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We analyzed 66 cases of immune-mediated thrombophilia in patients with lymphoma reported in the literature. Sixty-one cases had a lupus anticoagulant, three an antibody to protein S, one to protein C, and one to ADAMTS 13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Lupus anticoagulants occurred in all histological subtypes of non-Hodgkin lymphoma, except mantle cell lymphoma, MALT (mucosa-associated lymphoid tissue) lymphoma, and angioimmunoblastic T-cell lymphoma, and rarely in Hodgkin lymphoma. The largest number of cases was described in splenic marginal zone and lymphoplasmacytic lymphoma. Lupus anticoagulants were highly associated with immunoglobulin M (IgM) paraproteinemia, autoimmune hemolytic anemia, and immune thrombocytopenia. About half of the patients had thrombotic events (antiphospholipid antibody syndrome). Venous thromboembolism was more than twice as common as arterial thrombosis; 6.5%% had a catastrophic antiphospholipid antibody syndrome. The lupus anticoagulant could be eliminated by lymphoma treatment (chemoimmunotherapy or splenectomy) in more than one-third of patients. It is suggested that a search for lupus anticoagulant should be done in all patients with lymphoma, because a diagnosis of lupus anticoagulant may influence the management of lymphomas in some patients. [ABSTRACT FROM AUTHOR]

There is increasing evidence for the role of chronic antigenic stimulation (CS) in the development of cancer. Clinical data, however, are rare as is the information on outcome. In this study, the occurrence of chronic infections (CI) and autoimmune diseases (AI) in patients with malignant lymphoma at diagnosis was assessed. Of 367 patients [non-Hodgkin´s lymphoma (NHL) N = 297, Hodgkin´s lymphoma N = 70], 9.8% ( N = 36) had a history of chronic antigenic stimulation (4.4% AI, 5.4% CI) at diagnosis. After a median observation time of 74.7 months, 118 patients have died. There were more male patients in this cohort. However, sex ratio among patients with chronic antigenic stimulation was skewed in favor of women ( p = 0.018), in particular among lymphoma patients with AI ( p = 0.001). NHL patients with autoimmune diseases showed a tendency to develop diffuse large B cell lymphoma [8 of 12 AI + NHL patients (66.7%) vs. 100 of 266 non-CS NHL (37.6%); p = 0.066]. No significant difference in overall survival (OS) between CS and non-CS patients could be observed (median OS after 48 months was: CS 77.7% vs. non-CS 71.8%). In conclusion, chronic antigenic stimulation at diagnosis appears to be associated with a higher prevalence in women, in particular among patients with autoimmune disease. However, no difference in overall survival was observed. This suggests that the presence of chronic inflammatory conditions does not decisively influence the outcome of lymphoma patients. [ABSTRACT FROM AUTHOR]

18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has been used as a potential tool for imaging nodal follicular lymphoma (FL) and extranodal spread. As primary intestinal FL is increasingly being recognized, we have performed a study to investigate the usefulness of 18F-FDG-PET for staging of extranodal FL within the gastrointestinal tract. In eight patients with a diagnosis of FL localized in the duodenum (six cases in stage I and one each in stages II and IV, respectively) whole body 18F-FDG-PET scans were performed. Seven patients with duodenal FL were rated WHO grade 1 and one had FL grade 3, while both patients with secondary spread had FL WHO grade 1. All patients were imaged before initiation of therapy. None of the patients with primary duodenal FL showed pathologically elevated 18F-FDG uptake. 18F-FDG-PET findings were not influenced by histological grade or proliferative activity of FL. These findings suggest that 18F-FDG-PET is not useful for clinical assessment of primary duodenal FL. [ABSTRACT FROM AUTHOR]

