Mucosa-associated Lymphoid Tissue Lymphoma Patients Research Articles

Clinical characteristics and prognostic analysis of 34 patients with primary thyroid lymphoma

Objective: To investigate the clinical characteristics, diagnosis, treatment, and prognosis of primary thyroid lymphoma (PTL) . Methods: A retrospective analysis was conducted on the clinical and pathological data of 34 newly diagnosed PTL patients admitted to Beijing Tongren Hospital from September 2010 to February 2023. The Kaplan-Meier survival curve and Log-rank test were used for survival analysis, and the Cox regression model was applied for univariate analysis of prognostic factors. Results: All 34 PTL patients presented with cervical mass as the initial clinical manifestation. There were 9 males and 25 females. The pathological diagnosis was diffuse large B-cell lymphoma (DLBCL) in 29 patients and mucosa-associated lymphoid tissue (MALT) lymphoma in 5 patients. Among the DLBCL patients, 6 had B symptoms, 17 had an Eastern Cooperative Oncology Group (ECOG) score of ≥2, the Ann Arbor staging was stage Ⅰ-Ⅱ in 21 cases and stage Ⅲ-Ⅳ in 8 cases, the tumor diameter was ≥10 cm in 4 cases, and 14 had concurrent Hashimoto thyroiditis; 27 cases received chemotherapy, with 21 cases achieving complete remission (CR), 2 cases partial remission (PR), and 6 cases of disease progression; the 5-year progression-free survival and overall survival rates were 78.9% and 77.4%, respectively; univariate survival analysis showed that B symptoms, tumor diameter ≥10 cm, and Ann Arbor stage Ⅲ-Ⅳ were significant factors affecting patient prognosis (P<0.05). MALT lymphoma patients were all in stages Ⅰ-Ⅱ, had an ECOG score of 0-1, and were without B symptoms. All patients underwent surgical resection, with 4 cases achieving CR and 1 case PR. Conclusion: PTL is more common in females with concurrent Hashimoto thyroiditis, with the majority of pathological types being B-cell lymphoma. The main treatment is chemotherapy, supplemented by radiotherapy and surgery, and the prognosis is relatively favorable.

The prognosis of patients with primary pulmonary mucosa-associated lymphoid tissue lymphoma: Treated with surgery or chemotherapy?

The goal of this project was to evaluate the effect of surgical treatment and the long-term survival of patients with staged IE/IIE pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. From January 2004 to December 2018, we retrospectively analysed 96 patients diagnosed with low-stage primary pulmonary MALT lymphoma according to the modified Ann Arbor staging system (IE/IIE). We compared the outcomes of different treatment modalities for staged IE/IIE MALT lymphoma. Progression-free survival (PFS) and overall survival were estimated using Kaplan-Meier curves, and the differences were compared using the log-rank test. The Cox proportional hazards model was used in this study. The median PFS time of low-staged MALT lymphomas was 118 months. The overall survival and PFS of the radical surgery group and the biopsy + chemotherapy group suggested no significant difference (P = 0.63, P = 0.65). Patients positive for Blc-2 and Ki-67 suffered from a compromised PFS (P = 0.023, P = 0.006). The Cox adjusted proportional hazards model analysis suggested that surgical procedures were not protective factors for patients with low-staged (IE/IIE) pulmonary MALT lymphoma, whereas being positive for Blc-2 and Ki-67 was a risk factor for patients with low-staged pulmonary MALT lymphoma (hazard ratio: 9.567; P = 0.044; hazard ratio: 6.042, P = 0.049). Our findings suggested that for staged IE/IIE pulmonary MALT lymphoma, radical surgical resection did not provide a survival benefit compared with chemotherapy after biopsy. Thus, radical surgery may be avoided unless biopsy is necessary for a diagnosis that requires sublobar resection. For those lesions that were Blc-2- or Ki-67-positive, compromised survival may be suggested.

