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INTRODUCTION: Blastoid variant-mantle cell lymphoma (BV-MCL) represents an aggressive subset of patients with no established standard of care treatment approach. METHODS: We performed a retrospective analysis of the clinical characteristics and outcomes of 17 de novo BV-MCL patients treated at our institution between May 2009 and September 2023. In addition, we reviewed the literature supporting 2nd/3rd generation Brutons Tyrosine-kinase (BTKi)-based therapies for upfront management. RESULTS: The complete response rate to frontline and salvage therapy was 66.7% and 25%, respectively. Two-year overall survival (OS) was low at 62.5% (95% CI, 34.7%-81.1%). Variables associated with higher OS included receipt of consolidative HSCT (p = 0.017), TP53-wild type (p = 0.031), intermediate- versus high-risk Mantle Cell Lymphoma Prognostic Index score (p = 0.026), and achieving complete response with induction therapy (p = 0.027). DISCUSSION: Treatment outcomes with chemo-immunotherapy in BV-MCL patients are poor, especially among TP53-mutated patients. Recent findings describing positive outcomes with novel BTKi-based therapies are encouraging and should be considered in this high-risk population.

Chimeric Antigen Receptor T-cell (CAR-T) therapy uses genetically engineered T-cells with specific binding sites. This therapy allows for tumor specificity and durable treatment responses for patients with hematological malignancies. In this review, we study the risk of venous thromboembolism (VTE) associated with CAR-T therapy. We searched the National Institutes of Health library, Cochrane Library Databases, ClinicalTrials.gov database, and medical literature search engines PubMed and Google Scholar for Phase 2 and Phase 3 drug-efficacy and safety trials to determine the aggregate incidence and risk of VTE treated with CAR-T. Of 1127 search results, nine studies were identified and included in our meta-analysis. Of the 1017 patients who received therapy, 805 patients (79.15%) experienced some degree of CRS, and 122 patients (11.9%) experienced severe CRS (higher than grade 3). Only three out of one thousand and seventeen patients were reported to have experienced venous thromboembolism. Our study did not find a statistically significant association between increased VTE incidence (OR = 0.0005, 95% CI [0.0001, 0.0017]) and CRS/ICANS (p < 0.0001). There was a 0.0050 (95% confidence interval [0.0019, 0.0132]) relative risk for VTE. In our study, we did not find a statistically significantly increased risk of developing VTE despite CRS and underlying malignancy, which have been associated with increased risk of VTE.

BRAF mutations are associated with a small number of hematologic malignancies, including hairy cell leukemia and histiocytic disorders. In addition, BRAF mutations have also been detected in low frequency in other B-cell lymphomas, such as chronic lymphocytic leukemia and diffuse large B-cell lymphoma, but never in mantle cell lymphoma (MCL). We present a case of a 69-year-old female with classic MCL harboring a BRAFN581S mutation. To our knowledge, this is the first reported case of any BRAF mutation in MCL.

Mantle cell lymphoma (MCL) is a clinically heterogeneous B‐cell neoplasm with unique clinicopathological features, accounting for 5% of all non‐Hodgkin lymphoma. Although for many chemoimmunotherapy can lead to durable remissions, those with poor baseline prognostic factors, namely blastoid morphology, TP53 aberrancy and Ki67 >30%, will have less durable responses to conventional therapies. With this in mind, clinical trials have focused on novel targeted therapies to improve outcomes. This review details the recent advances in the understanding of MCL biology and outlines the recommended diagnostic strategies and evidence‐based approaches to treatment. [ABSTRACT FROM AUTHOR]

The article discusses the differential diagnosis of lymphocytosis using lymphocyte parameters generated by the Sysmex XR-1000 Hematology Analyzer. The study conducted at a hospital laboratory in France aimed to differentiate between reactive and malignant lymphocytosis, focusing on six lymphocyte positional parameters. Results showed that the parameters Ly-X, Ly-Y, and Ly-Z were the most discriminative among different pathological groups, aiding in distinguishing various lymphoproliferative disorders. The study suggests that integrating qualitative and quantitative parameters can improve the accuracy of diagnosing malignant lymphocytosis. [Extracted from the article]

Lymphoma growth, progression, and dissemination require tumor cell interaction with supporting vessels and are facilitated through tumor-promoted angiogenesis, lymphangiogenesis, and/or lymphoma vessel co-option. Vessel co-option has been shown to be responsible for tumor initiation, metastasis, and resistance to anti-angiogenic treatment but is largely uncharacterized in the setting of lymphoma. We developed an in vitro model to study lymphoma–vessel interactions and found that mantle cell lymphoma (MCL) cells co-cultured on Matrigel with human umbilical vein (HUVEC) or human lymphatic (HLEC) endothelial cells migrate to and anneal with newly formed capillary-like (CLS) or lymphatic-like (LLS) structures, consistent with lymphoma–vessel co-option. To inhibit this interaction, we constructed an antibody fusion protein, αCD20-EndoP125A, linking mutant anti-angiogenic endostatin (EndoP125A) to an αCD20-IgG1-targeting antibody. αCD20-EndoP125A inhibited both CLS and LLS formation, as well as MCL migration and vessel co-option. Lymphoma vessel co-option requires cell migration, which is regulated by chemokine–chemokine receptor interactions. CXCL12 and its receptor, CXCR4, are highly expressed by both endothelial cells forming CLS and by MCL cells during vessel co-option. αCD20-EndoP125A suppressed expression of both CXCL12 and CXCR4, which were required to facilitate CLS assembly and vessel co-option. We also tested αCD20-EndoP125A effects in vivo using an aggressive murine B cell lymphoma model, 38c13-hCD20, which demonstrated rapid growth and dissemination to tumor-draining lymph nodes (TDLNs) and the spleen, lung, and brain. The pattern of lymphoma distribution and growth within the lung was consistent with vessel co-option. As predicted by our in vitro model, αCD20-EndoP125A treatment inhibited primary tumor growth, angiogenesis, and lymphangiogenesis, and markedly reduced the number of circulating tumor cells and lymphoma dissemination to TDLNs and the lungs, spleen, and brain. αCD20-EndoP125A inhibited lymphoma vessel co-option within the lung. Marked inhibition of MCL primary tumor growth and dissemination were also seen using an MCL xenograft model. The ability of αCD20-EndoP125A to inhibit angiogenesis, lymphangiogenesis, and lymphoma vessel co-option provides a novel therapeutic approach for inhibition of lymphoma progression and dissemination. [ABSTRACT FROM AUTHOR]