We used nonpegylated liposomal doxorubicin (NPLD) in cytostatic drug combinations to treat 37 patients with non-Hodgkin's lymphoma and pre-existing cardiac disorder or elderly patients with reduced physical state who were ineligible for conventional anthracycline-containing therapy. High remission rates were observed in this poor-risk population: Complete remission rates were 75% for diffuse large B cell lymphoma (DLBCL) and 55% for T/NK cell neoplasm (overall response rate of 80% and 89%, respectively). Twenty-seven patients (73%) are still alive after a median observation time of 14 months. No major cardiac or gastrointestinal toxicity was observed. Extravasation of NPLD in two patients resulted in mild inflammation without tissue damage. Hematologic toxicity was comparable to that of conventional anthracycline-containing regimens. We conclude that NPLD is highly active in combination chemotherapy for lymphoma with low cardiac toxicity in patients with pre-existing cardiac disorders or higher age. Moreover, we also observed remarkable efficacy in T/NK cell lymphomas. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphomas (PTCL) have a variable outcome. We have investigated the prognostic value of molecular staging in non-anaplastic PTCL. T-cell receptor γ rearrangements were routinely determined in peripheral blood (n = 40) and bone marrow (n = 38) of patients with PTCL (75% unspecified) by conventional PCR at diagnosis. Tissue controls for PCR included 24 tumour biopsies. Twenty-four patients (60%) had a PCR-detectable clonal TCRγ rearrangement in PB or BM. These TCRγ PCR positive patients had significantly more stage IV disease (14 patients of 15 patients; P = 0.001), elevated LDH (14 of 18 patients; P = 0.04), higher IPI (16 of 21 patients; P = 0.03), more anemia (15 of 19 patients; P = 0.02) and lower platelet counts (seven of seven patients; P = 0.02). Clinical outcome of this clonal group was characterised by lower complete remission rates (37.5% vs. 62.5%), and overall response rates (58.3% vs. 87.5%; P < 0.05) as well as a significantly shorter median overall survival (12.8 vs. 30.0 months; P = 0.006). Patients with clinical stages I - III but molecular stage IV had an equally poor overall survival when compared with patients with clinical stage IV (15.8 vs. 13.9 months). In contrast, patients with CS I - III in the absence of a TCRγ rearrangement in PB or BM had a favourable outcome with an estimated overall survival of 70% at 3 and 5 years. Molecular staging in PB and BM by TCRγ PCR at diagnosis may serve as a useful prognostic tool in PTCL. [ABSTRACT FROM AUTHOR]

We analyzed 108 cases of non-CLL non-Hodgkin lymphoma (NHL) associated with autoimmune hemolytic anemia (AIHA) (+/- pure red cell aplasia (PRCA)) or Evans' syndrome. The analysis was based on cases reported in the literature, which were retrieved by means of Pubmed and Medline searches and of an original series of 121 patients with NHL as well as reference lists of papers in the field. The number of cases in various NHL subtypes was small (n = 6 - 25). Nevertheless, interesting and sometimes unexpected differences in sex prevalence, temporal relationship between onset of lymphoma and AIHA, stage of lymphoma, relative frequency of warm antibody-AIHA (WA-AIHA) and cold antibody (CA-AIHA), association with PRCA and response of AIHA to treatments were noted for various lymphoma entities. WA-AIHA was more frequent in B-cell lymphomas, while CA-AIHA and PRCA predominantly occurred in T-cell lymphomas. Anti-lymphoma treatment seemed to be more effective against AIHA than conventional therapy with steroids or immunoglobulin. Although generated by a literature survey, this compilation of data indicates a complex relation of lymphoma and AIHA and warrants more attention and specific studies. [ABSTRACT FROM AUTHOR]

