Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas.

OBJECTIVES: To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. METHODS: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I-IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit. RESULTS: Among 45 consecutively enrolled patients with a median age of 68 years (range 22-86), 26 (58%) were female. Thirty-one patients (69%) with a stage I-II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. CONCLUSIONS: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. ADVANCES IN KNOWLEDGE: This study shows the efficacy of LDRT in the treatment of MALT and MZL.

Prospective Phase II trial of radiation therapy in localised non-gastric marginal zone lymphoma with prospective evaluation of autoimmunity and Helicobacter pylori status: TROG 05.02/ALLG NHL15.

BACKGROUND: This Phase 2 multicentre trial in localised non-gastric marginal zone lymphoma (MZL) evaluated the effectiveness and safety of radiotherapy and documented markers of autoimmunity and Helicobacter pylori infection. PATIENTS AND METHODS: Eligible patients had Stages I and II or paired-organ, non-gastric MZL. Bone marrow evaluation, autoantibody panel, and H. pylori evaluation were mandatory. Involved-field or involved-site radiotherapy was delivered to 24-30.6 Gy. Detected H. pylori infections underwent eradication. RESULTS: Between 2006 and 2014, six centres enrolled 70 patients, and 68 commenced treatment. The median age was 59 (range: 23-84) years, and 31 (46%) were male. Overall, 55 patients had Stage I disease, nine patients had Stage II disease, and four patients had paired organ-confined disease. Involved extranodal sites with three or more cases were orbital (n = 18), conjunctiva (n = 13), lacrimal (n = 8), skin (n = 8), salivary (n = 7), and muscle (n = 4). Eight patients had primary nodal MZL. At the median follow-up of 5 years (range 0.7-9.4), progression-free survival and overall survival were 79% and 95%, respectively. One lymphoma-related death and two in-field failures (after 25 and 30 Gy, respectively) occurred. Distant relapse sites were skin (n = 2), lymph nodes (n = 2), duodenum, stomach, muscle, and conjunctiva (1 each). No paired-organ MZL relapsed. Apart from cataracts (n = 18), only three treatment-related late grade ≥3 adverse events occurred. Autoantibodies or autoimmune events were detected in 26 of 68 patients (38%). H. pylori infection was detected in 15 of 63 patients (24%) tested. Neither autoimmunity nor H. pylori was detected in 27 of 68 patients (40%). CONCLUSIONS: Radiotherapy was a potentially curative treatment with low toxicity in localised non-gastric MZL. Autoimmunity, H. pylori infection or both were detected in 60% of patients.

Rare lymphomas in routine practice - Treatment and outcome in marginal zone lymphoma in the prospective German Tumour Registry Lymphatic Neoplasms.

Owing to its heterogeneity and rarity, management of disseminated marginal zone B-cell lymphoma (MZL) remains largely understudied. We present prospective data on choice of systemic treatment and survival of patients with MZL treated in German routine practice. Of 175 patients with MZL who had been documented in the prospective clinical cohort study Tumour Registry Lymphatic Neoplasms (NCT00889798) collecting data on systemic treatment, 58 were classified as extranodal MZL of mucosa-associated lymphoid tissue (MALT) and 117 as non-MALT MZL. We analyzed the most commonly used first-line and second-line chemo(immuno)therapies between 2009 and 2016 and examined objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and prognostic factors for survival. Compared to patients with MALT MZL, those with non-MALT MZL more often presented with bone marrow involvement (43% vs. 14%), Ann Arbor stage III/IV (72% vs. 57%) and were slightly less often in good general condition (ECOG = 0; 41% vs. 47%). In German routine practice, rituximab-bendamustine for a median of 6 cycles was the most frequently used first-line (76%) and second-line treatment (36%), with no major differences between MZL subtypes. The ORR for patients encompassing any positive response was 81%. For patients with MALT and non-MALT MZL, respectively, 5-years PFS was 69% (95% CI 52%-81%) and 66% (95% CI 56%-75%), 5-years OS 79% (95% CI 65%-89%) and 75% (95% CI 66%-83%). Cox proportional hazards models showed a significantly increased risk of mortality for higher age in all patient groups. Our prospective real world data give valuable insights into the management and outcome of non-selected patients with MZL requiring systemic treatment and can help optimize therapy recommendations.