Association of Treatment Disparities and Primary Sites with the Survival of Non-Gastric Early-Stage MALT Lymphoma

To investigate the association between utilization of radiotherapy and differences in survival among patients with non-gastric early-stage mucosa-associated lymphoid tissue (MALT) lymphoma at different primary sites. A total of 5,995 patients with non-gastric early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Mediation analyses were conducted to quantitatively determine the proportion of the relationship between OS and primary sites mediated by radiotherapy. Inverse probability of treatment weighting (IPTW) was conducted to control confounding factors affecting treatment choice. After controlling for confounding factors, pulmonary MALT lymphoma was found to have the highest rate of omitted radiotherapy compared to other primary sites, including ocular adnexa, salivary gland, skin and other sites. Multivariate Cox analyses showed that lung MALT lymphoma patients had the lowest 10-year OS rate of 58.3%, while skin MALT lymphoma patients had the highest 10-year OS rate of 81.6%. After balancing confounding factors that potentially affected the choice of radiotherapy using IPTW, differences in utilization of radiotherapy explained a significant portion of the poor prognosis of lung MALT lymphoma (35.6%, P = 0.002) and the favorable prognosis of skin MALT lymphoma (6.1%, P <0.001). Differences in survival among patients with non-gastric early-stage MALT lymphoma at different primary sites are associated with disparities in the utilization of radiotherapy.

Radiomics analysis of T1WI and T2WI magnetic resonance images to differentiate between IgG4-related ophthalmic disease and orbital MALT lymphoma

BackgroundPreoperative differentiation between IgG4-related orbital disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma has a significant impact on clinical decision-making. Our research aims to construct and evaluate a magnetic resonance imaging (MRI)-based radiomics model to assist clinicians to better identify IgG4-ROD and orbital MALT lymphoma and make better preoperative medical decisions.MethodsMR images and clinical data from 20 IgG4-ROD patients and 30 orbital MALT lymphoma patients were classified into a training (21 MALT; 14 IgG4-ROD) or validation set (nine MALT; six IgG4-ROD). Radiomics features were collected from T1-weighted (T1WI) and T2-weighted images (T2WI). Student’s t-test, the least absolute shrinkage and selection operator (LASSO) and principal component analysis (PCA) were conducted to screen and select the radiomics features. Support vector machine (SVM) classifiers developed from the selected radiomic features for T1WI, T2WI and combined T1WI and T2WI were trained and tested on the training and validation set via five-fold cross-validation, respectively. Diagnostic performance of the classifiers were evaluated with area under the curve (AUC) readings of the receiver operating characteristic (ROC) curve, and readouts for precision, accuracy, recall and F1 score.ResultsAmong 12 statistically significant features from T1WI, four were selected for SVM modelling after LASSO analysis. For T2WI, eight of 51 statistically significant features were analyzed by LASSO followed by PCA, with five features finally used for SVM. Combined analysis of T1WI and T2WI features selected two and four, respectively, for SVM. The AUC values for T1WI and T2WI classifiers separately were 0.722 ± 0.037 and 0.744 ± 0.027, respectively, while combined analysis of T1WI and T2WI classifiers further enhanced the classification performances with AUC values ranging from 0.727 to 0.821.ConclusionThe radiomics model based on features from both T1WI and T2WI images is effective and promising for the differential diagnosis of IgG4-ROD and MALT lymphoma. More detailed radiomics features and advanced techniques should be considered to further explore the differences between these diseases.

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study.

The present study sought to understand how clinical factors and inflammatory biomarkers affected the prognosis of mucosa-associated lymphoid tissue (MALT) lymphoma and develop a predictive nomogram to assist in clinical practice. We conducted a retrospective study on 183 cases of newly diagnosed MALT lymphoma from January 2011 to October 2021, randomly divided into two groups: a training cohort (75%); and a validation cohort (25%). The least absolute shrinkage and selection operator (LASSO) regression analysis was combined with multivariate Cox regression analysis to construct a nomogram for predicting the progression-free survival (PFS) in patients with MALT lymphoma. To evaluate the accuracy of the nomogram model, the area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used. The PFS was significantly associated with the Ann Arbor Stage, targeted therapy, radiotherapy, and platelet-to-lymphocyte ratio (PLR) in MALT lymphoma. These four variables were combined to establish a nomogram to predict the PFS rates at three and five years. Importantly, our nomogram yielded good predictive value with area under the ROC curve (AUC) values of 0.841 and 0.763 in the training cohort and 0.860 and 0.879 in the validation cohort for the 3-year and 5-year PFS, respectively. Furthermore, the 3-year and 5-year PFS calibration curves revealed a high degree of consistency between the prediction and the actual probability of relapse. Additionally, DCA demonstrated the net clinical benefit of this nomogram and its ability to identify high-risk patients accurately. The new nomogram model could accurately predict the prognosis of MALT lymphoma patients and assist clinicians in designing individualized treatments.