FoxO transcription factors (FoxO1, FoxO3a, FoxO4, FoxO6) are a highly evolutionary conserved subfamily of the ‘forkhead’ box proteins. They have traditionally been considered tumor suppressors, but FoxO1 also exhibits oncogenic properties. The complex nature of FoxO1 is illustrated by its various roles in B cell development and differentiation, immunoglobulin gene rearrangement and cell‐surface B cell receptor (BCR) structure, DNA damage control, cell cycle regulation, and germinal center reaction. FoxO1 is tightly regulated at a transcriptional (STAT3, HEB, EBF, FoxOs) and post‐transcriptional level (Akt, AMPK, CDK2, GSK3, IKKs, JNK, MAPK/Erk, SGK1, miRNA). In B cell malignancies, recurrent FoxO1 activating mutations (S22/T24) and aberrant nuclear export and activity have been described, underscoring the potential of its therapeutic inhibition. Here, we review FoxO1's roles across B cell and myeloid malignancies, namely acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), Burkitt lymphoma (BL), Hodgkin lymphoma (HL), and multiple myeloma (MM). We also discuss preclinical evidence for FoxO1 targeting by currently available inhibitors (AS1708727, AS1842856, cpd10). [ABSTRACT FROM AUTHOR]

Lymph cancer, also known as lymphoma, refers to the uncontrolled proliferation of the body's defensive cells, resulting in their transformation into cancerous cells. Lymphoma belongs to the group of blood cancers and exhibits a higher incidence compared to other cancers within this category. Early and accurate diagnosis plays a crucial role in managing this disease. In this particular investigation, an expert support system was developed employing histopathological images of lymph cancer. The data set comprised images of various lymphomas, including chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). The initial approach involved utilizing the GLCM method to extract features from these images, while subsequent approaches adopted transfer learning architectures. Additionally, principal component analysis was employed for feature selection and dimension reduction. For the classification stage, a combination of machine learning algorithms such as random forests, k-nearest neighbors (KNN), naive Bayes, and decision trees, as well as deep learning methods including VGG16, ResNet50, and DenseNet201 architectures were employed. The models were trained separately for double and triple classes, and their performance was evaluated. The highest accuracy values in binary classification are: 94% for CLL and FL, 92% for FL and MCL, and 82% for MCL and CLL. In triple classification, the highest accuracy rate is 82%. The lowest accuracy values in binary classification are: 52% for CLL and FL, 57% for FL and MCL, and 49% for MCL and CLL. The methods by which these accuracy values were obtained are stated in "Results" section. However, due to the difficulty in distinguishing between MCL- and CLL-type lymphomas, the classification accuracy for these lymphomas was lower compared to the other classifications. On the other hand, the classification accuracy for FL was higher, as it exhibits more distinctive features than the other two lymphomas. The lowest success in the study was achieved at 36% as a result of the use of the KNN algorithm in triple classification. Notably, the DenseNet201 method achieved the highest success in the study, accurately classifying FL and CLL with a 94% accuracy rate. [ABSTRACT FROM AUTHOR]

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a tumour target currently used for the development of novel therapeutic modalities, such as antibody-drug conjugates, chimeric antigen receptor T-cell therapies, and others. Success of these new drugs depends on the selection of relevant indications based on ROR1 tumour prevalence, staining heterogeneity, and subcellular localization, among other parameters. We investigated ROR1 immunophenotype using validated antibody clones for immunohistochemistry (IHC) and flow cytometry (FC), analyzing 292 tumour specimens from 7 haematological malignancies and triple negative breast cancer (TNBC) as a reference solid tumour indication. ROR1 prevalence varied significantly across distinct tumour types, showing 100% of ROR1 positivity in all chronic lymphocytic leukaemia (n = 48) and hairy cell leukaemia (n = 14) specimens analyzed via FC with ranges between 1.1–99.8% and 0.8–62.1%, respectively. Samples analysed via IHC showed ROR1 membrane/cytoplasmic positivity in 44% of mantle cell lymphoma tumour samples (n = 27; H-score range: 10–285 in positive cases); 30% in TNBC (n = 46; H-score range: 1–200); 15% in diffuse large B-cell lymphoma (n = 45; H-score: 40–250); and 11% in follicular lymphoma (n = 34; H-score: 2–300). Finally, all acute myeloid leukaemia (n = 52) and most T-cell non-Hodgkin lymphoma (n = 31/32) tested samples were negative for ROR1 via IHC. In conclusion, ROR1 shows a heterogeneous tumour cell expression profile across multiple leukaemias and lymphomas, making it a tumour target that would require different patient selection strategies to develop novel therapeutic modalities. [ABSTRACT FROM AUTHOR]