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 from 4414 patients diagnosed with gastric mucosa-associated lymphoid tissue lymphoma from 2004 to 2015 were retrieved from the Surveillance, Epidemiology and End Results database. Multivariate analyses were conducted for the construction of the nomogram. Results: Age, sex, race, marital status, Ann Arbor stage and radiotherapy were significantly associated with overall survival, while age, marital status, Ann Arbor stage, surgery, chemotherapy and 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' Helicobacter pylori infection status and the chemotherapy regimen used were unknown. Conclusion: This study constructed and validated an accurate prognostic nomogram for gastric mucosa-associated lymphoid tissue lymphoma patients.

Rituximab Monotherapy or in Combination with Bendamustine Is Not Inferior to Rituximab-CHOP Regimen in the Treatment of Patients with Splenic Marginal Zone Lymphoma in the Real Life.

Splenic marginal zone lymphoma (SMZL) is a rare lymphoma belonging to the marginal zone lymphoproliferative disorders. Usually, SMZL occurs with indolent presentation and, when required, the standard of care is represented by rituximab-based regimens. No direct comparison of different rituximab-based combinations and polychemotherapy regimens has been conducted to date. In a monocentric cohort of 68 SMLZ patients, we showed that rituximab in monotherapy or in combination with bendamustine, compared with rituximab associated with the polychemotherapy cycle cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone (CHOP), resulted in a higher 5-year progression-free survival (91.3 ± 9% and 75 ± 15.7% vs. 30.8 ± 12.1%, p < 0.001). Platelets at diagnosis <100 ×109/L (p = 0.034, HR = 4.3) and transformation into diffuse large B-cell lymphoma (p = 0.031, HR = 4.3) were associated with a lower overall survival.

A phase II trial of bendamustine in combination with ofatumumab in patients with relapsed or refractory marginal zone B-cell lymphomas.

Marginal zone lymphomas (MZLs) are indolent yet incurable lymphomas with frequent relapses following therapy. For patients with relapsed/refractory disease, no standard therapies exist. Here we report results of an exploratory phase II study aimed at assessing the efficacy and safety of the alkylator agent bendamustine in combination with the second-generation anti-CD20 monoclonal antibody, ofatumumab, in patients with relapsed or refractory MZL. Patients with MZL and previously treated with at least one line of systemic therapy were eligible. Treatment consisted in bendamustine (90 mg/m2 on days 1 and 2) and ofatumumab (1000 mg on day 1) in 28-day cycles for up to six cycles. Sixteen patients were included in the trial. In one patient, the diagnosis was revised after two cycles of treatment and was excluded from the efficacy analysis. Among 15 patients with MZL, 14 were evaluable for response: the overall and complete response rates were 92.9% and 57.1%, respectively. The median duration of response was 30.4 months (95% confidence interval [CI], 15.5 -not estimable) and 2-years progression-free survival 77% (95% CI, 43%-92%). Fifteen patients (94%) experienced grade 3-4 adverse events. Toxicity was mostly hematological. Neutropenia grade ≥3 was recorded in 27% of patients, lymphocytopenia in 93%, and infections and febrile neutropenia each in 13%. One patient discontinued treatment due to myocardial infarction; no treatment-related deaths occurred. The combination of bendamustine with ofatumumab was active with an acceptable toxicity profile in this small phase II trial and can be considered for further investigation in relapsed/refractory MZL patients.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

A prognostic index for extranodal marginal-zone lymphoma based on the mucosa-associated lymphoid tissue International Prognostic Index and serum ß2-microglobulin levels.

