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In the zebrafish lateral line, non-sensory supporting cells readily re-enter the cell cycle to generate new hair cells and supporting cells during homeostatic maintenance and following damage to hair cells. This contrasts with supporting cells from mammalian vestibular and auditory sensory epithelia which rarely re-enter the cell cycle, and hence loss of hair cells results in permanent sensory deficit. Lateral line supporting cells are derived from multipotent progenitor cells that migrate down the trunk midline as a primordium and are deposited to differentiate into a neuromast. We have found that we can revert zebrafish support cells back to a migratory progenitor state by pharmacologically altering the signaling environment to mimic that of the migratory primordium, with active Wnt signaling and repressed FGF signaling. The reverted supporting cells migrate anteriorly and posteriorly along the horizontal myoseptum and will re-epithelialize to form an increased number of neuromasts along the midline when the pharmacological agents are removed. These data demonstrate that supporting cells can be readily reprogrammed to a migratory multipotent progenitor state that can form new sensory neuromasts, which has important implications for our understanding of how the lateral line system matures and expands in fish and also suggest avenues for returning mammalian supporting cells back to a proliferative state. [Display omitted] • Zebrafish neuromasts can be pharmacologically reprogrammed to a migratory state. • Reprogrammed progenitors migrate along midline. • Migratory progenitors reaggregate into sensory organs following washout. • Reconstituted sensory organs form functional sensory cells and are innervated. [ABSTRACT FROM AUTHOR]

Lymphomas are a diverse group of malignant proliferations that arise as discrete tissue masses. The most widely accepted taxonomy for lymphoma is the World Health Organization classification of tumours of haematopoietic and lymphoid tissues, the 5th edition of which was released in June 2022. Most (85% to 90%) lymphoid neoplasms are of B cell origin. Mature B-cell neoplasms are a heterogeneous group of malignancies with similar disease courses and treatment paradigms. This review focuses on the various mature B-cell lymphomas in Malaysia, including Hodgkin lymphoma. A literature search was performed in various bibliographic databases. A total of 64 papers were included in this review. We found 15 papers on Hodgkin lymphoma, 14 on follicular lymphoma, 12 on Burkitt lymphoma, 5 on mucosa-associated lymphoid tissue (MALT) lymphoma, 4 on plasmablastic lymphoma, 3 on mantle cell lymphoma, 1 each on primary mediastinal large B-cell lymphoma, B-lymphoblastic lymphoma, and 3 on other unspecified B-cell lymphomas. The site, age, distribution, prognostic markers, and the various subclassification of B cell lymphomas were studied from these papers. Prognostic genetic markers in B-cell lymphomas include C-MYC, BCL2 and BCL6 as they are the most prevalent mutations in this condition. Anecdotal outcomes range from rapid fatality to unexplained spontaneous remission. This review adds to the existing literature on lymphoma in Malaysia by compiling the evidence that may lead to further research on the diagnosis and treatment of lymphoma in Malaysia and worldwide. [ABSTRACT FROM AUTHOR]

The vast majority of oral cavity malignancies are primary squamous cell carcinomas. Far less common are lymphomas, sarcomas, and secondary cancers. We present an interesting case of a patient with relapsed lymphoma that presented as a submandibular duct-occupying, elongated mass on the floor of mouth, similar in presentation to a massive sialolith. Although metastasis to the oral cavity is rare, consideration of this possibility is necessary in the evaluation of a patient with prior malignancy. The diligent clinician should be aware that these oral metastases can resemble common and innocuous lesions, which may delay accurate diagnosis. Timely biopsy and proper utilization of specialized testing such as IHC and flow cytometry are crucial to early initiation of therapy and optimization of care.

Abstract CD19‐directed chimeric antigen receptor T‐cell therapy (CAR‐T) represents a significant advancement for patients with relapsed/refractory large B‐cell lymphoma (LBCL). Long‐term follow‐up confirms durable remissions in nearly half of the patients, a population that was previously estimated to have a median survival of around 6 months with standard salvage therapy. This initial success of CAR‐T has led to significant expansion across other lymphoma histologies resulting in the recent regulatory approval of CAR‐T in mantle cell lymphoma and follicular lymphoma. Additionally, multiple novel platforms of CAR‐T therapy are under development to improve efficacy and limit toxicity such dual antigen targeting, allogeneic and natural killer CARs. In this review, we focus on the new indications of CAR‐T in lymphomas beyond LBCL as well as emerging platforms of CAR‐T therapy.

