Cell Lymphoma Research Articles

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in Romania: First case series of all documented cases

SummaryBreast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon malignancy linked to textured breast implants by moderate evidence in 2021. Documenting Romanian cases provides valuable insights into epidemiology, management, and outcomes, enhancing global understanding and informing clinical practices. Our objectives were to analyze BIA-ALCL cases in Romania, focusing on patient demographics, implant characteristics, clinical presentation, diagnostic methods, treatment, and outcomes.We conducted a retrospective review of all known BIA-ALCL cases in Romania, examining patient demographics, implant details, clinical presentation, diagnostic methods, and outcomes. Data sources included medical records, surgical reports, follow-up data, and implant characteristics like shape, texture, and manufacturer.The mean age at diagnosis was 44.4 years. All patients had textured implants and no replacements, 4 with aesthetic indication and 1 reconstruction. The mean time from implantation to diagnosis was 7.2 years. Clinical presentations were primarily late seromas, diagnosed through fine needle aspiration and immunohistochemistry. Treatments involved multidisciplinary teams, with bilateral en-bloc explantation and adjuvant therapies in two cases. One patient had immediate reconstruction with smooth implants and Acellular Dermal Matrix. No disease recurrence was observed post-treatment.The low BIA-ALCL prevalence in Romania estimated at 1:44,500 compared to the mean of 1:13,745 in Europe indicates the need for an increased awareness and tracking. Establishing mandatory national implant registries, pathology databases, and enhancing physician and patient education will help identify potential cases. All cases involved textured implants, highlighting the need for ongoing research to identify risk factors and guide surgeons consulting patients with these implants.

A-194 Primary cutaneous anaplastic large cell lymphoma with locorregional lymph node involvement in a pregnant woman

A-194 Primary cutaneous anaplastic large cell lymphoma with locorregional lymph node involvement in a pregnant woman

Carfilzomib, lenalidomide, dexamethasone (KRD) in BTKi relapsed or refractory mantle cell lymphoma: A phase II study fromFondazione Italiana Linfomi.

Mantle cell lymphoma (MCL) is a rare lymphoproliferative neoplasm considered incurable, with a median survival of 3-5 years. In recent years, Bruton's tyrosine kinase inhibitors (BTKi) have been introduced, demonstrating high therapeutic activity. However, the prognosis for MCL patients failing ibrutinib therapy is particularly poor, with a survival expectation of a few months. In this phase II trial, we assessed the efficacy and safety of the carfilzomib-lenalidomide-dexamethasone (KRD) combination in MCL patients who were relapsed/refractory (R/R) or intolerant to BTKi and in need of treatment. The primary objective of the study was to evaluate the antitumor efficacy of the KRD combination in terms of 12-month overall survival (12-month OS). From September 2019 to December 2020, 16 patients were enrolled from 11 Italian centers. After a median follow-up of 2.37 months (95% CI 0.92-6.47), the 12-month OS was 13%. The rate of grade 3-4 adverse events (AEs) was 35%, and the overall response rate (ORR) was 19%. These results led to the premature termination of enrollment, as defined in the protocol stopping rules. The efficacy of the KRD combination in advanced-stage MCL patients who are R/R to BTKi is unsatisfactory and too toxic.

S2764 A Rare Case of Primary Gastrointestinal Mantle Cell Lymphoma Hiding in Plain Sight as Colon Polyps

S2764 A Rare Case of Primary Gastrointestinal Mantle Cell Lymphoma Hiding in Plain Sight as Colon Polyps

S2996 A Normal Screening Colonoscopy and Then a Polypoid Mass: Recurrent Mantle Cell Lymphoma in the Gastrointestinal Tract

S2996 A Normal Screening Colonoscopy and Then a Polypoid Mass: Recurrent Mantle Cell Lymphoma in the Gastrointestinal Tract

MO26-1 Efficacy and safety of zanubrutinib in patients with relapsed or refractory mantle cell lymphoma: a systematic review

MO26-1 Efficacy and safety of zanubrutinib in patients with relapsed or refractory mantle cell lymphoma: a systematic review

TARMAC trial—a new path for chimeric antigen receptor (CAR) T in relapsed mantle cell lymphoma (MCL)?

TARMAC trial—a new path for chimeric antigen receptor (CAR) T in relapsed mantle cell lymphoma (MCL)?