Novel therapies such as CAR-T, BTK inhibitors and PD-1 inhibitors have changed the management of aggressive B-cell lymphomas. Nonetheless, these novel therapies have their own risk of late toxicities including second malignancies. They also create a subgroup of patients with relapse, treatment failure, or indefinite maintenance. We discuss the current role of autologous and allogeneic stem cell transplantation in this context. In patients with recurrent diffuse large B-cell lymphoma, CAR-T cell treatment has largely replaced autologous transplant. Autologous transplant should be considered in patients with late relapses and in selected patients with T-cell-rich B-cell lymphoma, where CAR-T cell therapy may be less effective. It also remains the treatment of choice for consolidation of patients with primary CNS lymphoma. In mantle cell lymphoma, intensive chemotherapy combined with BTK inhibitors and rituximab results in excellent outcomes, and the role of autologous transplantation is declining. In Hodgkin's lymphoma, autologous transplant consolidation remains the standard of care for patients who failed initial chemotherapy. Allogeneic transplantation has lower relapse rates but more complications and higher non-relapse mortality than autologous transplantation. It is usually reserved for patients who fail autologous transplantation or in whom autologous stem cells cannot be collected. It may also have an important role in patients who fail CAR-T therapies. The increasing complexity of care and evolving sequencing of therapies for patients with aggressive B-cell lymphomas only emphasizes the importance of appropriate patient selection and optimal timing of stem cell transplantation. [ABSTRACT FROM AUTHOR]

The document discusses a study on mantle cell lymphoma (MCL) with cutaneous involvement, a rare subtype of non-Hodgkin lymphoma. The study conducted at MD Anderson Cancer Center over a decade found that cutaneous involvement in MCL is rare but associated with aggressive disease biology and poor prognosis. The research highlights the effectiveness of systemic therapy with or without low-dose radiotherapy and the potential promise of CAR T cell therapy in managing MCL with cutaneous involvement. The study emphasizes the importance of skin examination, biopsy confirmation, and further research to optimize treatment strategies for this condition. [Extracted from the article]

The letter to the editor discusses the importance of long-term follow-up of autologous stem cell transplantation (ASCT) for mantle cell lymphoma (MCL). A retrospective study in Alberta, Canada, involving 141 patients who underwent ASCT as part of first-line therapy for MCL between 2000 and 2022, revealed a median progression-free survival (PFS) of 11.3 years and an overall survival (OS) of 14.0 years. The study suggests that ASCT achieves durable remissions in MCL, with a subset of patients experiencing remissions lasting 10-20 years, indicating potential functional cure. The findings highlight the need for further research and longer-term follow-up data to determine the efficacy of ASCT in MCL treatment. [Extracted from the article]

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9–14.6) and 9.1 months (95% CI: 7.3–11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34–57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5–21.0) and 32.1 months (95% CI: 25.2–41.2), with a pooled ORR of 89% (95% CI: 86–91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is frequently diagnosed at advanced stages and is characterized by multiple extranodal sites of disease, most notably the bone marrow, peripheral blood, and gastrointestinal tract. Historically the prognosis of mantle cell lymphoma has been poor with median survival of four to five years. With new treatment regimens, however, patients have been able to achieve prolonged remissions and require special attention while being evaluated for relapse. This report describes four patients treated for stage IV mantle cell lymphoma at the University of Miami who developed soft tissue relapse presenting as non-tender large masses of the extremities, including one patient who presented without associated nodal involvement. Average time to soft tissue relapse was 99 months (range: 28–240) following initial diagnosis. Providers who care for patients with mantle cell lymphoma should be aware of soft tissue lesions as a presentation of mantle cell lymphoma that merits evaluation for disease relapse. [ABSTRACT FROM AUTHOR]

Bendamustine in combination with rituximab (BR) or with rituximab and cytarabine (R-BAC) is the standard first-line immunochemotherapy in mantle cell lymphoma (MCL) for elderly patients and patients ineligible for intensive regimens or autologous transplantation. As bendamustine causes prolonged lymphopenia and the literature lacks evidence of its persistence in patients with MCL, this retrospective analysis aims to estimate the lymphocyte recovery time, also in view of potential immunotherapy with CAR-T cells. Data were collected from 44 consecutive MCL patients who received bendamustine (BR or R-BAC) as first-line therapy at the Hematology Unit of Sapienza University Hospital between May 2011 and April 2022. Twenty patients (45%) were treated with R-BAC and 24 (55%) with BR. At baseline, the median lymphocyte count was 1795/µl (range: 370–11730/µL). One month after the end of therapy, it was 450/µl (range: 50–3300/µl) and 3 months after 768/µl (range: 260–1650/µl). After 6 and 9 months, we observed a gradual increase in median lymphocyte count of 900/µl (range: 370–2560/µl and 130–2770/µl, respectively). After 12 months median lymphocyte count was 1256/µl (range: 240–4140/µl). Median lymphocyte count at 1, 3, 6, and 9 months post-treatment was significantly lower than baseline but showed recovery by the 12 months. This finding is crucial for MCL patients considering CAR-T cell therapy, suggesting a minimum 9-month interval between bendamustine administration and leukapheresis. [ABSTRACT FROM AUTHOR]

The article discusses the glycolytic activity following anti-CD19 CAR-T cell infusion in non-Hodgkin lymphoma patients. The study conducted at Tours University Hospital observed an increase in blood lactate levels post-infusion, indicating immune cell activation. High lactate levels were associated with a higher CD8+/CD4+ CAR-T cell ratio and longer circulating CAR-T cell persistence. The findings suggest a glycolytic activity in immune responses post-CAR-T infusion, potentially serving as a marker for metabolic interventions in the future. [Extracted from the article]

