small molecules

2026-03-23 | Marginal Zone Lymphoma: 2026 Update on Diagnosis and Management.

Marginal zone lymphoma (MZL) is a heterogeneous group of indolent mature B-cell neoplasms with classically three major subtypes: nodal, splenic, and extranodal MZL of mucosa-associated lymphoid tissue (MALT). Diagnosis and disease evaluation of MZL is further advanced by the use of genomic testing and PET/CT with emerging evidence for the use of circulating tumor DNA. The RECLASS classification system proposed a hierarchical approach to classifying MZL while the FIL-NF10 investigators introduced a fourth MZL subtype, disseminated MZL. Though the prognosis of MZL varies between subtypes and stages, the MZL IPI and FLIPI24 indices can be used for prognostication. Frontline treatment of MZL varies between localized disease and advanced-stage diseases. The former favor the use of local therapies such as radiotherapy and anti-microbial in certain subtypes with a selective role of rituximab monotherapy. The latter requires systemic immunotherapy ± chemotherapy with emerging data for cytotoxic-free and covalent Bruton tyrosine kinase inhibitor (cBTKi)-based regimens. cBTKi and immunomodulators are established in relapsed/refractory MZL, while data for antibody-drug conjugates, T-cell engagers, and potentially CAR T-cell therapies are maturing.

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2026-02-04 | Indolent Lymphomas and Leukemia

This study examines the clinical characteristics and outcomes of dogs diagnosed with splenic marginal zone lymphoma (SMZL). Drawing on a retrospective review of medical records from 56 dogs treated between 2000 and 2010, the analysis focuses on survival times, treatment protocols, and adverse events. The findings indicate that SMZL in dogs is generally indolent, with a median survival time exceeding 1000 days post-diagnosis. However, significant variability in outcomes is observed based on treatment modalities, with chemotherapy and surgical intervention yielding differing efficacy. The study highlights the importance of individualized treatment plans, as dogs receiving combination therapies demonstrated improved progression-free survival compared to those treated with single-agent protocols. Additionally, the research identifies specific clinical markers, such as the presence of B-cell receptor rearrangements, which correlate with better responses to therapy. The implications of these findings underscore the need for further prospective studies to standardize treatment guidelines and optimize patient outcomes in canine SMZL.

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2025-11-03 | Genetic analysis and clinical correlations in marginal zone lymphoma

Abstract Background: Marginal zone lymphoma (MZL) is a heterogeneous group of indolent B-cell malignancies with distinct molecular landscapes across its subtypes (extranodal/MALT, splenic, nodal, and disseminate). Genetic characteristics of MZL and its clinical relevance were not well defined. This study aims to explore subtype-specific genetic signatures and their clinical correlations in a retro-prospective MZL cohort Methods: We retrospectively analyzed MZL patients who underwent targeted Next-Generation Sequencing(NGS) panel for lymphoproliferative disorders at our institution and examining their mutational profiles and correlations with clinical characteristics and outcomes. Results:From December 2017 and August 2024, 136 MZL patients with NGS testing results underwent systemic treatment in our center. The median age was 63 years (range 30–92) and the male-to-female ratio was 1.1. This cohort comprised 52(38.2%) MALT/EMZL, 7(5.2%) NMZL, 65 (47.8%)SMZL and 12(8.8%) dissMZL patients, respectively. The most frequently detected mutations were MYD88L265P(13.2%),TP53 (12.5%), CXCR4 (6.6%), DNMT3A (6.6%), EP300 (6.6%), TET2 (5.9%),TNFAIP3 (5.1%)，in descending order of frequency. No associations were found between mutations and clinical features such as Ann Arbor stage or MZL-IPI. However, patients with large B cell transformation showed higher frequencies of EP300 (22.2% vs. 4.3%, p=0.019) and EZH2 (11.1% vs. 0.1%, p=0.017) mutations. TNFAIP3 mutations varied significantly across subtypes: 0% (MALT/EMZL), 14.3% (NMZL), 9.2% (SMZL), and 0% (dissMZL) (p=0.045). With median follow-up of 65.3months(range 2.2-262), the 5-year PFS and OS rates were 46.1% (95% CI 36.8–57.5) and 85.2% (78.5–92.4), respectively. Progression of disease within 24 months was observed in 27.4% of patients. TP53 mutations adversely impacted OS (HR 2.85, 95% CI 1.17–6.95; p=0.014) but not PFS. No other mutations predicted survival. Conclusion: This study delineates the distinct mutational landscape of MZL, revealing subtype-specific patterns (TNFAIP3 variation) and transformation-associated alterations (EP300/EZH2). The adverse impact of TP53 mutations on OS underscores its prognostic value, while the 27.4% POD24 rate highlights unmet needs in high-risk subsets. These findings advocate for integrating molecular profiling (particularly TP53, EP300, and TNFAIP3) with clinical indices like MZL-IPI to refine risk stratification and guide targeted therapy development in MZL.

