Plasmacytic differentiation in MALT lymphomas following treatment with rituximab

Mucosa-associated lymphoid tissue (MALT) lymphomas are B cell neoplasms which commonly affect the gastrointestinal (GI) tract. Gastrointestinal MALT lymphomas rarely show plasmacytic differentiation (PCD), and limited data on the potential influence of the anti-CD20 antibody rituximab (R) on PCD exist in the current literature. We have retrospectively analyzed patients with GI MALT lymphomas treated with R-containing regimens because restaging is routinely performed by repeated biopsies with pathohistological response assessment. Twenty-one patients with GI MALT lymphoma were identified to have undergone R-containing therapy. In 19 patients, the lymphoma originated in the stomach, while the colon was the primarily affected organ in two cases. Four patients received R monotherapy and 17 combinations of R with various chemotherapeutic agents. Only two patients with gastric MALT lymphoma had PCD before initiation of therapy. In 7 of 19 patients (37%) without PCD at diagnosis, restaging revealed PCD after or while on treatment with R-containing regimens. Out of these seven patients, only one patient had a complete response as opposed to 10/12 without PCD. These data suggest that R or R-containing treatment regimens may not optimally eradicate the plasma cell component and thus lead to PCD in patients with GI MALT lymphoma. In view of this, rebiopsy and histological re-assessment appear mandatory in patients failing/relapsing after R-containing regimens.     

Diagnosis and treatment of gastric MALT lymphoma

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma represents approximately 40% of gastric lymphomas, and its incidence is increasing. An early diagnosis for gastric MALT lymphoma is important, but not easy due to non-specific symptoms and endoscopic findings. Diagnosis is based on the histopathologic evaluation of multiple, deep and repeated biopsies taken from normal and any abnormal appearing sites of the stomach. In addition, the presence of Helicobacter pylori (H. pylori) infection must be determined to determine therapeutic approach. Endoscopic ultrasonography (EUS) is essential for the evaluation of regional lymph nodes and the depth of tumor invasion in the gastric wall, for predicting response to H. pylori eradication, and for monitoring tumor regression or recurrence. The eradication of H. pylori is recommended as an initial treatment for low-grade gastric MALT lymphoma with H. pylori infection. Both radiation therapy and chemotherapy are suitable alternative options for H. pylori-negative, refractory, or high-grade gastric MALT lymphoma. But, the role of surgery is diminishing. After treatment, strict endoscopic regular follow-up including EUS is recommended with multiple biopsies. However, controversy remains regarding the best diagnosis, treatment and follow-up strategy for this disease.     

Primary duodenal lymphoma: successful rituximab treatment and evaluation by FDG-PET

A 68-year-old woman has been suffering from chronic inactive hepatitis with hepatitis C virus. Upper endoscopic and pathological findings revealed the typical features of duodenal follicular lymphoma and Helicobacter pylori (H. pylori) infection with her stomach was confirmed by the histological and cultural examinations. No other abnormal findings suspicious for tumor formation were observed by the various examinations such as computed tomography, abdominal ultrasonography and 67Ga-citrate scintigraphy. Primary duodenal follicular lymphoma: stage I according to the Modified Ann Arbor classification was diagnosed by these procedures. The eradication therapy was effective for the withdrawal of H. pylori but not for lymphoma. Four months later, abdominal ultrasonography and magnetic resonance imaging showed the progression of abdominal lymph nodes. Positron emission tomography (PET) with 18F-fluorodeoxyglucose showed radioactive uptake in mesenteric lymph nodes. Systemic chemotherapy using rituximab was started, since these findings suggested the clinical progression from stage I to II2. After 2 courses of the therapy, endoscopic and histological improvement of duodenal lymphoma and lower uptake in mesenteric lymph nodes suggested us complete remission. Rituximab may be useful for duodenal follicular lymphoma and PET with 18F-fluorodeoxyglucose has a potential value for the evaluation of mesenteric lymph nodes spread.     

Risk factors for late-onset neutropenia after rituximab treatment of B-cell lymphoma

Abstract

Objectives

Late-onset neutropenia after rituximab (RTX) therapy (R-LON) has been widely reported, but clinical studies on a large number of cases are limited. In this study, we aimed to investigate the incidence and risk factors of R-LON.

Patients and methods

In this study, we retrospectively analyzed data of 213 enrolled B-cell lymphoma patients (male 114; female 99) treated with RTX at a single institution. R-LON was defined as otherwise unexplained grade III–IV neutropenia after RTX. The median age of the patients was 62 years, and 129 of them were initially diagnosed at advanced stages (stage III–IV).

Results

R-LON occurred in 19 patients within a median of 121 (range, 49–474) days after the last RTX administration. The 1-year cumulative incidence was 9.0%. On univariate analysis, older age (>60 years), advanced stage, and purine analog or methotrexate administration were significant or borderline significant risk factors for R-LON, whereas sex, disease type, bone marrow invasion, combination with cytotoxic chemotherapeutic drugs, intensified therapy (compared with R-CHOP), prior autologous transplantation, and repeated RTX administration were not. On multivariate analysis, older age (hazard ratio (HR), 2.95) and advanced stage (HR, 3.56) were significant risk factors. Treatment with granulocyte colony-stimulating factor was feasible in grade IV R-LON patients with high risk of infection.

Discussion and conclusion

Careful follow-up is therefore necessary after B-cell lymphoma treatment, especially in high-risk patients with advanced disease or of older age.     