The mucosa-associated lymphoid tissue (MALT) International Prognostic Index (IPI) was recently proposed as a prognostic index for patients with MALT lymphoma. We aimed to investigate the prognostic value of the serum ß2-microglobulin level in the context of MALT-IPI, and we proposed a new prognostic index. Survival outcomes were analysed with regard to ß2-microglobulin level, MALT-IPI, and the new prognostic index in MALT lymphoma patients (n = 571). The validity of the new prognostic index was assessed using an independent cohort (n = 216). Patients with high ß2-microglobulin levels had significantly worse progression-free survival (PFS) and overall survival (OS) outcomes. A high ß2-microglobulin level was independently associated with poor PFS and OS. ß2-microglobulin levels further stratified patients in the MALT-IPI intermediate-risk group in terms of PFS and OS. A new prognostic index based on the MALT-IPI and the ß2-microglobulin level, MALT-IPI-B, was proposed. The MALT-IPI-B was able to stratify patients into subgroups having distinct PFS and OS outcomes in both the training and validation cohorts. MALT-IPI-B enabled the identification of patients with poor survival outcomes who were classified into the intermediate-risk group by the MALT-IPI. In conclusion, this new ß2-microglobulin-based prognostic index may have the specific advantage of identifying high-risk patients who may require systemic treatment.

Autologous stem cell transplantation for untreated transformed indolent B-cell lymphoma in first remission: an international, multi-centre propensity-score-matched study.

High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are used as consolidation in first remission (CR1) in some centres for untreated, transformed indolent B-cell lymphoma (Tr-iNHL) but the evidence base is weak. A total of 319 patients with untreated Tr-iNHL meeting prespecified transplant eligibility criteria [age <75, LVEF ≥45%, no severe lung disease, CR by positron emission tomography or computed tomography ≥3 months after at least standard cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab (R-CHOP) intensity front-line chemotherapy] were retrospectively identified. Non-diffuse large B-cell lymphoma transformations were excluded. About 283 (89%) patients had follicular lymphoma, 30 (9%) marginal-zone lymphoma and six (2%) other subtypes. Forty-nine patients underwent HDC/ASCT in CR1, and a 1:2 propensity-score-matched cohort of 98 patients based on age, stage and high-grade B-cell lymphoma with MYC, BCL2 and/or BCL6 rearrangements (HGBL-DH) was generated. After a median follow-up of 3·7 (range 0·1-18·3) years, ASCT was associated with significantly superior progression-free survival [hazard ratio (HR) 0·51, 0·27-0·98; P = 0·043] with a trend towards inferior overall survival (OS; HR 2·36;0·87-6·42; P = 0·1) due to more deaths from progressive disease (8% vs. 4%). Forty (41%) patients experienced relapse in the non-ASCT cohort - 15 underwent HDC/ASCT with seven (47%) ongoing complete remission (CR); 10 chimeric antigen receptor-modified T-cell (CAR-T) therapy with 6 (60%) ongoing CR; 3 allogeneic SCT with 2 (67%) ongoing CR. Although ASCT in CR1 improves initial duration of disease control in untreated Tr-iNHL, the impact on OS is less clear with effective salvage therapies in this era of CAR-T.

Low-dose radiotherapy (2×2 g) versus low doses and rituximab in the treatment of marginal zone b-cell lymphoma previously untreated.