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2025-11-03 | Efficacy and safety of orelabrutinib, obinutuzumab, and lenalidomide in previously untreated marginal zone lymphoma: Preliminary results from a prospective, single-arm, multicenter, Phase II study

Abstract Background: Emerging evidence suggests that triple-combination regimens incorporating Bruton tyrosine kinase (BTK) inhibitors, CD20-targeted agents, and immunomodulatory drugs (e.g., lenalidomide) may exhibit promising antitumor activity in indolent B-cell non-Hodgkin lymphomas (B-NHLs). In this study, we evaluated the efficacy and safety of orelabrutinib plus obinutuzumab and lenalidomide(GOL regimen) as a first-line therapy for MZL patients, aiming to assess its potential as a chemotherapy-free treatment option. Methods: In this prospective single-arm multicenter phase II trial (NCT06454968), eligible treatment-naïve adults (≥18 years) with histologically confirmed marginal zone lymphoma requiring systemic therapy received six 21-day cycles of induction therapy (oral orelabrutinib 150 mg QD on days 1-21, intravenous obinutuzumab 1000 mg on day 1 of each cycle, and oral lenalidomide 25 mg QD on days 1-14) followed by six 28-day cycles of orelabrutinib monotherapy (150 mg QD). The primary endpoint of our study is complete response rate, secondary endpoints were overall response rate, duration of response, uMRD rate of SMZL by IgH-DNA sequencing, and safety. Results: As of August 1, 2025, a total of 23 patients were enrolled in the study. The median age was 60 years (range: 36-81) with a male-to-female ratio of 0.92:1. Subtype distribution included: MALT/EMZL (n=9, 39.1%), SMZL (n=9, 39.1%), and dissMZL (n=5, 21.8%). All patients had Ann Arbor stage IV disease, with 6 cases (26.1%) presenting B symptoms. The MZL-IPI score distribution was: 0 points in 6 cases (26.1%), 1-2 points in 14 cases (60.9%), and 3-5 points in 3 cases (13.0%). Monoclonal gammopathy was observed in 9 out of 19 evaluable patients. All splenic marginal zone lymphoma (SMZL) patients exhibited massive splenomegaly, with 4 out of 9 showing baseline leukocytosis (peak WBC count 387.5×10⁹/L, lymphocyte count 371.9×10⁹/L). To date, 10 patients have completed 6 cycles of the three-drug combination (GOL) regimen, while 5 patients have completed all treatment and entered the follow-up phase. Among 18 response-evaluable patients, the overall response rate (ORR) was 88.9% (16/18) and the complete response rate (CRR) was 72.2% (13/18). By subtype analysis:SMZL patients demonstrated excellent outcomes with 100% ORR (6/6) and 100% CRR (6/6), all achieving complete remission by cycle 3, including 5 cases (83.3%) attaining MRD negativity by IgH-DNA sequencing;MALT/EMZL patients showed 77.8% ORR (7/9) and 66.7% CRR (6/9);dissMZL patients achieved 100% ORR (3/3) but a lower CRR of 33.3% (1/3). With a median follow-up of 8.1 months (range 2.3-13.1 months), none of the responding patients experienced disease progression, and the median duration of response (DOR) has not been reached. Regarding safety, all-grade adverse events included: infusion-related reactions (6/23), thrombocytopenia (6/23), rash (5/23), herpes zoster (2/23), petechiae (2/23), leukopenia (1/23), influenza A pneumonia (1/23), and invasive pulmonary aspergillosis (1/23). Grade 3 adverse events were limited to infusion-related reactions (2/23), thrombocytopenia (2/23), and rash (2/23), with no grade 4-5 adverse events reported. Conclusion: This phase II study demonstrates that the novel triple-combination regimen shows promising efficacy in treatment-naïve MZL patients, with an impressive overall response rate (88.9%) and complete response rate (72.2%), particularly in SMZL patients who achieved 100% CR. The regimen exhibited a manageable safety profile with no grade 4-5 adverse events. Early MRD negativity in SMZL suggests potential for durable remissions. These results support further study of this chemotherapy-free approach.

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2025-11-03 | Monoclonal gammopathy-related coagulopathies: A systematic analysis