A-226 Clonal evolution, antigens, and triggers in Cutaneous T Cell Lymphoma pathogenesis

A-226 Clonal evolution, antigens, and triggers in Cutaneous T Cell Lymphoma pathogenesis

Measurable Residual Disease Testing Following Nonintensive Chemoimmunotherapy is Predictive of Need for Maintenance Therapy in Previously Untreated Mantle Cell Lymphoma: A Wisconsin Oncology Network Study

IntroductionObinutuzumab is hypothesized to improve progression-free survival (PFS) combined with bendamustine induction in mantle cell lymphoma (MCL). Measurable-residual disease (MRD) testing may predict benefit from maintenance therapy. MethodsAdults (≥ 18 years) with untreated MCL ineligible for intensive therapies received 4 to 6 cycles of bendamustine + obinutuzumab (BO) followed by consolidation obinutuzumab (CO). Restaging after CO included MRD assessment by next-generation sequencing of bone marrow aspirate (BMA) and peripheral blood (PB). Maintenance obinutuzumab (MO) was omitted for patients with imaging complete response (CR) and MRD-negativity in PB/BMA. All other patients received 8 cycles MO. Primary endpoint is PFS; secondary endpoints are response rates, overall survival, and estimation of MRD status. ResultsTwenty-one patients enrolled, with median age 70 years and stage IV disease in 95%. Twenty patients completed BO; 10 patients received MO per protocol. Six patients did not complete MO due to progression (n = 4), infection (n = 1) and carcinoma (n = 1). Overall response is 95% (75% CR, 20% partial response). Concordance rate between postconsolidation MRD testing in PB and BMA was 70%.After a median follow-up of 43.9 months, median PFS is 46.5 months. The observed difference between 2-year PFS in groups receiving MO versus observation was not statistically significant (HR 0.45, 95% CI, 0.10-1.91). Most common grade 3/4 toxicities were neutropenia, leukopenia, and infections. ConclusionsBO is a tolerable induction regimen with higher rates of CR compared with historical rates with bendamustine + rituximab. Omission of MO did not worsen outcomes in patients achieving MRD-negative status after nonintensive induction/consolidation therapy.

P4-2 Efficacy and safety of chimeric antigen receptor-T cells in B cell lymphoma malignacy: a systematic review meta-analysis

P4-2 Efficacy and safety of chimeric antigen receptor-T cells in B cell lymphoma malignacy: a systematic review meta-analysis

P4-5 Patient characteristics and treatment patterns in patients with Mantle cell lymphoma in Japan: a real-world study

P4-5 Patient characteristics and treatment patterns in patients with Mantle cell lymphoma in Japan: a real-world study

A-295 Radiotherapy Dose for Primary Cutaneous Anaplastic Large Cell Lymphoma

A-295 Radiotherapy Dose for Primary Cutaneous Anaplastic Large Cell Lymphoma

Rituximab induces ferroptosis and RSL3 overcomes rituximab resistance in diffuse large B-cell lymphoma cells

Rituximab induces ferroptosis and RSL3 overcomes rituximab resistance in diffuse large B-cell lymphoma cells

A-221 The effect of Anthracycline treatment on primary cutaneous T-cell lymphoma cells

A-221 The effect of Anthracycline treatment on primary cutaneous T-cell lymphoma cells

A Multifunctional Biomimetic Nanoplatform for Dual Tumor Targeting-Assisted Multimodal Therapy of Colon Cancer.