Radiotherapy (RT)is considered the treatment of choice in patients with Extra-nodal marginal zone lymphoma (EMZL) at early stage, but the presence of late toxicities has been limited the acceptance. Recently, low doses of RT LDR) (2 x 2 Gy) and the use of limited fields has been observed that retain the efficacy but eliminate toxicities; rituximab is considered as a single agent useful in these setting of patients. Thus, we conducted a open label study to evaluate the use of LDR compared with LDR and rituximab, in a large number of patients without previous treatment. METHODS: Patients with pathological diagnosis or(EMZL)), stage I, without previous treatment, were allocated in a proportion 1:1 to received LDR) that were compared with a group that received LDR and rituximab. RESULTS: One hundred and fourteen patients were recruit ; overall response rate and complete response were : 58(98.3%) and 54 (96.4 %)in patients whose respectively in LDR that were no statistical different to the observed in the LDR + R arm: 53 (96.3%) and 51 (92.75 %) respectively. Actuarial curves at 5-years show that progression-free survival in LDR arm were: 98.4% (95% Confidence interval (CI): 93%-108%) and OS were 97.2% (95%CI: 92%-110%), that did no show statistical difference with the LDR-R arm: 96.4% (95%CI: 90%-110%), and 98.5%(95%CI:92%-107%) respectively. Univariate analysis did not show any statistical differences in the analysis of prognostic factors. Acute and late toxicities were not observed. CONCLUSION: We conclude that LDR will be considered as the treatment of choice in patients with EMZL, in early stage, localized in head and neck anatomical sites; because response and outcome were excellent, without any toxicity, addition of rituximab did not improve results and outcome.

Trends of Incidence and Survival Rates of Mucosa-associated Lymphoid Tissue Lymphoma in the Korean Population: Analysis of the Korea Central Cancer Registry Database.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-lymphoma) is an extranodal lymphoma that occurs at various sites in the body. There is a limited understanding of the incidence and survival rates of MALT-lymphoma. To investigate the nation-wide incidence and survival rates of MALT-lymphoma in Korea during 1999-2017, the data on MALT-lymphoma were retrieved from the Korea Central Cancer Registry. METHODS: During the time period of 1999-2017, 11,128 patients were diagnosed with MALT-lymphoma. The age and sex of the patients and the Surveillance, Epidemiology, and End Results (SEER) summary stage of the tumor were analyzed, and the relative survival rates (RSRs) were calculated. RESULTS: The age-standardized incidence rates of MALT-lymphoma in 2017 among males and females were 1.53 and 1.61 per 100,000 individuals, respectively, whereas those in 1999 among males and females were 0.21 and 0.20, respectively in Korea. The RSRs were more than 97% at 10 years post-diagnosis between 1993 and 2017. The 5-year RSRs were 87.4%, 94.8%, 97.8%, and 98.6% during 1996-2000, 2001-2005, 2006-2010, and 2013-2017, respectively. Based on SEER summary staging, the 5-year RSRs during 2013-2017 were 100.3%, 90.8%, 91.3%, and 97.9% for patients with localized, regional, distant, and unknown stages of MALT-lymphoma, respectively. CONCLUSION: Although the incidence of MALT-lymphoma is low in Korea, it has been increasing in recent years. The prognosis of MALT-lymphoma is good even at advanced stages. These findings provide useful insights to clinicians about MALT-lymphoma and inform patients about the survival rate.

Analysis of the response time to involved-field radiotherapy in primary gastrointestinal low-grade B-cell lymphoma.

BACKGROUND: Early-stage primary gastrointestinal (GI) low-grade B-cell lymphoma shows good therapeutic response to primary radiotherapy. However, there is no clear guideline for the evaluation of response to radiation therapy currently. The aim of this study was to analyze the relationship between the best response time and the clinical course after radiotherapy. METHODS: Patients who underwent radiotherapy for treatment of primary GI low-grade B-cell lymphoma from September 2007 to December 2018 at Seoul St. Mary's Hospital were included. Early responders were defined by best response within 6 months after radiotherapy, and delayed responders after 6 months. Clinical and pathological factors associated with delayed response and survival analyses were performed to investigate the recurrence and survival during follow-up. RESULTS: A total of 43 patients were evaluated and the number of gastric mucosa-associated lymphoid tissue and duodenal follicular lymphoma was 36 and 7, respectively. All of 43 patients showed complete remission to radiotherapy and the best response time after radiotherapy was a median of 3 months. There were 8 delayed responders with a median duration of 8.9 months. Early and delayed responders were characterized by a significant difference in depth of invasion beyond the mucosal layer. CONCLUSIONS: Delayed responders did not show differences in oncological outcomes compared with early responders. They were allowed to watch and wait for an additional 6 to 12 months without further treatment.