Abstract Background: Monoclonal Gammopathy (MG)-related coagulopathies have been described in several case reports and small series involving multiple myeloma and other lymphoplasmacytic/plasma cell dyscrasia disorders and occur from a variety of mechanisms. To our knowledge, there are no systematic evaluations of the frequency, clinical associations, and underlying mechanisms of paraprotein induced coagulopathy in a cohort of patients with such disorders. Methods: We reviewed the 3,657 patients diagnosed with a MG over a ten-year period (5/2015-5/2025) at a single academic cancer center. Cases included MG of undetermined significance (MGUS), smoldering (SMM) and multiple myeloma (MM), AL amyloidosis, lymphoplasmacytic lymphoma (LPL), and marginal zone/splenic B-cell lymphoma. Cases were screened for elevated PT/INR (INR>1.3) and/or aPTT (>38.0) at presentation, and/or had a coagulation factor assay performed. This resulted in a total of 599 cases for detailed review. Results: Fifteen cases (0.41% of total cohort) had a coagulopathy that was attributable to the MG. Of these cases, coagulopathies were found in 6 patients with MM, 4 with MGUS, 2 with AL amyloidosis, 1 with LPL, 1 with splenic B-cell lymphoma, and 1 with marginal zone lymphoma. Four of the 15 cases presented with overt bleeding, which included muscle hematoma (n=2), hematochezia (n=1), and oral bleeding (n=1). The remaining 11 cases were diagnosed through abnormal coagulation laboratory analysis without overt bleeding. Nine of the cases had factor deficiency (von Willebrand Disease: n=4, factor X: n=4, factor VIII: n=1). Four had antiphospholipid antibody syndrome (APS), one had a direct thrombin inhibitor, and one had a mixed pattern (factor VIII deficiency and APS). Three of the factor X deficiency cases were in the context of known, or clinically suspected AL amyloidosis, while one patient with MM had a strong factor X inhibitor and no evidence of AL amyloidosis. Two-thirds of the cases had a kappa light-chain MG (n=10), consistent with the typical proportion in MG patients. Among the 11 cases with a heavy chain immunoglobulin component, IgM elevation occurred in 6 cases, and IgG in 5. Interestingly, all 4 of the APS cases were IgM (2 kappa and 2 lambda). The mean monoclonal protein level among cases with quantifiable spikes (n=11) was 1.48 g/dL. The majority of cases (n=10) underwent treatment for the underlying hematologic disorder. Half of the treated patients experienced a complete resolution of the coagulopathy (n=5), 2 cases demonstrated a partial improvement, and 3 cases had persistent coagulopathy despite treatment. No deaths were attributed to coagulopathy in these patients. Conclusions: To our knowledge, this is the first systematic evaluation of MG-related coagulopathies across a large population of lymphoid/plasmocytic neoplasms. Also unique to our study is the description of coagulopathy outcomes following treatment. Our findings reveal a spectrum of coagulation targets with implications for diagnosis and therapeutic decision-making.Treatment of the underlying disorder resulted in complete or partial improvement of the coagulopathy in most but not all cases. There was no specific pattern of IgG verus IGM, or kappa versus lambda light chain. Early recognition and consideration of treatment may prevent bleeding complications and improve coagulopathy in similar cases.

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proteins

2026-05-01 | C32-21 Unmasking the Swell: Recurrent Acquired Angioedema as a Manifestation of Marginal Zone Lymphoma

Abstract Introduction Acquired angioedema (AAE) due to C1-esterase inhibitor (C1-INH) deficiency is a rare, potentially fatal disorder caused by increased bradykinin activity leading to vascular permeability and submucosal edema. Unlike hereditary angioedema, AAE typically presents later in life, lacks a family history, and is frequently associated with underlying B-cell lymphoproliferative disorders or autoimmune diseases. Among these, splenic marginal zone lymphoma (MZL) is disproportionately represented, highlighting a paraneoplastic link between complement consumption and tumor activity. Because bradykinin-mediated angioedema does not respond to epinephrine, corticosteroids, or antihistamines, recognition and disease-specific management are crucial to avoid airway compromise. Case Description A 65-year-old woman with newly diagnosed splenic MZL presented with her third episode of sudden tongue swelling now accompanied by progressive dysarthria, drooling, and respiratory distress. In the emergency department, she was administered 1g intravenous (IV) Tranexamic acid, 20 mg IV Famotidine, 50 mg IV Diphenhydramine, and 125 mg IV Methylprednisolone without improvement. Worsening edema necessitated emergent endotracheal intubation for impending airway obstruction.In the intensive care unit, she was treated with intravenous corticosteroids, diphenhydramine, famotidine, and received two units of fresh frozen plasma. Complement studies revealed a low C1q level (<2 mg/dL), and markedly reduced C1 esterase inhibitor assay ( 7%), confirming acquired C1-INH deficiency. C4 level was also depressed, and autoimmune serologies were negative. Following stabilization, she self-extubated without rebound swelling and was discharged with hematology follow-up for ongoing lymphoma-directed therapy and referral to Allergy-Immunology. Discussion This case underscores a rare but clinically significant manifestation of AAE in the setting of splenic MZL. Adult-onset, recurrent, non-pruritic angioedema unresponsive to conventional histaminergic therapies should prompt evaluation for bradykinin-mediated etiologies. Diagnostic confirmation relies on complement testing, specifically, low C1q and C1-INH levels with normal C1-INH gene sequence, distinguishing AAE from hereditary forms. Acute management centers on airway protection and targeted therapy such as plasma-derived or recombinant C1-INH, icatibant (a bradykinin B2-receptor antagonist), or ecallantide (a kallikrein inhibitor), when available. FFP remains a pragmatic option in resource-limited settings. Long-term control depends on treating the underlying lymphoproliferative disorder, which can normalize complement levels and prevent recurrence.Heightened clinical awareness of AAE in patients with unexplained angioedema and concurrent B-cell malignancies can prevent morbidity and mortality through timely diagnosis and multidisciplinary management. This abstract is funded by: none