Predictive factors for regression of gastric MALT lymphoma after anti-Helicobacter pylori treatment

BACKGROUND AND AIMS: Discrepant remission rates (41-100%) have been reported for patients with localised low grade gastric mucosa associated lymphoid tissue (MALT) lymphoma after eradication of Helicobacter pylori. The aim of this study was to explain these discrepancies and to determine the predictive factors of gastric lymphoma regression after anti- H pylori treatment. PATIENTS AND METHODS: Forty six consecutive patients with localised gastric MALT lymphoma (Ann Arbor stages I(E) and II(E)) were prospectively enrolled. All had gastric endoscopic ultrasonography and H pylori status assessment (histology, culture, polymerase chain reaction, and serology). After anti-H pylori treatment, patients were re-examined every four months. RESULTS: Histological regression of the lymphoma was complete in 19/44 patients (43%) (two lost to follow up). Median follow up time for these 19 responders was 35 months (range 10-47). No regression was noted in the 10 H pylori negative patients. Among the 34 H pylori positive patients, the H pylori eradication rate was 100%; complete regression rate of the lymphoma increased from 56% (19/34) to 79% (19/24) when there was no nodal involvement at endoscopic ultrasonography. There was a significant difference between the response of the lymphoma restricted to the mucosa and other more deep seated lesions (p<0.006). However, using multivariate analysis, the only predictive factor of regression was the absence of nodal involvement (p<0.0001). CONCLUSION: In H pylori positive patients with localised gastric MALT lymphoma, carefully evaluated and treated without any lymph node involvement assessed by endoscopic ultrasonography, complete remission of lymphoma was reached in 79% of cases.     

MALT lymphoma of the larynx

We describe a 25-year-old Japanese woman with a MALT-type lymphoma of the larynx. She presented with a one-year history of hoarseness and increasing pain in the larynx. A small tumor was found on the left side of the false cord, and was biopsied under laryngoscopy in the department of laryngology. Histological examination showed the presence of centrocyte-like cells infiltrating the submucosa and forming lymphoepithelial lesions. The neoplastic cells were CD20+, CD79a+, and CD5-. Staining for keratin with CAM 5.2 highlighted the infiltrated epithelium. Analysis of DNA extracted from the biopsy specimen showed a clonal immunoglobulin heavy chain gene rearrangement, confirming the histological diagnosis of extranodal marginal zone B-cell lymphoma of the MALT type. To our knowledge, only 6 cases of MALT lymphoma of the larynx have been reported previously. The presence of MALT lymphomas arising at rare sites emphasizes the importance of accurate diagnosis and appropriate clinical management. Patients require careful periodic evaluation in order to time the therapy appropriately, and to avoid overtreatment and complications of therapy, including secondary malignancies.     

Successful treatment of splenic lymphoma with villous lymphocytes by rituximab and laparoscopic splenectomy

We report on a case of splenic lymphoma with villous lymphocytes (SLVL) which responded well to rituximab. A 50-year-old man was admitted because of splenomegaly. Abnormal lymphocytes of B cell lineage with moderately basophilic cytoplasm and unevenly distributed villi (villous cells) were found, both in the peripheral blood and bone marrow. CHOP and CHOP-E were performed, without any remarkable change in the size of the spleen. However, after infusion of rituximab (375 mg/m2, once weekly for 2 weeks), there was a marked reduction of the spleen size and the number of circulating villous cells. Splenectomy was performed afterwards, followed by 2 cycles of rituximab infusion. The patient is now followed on an outpatient basis without any sign of relapse.     

胃粘膜相关淋巴样组织淋巴瘤抗H.Pylori治疗的有效预测因子

胃粘膜相关淋巴样组织(MALT)型结外边缘区B细胞淋巴瘤发病机制主要与幽门螺杆菌(H.pylori)感染有关,目前认为根治H.pylori治疗已成为胃粘膜相关淋巴样组织淋巴瘤的一线治疗。然而,抗H.pylori治疗不能使胃MALT淋巴瘤100%完全缓解,即使完全缓解后仍有复发的可能。随着研究的深入,哪些患者更能从抗H.pylori治疗中受益,抗H.pylori治疗后随访是目前研究的热点。此文对胃MALT淋巴瘤与H.pylori的关系,抗H.pylori治疗的有效预测、随访作一综述。     

Primary MALT lymphoma of the kidney

A primary mucosa associated lymphoid tissue tumor (MALT) of the kidney in a 50-year-old man who suffered from on therapy resistant high blood pressure over 15 years period is presented. A mass in the right kidney (6x5x3 cm) during routine check up was discovered on ultrasonography and confirmed on CT scan and NMR. The patient was submitted to nephrectomy. A mass involving kidney, pyelon and upper part of the ureter was found. Histology showed low grade non-Hodgkin B-cell lymphoma of MALT type. The neoplastic cells were positive for monoclonal antibodies CD20, CD79alpha, surface and cytoplasmic and IgM immunoglobulins and showed light chain restriction (kappa+). After histology was available, a careful staging was performed. The disease was not found anywhere else. It was concluded that the patient belonged to the stage IE of primary kidney MALT lymphoma. Gastroscopy showed signs of chronic superficial gastritis. Urease test was positive and IgG antibodies against Helicobacter pylori in titer 421 were found as well. Except for Helicobacter pylori no additional therapy was given.     

Cytomegalovirus gastritis after rituximab treatment in a non-Hodgkin''s lymphoma patient

TO THE EDITOR Rituximab is a chimeric monoclonal antibody against CD20 antigen expressed on most B cells and is used for the treatment of malignant lymphomas expressing the CD20 antigen[1].