Radiotherapy in Early-stage Gastric MALT: Improved Survival Without Increased Cardiac Death.

PURPOSE: Radiotherapy (RT) is an effective treatment for localized gastric mucosa-associated lymphoid tissue (MALT) lymphomas unresponsive to antibiotic therapy; however, irradiating the stomach can result in significant radiation to the heart, a risk factor for cardiac disease. We analyzed the Surveillance, Epidemiology, and End Results database to evaluate outcomes related to cardiac disease among patients treated with RT for stage I gastric MALT. MATERIALS AND METHODS: We identified adult patients treated between 1993 and 2014. The relationship between treatment modality (RT, chemotherapy, combination, and no treatment) and overall survival (OS), mucosa-associated lymphoid tissue-specific survival (MSS), non-mucosa-associated lymphoid tissue-specific survival (non-MSS), and cardiac-specific survival (CSS) was assessed using the Kaplan-Meier estimator and Cox proportional hazards analyses. RESULTS: A total of 2996 patients (median follow-up, 5.6 y) were analyzed: 27.5% had received RT alone, 12.1% chemotherapy alone, 3.9% chemoradiotherapy, and 56.5% no/unknown treatment (including antibiotic therapy). Compared with RT alone, patients who received chemotherapy alone exhibited worse OS (hazard ratio [HR]: 1.67; 95% confidence interval [CI]: 1.32-2.10; P<0.001) and MSS (HR: 2.10; 95% CI: 1.36-3.23; P=0.001). Although CSS appeared worse in patients who received chemotherapy (HR: 1.56; 95% CI: 0.92-2.66; P=0.10), it was not statistically significant. When comparing orbital and gastric MALT patients, there was no significant difference in CSS (HR: 0.80; 95% CI: 0.49-1.31; P=0.38). CONCLUSIONS: RT improved survival among patients with stage I gastric MALT without increasing the risk of cardiac death. Those with gastric MALT exhibited similar CSS to those with orbital MALT. Although we cannot analyze nonfatal cardiac toxicity, these results suggest that, absent antibiotic therapy, RT should remain first-line treatment for early-stage gastric MALT.

Splenic marginal zone lymphoma: A US population-based survival analysis (1999-2016).

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare tumor without a uniform treatment approach. The authors describe a large population-based study evaluating survival outcomes of patients with SMZL according to the treatment received. METHODS: From the Surveillance, Epidemiology, and End Results database, patients were selected who had SMZL diagnosed from 1999 to 2016. Observation, splenectomy, chemotherapy, and splenectomy with chemotherapy were the evaluated treatment strategies. Cox and Fine and Gray regression models were used to evaluate overall and SMZL-specific survival, respectively. RESULTS: In total, 1671 patients were selected for the analysis. Most patients were aged >60 years (71.3%), White (89.7%), and non-Hispanic (91.7%). Transformation to diffuse large B-cell lymphoma (DLBCL) occurred in 71 patients (4.2%), and the 10-year transformation rate was 8.6% (95% CI, 6.6%-10.9%). In multivariable analysis, shorter SMZL-specific survival was associated with age ≥60 years (subdistribution hazard ratio [SHR], 1.85; 95% CI, 1.40-2.45; P < .001), Hispanic ethnicity (SHR, 1.50; 95% CI, 1.06-2.13; P = .023), DLBCL transformation (SHR, 2.10; 95% CI, 1.48-2.97; P < .001), and the presence of B-symptoms (SHR, 1.67; 95% CI, 1.23-2.27; P < .001). Compared with splenectomy, observation (SHR, 0.92; 95% CI, 0.67-1.28; P = .636), chemotherapy only (SHR, 1.28; 95% CI, 0.93-1.76; P = .127), and splenectomy plus chemotherapy (SHR, 1.43; 95% CI, 0.96-2.13; P = .089) showed no significant differences in SMZL-specific survival. Predictors of shorter overall survival were age ≥60 years (hazard ratio, 2.98; 95% CI, 2.37-3.76; P < .001) and the presence of B-symptoms (hazard ratio, 1.33; 95% CI, 1.06-1.67; P = .014). CONCLUSIONS: There were no significant differences in overall or SMZL-specific survival by treatment strategy. Older age, Hispanic ethnicity, DLBCL transformation, and B-symptoms were associated with a worse prognosis.