Comprehensive Analysis of Gene Expression Profiling to Explore Predictive Markers for Eradication Therapy Efficacy against Helicobacter pylori-Negative Gastric MALT Lymphoma

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein-protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.

Identifying tumor antigens and immune subtypes of gastrointestinal MALT lymphoma for immunotherapy development.

MALT lymphoma is an extranodal B-cell lymphoma of the marginal zone of mucosa-associated lymphoid tissue (MALT), caused by malignant transformation of B-cells in the marginal zone. In this work, we aim to explore the potential relationship between MALT lymphoma and DLBCL. Vaccines derived from messenger ribonucleic acid (mRNA) may provide satisfactory results. Despite being a promising treatment option, immunotherapy isn't widely used in treating renal cell carcinoma, as only a few patients respond to the treatment. The Cancer Genome Atlas (TCGA) analysis revealed gene expression profiles and clinical information. Antigen-presenting cells infiltrated the immune system using TIMER tool (http://timer.cistrome.org/). GDSC (Genomics of Drug Sensitivity in Cancer) data were used to estimate drug sensitivity. Immune-related genes were associated with a better prognosis in MALT lymphoma patients and higher levels of antigen-presenting cells. There is a significant relationship between these immune subtypes and immunological checkpoints, immunogenic cell death regulators, and prognostic variables for MALT lymphoma patients. In this study, we provide a theoretical foundation for the development of mRNA vaccines and suggest that KLHL14 could potentially be used as antigens to develop mRNA vaccines for MALT lymphoma.

First in Human (FIH) Study of GFH009, a Highly Selective Cyclin-Dependent Kinase 9 (CDK9) Inhibitor, in Patients with Relapsed/Refractory (r/r) Hematologic Malignancies

Background: The key roles of cyclin-dependent kinases in cell proliferation and various aspects of transcription have led to efforts to develop CDK inhibitors as cancer therapeutics. Positive transcription elongation factor b (PTEFb) consisting of Cyclin T and CDK9 is a key regulator of transcription in cancer cells. It is vital for transcription of short-lived gene products, such as MYC and MCL-1, that maintain cancer cell survival. GFH009 is a potent and highly selective CDK9 inhibitor. Here we report preliminary safety and efficacy data from the FIH study of GFH009 in patients with r/r hematologic malignancies (NCT04588922). Methods: This is a phase I, multicenter, dose-escalation trial of GFH009 enrolling patients with relapsed/refractory acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) or lymphoma. The Bayesian optimal interval (BOIN) design is employed in the dose escalation cohorts of 3-6 patients. In the first part of the trial, GFH009 was administered intravenously over 30-60 minutes twice per week. The primary endpoint was to evaluate the safety of GFH009 measured by adverse events using common terminology criteria for adverse event (CTCAE) v5.0 and dose limiting toxicities (DLTs). Disease responses were evaluated using Lugano (2014) for lymphoma, IWG criteria (2003) for AML, and iwCLL (2018) for CLL/SLL. Blood samples were collected and analyzed for pharmacokinetics (PK) and pharmacodynamics (PD). Results: As of 15 July 2022, a total of 46 patients were screened, and 30 received at least one dose of GFH009 as monotherapy, including 16 lymphoma patients in 2.5, 4.5, 9 and 15 mg dose cohorts and 14 AML patients in 9, 15, 22.5 and 30 mg dose cohorts. The median age was 52 (range 18-73), and 53% were male. Nine patients (30%) discontinued treatment due to disease progression, eight (27%) due to subjects’ decision and six (20%) due to lack of efficacy. No DLTs were observed to date. The most common drug related AEs were white blood cell decreased [20.0% (6/30), 6.7% (2/30) of which was ≥ G3], neutrophil count decreased [16.7% (5/30), 6.7% (2/30) ≥ G3] and anemia [13.3% (4/30), 3.3% (1/30) ≥ G3]. G3/G4 treatment emergent AEs recorded in >10% of patients included anemia, white blood cell decreased, platelet count decreased, neutrophil count decreased and pneumonia. The total of 12 serious adverse events (SAEs) occurred in 11 subjects, three of which were drug related. All the drug related SAEs were G3 pneumonia. One death was recorded due to disease progression of AML. Four lymphoma patients (3 in 4.5 mg and 1 in 9 mg) achieved stable disease (SD) including one peripheral T cell lymphoma (PTCL), one diffuse large B-cell lymphoma, one Hodgkin lymphoma and one mucosa-associated lymphoid tissue (MALT) lymphoma. The patient with PTCL at 9 mg dose had 62% decrease in sum of the product of the perpendicular diameters for multiple lesions (SPD) based on computed tomography (CT). The duration of treatment of the PTCL patient and MALT lymphoma patient was 12 weeks and 41 weeks respectively and they continue treatment at the cut-off date. No objective response was observed in AML patients, but two patients, one at 9 mg dose level and one at 15 mg dose level, had decrease of bone marrow blasts ≥ 50%. PK exposure increased in a dose-proportional manner as increasing dose from 2.5 mg to 22.5 mg. The mean half-life ranged from 14.9 h to 17.7 h. Pharmacodynamic assessment of MYC and MCL1 mRNA in whole blood showed post-dose reduction of short half-life mRNA transcripts at higher dose levels. Conclusion: GFH009 as monotherapy is well tolerated at the tested doses and has shown clinical activity in patients with r/r lymphoma. The dose escalation in patients with AML and lymphoma is ongoing. Different dosing regimens are currently being explored for potentially better inhibition on the target. GFH009 add-back in patients refractory to or relapsed while on venetoclax and hypomethylating agents is planned in AML patients. Key words: cyclin-dependent kinases, CDK9 inhibitor, MYC, MCL-1, AML, lymphoma, CLL, SLL, PTCL, MALT lymphoma