The biomimetic nanoparticles (NPs) possessing abilities of tumor targeting and multimodal therapy show great potential for efficient combat of colon cancer. Herein, we developed a multifunctional biomimetic nanoplatform (Fe3O4@PDA@CaCO3-ICG@CM) based on CaCO3-modified magnetic polydopamine (PDA) loaded with indocyanine green (ICG), which was encapsulated by a mouse lymphoma cell (EL4) membrane (CM) expressing functional proteins (i.e., lymphocyte function-associated antigen 1, LFA-1; transforming growth factor-β receptor, TGF-βR; programmed cell death protein 1, PD-1; and factor related apoptosis ligand, FasL). Under magnetic attraction and LFA-1/PD-1-mediated endocytosis, Fe3O4@PDA@CaCO3-ICG@CM efficiently targeted CT26 colon tumor cells. The released calcium ion (Ca2+) from the NPs triggered by acidic tumor microenvironment, the enhanced photothermal effect contributed by the combination of PDA and ICG, and FasL's direct killing effect together induced tumor cells apoptosis. Moreover, the apoptosis of CT26 cells induced immunogenic cell death (ICD) to promote the maturation of dendritic cells (DCs) to activate CD4+/CD8+ T cells, thereby fighting against tumor cells, which could further be boosted by programmed death-ligand 1 (PD-L1) blockage and transforming growth factor-β (TGF-β) scavenging by Fe3O4@PDA@CaCO3-ICG@CM. As a result, in vivo satisfactory therapeutic effect was observed for CT26 tumor bearing-mice treated with Fe3O4@PDA@CaCO3-ICG@CM under laser irradiation and magnetic attraction, which could eradicate primary tumors and restrain distant tumors through dual tumor targeting-assisted multimodal therapy and eliciting adaptive antitumor immune response, generating the immune memory for inhibiting tumor metastasis and recurrence. Taken together, the multifunctional biomimetic nanoplatform exhibits superior antitumor effects, providing an insightful strategy for the field of nanomaterial-based treatment of cancer.

CORRELATION OF T-CELL LYMPHOMA SUBTYPES WITH ANEMIA AT DR MOHAMMAD HOESIN HOSPITAL PALEMBANG 2018-2022

Lymphoma is divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Among NHL T-cell lymphoma is a rare malignancy of T cells, accounts for 12% of all NHL cases, it is further classified into 53 subtypes by WHO. T-cell lymphoma generally have worse prognosis than those B cells. In 2020 there were 16.125 new cases in Indonesia with 9.024 deaths for all ages and genders. Anemia occurs in some cases of lymphoma, which will make the prognosis of lymphoma worse. This study aims to determine the relationship between T-cell lymphoma subtype and anemia. This observational analytic study utilized a cross-sectional design conducted at the Department of Anatomic Pathology Faculty of Medicine Sriwiaya University/Dr. Mohammad Hoesin Palembang Hospital (RSMH) and the central laboratory of RSMH. The samples from this study were all patients who were diagnosed histopathologically and immunohistochemically as T cell lymphoma at RSMH Palembang from 2018 to 2022. Among 38 samples, T-cell lymphoma predominated in the age group <55 years (73,7%), male gender (73,7%), extranodal location (73,7%), and ENKTCL, nasal subtype (55,3%). Anemia occurred in 60,5% cases and most often it is mild anemia (60,9%). There was no significant correlation between T-cell lymphoma subtype and anemia status (*p = 0.178) and T-cell lymphoma subtype and anemia degree (*p = 0.342). It can be concluded that there is no significant correlation between the T-cell lymphoma subtype and anemia.

Neoadjuvant Immunotherapy and De-Escalation of Surgery in Locally Advanced Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T cell lymphoma diagnosed in patients with a history of breast implants. Most patients develop a periprosthetic effusion at early stages of disease while less common presentations include a palpable mass, severe capsular contracture, lymphadenopathy, or cutaneous erythema. Due to the complex nature of this disease, a multidisciplinary approach is necessary for optimal management, particularly in locally advanced disease or inoperable patients. We present the successful use of neoadjuvant therapeutic protocols in two cases of locally advanced BIA-ALCL. The first case, a 52-year-old patient with a left breast mass-like stage III disease who underwent combined targeted immunotherapy and chemotherapy (BV-CHP). Following a complete radiological and metabolic response, the patient underwent bilateral implant removal, right total intact capsulectomy, left en bloc capsulectomy and skin resection from the left inframammary fold in continuity with the capsule. The second case, a 65-year-old patient with a right breast swelling and mass-like stage IIA disease who received targeted immunotherapy, Brentuximab vedotin (BV). Following a complete metabolic response, she underwent bilateral implant removal and en bloc capsulectomy. A literature review and the reported cases suggest the effectiveness of targeted immunotherapy as monotherapy or in combination with chemotherapy in locally advanced BIA-ALCL in disease downstaging, surgical de-escalation, reduction of significant post-operative complications and an acceptable tolerance profile. Although surgery is an essential part of treatment, timing and type of intervention should be carefully planned, especially when primary, radical resection is uncertain.