Risk adapted approach: How to treat splenic marginal zone lymphoma in resource-poor settings? - The real-life experience of a Brazilian cancer treatment center.

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is a rare lymphoid B-cell malignant neoplasm with primary involvement of the spleen. It is a chronic disease, of indolent behavior and prolonged survival. However, 25% of cases have higher biological aggressiveness, propensity for histological transformation to high grade B-cell non-Hodgkin lymphoma and shortened survival. Recognition of these cases of reserved outcome is important for selecting a risk-adapted therapeutic approach in a resource-poor settings. METHODS: We described clinical and epidemiological characteristics, survival analysis and prognostic factors in a retrospective cohort of 39 SMZL patients, treated in Latin America. RESULTS: We observed a predominance of female (71.8%), median age of 63 years and higher incidence of B symptoms (56.4%) and extra-splenic involvement (87.1%) than in European and North-American series. With a median follow-up of 8.7 years (0.6-20.2 years), estimated 5-year overall survival (OS) and progression-free survival (PFS) were 76.9% and 63.7%, respectively. Factors with adverse prognostic impact on OS and PFS were Hb < 100 g/L, platelet count < 100 x 109/L, albumin < 3.5 g/dL, LDH > 480 U/L and high-risk Arcaini and SMZL/WG scores. Despite a relative low number of patients, no superiority was observed among the therapeutic regimens used including rituximab monotherapy, splenectomy and cytotoxic chemotherapy. CONCLUSION: Therefore, in resource-poor settings, where access to immunotherapy is not universal for all SMZL patients, we suggest that first-line should consist on rituximab therapy for elderly patients or with high surgical risk or with at least 1 risk factor identified in our study. Remainders can be safely managed with splenectomy.

Prognostic significance of interim PET/CT response for the treatment of advanced-stage marginal zone lymphoma in the post-rituximab era.

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2-3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p < 0.001). Particularly, there was a significant difference in PFS between patients with interim score 1-2 and those with score 3. However, ΔSUVmax did not predict the survival outcome using 59.8% of the optimal cutoff value. In the multivariate analysis, failure to achievement of grade 1-2 in interim PET/CT was significantly associated with inferior PFS (HR, 2.154; 95% CI 1.071-4.332; p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.

Clinical and radiological characteristics of patients with pulmonary marginal zone lymphoma: A single center analysis.

Pulmonary marginal zone lymphoma (PMZL) is the most common non-Hodgkin lymphoma affecting the lung. PMZL is usually an indolent disease. Clinical and radiological variables associated with shorter survival are largely unknown and no consensus exists on preferred treatment strategy in PMZL. Herein we aimed to identify clinical and radiological features associated with shorter survival and inferior treatment outcomes. Forty patients with PMZL were analyzed. FDG-avid disease was evident in most patients (93%) with staging PET/CT (n = 15). With a median follow-up in treated patients (n = 38) of 8.4 years (range 0.07-18.44), the median progression-free survival (PFS) and overall survival (OS) were 7.5 years (95% CI 1.8-9.5) and 15.7 years (95% CI 9.3-NE) respectively. Shorter PFS was observed in patients who presented at diagnosis with elevated LDH, B symptoms, advanced stage and failed to achieve complete response (CR) after initial treatment. Patients with multifocal lung disease, extrapulmonary MZL and cavitary lesions on CT scans exhibited shorter PFS. Nevertheless, no clinical or radiologic findings were associated with shorter OS. All patients treated with surgery (n = 4) and radiation therapy (n = 3) achieved and remained in CR. No higher grade transformations occurred during the follow-up period. PMZL exhibited excellent outcomes with a 15-year PMZL-related OS of 94.9% (95% CI: 81.25%-98.7%). Radiation therapy and surgery are potentially curative strategies in localized PMZL.