NOT YOUR USUAL PULMONARY NODULE: CASE OF PULMONARY MALTOMA

NOT YOUR USUAL PULMONARY NODULE: CASE OF PULMONARY MALTOMA

Evaluation of Orbital Lymphoproliferative and Inflammatory Disorders by Gene Expression Analysis.

Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000–2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.

Influence of age on long-term net survival benefit for early-stage MALT lymphomas treated with radiotherapy: A SEER database analysis (2000–2015)

BackgroundGiven the lower incidence of lymphoma-related death but higher background mortality in patients with early-stage mucosa-associated lymphoid tissue (MALT) lymphoma, it is critically important to examine how age affects a treatment’s survival benefit. Methods9,467 patients with early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000–2015 were extracted and analyzed. Primary therapy was classified as radiotherapy (n = 3,407), chemotherapy (n = 1,294), and other/unknown treatments including observation (n = 4,766). Inverse probability of treatment weighting (IPTW) was conducted to balance baseline characteristics between groups. Relative survival (RS), standardized mortality ratio (SMR), and transformed Cox regression were conducted to compare survival differences between treatment modalities by controlling for the background mortality. Radiotherapy–age interaction was examined. ResultsAcross age-groups, early-stage MALT lymphoma patients were at lower risk of lymphoma-related death than death due to other causes. The 10-year overall survival (OS, 73.8 %) and RS (96.6 %) rates were significantly higher, and the SMR (1.14) significantly lower, with radiotherapy than with chemotherapy (OS, 61.7 %; RS, 86.4 %; SMR, 1.54; P < 0.001) or other/unknown treatments (OS, 61.1 %; RS, 87.2 %; SMR, 1.41; P < 0.001). By multivariable analysis and IPTW, radiotherapy remained an independent predictor of better RS (HR 0.81, 95 %CI, 0.73–0.89; P < 0.001). A significant interaction between age and radiotherapy was identified for both RS (Pinteraction = 0.016) and OS (Pinteraction = 0.024), indicating greater benefit in young adults. ConclusionRadiotherapy was associated with significantly better survival in early-stage MALT lymphoma, especially in young adults.