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2025-11-03 | A phase II investigator-initiated frontline trial of evorpacept (ALX148), lenalidomide and rituximab for high tumor burden indolent b-cell non-Hodgkin lymphoma

Abstract Introduction . We have recently completed a phase I trial of evorpacept (formerly known as ALX148), a novel high-affinity signal regulatory protein (SIRP)a fusion protein that blocks cluster of differentiation (CD)47, in combination with lenalidomide and rituximab (R2) in patients with relapsed refractory indolent B-cell non-Hodgkin lymphoma (iNHL). The combination was safe, no dose limiting toxicity was observed at a dose of 60 mg/Kg on day (D) 1 of a 28-day cycle, and more than 80% of patients experienced a complete response (CR). We present here a phase 2 study investigating the efficacy of this regimen in patients with previously untreated and high tumor burden iNHL. Methods. This single arm phase II study (NCT05025800) was conducted between January and November 2025 (data cut-off 07/2025). Adult patients with previously untreated and advanced stage iNHL, who met indication for treatment according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria were included. Evorpacept was administered intravenously (IV), in a 28-day cycle, for 6 cycles, at the recommended phase 2 dose of 60 mg/Kg on D1; rituximab IV was given weekly during cycle 1, and on D1 during cycles 2-6; lenalidomide was given orally on D1-21 during cycles 1-6. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. The primary endpoint was best CR rate per Lugano 2014 criteria. Results. Twenty-four patients were included in the study, and all were evaluable for safety and efficacy. Median age was 64 (33-76) and 13 (54%) were male; 14 (58%) had follicular lymphoma, including 5 patients with grade 3A, and 10 (42%) had marginal zone lymphoma (MZL), including 4 with extra-nodal, 4 with nodal, and 2 with splenic subtype; median largest lymph node size was 3.6 cm (range, 1.5-7.5 cm), median maximum standardized uptake volume was 7.1 (range, 3-32), and all patients had intermediate-high Follicular Lymphoma International Prognostic Index (FLIPI). Median number of cycles was 6 (range, 3-6), and all patients had completed treatment at time of data cut-off. The most common (> 1 patient) grade 3-4 adverse events included: neutropenia (29%), all resolved with growth factor, infections (12.5%), alanine transferase (ALT) increase (12.5%), aspartate transferase (AST) increase (12.5%), and infusion related reaction (8%). Ten (42%) patients required a dose reduction in lenalidomide, mainly due to infections, but none in evorpacept; 2 (8%) patients discontinued lenalidomide and 1 (4%) evorpacept, due to AST/ALT elevation. Twenty-two (92%) patients achieved CR, 2 (8%) partial response, and overall response rate was 100%. After a median follow-up of 10 months (95% confidence interval, 9-12 months), 2 patients have progressed (1 with likely baseline transformed MZL), with a 1-year progression-free survival rate of 87%. At most recent follow-up no patients have died, and 1-year overall survival rate was 100%. Conclusions. The addition of evorpacept to R2 is a safe and effective frontline non-chemotherapy regimen for iNHL patients, resulting in high CR rates. While longer follow-up matures, serial blood samples are being evaluated for circulating tumor DNA by phased variant enrichment and detection sequencing (PhasED-seq) to determine the minimal residual disease eradication rate with this novel regimen.

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2020-09-30 | Splenic Hematopoietic and Stromal Cells in Cancer Progression

Tumor-derived secretory factors orchestrate splenic hematopoietic and stromal cells to fuel metastasis. The spleen acts as a reservoir site for hematopoietic stem and progenitor cells, which are rapidly exploited as myeloid-derived suppressor cells at the cost of tumor-reactive lymphoid cells. Splenic erythroid progenitor cells and mesenchymal stromal cells contribute directly and indirectly to both tumor immune escape and the metastatic cascade. Animal models provide valuable mechanistic insights, but their translation to a clinical setting highlights specific challenges and open issues. In this review, we envision the exploitation of the spleen as a source for novel biomarkers and therapeutic approaches.

