Mucosa-associated Lymphoid Tissue non-Hodgkin Lymphoma Research Articles

Gastric MALT Lymphoma: A 8-Year Experience.

Gastric mucosa-associated lymphoid tissue non-Hodgkin lymphoma (gMALT NHL) is the second most common gastrointestinal lymphoma (50% of all gastric lymphomas), being closely associated withHelicobacter pyloriinfection, justifying that antibiotic therapy is effective in over 75% of all cases. This is a retrospective study analyzing all adult gMALT NHL cases diagnosed and treated in a single center for 8years, focusing on demographic features, treatment outcomes, and survival analysis. Sixty patients with a median age of 61years (53.3% female gender) were analyzed. Most of the cases had localized disease (66.7% were Lugano stage I) and had low IPI scores (median: 1). There was a high prevalence ofHelicobacter pyloriinfection (68.3%). Nearly 97% of the cases received treatment for the disease, a median of one line; 55% of the patients treated endured complete response after first-line therapy (mostly antibiotics). Median overall survival time and median progression-free survival time were not reached. The mean follow-up time was 81.8months (95% CI: [73.3-90.3]). Thirty-six patients (60%) achieved a 3-year follow-up time; the mortality rate was 15% at the end of the study. Age superior to 65years and transformation into DLBCL were statistically significant negative prognostic markers for survival in this study (p = 0.006 and p = 0.033, respectively). Our study confirms that gMALT NHL is an indolent disease with long-term survival. Many patients, however, are exposed to several treatment lines along their disease course.

The P2X7 receptor-NLRP3 inflammasome complex predicts the development of non-Hodgkin's lymphoma in Sjogren's syndrome: a prospective, observational, single-centre study.

P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjögren's syndrome (SS), where it stimulates IL-18 production. Some patients with SS develop a mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). To prospectively evaluate the involvement and the putative prognostic role of this inflammatory pathway in the development of MALT-NHL. A total of 147 women with SS have been prospectively followed for a mean of 52 months, relating the expression and function of the P2X7R-inflammasome axis in salivary glands and circulating lymphomonocytes to the prognosis and the degree of the disease. At baseline, gene expression of P2X7R and of the inflammasome components NLRP3, caspase-1 and IL-18 increased according to the presence of germinative centres and was higher in autoantibody-positive individuals and strongly higher in those developing a MALT-NHL over the follow-up. Glandular expression of IL-18 was threefold higher in MALT-NHL than in controls or in the other patients with SS. P2X7R did not colocalize with generic markers of inflammatory infiltrate, like CD20, being selectively expressed by epithelial cells. P2X4R, sharing functional characteristics with P2X7R, did not differ in SS and controls. The increased P2X7R gene and protein expression was tissue specific, no difference being observed in peripheral lymphomonocytes between SS with MALT-NHL and SS not developing MALT-NHL. We propose the P2X7R-inflammasome axis as a novel potential pathway involved in both SS exocrinopathy and lymphomagenesis, reinforcing the hypothesis of a key role of IL-18, via its increased P2X7R-mediated production, in the pathogenesis of lymphoproliferative malignancies, and opening novel opportunities for the early diagnosis of lymphoproliferative complications and the development of potential targeted therapies.

Late-onset sarcoidosis in a patient with gastric mucosa-associated lymphoid tissue non-Hodgkin lymphoma: A case report.

The simultaneous presence of hematological malignancies and sarcoidosis, defined as sarcoidosis-lymphoma syndrome, has been reported in 79 patients in the literature to date. The majority of these patients were affected by sarcoidosis and developed non-Hodgkin lymphoma or acute leukemia after 1–2 years; however, in <20 cases the malignancy developed first. This report presents the case of an 83-year-old male with a clinical history of Helicobacter pylori-positive gastric mucosa-associated lymphoid tissue lymphoma. The patient developed sarcoidosis 10 years after the first diagnosis, which caused the diagnostic work-up and differential diagnosis between a lymphoma relapse and de novo sarcoidosis to be challenging.