Effects ofHelicobacter pyloriinfection in gastrointestinal tract malignant diseases: From the oral cavity to rectum

Helicobacter pylori (H. pylori) has infected approximately fifty percent of humans for a long period of time. However, improvements in the public health environment have led to a decreased chance of H. pylori infection. However, a high infection rate is noted in populations with a high incidence rate of gastric cancer (GC). The worldwide fraction of GC attributable to H. pylori is greater than 85%, and a high H. pylori prevalence is noted in gastric mucosa-associated lymphoid tissue lymphoma patients. These results indicate that the majority of GC cases can be prevented if H. pylori infection is eliminated. Because H. pylori exhibits oral-oral or fecal-oral transmission, the relationship between this microorganism and other digestive tract malignant diseases has also attracted attention. This review article provides an overview of H. pylori and the condition of the whole gastrointestinal tract environment to further understand the correlation between the pathogen and the host, thus allowing improved realization of disease presentation.

Long-Term Clinical Outcomes of Gastric MALT Lymphoma: A Nationwide Multicenter Study in Korea.

BackgroundTreatment recommendations for gastric mucosa-associated lymphoid tissue (MALT) lymphoma are based on case series and expert opinions. Only a few previous studies have focused on the long-term outcomes of gastric MALT lymphoma, especially according to stage.MethodsPatients diagnosed with gastric MALT lymphoma from January 2000 to December 2018 at nine university hospitals in Korea were included. Clinical data of medical history, endoscopic features, histological diagnosis, results of Helicobacter pylori (H. pylori) testing, stage, treatment conditions, and outcomes were collected.ResultsA total of 1,163 patients was enrolled, and 97.6% (n=1,038) of patients were diagnosed as stage IE. 10-year overall survival (OS) for the entire population was 99.1% and was better for patients in stage IE compared with patients in stage III/IV (p=0.002). The 10-year OS for H. pylori-positive patients was better than that of H. pylori-negative patients (p=0.022). Multivariate analyses revealed initial stage III/IV as a prognostic factor associated with over-all survival.ConclusionThe majority of gastric MALT lymphoma patients are diagnosed at an early localized stage in Korea. The overall survival rate of gastric MALT lymphoma is excellent and is associated with the initial stage of the disease.

Evaluation of HRCT for the Differential Diagnosis of Pneumonia-Like Consolidation Pattern of Pulmonary MALT Lymphoma from Lobar Pneumonia.

PurposeTo assess the performance of high-resolution computed tomography (HRCT) in discriminating the consolidation pattern of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma from lobar pneumonia.Patients and MethodsThis retrospective study comprised 26 patients with pathologically confirmed consolidation pattern of pulmonary MALT lymphoma (12 men and 14 women; mean age, 59.4±12.1 years) and 36 patients with lobar pneumonia confirmed by body fluids or respiratory secretion culture (16 men and 20 women; mean age, 41.8±26.3 years). Two radiologists independently evaluated the CT images. The effectiveness of these variables in distinguishing lobar pneumonia from MALT lymphoma was analyzed using logistic regression analysis.ResultsThe average age of lobar pneumonia patients was younger than that of MALT lymphoma patients (p=0.002). The respiratory symptom was more common in lobar pneumonia than MALT lymphoma (p=0.002). Signs of bronchiectasis within the consolidation and bulging of interlobar fissure occurred significantly more often in MALT lymphoma than pneumonia (69.2% vs 11.1%, p<0.0001; 46.2% vs 19.4%, p=0.024). We used the predictors with p<0.05 (age, respiratory symptoms, bronchiectasis, and bulging of interlobar fissure) to construct a logistic regression model. The area under curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, specificity, and accuracy were 0.891, 84.21%, 83.33%, 88.89%, 76.92%, and 83.87% for discriminating lobar pneumonia from MALT lymphoma.ConclusionMiddle-aged, presence of mild clinical symptoms, bronchiectasis and bulging of the interlobar fissure on chest CT images are potential markers to distinguish pulmonary MALT lymphoma from lobar pneumonia.

Gastric microbiota in patients with Helicobacter pylori-negative gastric MALT lymphoma.