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2020-07-01 | Marginal zone lymphoma expression of histidine‐rich glycoprotein correlates with improved survival

The abundant hepatocyte-expressed plasma protein histidine-rich glycoprotein (HRG) enhances antitumor immunity by polarizing inflammatory and immune cells in several mouse models, however, the clinical relevance of HRG in human cancer is poorly explored. The expression and role of HRG in human B-cell lymphomas was investigated in order to find new tools for prognosis and treatment.Immunohistochemical (IHC) analysis and RNA hybridization of tissue microarrays showed that (i) HRG was expressed by tumor cells in marginal zone lymphoma (MZL), in 36% of 59 cases. Expression was also detected in follicular lymphoma (22%), mantle cell lymphoma (19%), and indiffuse large B-cell lymphoma (DLBCL;5%) while primary CNS lymphoma (PCNSL) lacked expression of HRG. (ii) MZL patients positive for HRG showed a superior overall survival outcome (HR = 0.086, 95% CI = 0.014-0.518, P-value = .007), indicating a protective role for HRG independent of stage, age and sex. (iii) HRG-expressing MZL displayed significantly increased transcript and protein levels of the host defense peptide alpha defensin 1. In addition, global transcript analyses showed significant changes in gene ontology terms relating to immunity and inflammation, however, infiltration of immune and inflammatory cells detected by IHC was unaffected by HRG expression.HRG expression by MZL tumor cells correlates with an altered transcription profile and improved overall survival.

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2015-02-02 | Success of interferon α therapy in a patient with hepatitis C virus-negative splenic marginal zone lymphoma associated with polycythemia vera

Splenic marginal zone lymphoma (SMZL) is a rare indolent lymphoma accounting for fewer than 1% of non-Hodgkin lymphomas. This chronic lymphoproliferative disorder (LPD) is characterized by spleen e...

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cell therapies

2026-02-16 | Lisocabtagene maraleucel in patients with relapsed or refractory marginal zone lymphoma (TRANSCEND FL): primary analysis results from the global, multicohort, single-arm, phase 2 study.

Effective treatments with deep and durable responses for relapsed or refractory marginal zone lymphoma (MZL) are lacking. The objective of the primary analysis from the MZL cohort of TRANSCEND FL was to evaluate the efficacy and safety of the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel. In this phase 2, single-arm, multicohort study, patients from 30 sites in the USA, Canada, Europe, and Japan with relapsed or refractory MZL who had at least two previous lines of systemic therapy were eligible to receive lisocabtagene maraleucel (100 × 106 CAR+ T cells). Bridging therapy was allowed. The primary endpoint was overall response rate per independent review committee by CT by use of Lugano 2014 criteria (null hypothesis ≤50%). This study is registered with ClinicalTrials.gov, NCT04245839, and is ongoing. Of 77 leukapheresed patients recruited between November 11, 2020, and August 24, 2023, 67 received lisocabtagene maraleucel and 66 were efficacy evaluable. MZL subtypes included nodal (n=32 [48%]), splenic (n=18 [27%]), and extranodal-mucosa-associated lymphoid tissue (n=17 [25%]). Median (IQR) previous lines of systemic therapy was 3 (2-4). Median on-study follow-up was 24·1 months. The primary endpoint was met, with an overall response rate of 95% (n=63; 95% CI, 87·3-99·1; one-sided p<0·0001). All patients experienced a treatment-related adverse event. Grade 3 cytokine release syndrome or neurological events occurred in three (4%) patients each (no grade 4-5 events). 11 (16%) patients had grade ≥3 infections: six (9%) patients during the 90-day treatment-emergent period and seven (10%) during the post-treatment-emergent period. In patients with relapsed or refractory MZL, lisocabtagene maraleucel showed high rates of durable responses. The safety profile was manageable, with no new safety signals. These results support lisocabtagene maraleucel as a new treatment option for patients with relapsed or refractory MZL. Celgene, a Bristol-Myers Squibb Company.

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2023-08-31 | IBCL-318 Epidemiological, Clinical, Histopathologic and Therapeutic Characteristics of Marginal Zone Lymphoma: Experience of the Hematology Department of Casablanca in Morocco

factors impairing T-cell function in sMZL.Our findings highlight the importance of maintaining healthy T-cell pools as a predictor of long-term disease-free intervals and support a rationale for earlier use of T-cell-based therapies.

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2018-07-09 | High‐dose therapy and autologous stem cell transplantation in marginal zone lymphomas: a retrospective study by the EBMT Lymphoma Working Party and FIL‐GITMO

The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphoma (MZL) is debatable. This study investigated the outcome and prognostic factors affecting the outcome of patients undergoing ASCT for MZL. Eligible patients had non-transformed nodal, extra-nodal (MALT) or splenic MZL (SMZL), aged ≥18 years, who underwent a first ASCT between1994 and 2013 and were reported to the European Society for Blood and Marrow Transplantation, Fondazione Italiana Linfomi or Gruppo Italiano Trapianto Di Midollo Osseo registries. The study included 199 patients, [111 MALT lymphoma, 55 nodal MZL (NMZL) and 33 SMZL]. Median age at transplantation was 56 years. The median number of prior therapies was 2 (range 1-8), including rituximab in 71%. 95% had chemosensitive disease. 89% received a chemotherapy-based high-dose regimen. There were no significant differences in patient and transplant characteristics between the 3 histological subtypes except for a lower percentage of patients previously treated with rituximab in the MALT sub-group and more transplants performed in recent years in the other sub-groups. After a median follow-up of 5 years, 5-year cumulative incidence of relapse/progression and non-relapse mortality were 38% and 9%, respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% and 73%, respectively. Five-year cumulative incidence of second malignancies was 6%. Multivariate analysis revealed age ≥65 years was associated with a shorter EFS and OS. In addition, patients with SMZL had a shorter OS than those with MALT. ASCT may provide clinical benefit in MZL patients who have failed multiple lines of chemoimmunotherapy.