Summary During a fatal disease, patients often request updated information on their prognosis. After patients have already survived a certain time, conditional survival captures their future survival probability. We investigated conditional overall and failure‐free survival in 473 younger mantle cell lymphoma (MCL) patients from a randomized phase III trial comparing immunochemotherapies R‐CHOP and alternating R‐CHOP/R‐DHAP before autologous transplantation. Using conditional Kaplan–Meier method and Cox regression, we estimated subsequent survival of patients who had survived 1–8 years, considering MIPI, Ki‐67, and treatment failure status. Starting at a lower level, R‐CHOP patients only showed increasing subsequent survival as they survived longer (5‐year conditional survival: 72% and 81% after surviving 1 and 7 years), while R‐CHOP/R‐DHAP patients had stable future survival over time (77% and 78%). The prognostic value of MIPI diminished after 3 years in R‐CHOP patients but remained unchanged after R‐CHOP/R‐DHAP. Patients with treatment failure had markedly inferior survival compared with those in ongoing remission, regardless of the time survived. The longer patients remained in remission, the longer they would stay free of treatment failures. Our results enable personalized counselling for younger MCL patients by offering dynamic prognosis and underscore the importance of highly effective first‐line treatment to improve survival. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionWe describe a case of bilateral pseudo-uveitis and secondary glaucoma associated with recurrent mantle cell lymphoma (MCL) that was successfully treated with ibrutinib.Retrospective case report.A 75-year-old man presented with uveitis masquerade syndrome while undergoing treatment for MCL with rituximab–bendamustine. Initial ophthalmologic examination revealed pseudohypopyon, iris thickening, and considerable vitreous opacity of both eyes. Evaluation via anterior segment optical coherence tomography revealed iris thickening in both eyes. His best-corrected visual acuities were reduced to 20/28 and 20/2000 on the right eye (OD) and left eye (OS), respectively, and his intraocular pressure (IOP) was elevated at 40 (OD) and 52 (OS) mmHg. The patient had findings suggestive of recurrent MCL, such as skin lesions, hyponatremia, elevated blood lactase dehydrogenase, and the results of the skin biopsy were consistent with the pathological diagnosis of MCL in the bone marrow biopsy that had already been performed. He was diagnosed with MCL recurrence and treated by switching to ibrutinib, a Bruton’s tyrosine kinase inhibitor. After 1 week of treatment, all anterior ocular and vitreous lesions disappeared. Moreover, the skin lesions also disappeared, and the blood sample findings improved. On day 11 of treatment, BCVA improved to 20/20 in both eyes and IOP decreased to 8 (OD) and 11 (OS) mmHg. During the study course, CD5 and CD20 positive cells were identified in the anterior chamber of the eyes via flow cytometry, which was consistent with the pathological findings of biopsies.Ibrutinib may improve recurrent MCL intraocular lesions. [ABSTRACT FROM AUTHOR]

The article published in the British Journal of Haematology explores the clinicopathologic correlates and prognostic impact of lymphoid aggregates in patients with myelodysplastic syndromes (MDS). The study found that the presence of B-cell clonal or non-clonal lymphoid aggregates in MDS does not have a negative prognostic relevance. Patients with lymphoid aggregates, regardless of clonality, did not show adverse effects on survival. The research suggests that MDS patients with B-cell clonal aggregates should not be excluded from clinical trials, as these aggregates do not typically progress to overt lymphoid neoplasms. [Extracted from the article]

The article in the British Journal of Haematology discusses the treatment of refractory severe idiopathic immune thrombocytopenia (ITP) with daratumumab, an anti-CD38 antibody. The study reports on a case series of seven patients who received daratumumab treatment, with four patients achieving sustained complete remission. The findings suggest that daratumumab may be a valid treatment option for refractory ITP patients, leading to durable responses in some cases. Additional data from prospective clinical trials are needed to further evaluate the efficacy of daratumumab in treating ITP. [Extracted from the article]

Summary: 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. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin's lymphoma (NHL), which generally has an aggressive course. Its pathophysiology seems to be related with the malignant transformation of B-cell mantle zone lymphocytes due to the CCND1 rearrangement. The occurrence of MCL in the oral cavity is especially rare. In this report, we present an exceptional case of oral MCL diagnosed in the palate in a 56-year-old male patient, highlighting its distinct morphological and immunohistochemical features that may assist in the accurate diagnosis. [ABSTRACT FROM AUTHOR]

Acalabrutinib (ACL) was approved in the United States in the year of 2017 and 2019 for the treatment of chronic lymphocytic leukemia (CLL) and relapsed mantle cell lymphoma (MCL). Low-energy method was employed to curate nanoemulsion (NE) for which various components were screened through solubility study and optimization was done through a pseudo-ternary phase diagram. The NE was evaluated for its droplet size, polydispersity index (PDI), transmittance, morphology, rheology, robustness to dilution, the effect of pH, storage stability, and ex vivo permeation study. The optimized ACL-NE demonstrated an appropriate droplet size (94.35 ± 0.3 nm), PDI (0.27 ± 0.03), and an entrapment efficiency of 67.38 ± 2.69%. It showed non-Newtonian (shear thinning behavior) due to reduced viscosity with an increasing shear rate. The apparent permeability was 3.09-fold higher for ACL-NE than ACL suspension. An in vitro drug release study depicted a higher release of ACL (71.10 ± 10.99%) from the optimized NE in a sustained fashion than the suspension (49.01 ± 1.65%). A dose-dependent cytotoxicity was observed in MOLT-4 and HH-cell lines where the IC50 values of ACL were 5.62- and 16.49-fold reduced when encapsulated in oil globules for the respective cell lines. Blank-NE did cause a reduction in cellular toxicity at higher doses. A 7.31- and 5.1-fold increase in Cmax and bioavailability was noted between ACL suspension and ACL-NE. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the efficacy/safety of pirtobrutinib in the treatment of B-cell malignancies and distinguish it from other available Bruton's tyrosine kinase (BTK) inhibitors. Data sources: A literature search of PubMed (January 2021 through November 2023) and Clinicaltrials.gov was conducted using terms pirtobrutinib, Jaypirca, and LOXO 305. Licensing trials of available BTK inhibitors were also reviewed. Study selection and data extraction: Relevant English-language clinical trials were evaluated. Data synthesis: Pirtobrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) based largely on a phase 1/2 study in B-cell malignancies. Pirtobrutinib demonstrated a 73% overall response rate (ORR) in the CLL population and 58% in MCL. Pirtobrutinib has activity in patients resistant to earlier-generation, covalent BTK inhibitors. In fact, the ORRs were similar in BTK-pretreated and naïve patients. Adverse effects include fatigue, diarrhea, bleeding, and infection. Atrial fibrillation, a class effect of BTK inhibitors, may be less common with pirtobrutinib. Relevance to patient care and clinical practice in comparison with existing drugs: Compared with earlier-generation BTK inhibitors, pirtobrutinib is more selective for BTK and binds noncovalently to the receptor. Ongoing studies are evaluating pirtobrutinib's use in multiple B-cell malignancies and comparing it with other BTK inhibitors. Conclusion: The characteristics of pirtobrutinib render it useful in the treatment of B-cell malignancies no longer responding to a previous BTK inhibitor, and results from ongoing clinical trials may support future expanded use. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin’s lymphoma. Ferroptosis, an iron-dependent programmed cell death, is closely related to cancer prognosis. In this study, we established a model of ferroptosis related genes for prognostic evaluation of patients with MCL.