FOXO1 is a tumor suppressor in classical Hodgkin lymphoma

AbstractThe FOXO transcription factors control proliferation and apoptosis in different cell types. Their activity is regulated by posttranslational modifications, mainly by the PI3K-PKB pathway, which controls nuclear export and degradation. We show that FOXO1 is highly expressed in normal germinal center B cells as well as in non-Hodgkin lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma, mucosa-associated lymphoid tissue non-Hodgkin lymphoma, B-cell chronic lymphocytic leukemia, and mantle cell lymphoma. In contrast, in 31 of 32 classical Hodgkin lymphoma (cHL) cases, Hodgkin and Reed-Sternberg cells were FOXO1 negative. Neoplastic cells of nodular lymphocyte-predominant Hodgkin lymphoma were negative in 14 of 20 cases. FOXO1 was down-regulated in cHL cell lines, whereas it was expressed in non-Hodgkin lymphoma cell lines at levels comparable with normal B cells. Ectopic expression of a constitutively active FOXO1 induced apoptosis in cHL cell lines and blocked proliferation, accompanied with cell-cycle arrest in the G0/G1 phase. We found that, in cHL cell lines, FOXO1 is inactivated by multiple mechanisms, including constitutive activation of AKT/PKB and MAPK/ERK kinases and up-regulation of microRNAs miR-96, miR-182, and miR-183. These results suggest that FOXO1 repression contributes to cHL lymphomagenesis.

Efficacy of 90 Y - Ibritumomab Tiuxetan in Relapsed or Refractory Primary Gastric Non Hodgkin Lymphoma

BACKGROUND: A prospective, single arm, open-label, phase II trial was performed to evaluate efficacy of 90Y-Ibritumomab Tiuxetan at conventional activity of 0,4 mCi/kg in Primary Gastric Non Hodgkin Lymphoma (NHL).PATIENTS AND METHODS: From May 2004 to May 2008, 13 patients affected by Primary Gastric NHL - either Mucosa Associated Lymphoid Tissue (MALT) or Diffuse Large B Cell (DLBC) NHL, relapsed/refractory disease - were enrolled to receive 90Y-Ibritumomab Tiuxetan at the activity of 0,4 mCi/kg. Median age was 57 ys (range 36–83), 6 female and 7 male. Nine out of 13 patients had gastric MALT NHL, the remaining 4 patients had DLBC NHL. At time of treatment 11 out of 13 patients had stage I/II, 2 patients had stage III/IV disease. Helicobacter Pylori was negative in all patients except one at time of treatment and positive at diagnosis in 5 of them. Median number of previous therapies received was 1 (1–4): all patients except 3 had received prior CT, 7 patients prior Rituximab, no one had received prior RT.RESULTS: Toxicities were primarily haematological and reversible. All patients had serial testing for HAMA and none developed antibodies to date. MALT-1 gene rearrangement was detected in 3 of the 9 cases analyzed, while none of the cases showed bcl-10 gene rearrangement. All patients are now evaluable for response: 10 out of 13 patients experienced a complete response (CR) (9 MALT, 1 DLBC); progressive disease (PD) was observed in 2 out of 13 patients, both DLBC NHL; finally another patient affected by DLBC NHL did not respond. After a median follow up of 24 months (range 3–50 months) 9 out of 10 CRs are disease free and 5 of them can be considered long term responders at 50, 43, 40, 32 and 31 months, respectively, following radioimmunotherapy (RIT). At the time of the analysis only 1 relapse occurred 17 months after RIT (MALT). Two patients - both DLBC - died due to disease progression. There was no statistically significant associations between response to RIT and the occurrence of the MALT-1 translocation.CONCLUSIONS: 90Y-Ibritumomab Tiuxetan seems to be very active in patients with primary gastric NHL relapsed or refractory to conventional systemic treatment, especially in gastric MALT NHL. Despite the relative short median follow-up (24 months), we observed durable long-term responses at least in 5 patients. High response rate and durable remissions could be related to the low tumor burden and consequently to higher absorbed doses to tumor, confirming the possible relationship between absorbed doses to tumor, efficacy and duration of response. If preliminary results can be confirmed in larger series, RIT could be offered as valid alternative approach in this setting because of its efficacy and low rate of side effects. These preliminary results warrant further studies.