Extranodal Marginal Zone Lymphoma of the Central Nervous System Includes Parenchymal-Based Cases With Characteristic Features.

OBJECTIVES: To define the clinicopathologic features of extranodal marginal zone lymphoma (EMZL) of the central nervous system (CNS), including cases arising in CNS parenchyma, which have been reported only rarely. METHODS: Twelve cases of CNS EMZL were identified, including 5 based in CNS parenchyma and 7 nonparenchymal cases arising in dura or choroid plexus. RESULTS: Histologically, parenchymal cases were perivascular infiltrates without a dominant lymphoid mass, whereas nonparenchymal cases were masses of small lymphocytes. Plasma cells were a larger component of the infiltrate in parenchymal cases (median, 30%; range, 20%-50%) than nonparenchymal cases (median, 0%; range, 0%-5%; P < .001), and plasma cells were clonal by immunohistochemistry in 4 of 5 parenchymal vs 1 of 7 nonparenchymal cases (P = .07). Fluorescence in situ hybridization for MALT1 rearrangement was positive in 1 of 3 parenchymal and none of 3 nonparenchymal cases. Chromosomal microarray was abnormal in 5 of 7 cases (71%), with chromosome 6/6q alterations identified in 3 cases. No patients with parenchymal disease but all 6 (100%) with nonparenchymal disease achieved complete remission. CONCLUSIONS: This case series, the first to include multiple parenchymal cases, clarifies the spectrum of clinical, pathologic, and genetic findings in CNS EMZL and suggests that parenchymal-based lesions may show less favorable prognosis than dural-based disease.

Radiotherapy alone for stage IE ocular adnexal mucosa-associated lymphoid tissue lymphomas: long-term results.

BACKGROUND: To evaluate the long-term efficacy and toxicity of radiation therapy in patients with Stage IE primary ocular adnexal mucosa-associated lymphoid tissue lymphoma. METHODS: We designed a retrospective analysis to evaluate 81 patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation therapy between 2006 and 2016. The median radiation dose was 30 Gy (range, 30-36 Gy in 15-18 fractions). Local control, progression-free survival, overall survival, and cumulative incidence of Grade 3 cataract were calculated by using the Kaplan-Meier method. RESULT: The median follow-up time was 74 months (range, 4-157 months). The 5-year local control was 100%. Although local relapse was suspected in 3 patients after radiation therapy, 2 patients were pathologically diagnosed as IgG4-related inflammation and in 1 patient as intense inflammatory cell infiltration. The 5-year progression-free survival was 94.4%. Five patients had relapse at distant sites. The 5-year overall survival was 98.8%. Twenty patients had Grade 3 cataract. The 5-year cumulative incidences of Grade ≥ 3 and Grade ≥ 2 cataract for 58 patients treated without a lens shield were 38 and 40%, respectively. The incidence of Grade ≥ 3 cataract was 42% for 50 patients treated with 6-MV X-rays (estimated lens dose: 29 Gy) and 17% for 8 patients treated with 9-MeV electrons (estimated lens dose: 24 Gy). CONCLUSIONS: Radiation therapy alone yielded excellent local control and long-term survival in Stage IE ocular adnexal mucosa-associated lymphoid tissue lymphoma. Long-term observation with careful attention to relapse at distant sites is necessary. In the case of suspected local relapse, IgG4-related disease should be carefully ruled out.