We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis. An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes. The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Introduction: The introduction of CAR-T cell treatment for relapsed/refractory (r/r) mantle cell lymphoma improved survival rates of these patients. Along with its introduction in clinical routine, long-term events after CAR-T cell treatment are increasingly emerging. Case Presentation: We report the case of a patient developing acute erythroid leukemia with biallelic TP53 inactivation occurring 26 months after CAR-T therapy with brexucabtagene autoleucel (brexu-cel) for r/r mantle cell lymphoma. The patient presented with a healthy bone marrow prior to lymphoma treatments. Discussion: Secondary malignancies seem more frequent after CAR-T therapies. More studies are needed to assess potential long-term toxicities of CAR-T cell therapies including the frequency of secondary myeloid malignancies.

Objective: to conduct a clinical and economic study of acalabrutinib for the treatment of adult patients with relapsed/refractory form of mantle cell lymphoma who previously received at least one line of therapy in the Russian Federation.Material and methods. Acalabrutinib and ibrutinib were considered as compared treatment options. Based on the adjusted indirect comparison, they were found to be comparable in terms of overall survival and progression-free survival. Therefore, a cost minimization analysis method was selected for the study. Based on results of ACE-LY-004 clinical trial a distributed survival model was developed. The model was used to calculate drug costs over a 3-year horizon. To explore uncertainty in the results of economic evaluations we conducted a sensitivity analysis. A number of patients in the hypothetical cohort who could be further treated with a less expensive drug was determined during a missed opportunity analysis. Both mean life years gained and mean progression-free life years were calculated too.Results. Based on simulations over a 3-year horizon, the mean life years gained were 2.45, and the mean progression-free life years were 1.75. The average costs of acalabrutinib therapy both over 1 year and in total over 3 years were 36.6% lower compared to ibrutinib. So, in the 1st year, the costs for acalabrutinib were 3,546,237,60 rubles, for ibrutinib – 5,591,391,00 rubles (a difference of 2,045,153,40 rubles). Using acalabrutinib for 3 years was associated with costs of 7,252,980,60 rubles compared to 11,435,852,60 rubles for ibrutinib (a decrease of 4,182,872,00 rubles). Univariate multi-way sensitivity analysis showed the robustness of modeling results to price fluctuations in the range ±10%. For a hypothetical cohort of 100 patients, using acalabrutinib instead of the more expensive ibrutinib within the same budget will provide therapy to additional 57 patients per year.Conclusion. The results of the study demonstrated that acalabrutinib compared to ibrutinib for the treatment of adult patients with relapsed/ refractory form of mantle cell lymphoma can reduce costs for the 1st year of therapy by 2,045,153,40 rubles (36.6%), and by 4,182,872,00 rubles (36.6%) for 3 years. Thus, acalabrutinib is the cost-saving option for previously treated adult patients with relapsed/refractory mantle cell lymphoma in the Russian Federation.

Abstract Rationale Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor.

Abstract The use of Bruton's tyrosine kinase inhibitors (BTKi) is rapidly increasing for patients with mantle cell lymphoma (MCL). Side effects reported so far are usually manageable. However, here we present two cases of life‐threatening aplastic anemia (AA) upon treatment with the BTKi acalabrutinib for MCL. The first patient died of neutropenic infection secondary to AA. The second patient was successfully treated with immunosuppressive treatment but the MCL relapsed shortly thereafter. AA is a potentially fatal complication that should be considered when patients present with pancytopenia during treatment with BTKi.

Chimeric Antigen Receptor T-cell (CAR-T) therapy uses genetically engineered T-cells with specific binding sites. This therapy allows for tumor specificity and durable treatment responses for patients with hematological malignancies. In this review, we study the risk of venous thromboembolism (VTE) associated with CAR-T therapy. We searched the National Institutes of Health library, Cochrane Library Databases, ClinicalTrials.gov database, and medical literature search engines PubMed and Google Scholar for Phase 2 and Phase 3 drug-efficacy and safety trials to determine the aggregate incidence and risk of VTE treated with CAR-T. Of 1127 search results, nine studies were identified and included in our meta-analysis. Of the 1017 patients who received therapy, 805 patients (79.15%) experienced some degree of CRS, and 122 patients (11.9%) experienced severe CRS (higher than grade 3). Only three out of one thousand and seventeen patients were reported to have experienced venous thromboembolism. Our study did not find a statistically significant association between increased VTE incidence (OR = 0.0005, 95% CI [0.0001, 0.0017]) and CRS/ICANS (p < 0.0001). There was a 0.0050 (95% confidence interval [0.0019, 0.0132]) relative risk for VTE. In our study, we did not find a statistically significantly increased risk of developing VTE despite CRS and underlying malignancy, which have been associated with increased risk of VTE.

