the prognostic value of total serum LDH. [ABSTRACT FROM AUTHOR]