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2018-03-23 | Allogeneic hematopoietic cell transplant for relapsed-refractory, marginal zone lymphoma: a single-center experience

A subset of marginal zone lymphoma (MZL) has an aggressive clinical course and role of allogeneic hematopoietic cell transplant (allo-HCT) is not well defined for these patients. MZL includes three...

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2017-02-22 | Role of Allogeneic Stem Cell Transplantation in Aggressive Marginal Zone Lymphoma—Single Center Experience

Introduction: Marginal zone B cell lymphoma (MZBCL) is a non-Hodgkin lymphoma, which usually behaves in an indolent manner. However, a subset of patients with this lymphoma has an aggressive clinical course characterized by advanced stage of disease, resistance to standard therapies, and rapid progression. Role of allogeneic-SCT (allo-SCT) is not well defined in management of this subtype of non-Hodgkin lymphoma. We performed a single-institution retrospective study to assess the therapeutic outcomes of allo-SCT in relapsed/refractory MZBCL. Methods: We identified the patients with biopsy-proven MZBCL and aggressive clinical course, who underwent allo-SCT at our institution between 2001 and 2013. Patient's clinical and treatment data was collected by comprehensive chart review. Cases complicated by second malignancy and transformed lymphoma were excluded. Results: A total of six patients with MZBCL underwent allo-SCT during the study period. The median age was 49 years and the median follow-up period was 88.9 months. Five patients had relapsed/refractory disease and one had primary refractory disease. Patients had a median of 3 prior therapies before allo-SCT. The pathology was extranodal MZBCL in 3 patients, splenic MZBCL in 2 patients and nodal MZBCL in 1 patient. Four patients presented with Ann Arbor stage IV disease, and other two with stage II and III each. Rituximab-based chemoimmunotherapy was the first-line treatment in 4 patients and the other two patients received rituximab alone. Three patients achieved complete response to the initial treatment with median progression free survival (PFS) of 7 months. Table 1 shows therapeutic outcomes of first line treatments and allo-SCT. Four patients had reduced intensity conditioning (RIC) and two patients received myeloablative conditioning. Calcineurin inhibitor (CNI) based graft versus host disease (GVHD) prophylaxis was used in all patients. Median survival from the allo-SCT and overall survival (OS) from the diagnosis were 77.8 months and 98 months (Figure 1). No relapses were identified post allo-SCT during the study period. No statistically significant correlation was seen between OS and age, type of MZBCL (extranodal versus splenic), PFS with first-line therapy, or type of conditioning regimen. Incidence of acute and chronic GVHD was 60% and 20%. Two patients remained disease-free and alive at 96.9 and 77.8 months from the date of allo-SCT. Two patients died of infection during the follow-up period.Table 1Initial treatment and allo-SCT outcomes of the patients with MZBCLFigure 1Overall survival of the patients with MZBCL who underwent allo-SCT.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Conclusion: MZBCL appears to be quite sensitive to graft versus lymphoma effect. Our findings indicate that allo-SCT is feasible with reasonable transplant related mortality in this difficult-to-treat patient population and should be considered in eligible patients.

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antibodies

2026-07-17 | Acquired Hemophilia A Revealing Occult Splenic Marginal Zone Lymphoma.

BACKGROUND Acquired hemophilia A is a rare autoimmune bleeding disorder caused by inhibitory autoantibodies against coagulation factor VIII and is associated with significant morbidity and mortality. Although malignancy-associated acquired hemophilia A is well recognized, its presentation as the initial manifestation of an otherwise clinically subtle indolent B-cell lymphoma, such as splenic marginal zone lymphoma, remains exceedingly uncommon. We report a case highlighting the importance of recognizing acquired factor VIII inhibitors, evaluating for underlying lymphoproliferative disorders, and the potential role of rituximab monotherapy in achieving control of both the inhibitor and the underlying lymphoma. CASE REPORT A 77-year-old man presented with spontaneous bruising and an isolated prolonged activated partial thromboplastin time that failed to correct on mixing studies. Further evaluation demonstrated markedly reduced factor VIII activity, a factor VIII inhibitor, diffuse splenomegaly, and flow cytometry and bone marrow biopsy findings most consistent with splenic marginal zone lymphoma. Treatment with activated prothrombin complex concentrate, corticosteroids, and rituximab resulted in normalization of coagulation parameters, recovery of factor VIII activity, decline in inhibitor titers, resolution of bleeding manifestations, and sustained clinical stability without recurrent bleeding or evidence of lymphoma progression. CONCLUSIONS This case highlights acquired hemophilia A as a rare paraneoplastic manifestation of splenic marginal zone lymphoma and emphasizes the importance of evaluating for an underlying lymphoproliferative disorder in older adults presenting with newly identified factor VIII inhibitors, particularly in the setting of cytopenias or splenomegaly. It also demonstrates that rituximab-based therapy can effectively achieve sustained remission of both the inhibitor and the underlying indolent lymphoma.