To investigate the mucosal microbiota in the stomach of patients with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma by means of metagenomic analysis.Although some gastric MALT lymphomas are associated with the presence of H. pylori, other gastric MALT lymphomas occur independently of H. pylori infection. The pathogenesis of H. pylori-negative MALT lymphoma remains unclear.Mucosal biopsy specimens were collected from the gastric body from 33 MALT lymphoma patients with gastric lesions, including both H. pylori-infection naïve patients and posteradication patients, as well as 27 control participants without H. pylori infection or cancer. Subsequently, the samples were subjected to 16S rRNA gene sequencing. Quantitative insights into microbial ecology, linear discriminant analysis effect size, and phylogenetic investigation of communities by reconstruction of unobserved states softwares were used to analyze the participants’ microbiota.H. pylori-negative MALT lymphoma patients had significantly lower alpha diversity (P = .04), compared with control participants. Significant differences were evident in the microbial composition (P = .04), as determined by comparison of beta diversity between the 2 groups. Taxonomic composition analysis indicated that the genera Burkholderia and Sphingomonas were significantly more abundant in MALT lymphoma patients, while the genera Prevotella and Veillonella were less abundant. Functional microbiota prediction showed that the predicted gene pathways “replication and repair,” “translation,” and “nucleotide metabolism” were downregulated in MALT lymphoma patients.H. pylori-negative MALT lymphoma patients exhibited altered gastric mucosal microbial compositions, suggesting that altered microbiota might be involved in the pathogenesis of H. pylori-negative MALT lymphoma.

CXCR4 PET/MRI for follow-up of gastric mucosa–associated lymphoid tissue lymphoma after first-line Helicobacter pylori eradication

AbstractPosttreatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G protein–coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate positron emission tomography (PET) with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow up biopsies for assessment of residual disease (noncomplete remission [CR]) after first-line Helicobacter pylori eradication. Forty-six post–H pylori eradication [68Ga]Pentixafor–PET/magnetic resonance imaging (MRI) examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor–PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard and showed CR in 6 cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive values of [68Ga]Pentixafor–PET for detection of residual gastric MALT lymphoma at follow-up were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r = 0.51 and r = 0.52 (P = .008 and P = .006). In summary, CXCR4 imaging with [68Ga]Pentixafor–PET may represent a promising test for assessment of residual gastric MALT lymphomas after H pylori eradication.

Serum Immunoglobulin Paraprotein Associated with Inferior Progression Free Survival in Patients with Mucosa-Associated Lymphoid Tissue Lymphoma

IntroductionIn order to investigate the clinical and certain laboratory features of mucosa-associated lymphoid tissue (MALT) lymphoma patients with immunoglobulin (Ig) paraproteinemia and identify the potential prognostic value of Ig paraproteinemia in MALT lymphoma.Methodswe reviewed the medical records of all patients diagnosed with MALT lymphoma and performed Ig paraprotein test at the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital from April 2010 to December 2016. A total of 115 patients were diagnosed with MALT lymphoma, of which 78 patients had been tested for serum Ig paraprotein. The correlations between serum Ig paraprotein and other prognostic factors were analyzed. Univariate and cox regression analyses were used to assess associations between survival time and potential risk factors.ResultsAmong 78 MALT lymphoma cases, 16 (20.5%) had Ig paraproteinemia, mostly IgM-K (5, 31.3%), followed by IgM-L, IgG-L, IgM-K/IgA-K, IgA-L, IgM-L/IgA-L. According to the correlation analysis, male (P=0.022), advanced Ann Arbor stage (P <0.001), lymph nodes involvement (P <0.001), high level of serum β2-microglobulin (P <0.001) and low level of serum albumin (P= 0.001) were significantly related to the presence of Ig paraproteinemia. Survival analysis illustrated that patients with IgM paraproteinemia had significantly shorter progression-free survival (PFS) (P=0.005) than those without IgM paraproteinemia (Figure 1). Cox regression analysis showed that IgM paraproteinemia was an independent prognostic factor for PFS of MALT lymphoma patients (P=0.037). Risk stratification based on IPI together with IgM paraproteinemia could divide patients with MALT lymphoma into four groups and better identify high or low risk of PFS (P <0.0001) and OS (P <0.0001) in MALT lymphoma patients (Figure 2).ConclusionMALT lymphoma patients with Ig paraproteinemia represent a subgroup with inferior PFS. Serum Ig paraprotein might be applied for the assessment of prognosis in patients with MALT lymphoma. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

IELSG-38: A Phase II Study of Chlorambucil in Combination with Rituximab Followed By Maintenance Therapy with Subcutaneous Rituximab in Patients with Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT)