Abstract Background Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20–30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. Case presentation A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. Conclusions The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.

Wen Jun Zhang,&ast; Chong Ling Hu,&ast; Bing Ling Guo, Xi Ping Liang, Chao Yu Wang, Tao Yang Department of Hematology Oncology, Chongqing University Cancer Hospital, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Yang, Department of Hematology Oncology, Chongqing University Cancer Hospital, No. 181, Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel +86-13527363925, Email ppyangtao@163.comObjective: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.Methods: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.Results: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.Conclusion: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.Keywords: mantle cell lymphoma, STAT5B, DCAF13, ferroptosis

Cyclin D1 has been recognized as an oncogene due to its abnormal upregulation in different types of cancers. Here, we demonstrated that cyclin D1 is SUMOylated, and we identified Itch as a specific E3 ligase recognizing SUMOylated cyclin D1 and mediating SUMO-induced ubiquitination and proteasome degradation of cyclin D1. We generated cyclin D1 mutant mice with mutations in the SUMOylation site, phosphorylation site, or both sites of cyclin D1, and found that double mutant mice developed a Mantle cell lymphoma (MCL)-like phenotype. We showed that arsenic trioxide (ATO) enhances cyclin D1 SUMOylation-mediated degradation through inhibition of cyclin D1 deSUMOylation enzymes, leading to MCL cell apoptosis. Treatment of severe combined immunodeficiency (SCID) mice grafted with MCL cells with ATO resulted in a significant reduction in tumor growth. In this study, we provide novel insights into the mechanisms of MCL tumor development and cyclin D1 regulation and discover a new strategy for MCL treatment.

Introduction: The introduction of CAR-T cell treatment for relapsed/refractory (r/r) mantle cell lymphoma improved survival rates of these patients. Along with its introduction in clinical routine, long-term events after CAR-T cell treatment are increasingly emerging. Case Presentation: We report the case of a patient developing acute erythroid leukemia with biallelic TP53 inactivation occurring 26 months after CAR-T therapy with brexucabtagene autoleucel (brexu-cel) for r/r mantle cell lymphoma. The patient presented with a healthy bone marrow prior to lymphoma treatments. Discussion: Secondary malignancies seem more frequent after CAR-T therapies. More studies are needed to assess potential long-term toxicities of CAR-T cell therapies including the frequency of secondary myeloid malignancies. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is genetically characterized by the IG::CCND1 translocation mediated by an aberrant V(D)J rearrangement. CCND1 translocations and overexpression have been identified in occasional aggressive B-cell lymphomas with unusual features for MCL. The mechanism generating CCND1 rearrangements in these tumors and their genomic profile are not known. We have reconstructed the IG::CCND1 translocations and the genomic profile of 13 SOX11-negative aggressive B-cell lymphomas using whole genome/exome and target sequencing. The mechanism behind the translocation was an aberrant V(D)J rearrangement in three tumors and by an anomalous IGH class-switch recombination (CSR) or somatic hypermutation (SHM) mechanism in ten. The tumors with a V(D)J-mediated translocation were two blastoid MCL and one high-grade B-cell lymphoma. None of them had a mutational profile suggestive of DLBCL. The ten tumors with CSR/SHM-mediated IGH::CCND1 were mainly large B-cell lymphomas, with mutated genes commonly seen in DLBCL and BCL6 rearrangements in 6. Two cases, which transformed from marginal zone lymphomas, carried mutations in KLF2, TNFAIP3 and KMT2D. These findings expand the spectrum of tumors carrying CCND1 rearrangement that may occur as a secondary event in DLBCL mediated by aberrant CSR/SHM and associated with a mutational profile different from that of MCL. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor published in the journal Leukemia & Lymphoma. The letter discusses the results of a phase 1 trial that tested the combination of abexinostat and ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) and non-germinal center diffuse large B cell lymphoma (DLBCL). The trial aimed to determine the maximum tolerated dose of the combination therapy and assess its safety and efficacy. The results showed that the combination had favorable activity in the MCL group, with an overall response rate of 86% and complete response observed in 71%. However, there was no appreciable activity in the non-GCB DLBCL group. The authors suggest that further studies with a larger sample size are warranted to confirm these findings. The document also suggests that future studies should explore alternative dosing schedules and second-generation BTK inhibitors. [Extracted from the article]

Background: Chimeric antigen receptor (CAR) T-cell therapy (CAR-T therapy) has demonstrated significant efficacy in the ZUMA-2 study. After regulatory approvals, several clinical trials and real-world studies on CAR-T therapy for relapsed or refractory mantle cell lymphoma (R/R MCL) were conducted. However, data on clinical safety and efficacy are inconsistent. In this study, we aimed to conduct a systematic analysis of the effectiveness and safety of CAR-T therapy across a wider and more representative cohort of patients with R/R MCL. Methods: We performed a systematic review and meta-analysis of studies on patients with R/R MCL who received CAR-T cell therapy. Data were extracted and consolidated, with primary focus on the evaluation of safety and efficacy outcome measures. This study has not been registered with PROSPERO. Results: This meta-analysis identified and included 16 studies with 984 patients. The pooled estimate for overall response rate (ORR) was 89%; complete remission (CR) rate was 74%. The 6-month and 12-month progression-free survival (PFS) rates were 69% and 53%, respectively, while the overall survival (OS) rates were 80% and 69%, respectively. Cytokine release syndrome (CRS) of grade 3 or higher was observed in 8% of patients, whereas neurotoxicity of grade 3 or higher was observed in 22% of patients. The risk of bias was assessed as low in 9 studies and moderate in 7 studies. Conclusion: CAR-T therapy exhibited promising efficacy and manageable adverse reactions in patients with R/R MCL. [ABSTRACT FROM AUTHOR]

Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. Here, we investigate the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using an in vitro model for exhaustion, RNA and ATAC sequencing on baseline and exhausted CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identify interleukin (IL)-4 as a regulator of CART cell dysfunction. Further, IL-4-treated CD8+ CART cells develop signs of exhaustion independently of the presence of CD4+ CART cells. Conversely, IL-4 pathway editing or the combination of CART cells with an IL-4 monoclonal antibody improves antitumor efficacy and reduces signs of CART cell exhaustion in mantle cell lymphoma xenograft mouse models. Therefore, we identify both a role for IL-4 in inducing CART exhaustion and translatable approaches to improve CART cell therapy. The application and therapeutic success of CAR-T cell approaches are limited by the development of T cell exhaustion. Here, Stewart et al discover a role for IL-4 in driving CD8+ CAR-T cell exhaustion and demonstrate the improvement of CAR-T cell effectivity with interruption of IL-4 signalling. [ABSTRACT FROM AUTHOR]

Simple Summary: In recent years, advanced therapy medicinal products (ATMPs) have revolutionised medicine with the promise of new treatments for previously incurable diseases. Chimeric antigen receptor (CAR T) cell therapies, in particular, have emerged as a highly active area of research and entrepreneurship. CAR T-cells are generated by introducing into T-cells a chimeric receptor (CAR). The CAR confers the T-cells the capacity to recognise a molecule expressed by the tumour. There are at least 10 different CAR T-cells with approval by different regulatory agencies around the globe. Several clinical trials have been performed in patients with solid tumours, as well as in patients with autoimmune conditions. There are several studies showing the potential benefit of CAR T-cells for other non-malignant diseases such as asthma and even fungal infections. We offer a brief summary of some of the most relevant aspects of the use of CAR T-cells for some of these conditions. The use of chimeric antigen receptors (CAR T-cells) for the treatment of patients with malignant haematological diseases has become a well-established application for conditions such as refractory or relapsed B-cell acute lymphoblastic leukaemia (B-ALL), B-cell lymphomas (BCL), and multiple myeloma (MM). Nearly 35,000 patients have received autologous CAR T-cells for the treatment of these conditions only in the USA. Since their approval by the Food and Drug Administration (FDA) in 2017, over 1200 clinical trials have been initiated globally and there are at least 10 different CAR T-cells with approval by different regulatory agencies around the globe. In the USA, the FDA has approved six commercial CAR T-cells that are widely distributed worldwide. At the time of writing, several clinical trials have been performed in patients with solid tumours such as glioblastoma, renal and pancreatic cancer, as well as in patients with autoimmune conditions such as systemic lupus erythematosus (SLE), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SS). There are also several studies showing the potential benefit of CAR T-cells for other non-malignant diseases such as asthma and even fungal infections. In this review, without pretending to cover all current areas of treatments with CAR T-cells, we offer a brief summary of some of the most relevant aspects of the use of CAR T-cells for some of these conditions. [ABSTRACT FROM AUTHOR]

HbA1c is a pivotal biomarker in diabetes management, reflecting long-term glycaemic control. HbA1c is often measured with capillary electrophoresis, which generally is a very precise technique, but there can be interference, especially in the case of haemoglobin diseases. Thus, in patients with underlying conditions, the accurate measurement of HbA1c can be challenging. We present a case of special interference in a 74-year-old female patient referred to a HbA1c test, in whom the measurement was thought to be significantly affected by hyperleukocytosis and led to an unexpected diagnosis of leukemic low-grade lymphoma. This case report highlights the underrecognized potential interference of leukocytosis in HbA1c measurement. It underscores the importance of clinical vigilance when interpreting HbA1c results in patients with underlying haematological conditions. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare and aggressive form of non‐Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog/GLI1 (Hh/GLI1) and Wnt/β‐catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co‐expression of key proteins from the Hh/GLI1 and Wnt/β‐catenin pathways was observed in MCL. Targeting the Hh/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt/β‐catenin pathway with the CBP/β‐catenin transcription inhibitor ICG‐001, dual‐target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0/G1 phase blockade, decreased the percentage of S‐phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG‐001 downregulated GLI1 and β‐catenin while upregulating GSK‐3β expression. The interaction between Hh/GLI1 and Wnt/β‐catenin pathways was mediated by GANT61‐dependent Hh/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG‐001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of β‐catenin and decreased the inhibition of GSK‐3β in MCL cells. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β‐catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients. [ABSTRACT FROM AUTHOR]

The article discusses the use of ibrutinib therapy in the treatment of chronic lymphocytic leukemia (CLL). It highlights the shift from chemo-immunotherapy to targeted therapy, specifically Bruton's tyrosine kinase (BTK) inhibitors like ibrutinib. The article emphasizes the long-term outcomes and benefits of ibrutinib, particularly for patients with TP53 mutations. It also addresses concerns about the safety profile of ibrutinib, including cardiovascular events. The article presents real-world studies that demonstrate improvements in the management of adverse events and retention rates with ibrutinib. It suggests that dose reduction of ibrutinib can optimize treatment outcomes without compromising efficacy. The article concludes by emphasizing the need for a personalized and patient-centered approach to CLL treatment, integrating real-world insights, proactive management strategies, and patient-reported outcomes. [Extracted from the article]