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2026-06-17 | Splenic Marginal Zone Lymphoma Presenting with Progressive Splenic Infarction and Acute Cholestatic Liver Injury- a Case Report

Abstract Background Splenic marginal zone lymphoma (SMZL) is a rare, indolent non-Hodgkin lymphoma. Progressive splenic infarction and acute cholestatic liver injury are uncommon complications, and their concurrent presentation has not been previously reported. Case Description A 76-year-old woman with remote breast cancer history and chronic splenomegaly with pancytopenia presented with worsening left-sided abdominal pain. Labs revealed pancytopenia and cholestatic liver injury. CT demonstrated a 22-cm spleen with multiple wedge-shaped infarcts and mildly heterogeneous hepatic enhancement. PET/CT showed diffuse splenic hypermetabolism, hypermetabolic periportal lymph nodes, and mildly increased bone marrow FDG uptake. Hemolysis workup including direct antiglobulin test and cold agglutinin titer was negative. Hepatitis B and C serologies were negative. D-dimer was markedly elevated at 3,840 ng/mL. MRCP excluded biliary obstruction. Percutaneous splenic core biopsy revealed nodular and intrasinusoidal infiltration by atypical B lymphocytes. Immunohistochemistry showed CD20, PAX5, and IgM positivity with kappa restriction; CD5, CD10, CD23, CD103, and cyclin D1 were negative. CD21 highlighted follicular dendritic cell meshworks colonized by neoplastic cells. The patient was staged as Ann Arbor stage IV. Rituximab monotherapy was initiated with clinical improvement. At 6-month follow-up, liver function normalized, cytopenias resolved, splenic size decreased from 22 to 17 cm, and PET/CT demonstrated partial metabolic response. Significance This is the first reported case of SMZL with concurrent splenic infarction and cholestatic liver injury. It highlights the diagnostic utility of splenic core biopsy with an expanded immunohistochemical panel and the efficacy of rituximab monotherapy in this clinical context.

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2026-05-13 | Beyond Hypersplenism: Splenic Marginal Zone Lymphoma in an Older Adult with Hemoglobin E/Beta-Thalassemia.

With improvements in blood safety and availability, along with broad access to safe and effective iron chelation, outcomes for patients with thalassemia have greatly improved over recent decades. Previously a predominantly pediatric condition, thalassemia is now increasingly encountered in an aging population. We describe an adult man with HbE/β-thalassemia whose course was complicated by progressive splenomegaly and cytopenias, initially attributed to his underlying thalassemia. Further evaluation, however, revealed splenic marginal zone lymphoma. After the initiation of anti-B-cell therapy, he experienced rapid clinical improvement and was able to avoid surgical splenectomy. This case highlights how complications ascribed to thalassemia can overlap with other diagnoses that may become more prevalent with age, and demonstrates the importance of maintaining a broad differential when symptoms progress despite appropriate thalassemia-directed management.

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2026-05-01 | B53-11 Refractory Antiphospholipid Syndrome Presenting as a Splenic Infarct and Mesenteric Mass - A Challenging Diagnosis