Efficacy of 90Y Ibritumomab-Tiuxetan Treatment in a Case of Resistant Gastric Malt Non Hodgkin's Lymphoma

Treatment modalities for resistant/relapsing gastric mucosa associated lymphoid tissue (MALT) non-Hodgkin’s lymphoma (NHL) are not yet well standardized. In the past, most patients were treated surgically with a gastrectomy, while, more recently, radiotherapy and systemic approaches (chemotherapy and immunotherapy) have been used with improving results.Here, we report the case of a patient affected by MALT NHL resistant to antibiotics, chemotherapy and immunotherapy, who achieved a durable complete remission after radio-immunotherapy treatment with Zevalin (90Y ibritumomab-tiuxetan), administered in a single-standard dose. This observation must be confirmed on a larger series but suggests that radio-immunotherapy may be a valid approach in treating relapsing MALT NHL patients, or those resistant to conventional therapies, so avoiding more aggressive and toxic approaches.

Gastric lymphomas compared with lymph node lymphomas in a population-based registry differ in stage distribution and dissemination patterns but not in patient survival.

Non-Hodgkin's lymphoma (NHL) originating in mucosa-associated lymphoid tissue (MALT) is supposed to have different clinical behavior from lymph node NHL. To test this hypothesis, the authors compared data of gastric NHL patients with lymph node NHL patients in a population-based registry for differences in clinical presentation and prognosis. Data from 1981-1989 on patients with primary gastric NHL (n = 109) and patients with primary lymph node NHL (n = 658) were retrieved from a Dutch population-based NHL registry. Patients were compared for stage distribution, involved sites, and survival. The prognostic value of grading lymphomas according to the malignancy grades of the Working Formulation for Clinical Usage was compared with the value of grading MALT NHLs as either low grade or high grade malignancies. Patients with gastric NHL presented more often with localized disease. Stage IV patients had a higher rate of dissemination to other non-lymph node sites but less frequent localization in the bone marrow. The restricted pattern of dissemination was reflected in a significantly lower recurrence rate for gastric NHL. Gastric NHL patients had significantly better disease free survival than lymph node NHL patients (80% and 44% at 5 years, respectively; P < 0.001). In contrast, overall survival did not significantly differ between the two groups, and it appeared to depend on disease stage. Grading MALT lymphoma as either low grade (26%) or high grade (70%) malignancies did not provide better prognostic information than grading according to the Working Formulation for Clinical Usage (low 8%, intermediate 75%, high 9%). Primary gastric NHL shows a restricted dissemination pattern, which gives support to the MALT lymphoma concept. Although this might explain the superior disease free survival observed for gastric NHL patients, it does not translate into better overall survival for these patients.

Temperature gradient gel electrophoresis for analysis of clonal evolution in non-Hodgkin's lymphoma of the thyroid.

To analyze the transition of an autoimmune disease into a mucosa-associated lymphoid tissue-non-Hodgkin's lymphoma (MALT-NHL), we investigated a total of 27 cases of clinically diagnosed autoimmune thyroiditis with lymphoid hyperplasia. Three cases of thyroid hyperplasia served as controls. Monoclonal B cells were detected by studying rearrangement patterns of the hypervariable CDR III regions within the immunoglobulin heavy chain gene locus and the T-cell receptor gamma chain gene (TCRG). We used a seminested polymerase chain reaction (PCR) to demonstrate immunoglobulin rearrangements and a multiplex PCR for TCRG rearrangements. The PCR products were analyzed by temperature gradient gel electrophoresis to expand mixtures of homo- and hetero-duplices within heterogeneous populations of B cells. With this approach we found monoclonality in 14 of the 27 cases of Hashimoto's disease. In a reinvestigation we discovered additional histological and immunohistochemical features of MALT-NHL in 17 cases. The 14 cases of thyroiditis with clonally expanded B cells clearly demonstrate the transition from autoimmune disease to non-Hodgkin's lymphoma.