Objective: According to recent reports, nodal marginal zone lymphoma (MZL) appears to be a distinctive lymphoma entity rather than a more advanced stage of extranodal MZL of mucosa-associated lymphoid tissue (MALT). We have therefore retrospectively evaluated all patients diagnosed with nodal or extranodal MZL who have been referred to our unit for imaging using [sup 18] F-fluorodeoxyglucose positron emission tomography ([sup 18] F-FDG-PET). Patients and Methods: A total of 21 patients with a diagnosis of MZL upon referral for imaging with [sup 18] F-FDG-PET were identified. Histological reassessment of biopsy specimens confirmed the diagnosis of extranodal MZL of MALT in 14 patients, while a diagnosis of nodal MZL was verified in 6 patients. Lymphoma cell proliferation was assessed immunohistochemically using a Ki-67 antibody. Whole-body [sup 18] F-FDG-PET scans were performed on a GE advanced PET scanner 40 min after intravenous injection of 300–380 MBq [sup 18] F-FDG. Results: None of the patients with extranodal MZL showed focal tracer uptake within verified tumor sites. In contrast, 5 of the 6 patients with nodal MZL showed significant FDG uptake within the affected lymph nodes. These results did not simply reflect the different growth fractions of the two lymphoma entities since the proliferation indices of the two groups did not differ significantly. Conclusion:[sup 18] F-FDG-PET visualizes nodal MZL in a high proportion of patients whereas FDG uptake is undetectable in extranodal MZL. Although limited by the small number of patients, this study suggests that imaging with [sup 18] F-FDG-PET might play a potential role in the diagnostic workup of patients with nodal MZL involvement.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Acute hematological diseases (leukemiasand aggressive lymphomas) can be cured in approximately half of thepatients, while the other patients die from their disease. Chronicleukemias and indolent lymphomas can be well controlled for yearsin most cases. However, the cure rate of these patients is low andthe course of the disease is characterized by frequent recurrence.Therefore, novel agents for monotherapies or combination therapiesstill need to be explored. The presented study describes the identificationof the chalcone derivative 15on different types of humanmalignant cells of the lymphoid and myeloid lineage. Further experimentsperformed with compound 15on peripheral blood mononuclearcells (PBMCs) of chronic lymphocytic leukemia (CLL) patients clearlystated a higher cytotoxicity in PBMC from CLL patients compared tohealthy donors (HD). The newly identified chalcone derivative 15showed a higher therapeutic potential than fludarabine,a drug already in use in lymphoma treatment. [ABSTRACT FROM AUTHOR]

Abstract: Human adenoviruses possess oncogenic capacity which is well documented in mammalian animal models, but their possible implication in human malignancy has remained enigmatic. Following primary infection, adenoviruses can persist in a latent state in lymphocytes where the virus is apparently able to evade immune surveillance. In the present study, we have employed a broad-spectrum adenovirus polymerase chain reaction (PCR) assay to systematically screen more than 200 diagnostic specimens of different lymphoid malignancies including acute lymphocytic leukaemia (n =50), chronic lymphocytic leukaemia (n =50), various types of malignant lymphoma (n =100) and multiple myeloma (n =11) for the presence of adenoviral sequences. While most entities analysed revealed negative findings in virtually all specimens tested, adenoviral DNA was detected in 15/36 (42%) mantle cell lymphomas investigated. The most prevalent adenoviral species detected was C, and less commonly B. Adenovirus-positive findings in patients with mantle cell lymphoma were made at different sites including bone marrow (n =7), intestine (n =5), lymph nodes (n =2) and tonsillar tissue (n =1). The presence of adenoviral sequences identified by PCR was confirmed in individual cells by fluorescence in-situ hybridisation (FISH). The frequent observation of adenoviruses in mantle cell lymphoma is intriguings, and raises questions about their possible involvement in the pathogenesis of this lymphoid malignancy. [Copyright &y& Elsevier]

Abstract: A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor genes, and to the corresponding strong activity of the immune enhancers/promoters at that stage of cell development, B- and T-cell differentiation pathways represent propitious targets for chromosomal translocations and oncogene activation. Recent progress in the understanding of the V(D)J recombination process has allowed a more accurate definition of the translocation mechanisms involved, and has revealed that V(D)J-mediated translocations result both from targeting mistakes of the recombinase, and from illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J-mediated translocations turn out to be restricted to two specific sub-types of lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set of mature B-cell Non-Hodgkin''s lymphomas. [Copyright &y& Elsevier]