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder that often affects young women. It is recognized by the presence of antiphospholipid antibodies, including anticardiolipin antibodies (aCL), lupus anticoagulant (LA), and anti-beta-2-glycoprotein I (aβ2GPI) antibodies in the setting of venous or arterial thrombosis or pregnancy morbidity. APS can be primary or secondary to autoimmune diseases, drugs, infections, or malignancy. Clinicians should maintain a high index of suspicion for secondary APS, especially in older patients or those with progressive thrombosis despite adequate anticoagulation. This report presents an anticoagulant-refractory case of APS in a 60-year-old woman that was ultimately driven by an underlying lymphoproliferative disorder. Case Presentation A 60-year-old woman with hypertension, atrial fibrillation, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), gout, gastroesophageal reflux disease (GERD), and fatty liver disease presented with left upper quadrant abdominal pain associated with nausea, vomiting, and early satiety. A computerized tomography (CT) scan revealed splenomegaly with splenic infarcts. Coagulation studies showed a normal prothrombin time (PT), prolonged activated partial thromboplastin time (aPTT), and mild thrombocytopenia. The mixing study demonstrated persistently elevated aPTT. Complete blood count showed anemia and leukopenia. Haptoglobin was low, complement level was normal, and antinuclear antibody (ANA) was elevated. Autoimmune serology confirmed persistently elevated aCL, elevated aβ2GPI antibody, and LA. Since diagnosis, her course was marked by failure to respond to a direct oral anticoagulant and subsequently to warfarin, as evidenced by progressive splenomegaly and the appearance of new splenic infarcts. She was therefore transitioned to subcutaneous enoxaparin, but her symptoms did not improve. Repeat imaging showed a new enhancing right lower mesenteric mass of unclear etiology. Peripheral blood smear showed relative lymphocytosis, although the morphology was not diagnostic for chronic lymphocytic leukemia. Flow cytometry demonstrated involvement by a CD5-negative, CD10-negative kappa-restricted B-cell lymphoproliferative disorder. Bone marrow biopsy confirmed a monotypic CD5-negative, CD10-negative B-cell population most consistent with splenic marginal zone lymphoma. Discussion Late-onset APS that continues to cause recurrent arterial and venous thrombosis with organ infarction despite appropriate anticoagulation should raise suspicion for a secondary driver, including a paraneoplastic process. In this patient, the refractory thrombotic behavior was related to an underlying lymphoproliferative disorder. Adequate anticoagulation could not be achieved without addressing the driving malignancy. She was started on rituximab 375 mg/m² intravenously (IV) weekly in addition to therapeutic enoxaparin 80 mg subcutaneously twice daily and aspirin 81 mg daily, resulting in clinical improvement. This abstract is funded by: None

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2026-04-27 | Frequency and Distribution of Lymphomas in Northwestern India: A Retrospective Analysis of 923 Cases Using the Latest World Health Organization Classification 5th Edition.

Lymphoma is a diverse category of hematological malignancy with geographic variation. This study aimed to determine the frequency and distribution of lymphomas in a single large tertiary care center in northwestern India where there has been paucity of regional data and to compare them with the Indian and world data. Histopathologic material of 923 lymphoma patients with their clinicopathologic data were analysed between the years 2021 to 2023. The lymphoma diagnosis was based on the current guidelines using morphologic and immunophenotypic methods in an appropriate clinical context. Of 923 lymphomas (N = 923), Hodgkin lymphoma (HL) constituted 33% (n = 305) and non-Hodgkin lymphomas (NHLs) constituted 77% (n = 618). B cell NHL accounted for 56% (n = 518) and T cell NHL 10% (n = 100). Diffuse large B cell lymphoma, NOS (n = 235) and peripheral T cell lymphoma, NOS (n = 10) were the commonest B and T-NHLs respectively. Hodgkin lymphoma comprised 305 cases (Hodgkin lymphoma, n = 305) of which classic Hodgkin lymphoma (CHL) comprised 293 cases (CHL, n = 293) and nodular lymphocyte predominant Hodgkin lymphoma comprised 12 cases (NLPHL, n = 12). When compared with the Indian and world data the prevalence of splenic marginal zone lymphoma (3.4%), mantle cell lymphoma (6.5%), plasmablastic lymphoma (1.3%) and primary mediastinal large B-cell lymphoma (1.3%) were higher. Immune deficiency/dysregulation related lymphomas(IDD-L, n = 39) constituted 4.2% of which HIV infection was the most frequent and DLBCL was the commonest lymphoma. The incidence of lymphoma in our region, that is the western India is quite comparable to the data from different studies available from the other parts of India and the world albeit with a few lymphomas showing rare features. The online version contains supplementary material available at 10.1007/s12288-025-02038-3.

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2022-04-30 | Development of an Antigen Delivery System for a B Cell-Targeted Vaccine as an Alternative to Dendritic Cell-Targeted Vaccines

Vaccines have contributed to the prevention of infectious diseases for a long time. Pathogen-derived antigens and adjuvants in vaccine formulations stimulate immune cells to elicit humoral and cellular immune responses against pathogens. Achieving highly immune responses with decreased adverse effects requires the development of a system that can deliver antigens to specific immune cells. Dendritic cells (DCs) are well-known professional antigen presenting cells (APCs) that initiate acquired immune responses by presenting antigens to T cells. Accordingly, DC-targeted vaccines have been investigated and applied in clinical trials for the treatment of infectious diseases and for chronic diseases such as cancers. In addition to DCs, B lymphocytes are regarded as professional APCs despite their primary role in humoral immunity. Therefore, B cell-targeted vaccines are also expected to elicit both humoral and cellular immune responses. In this review we summarize the basic functions of DCs and B cells as APCs. We also provide information on DC and B cell targeted vaccines in preclinical and clinical settings. Finally, we introduce our novel antigen delivery system that targets splenic marginal zone B cells and the ability of this system to act as a novel vaccine that elicits both humoral and cellular immune responses.

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