Developing new drugs for adult T-cell leukemia/lymphoma by targeting hypoxia: insights from toxicity of MS-275 and its analogs

The low survival rate of adult T-cell leukemia/lymphoma (ATL) underscores the critical need for innovative therapeutic agents. While the pharmacokinetics of HDACis have been documented in several hematological neoplasms, there is a notable gap in research regarding their activity against ATL. Given that hypoxia can induce unpredictable effects on lymphoma cells, this study aimed to evaluate the toxic effects of MS-275 and novel analogs on ATL cells in hypoxic condition for the first time. Protein-protein interaction and gene set enrichment analyses were performed, the expression of HIF1A and downstream targets were assessed, and molecular docking was conducted on MS-275 and novel analogs with HIF-1α. For in vitro studies, at first benzamide analogs of MS-275 were synthesized and then, viability of MT-2 cells was evaluated in hypoxic condition. Enrichment analyses confirmed the involvement of hub genes in HIF-1 signaling pathway and volcano plot revealed over expression of HIF1A, GAL3ST1 and CD274. Molecular docking indicated favorable interaction between MS-275 and analogs with HIF-1α PAS-B domain. Results of alamarBlue assay demonstrated that MS-275 and analogs significantly (p < 0.001) reduced viability of MT-2 cells in hypoxic condition. Findings of the present study hold promise for developing new drugs targeting hypoxia-induced changes in ATL.

Mantle cell lymphoma with skin involvement: Case report of a rare manifestation in a patient with initial diagnosis of chronic lymphocytic leukemia

Mantle cell lymphoma is a rare subtype of B-cell non-Hodgkin's lymphoma, which mainly affects males. It has a variable clinical presentation, with a course ranging from indolent cases that do not require treatment for years to very aggressive cases. Skin involvement is a rare event. Although most patients have disease in stage III or IV at diagnosis, they generally present with good functional status. In immunohistochemistry, CD5 is commonly expressed, a feature it shares with chronic lymphocytic leukemia. Cyclin D1 and SOX11 expression are present in almost all cases. Treatment depends on multiple factors such as age, frailty, comorbidities, disease stage, symptoms and morphological characteristics. We present the case of a male patient initially diagnosed with chronic lymphocytic leukemia who was started on treatment with ibrutinib. A biopsy of the right earlobe was subsequently performed, which documented secondary skin involvement due to a classic histological variant of mantle cell lymphoma. The patient was treated with chemotherapy between March and July 2022, with positron emission tomography at the end of the proposed cycles with complete metabolic response, so maintenance treatment with rituximab was performed and subsequently consolidated with an autologous bone marrow transplant. To date, the patient is in remission of the disease.

Novel hydrazide-hydrazone containing 1,2,4-triazole as potent inhibitors of antiapoptotic protein Bcl-xL: Synthesis, biological evaluation, and docking studies.

This study describes the synthesis and characterization of a series of novel hydrazide-hydrazone derivatives containing a 1,2,4-triazole ring. The compounds were characterized using various spectroscopic techniques, such as FT-IR, 1H-NMR, 13C-NMR, HRMS, and elemental analysis. The antiproliferative activity of the synthesized compounds was evaluated against a panel of human cancer cell lines (HCT-116, HepG-2, KLN205, LTPA, U138, and SW620) and healthy cell lines (HSkMC and iPSCs). Among the compounds tested, compounds 4, 5p, 5r, and 5s showed the highest effectiveness in inhibiting the growth of cancer cells with Bcl-xL inhibitory concentration (IC50) values. These compounds further demonstrated selective cytotoxicity against the Bcl-xL-dependent lymphoma cell line (DBs). Molecular docking studies were also performed to investigate the potential binding interactions of compounds 4, 5p, 5r, and 5s with the active site of Bcl-xL (PDB ID: 7LH7, 1.4 Å). Mechanistic studies revealed that compounds 4, 5r, and 5s induced apoptosis predominantly through the intrinsic mitochondrial pathway, while compound 5p exhibited a distinct cell cycle arrest profile, impacting both the S and G2/M phases. Western blot analysis suggested that these compounds may downregulate cyclin expression, thereby blocking its association with Bcl-xL. Overall, these results demonstrate the potential of these novel hydrazide-hydrazone derivatives as anticancer agents with activity comparable or superior to doxorubicin and 5-fluorouracil.