Pathways towards indolent B-cell lymphoma - Etiology and therapeutic strategies.

Although patients with indolent B-cell lymphomas have a relatively good survival rate, conventional chemotherapy is not curative. Disease courses are typically characterized by multiple relapses and progressively shorter response duration with subsequent lines of therapy. There has been an explosion of innovative targeted agents in the past years. This review discusses current knowledge on the etiology of indolent B-cell lymphomas with respect to the role of micro-organisms, auto-immune diseases, and deregulated pathways caused by mutations. In particular, knowledge on the mutational landscape of indolent B-cell lymphomas has strongly increased in recent years and harbors great promise for more accurate decision making in the current wide range of therapeutic options. Despite this promise, only in chronic lymphocytic leukemia the detection of TP53 mutations and/or del17p currently have a direct effect on treatment decisions. Nevertheless, it is expected that in the near future the role of genetic testing will increase for prediction of response to targeted treatment as well as for more accurate prediction of prognosis in indolent B-cell lymphomas.

Interleukin 21 - its potential role in the therapy of B-cell lymphomas.

Interleukin-21 (IL-21), a member of IL-2 cytokine family, has pleotropic biological effects on lymphoid and myeloid cells. During the past 15 years, since the discovery of IL-21, great advances have been made regarding its biological activity and the mechanisms controlling IL-21-mediated cellular responses, especially in hematological malignancies. Preclinical studies have shown that IL-21R is expressed on healthy and neoplastic B-cells and exogenous IL-21 can induce direct apoptosis of IL-21R expressing B-cell non-Hodgkin lymphomas (NHL), making it a potentially attractive anti-lymphoma therapy. However, in some hematological malignancies such as multiple myeloma, Hodgkin lymphoma and Burkitt lymphoma, IL-21 can induce proliferation of neoplastic B-cells. In NHL, the underlying mechanism of cell death was found to be different between the various subtypes, including activation of different JAK/STAT signal transduction pathways or other factors. Immunomodulatory effects of IL-21 have also been reported to contribute to its anti-tumor effects as described by earlier studies in solid tumors and B-cell associated malignancies. These effects are predominantly mediated by IL-21's ability to activate cytolytic activities by NK-cells and CD4+/CD8+ T-cells. In this review, we provide an overview of IL-21's effects in NHL, results from clinical trials utilizing IL-21, and propose how IL-21 can be therapeutically exploited for treating these lymphomas.

Trans fatty acid intake is associated with increased risk and n3 fatty acid intake with reduced risk of non-hodgkin lymphoma.

We evaluated the association of dietary fat and protein intake with risk of non-Hodgkin lymphoma (NHL) in a clinic-based study in 603 cases (including 218 chronic lymphocytic leukemia/small lymphocytic lymphoma, 146 follicular lymphoma, and 105 diffuse large B-cell lymphoma) and 1007 frequency-matched controls. Usual diet was assessed with a 128-item food-frequency questionnaire. Unconditional logistic regression was used to estimate ORs and 95% CIs, and polytomous logistic regression was used to assess subtype-specific risks. trans Fatty acid (TFA) intake was positively associated with NHL risk [OR = 1.60 for highest vs. lowest quartile (95% CI = 1.18, 2.15); P-trend = 0.0014], n3 (ω3) fatty acid intake was inversely associated with risk [OR = 0.48 (95% CI = 0.35, 0.65); P-trend < 0.0001], and there was no association with total, animal, plant-based, or saturated fat intake. When examining intake of specific foods, processed meat [OR = 1.37 (95% CI = 1.02, 1.83); P-trend = 0.03], milk containing any fat [OR = 1.47 (95% CI = 1.16, 1.88); P-trend = 0.0025], and high-fat ice cream [OR = 4.03 (95% CI = 2.80, 5.80); P-trend < 0.0001], intakes were positively associated with risk, whereas intakes of fresh fish and total seafood [OR = 0.61 (95% CI = 0.46, 0.80); P-trend = 0.0025] were inversely associated with risk. Overall, there was little evidence for NHL subtype-specific heterogeneity. In conclusion, diets high in TFAs, processed meats, and higher fat dairy products were positively associated with NHL risk, whereas diets high in n3 fatty acids and total seafood were inversely associated with risk.

Primary intestinal lymphoma in patients with inflammatory bowel disease: a descriptive series from the prebiologic therapy era.

