Clinical Characteristics, Treatment and Evolution of Splenic and Nodal Marginal Zone Lymphomas-Retrospective and Multicentric Analysis of Portuguese Centers.

INTRODUCTION: Treatment of Splenic (SMZL) and Nodal (NMZL) Marginal Zone Lymphoma is not consensual. Histologic transformation (HT) to aggressive lymphoma is a poorly understood event, with an unfavorable outcome. OBJECTIVES: Describe the clinical characteristics, treatment, outcomes and incidence of HT. METHODS: Characteristics of patients with SMZL and NMZL consecutively diagnosed in 8 Portuguese centers were retrospectively reviewed. Endpoints were overall survival (OS), time to first systemic treatment (TTFST), frequency of HT and time to transformation (TTT). RESULTS: This study included 122 SMZL and 68 NMZL, most of them received systemic treatment: 55.4% and 76.5%, respectively. Splenectomy was performed in 58.7% of patients with SMZL. Different treatment protocols were used. OS or TTFST did not differ significantly according to treatments. Given the small sample size, no conclusion can be made concerning the role of Rituximab in the treatment of NMZL and SMZL based in these results. HT was documented in 18 patients, mainly in SMZL, with a cumulative incidence at 5 years of 4.2%. We confirmed that age is a prognostic factor. CONCLUSION: Randomized prospective trials are needed to standardize treatment in MZL. Patients with HT did appear to have shorter OS in comparison with those who did not experience HT (OS 5 years of 68.4% vs. 80.4%), but the number of HT was too small to reach statistical significance.

Watch-and-wait or immediate immunotherapy/immunochemotherapy in patients with phase IE primary pulmonary MALT lymphoma? A multicenter retrospective study.

Primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is rare, and the optimal frontline treatment has not taken shape so far. It is still debatable whether the watch-and-wait (W&W) policy is beneficial to patients, especially in the early stage. This study was to compare the efficacy of W&W with rituximab single agent or combined chemotherapy (R/R-Chemo) on primary pulmonary MALT patients with localized disease. Clinical characters and effect on 28 patients with primary pulmonary MALT (IE phase) were analyzed. Among the 28 patients, 14 were grouped into W&W cohort, and 14 were immediately treated with R/R-Chemo. The median follow-up duration was 62 months. The estimated median time to treatment failure (TTF) in the W&W cohort and immediate R/R-Chemo cohort was 29 months and 59 months, which were not significantly different (P = 0.667). The estimated median time of overall survival (OS) in the W&W cohort and immediate R/R-Chemo cohort was 78 months and 76 months, which were also not statistically significant (P = 0.696). Concerning prognosis, there is no difference between patients with primary pulmonary MALT (IE phase) treated with W&W and with timely R/R-Chemo.

MALT lymphoma: epidemiology, clinical diagnosis and treatment.

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

Optimizing therapy for nodal marginal zone lymphoma.

Nodal marginal zone lymphoma (NMZL) is a rare form of indolent small B-cell lymphoma which has only been clearly identified in the last 2 decades and which to date remains incurable. Progress in therapeutic management has been slow, largely due to the very small number of patients treated and the heterogeneity of treatments administered; thus, standard-of-care treatment is currently nonspecific for this lymphoma entity. In this review, treatments routinely used to manage adult NMZL patients are presented, principally based on immunochemotherapy (when treatment is needed). Biological research behind the key axes of agents currently under development is described; development of novel agents is heavily based on data from gene profiling and genome-wide sequencing research, uncovering a number of critical deregulated pathways specific to NMZL tumors. These include B-cell receptor, JAK/STAT, NF-κB, NOTCH, and Toll-like receptor signaling pathways, as well as intracellular processes such as the cell cycle, chromatin remodeling, and transcriptional regulation in terms of epigenetic modifiers, histones, or transcriptional co-repressors, along with immune escape via T-cell-mediated tumor surveillance. These pathways are examined in detail and a projection of how the field may evolve in the near future for an efficient personalized treatment approach for NMZL patients is presented.

Trends in incidence, therapy and outcome of localized nodal and extranodal marginal zone lymphomas: declining incidence and inferior outcome for gastrointestinal sites.

Population-based series analyzing clinical implications of nodal versus extranodal presentation of marginal zone lymphoma (MZL) are lacking. We studied clinical differences and trends in incidence, therapy and survival of nodal and extranodal MZL, and of MZL at different extranodal sites, in a population-based cohort. All patients with localized (Ann Arbor stage I and II) nodal (n = 211), splenic (n = 54) and extranodal (n = 1449) MZL, diagnosed between 1994 and 2010, were selected from The Netherlands Cancer Registry. Between 1994 and 2010 the incidence of nodal and extranodal MZL increased. The incidence of gastric MZL decreased. Patients with nodal MZL received more chemotherapy and targeted therapies than their extranodal counterparts. A trend in time toward less chemotherapy and more irradiation was observed. Overall survival (OS) curves for nodal and extranodal MZL overlapped (5-year OS 76% and 77%, respectively). Patients with a primary gastrointestinal (GI) localization had inferior OS compared to patients with non-GI extranodal MZL (5-year OS 71% and 85%, p < 0.0001). Patients with localized extranodal MZL presented more commonly with stage I disease, but their clinical presentation and survival were otherwise similar to patients with localized nodal MZL. MZL arising in the GI tract does not have a good prognosis and requires a different treatment approach.

Long-term treatment of localized gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer.

BACKGROUND AND AIM: According to a few recent reports on the long-term clinical outcome of gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long-term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. METHODS: Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II(1) according to Lugano classification) were analyzed retrospectively. RESULTS: Forty-eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second-line treatment, and all of them achieved remission. The median follow-up period was 76 months (range, 12-157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. CONCLUSION: Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long-term outcome, though regular follow-up endoscopy should be performed for detecting metachronous early gastric cancer.

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.

A cirurgia no tratamento do linfoma gástrico primário do tipo Malt / Surgery in the treatment of primary gastric lymphoma of MALT

O autor relata um estudo retrospectivo de 21 prontuários de pacientes portadores de linfoma gástrico primário do tipo MALT submetidos a tratamento cirúrgico exclusivo ou associado à radioterapia e/ou quimioterapia, durante o período de 1982 a 1996 no Hospital do câncer - Ministério da Saúde...O tratamento adjuvante foi preconizado em 10 pacientes e consistiu em radioterapia em três pacientes no estágio IE, quimioterapia em cinco casos, quatro no estágio IE e um no IIE1. A associação de radioterapia e quimioterapia foi realizada em dois pacientes no estágio IE. O seguimento variou de 3 a 132 meses e evidenciou que dois pacientes faleceram por evolução da doença e um por complicações decorrentes da quimioterapia. Considera-se que o linfoma é uma doença pouco frequente, com diagnóstico baseado na endoscopia digestiva alta e que a cirurgia é essencial para o estagiamento e tratamento da doença.