IELSG-38: A Phase II Study of Chlorambucil in Combination with Rituximab Followed By Maintenance Therapy with Subcutaneous Rituximab in Patients with Extranodal Marginal Zone B-Cell Lymphoma of Mucosa Associated Lymphoid Tissue (MALT)

Development and Validation of a Prognostic Nomogram for Gastric Marginal Zone Lymphoma: a Surveillance, Epidemiology and End Results-based population Study

Aim: This initial study was conducted with the aim of constructing an accurate nomogram for gastric marginal zone lymphoma patients. Methods: Data from4414patients diagnosed with gastric mucosa-associated lymphoid tissue lymphoma from 2004 to 2015 were retrieved from the Surveillance, Epidemiologyand End Resultsdatabase. Multivariate analyses were conducted for the construction of the nomogram. Results: Age, sex, race, marital status, Ann Arbor stageand radiotherapy were significantly associated with overall survival, while age, marital status, Ann Arbor stage, surgery, chemotherapyand radiotherapy were independent prognostic predictors of cause-specific survival. Stratified analysis indicated that radiotherapy alone resulted in better overall survival and cause-specific survival than chemotherapy alone. However, the present study also has several limitations; for example, patients'Helicobacterpylori infection statusand the chemotherapy regimen used were unknown. Conclusion: This study constructed and validated an accurate prognostic nomogram for gastric mucosa-associated lymphoid tissue lymphoma patients.

First Line Systemic Treatment for MALT Lymphoma-Do We Still Need Chemotherapy? Real World Data from the Medical University Vienna.

Simple SummaryThe Division of Oncology at the Medical University Vienna is a tertiary referral center for extranodal lymphoma of mucosa-associated lymphoid tissue (MALT)-type and currently oversees more than 400 patients with this diagnosis, including a relevant percentage of patients being treated with systemic therapies. In the current analysis, we present response and long-term data of 159 patients (not eligible for Helicobacter pylori eradication) treated upfront with systemic treatment focusing on chemotherapy- versus immunotherapy-based strategies. We show that despite higher response and complete remission rates for chemo- versus immunotherapy, there appears to be no difference in progression-free survival, thus suggesting comparable long-term results. Considering the biological background of MALT lymphoma—and particularly its high dependence on the tumor microenvironment—but also the favorable toxicity profile of assessed immunomodulatory agents such as IMiD lenalidomide or macrolide clarithromycin, we suggest that these data support further investigation of chemotherapy-free treatment concepts for MALT lymphoma.There is no clear therapeutic algorithm for mucosa-associated lymphoid tissue (MALT) lymphoma beyond Helicobacter pylori eradication and while chemotherapy-based regimens are standard for MALT lymphoma patients in need of systemic treatment, it appears of interest to also investigate chemotherapy-free strategies. We have retrospectively assessed MALT lymphoma patients undergoing upfront systemic treatment, classified either as chemotherapy (=classical cytostatic agents +/− rituximab) or immunotherapy (=immunomodulatory agents or single anti-CD20 antibodies) at the Medical University Vienna 1999–2019. The primary endpoint was progression-free survival (PFS). In total, 159 patients were identified with a median follow-up of 67 months. The majority of patients had extragastric disease (80%), but we also identified 32 patients (20%) with Helicobacter pylori negative or disseminated gastric lymphoma. Regarding the type of first line treatment and outcome, 46% (74/159) received a chemotherapy-based regimen and 54% (85/159) immunotherapy including IMiDs lenalidomide/thalidomide (37%), anti-CD20-anitbodies rituximab/ofatumumab (27%), macrolides clarithromycin/azithromycin (27%) and proteasome inhibitor bortezomib (9%). Median PFS was 76 months (95%CI 50–102), and while the overall response (90% vs. 68%, p < 0.01) and the complete remission rate (75% vs. 43%, p < 0.01) was significantly higher for chemotherapy, there was no difference in PFS between chemotherapy (median 81 months, 95%CI 47–116) and immunotherapy (76 months, 95%CI 50–103, p = 0.57), suggesting comparable long-term outcomes. To conclude, our data show higher response rates with chemo- compared to immunotherapy, but this did not translate into a superior PFS. Given the biological background of MALT lymphoma, and the favorable toxicity profile of novel immunomodulatory treatments, this should be further investigated.