BACKGROUND: Primary intestinal lymphoma in the setting of inflammatory bowel disease (IBD) is uncommon and may be associated with immune suppressive therapy. We report clinical features and outcomes in patients with both conditions prior to use of biologic therapy. METHODS: All patients with primary intestinal lymphoma and IBD at our institution from 1960-2000 were retrospectively identified. Data reported are frequency (proportion) or median (interquartile range). Kaplan-Meier analysis was performed. RESULTS: Fifteen patients were identified: 14 (93%) were male, 10 (66%) had Crohn's disease. Median age at diagnosis of IBD and lymphoma was 30 (22-51) and 47 (28-68) years, respectively, with bloody diarrhea the most common presenting symptom for each diagnosis. Lymphoma location was colorectal in nine (60%), small bowel in four (27%), and one (6.25%) each: stomach, duodenum, and ileal pouch. Treatments were surgery plus chemotherapy (n = 6), surgery alone (n = 3), chemotherapy alone (n = 2), chemotherapy and radiation (n = 1), surgery and radiation (n = 1); two patients died before treatment. Most patients (n = 11, 73%) were Ann Arbor stages I or II. Large cell B-type histology was most common (n = 9, 60%). Three patients died within 30 days of lymphoma diagnosis. Survival free of death from lymphoma at 1- and 5-years was 78% and 63%, respectively, and was associated with advanced lymphoma stage (P = 0.004). CONCLUSIONS: Diagnosis and treatment of primary intestinal lymphoma in patients with IBD can be challenging and requires a high index of suspicion. Optimal survival requires multimodality therapy.

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.

Postlymphoproliferative disorder affecting bone after a renal transplantation.

OBJECTIVE: To illustrate a posttransplant lymphoproliferative lymphoma presenting as a solitary osseous lesion situated in the rib. CLINICAL FEATURES: A 53-year-old man was referred to a surgical department because of persistent local pain over the lower part of his left posterior hemithorax. Due to a previous history of chronic glomerulonephritis, a renal transplant was performed 7 years previously, followed by immunosuppressive therapy with azathioprine cyclophosphamide. INTERVENTION AND OUTCOME: Surgical removal of the rib lesion was performed because of the patient's history of the organ transplant. The histological study of the surgically removed tissue revealed diffuse infiltration of the marrow by lymphoid-like cells. There was evidence of interstitial fibrosis, and further immunohistochemical examination showed the presence of B cells in the specimen confirming the diagnosis of B-cell lymphoma. CONCLUSION: This case report discusses an unusual presentation of a lymphoma induced by immunosuppressive therapy in a patient who had received an organ transplant. Such lesions may appear in any organ or system, although this is distinctively unusual to involve the skeletal system.

[Subcutaneous manifestations of a centrocytic non-Hodgkin lymphoma at the injection site of a mistletoe preparation]. / Subkutane Manifestationen eines zentrozytischen Non-Hodgkin-Lymphoms an Injektionsstellen eines Mistelpräparats.

HISTORY AND CLINICAL FINDINGS: A 73-year-old man, first diagnosed as having centrocytic Non-Hodgkin lymphoma 5 years previously, presented with subcutaneous nodes of the abdominal wall at precisely the sites of previous regular injections of a mistletoe preparation. These nodes had first appeared 5 weeks after the first injection. Injections were stopped and he reported to the out-patient clinic. Except for the visible and easily nodes in the anterior wall no other subcutaneous nodes were palpated. Prominent cervical lymphomas and swelling of the epicranial aponeurosis and lower lip had, according to the patient, been present for some time. INVESTIGATIONS: There was a T-lymphocytopenia, lactate dehydrogenase activity was raised to 255 U/l. The subcutaneous nodes in the anterior abdominal wall were also demonstrated by ultrasound. Computed tomography showed them as having the density of connective tissue and being up to 5 cm in diameter. The excised nodes histologically revealed to be infiltrations by the centrocytic lymphoma. TREATMENT AND COURSE: Once the mistletoe injections had been discontinued no further subcutaneous infiltrates were seen despite the progression of the lymphoma. Six weeks later the patient died of bilateral pneumonia. CONCLUSION: There are pointers that high concentrations of mistletoe preparations subcutaneously injected can have a growth-promoting action on cells of a centrocytic lymphoma. As part of a leukaemic "wash-out", these cells reach the subcutaneous tissue. This proliferative stimulus may have been mediated by a high local concentration of interleukin-6 liberated from the skin by mistletoe lectins.

[Lymphomas of the colon complicating hemorrhagic rectocolitis]. / Lymphomes du côlon compliquant une rectocolite hémorragique.

Colonic lymphoma is a rare complication of ulcerative colitis. We report two cases of B cell colonic lymphoma occurring in two patients who had a left-sided ulcerative colitis for 7 and 24 years respectively. The diagnosis was made during surgery in one case and at colonoscopy in the other. Complete remission was achieved after surgery and chemotherapy with a 8-year and 15-month follow-up respectively.