This letter to the editor discusses the results of a survey conducted in Italy on routine follow-up practices for patients with lymphoma. The survey examined the duration of follow-up, use of imaging techniques, role of lymph node biopsy, and repetition of bone marrow biopsy. The results showed variations in follow-up practices depending on the type of lymphoma. The article references European guidelines and the Lugano Classification, which highlight the importance of physical examination and discourage routine imaging in asymptomatic patients. The article emphasizes the need for harmonization of follow-up strategies and the role of imaging as a complement to clinical assessment. [Extracted from the article]

Rationale: Warthin tumor (WT) is the second most common benign tumor in salivary gland. It has a slow growth rate and most frequently occurs in the parotid gland. Most patients present with an incidental finding of a painless mass inferior/anterior to the ear. Besides the epithelial component of the tumor, WT is characteristically associated with lymphoid stroma that is considered benign. While there have been a few reports of malignant transformation of the lymphoid components in WT, cases of WT concomitant with mantle cell lymphoma (MCL) are extremely rare. To the best of our knowledge, two cases have been described in the English literature. Herein, we report a case of WT concomitant with MCL in a 70-year-old female patient, and emphasize the importance of careful examination of lymphoid stroma in WT so that concurrent lymphoma is not missed. Patient concerns: A 70-year-old Chinese woman with a 40-year history of cigarette smoking presented with a one year history of a right submaxillary mass with recent enlargement. Diagnosis: Cervical ultrasound (US) and computed tomography (CT) scans of the neck revealed a well-circumscribed mass in the right parotid with a maximum diameter of 3.1 cm. Surgical resection of the mass was performed. Histopathological examination revealed a characteristic double-layer of neoplastic epithelium with prominent lymphoid stroma, suggesting WT. In addition, morphology and immunohistochemistry studies confirmed the coexistence of MCL. Thereafter, the final diagnosis of this case was WT concomitant with MCL. Interventions: The patient was staged as stage I after clinical assessment. Due to the slow growth of parotid lesions, close observation was decided with periodic clinical and radiological monitoring. Outcomes: Currently, the patient demonstrates a stable disease by clinical evaluation. Lessons: To the best of our knowledge, reported cases of WT concomitant with MCL are very rare. This case highlights the importance of a comprehensive assessment of the lymphoid stroma of WT to avoid missed diagnosis of a lymphoma component in a collision tumor. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the use of CAR T-cell therapy in elderly lymphoma patients aged 80 years and older. The authors report on the outcomes of 12 patients who received CAR T-cell therapy and found that it was feasible and provided some clinical benefit, although efficacy outcomes were slightly lower compared to previous studies. Adverse events were reported, but no severe events occurred. The study suggests that CAR T-cell therapy may be beneficial for selected elderly patients with lymphoma, but more research is needed to confirm these results. [Extracted from the article]

This letter published in the Blood Cancer Journal discusses the clinical presentation, outcomes, and management of chimeric antigen receptor T-cell (CAR-T) therapy-associated hemophagocytic lymphohistiocytosis (HLH) syndrome. The study found that 3% of patients receiving CAR-T therapy developed CAR-T-associated HLH. The document provides detailed information on the clinical presentation, treatment strategies, and outcomes in adult patients with CAR-T-associated HLH. It includes a table with information on different treatment options, toxicities, and laboratory markers. The article emphasizes the importance of early recognition and intervention to prevent fatal outcomes. [Extracted from the article]

This article discusses a case of small-cell melanoma with isolated adrenal metastasis. The patient experienced symptoms such as pain, weight loss, and loss of appetite. Imaging tests revealed lesions in the adrenal gland and inguinal region. The article explores the diagnosis, immunocytochemical profile, metastasis rates, and genetic abnormalities associated with this type of tumor. It also emphasizes the challenges in diagnosing small-cell melanoma and the importance of immunocytochemistry in confirming the diagnosis. The text highlights the deceptive features of small-cell melanoma and identifies key mimics. [Extracted from the article]

Background: There are few reports of clinical practice treatment patterns and efficacy in mantle cell lymphoma (MCL). Materials and Methods: We retrospectively studied a large, multicenter, cohort of patients with MCL diagnosed between 2000 and 2020 in eight institutions. Results: 536 patients were registered (73% male, median of 70 years). Front‐line treatment was based on high‐dose cytarabine, bendamustine, and anthracyclines in 42%, 12%, and 15%, respectively. The median PFS for all patients was 45 months; 68, 34, and 30 months for those who received high‐dose cytarabine‐based, bendamustine‐based and anthracycline‐based therapy. 204 patients received second‐line. Bendamustine‐based treatment was the most common second‐line regimen (36% of patients). The median second‐line PFS (sPFS) for the entire cohort was 14 months; 19, 24, and 31 for bendamustine‐, platinum‐, and high‐dose cytarabine‐based regimens, with broad confidence intervals for these latter estimates. Patients treated with cytarabine‐based therapies in the front‐line and those with front‐line PFS longer than 24 months had a substantially superior sPFS. Conclusion: Front‐line treatment in this cohort of MCL was as expected and with a median PFS of over 3.5 years. Second‐line treatment strategies were heterogeneous and the median second‐line PFS was little over 1 year. [ABSTRACT FROM AUTHOR]

In this review we summarize the current evidence describing the management of patients with relapsed/refractory MCL and outline the various novel therapeutics that have been developed over the past two decades. We also describe how overall response rates, complete response rates, duration of responses, and life expectancy have dramatically increased with the introduction of novel therapies, particularly covalent Bruton Tyrosine Kinase inhibitors (BTKi) and chimeric antigen receptor T-cell (CAR-T) therapy. The most recent emerging options for patients with progressive disease following BTKi or CAR-T, including non-covalent BTKi, antibody-drug conjugates, Bcl-2 inhibitors, and bispecific antibodies, may further improve response rates and outcomes. Future directions should focus on identifying the best sequencing and/or combinations of the increasingly available treatment options while prioritizing strategies with curative potential. [ABSTRACT FROM AUTHOR]