Introduction: Primary Gastrointestinal Lymphoma (PGIL) is a heterogeneous disease in terms of patient characteristics, site, histologic types and treatment modalities. Although rare disease, it is the most common site for extranodal lymphomas accounting for 10-15% of all non-Hodgkin lymphoma and 30-40% of all extranodal lymphoma. Aim: To study the different types of PGIL and its anatomic distribution along with its association with the clinical outcomes. Materials and Methods: This was a retrospective study conducted in Department of Pathology of a tertiary care hospital, South India over a period of five years (2009 to 2013). A total of 61 cases of PGIL were identified, which included both resected surgical and endoscopic biopsy specimens. Histopathological classification of all cases was done based on morphologic and immunophenotypic criteria according to latest World Health Organisation (WHO) 2008 classification. Anatomic distribution of various types of lymphoma and associated clinical features were studied. The cases were then followed-up and survival analysis was also done. Descriptive statistical analysis methods were used to analyse the data. Overall Survival (OS) rates were calculated using Kaplan Meier method for 33 cases. results: There was predominance of men with peak incidence in 7th decade. Abdominal pain was the commonest presenting symptom seen in 77% of the cases. The most common site of involvement was stomach (41%) followed by large intestine (37.7%). All cases of primary GI lymphomas were of non-Hodgkin type. B cell lymphomas (n=54; 88.5%) were more frequent than T cell lymphomas (n=7; 11.5%). Diffuse Large B Cell Lymphoma (DLBCL) was the most common subtype accounting for 67.2% of cases (n=41) followed by MALT lymphoma (n=9; 14.8%). Followup was possible in 33 cases out of which 20 patients (32.8%) died with a median overall survival period of 13 months (95% CI, 7.8-18.2). The five-year overall survival (OS) for 33 patients who were followed-up was 67.2%. conclusion: Diagnosing PGILs correctly according to the recent WHO classification is important so that correct treatment protocols can be followed. [ABSTRACT FROM AUTHOR]

Objectives: Immunohistochemistry (IHC) is a useful method for mantle cell lymphoma (MCL) detection in the bone marrow (BM). However, recognition of the neoplastic B cells can be challenging, especially when there is low-level disease.Methods: We examined BM from 105 patients with MCL. IHC was performed using cyclin D1/CD79a and PAX5/CD5 dual stains, which were compared with single stains that included CD20, CD79a, cyclin D1, and CD5 and with multiparameter flow cytometry (FC).Results: Based on the FC data, the overall sensitivity of the dual IHC stains was 95.6%. Both dual IHC stains showed better efficacy for detecting MCL cells compared with the aggregated single stains (P = .012). While three cases were positive by FC analysis but negative for dual staining, four cases showed cells positive for cyclin D1/CD79a and PAX5/CD5 dual staining that were not detected by FC. Two of these latter cases were in patients with minimal or focal disease involvement.Conclusions: Cyclin D1/CD79a and PAX5/CD5 dual IHC staining is an efficient procedure for the detection of MCL in the marrow and is particularly helpful in low-level or focal involvement by MCL. This approach can be particularly useful when marrow aspirates are inadequate or unavailable. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare, often aggressive type of B‐cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health‐related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ‐C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG‐MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab‐bendamustine (R‐B) as first‐line treatment. Fifty‐one patients were enrolled, median age was 71 years (range 62–84), 37 were men (73%). Pre‐treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre‐treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long‐term HRQOL. [ABSTRACT FROM AUTHOR]

Lymphoproliferative Disorders (LPDs) are a group of neoplasms affecting various cells within lymphoid system. Each type has different treatment and prognosis. Objective: To measure the prevalence of LPDs in a sample of Iraqi patients delineating its specific phenotypes in terms of their prevalence and male to female ratio. Design: Cross sectional study. Materials and methods: Cross sectional study that is done at National Centre of Haematology from November 2019 till March 2020 on 64 patients who were diagnosed to have one subtype of MPDs. Blood samples were taken from them and analysed to get complete blood count using automated electronic counter (Haematology auto-analyser-BECKMAN COULTER, ACT. 5 diff. USA). Blood film, Bone marrow aspirate and biopsy were analysed for each patient. Data were presented in frequencies and percentages and analysed using Chi-Square, student t test and ANOVA test when applicable using Graph pad 8 software and p=0.05 as significance level. Results: CLL is the most common pathologic type that accounts for (42.2%), followed by follicular lymphoma (23.4%), mantle cell lymphoma (10.94%), B-cell lymphoblastic leukaemia/lymphoma (9.38%), lymphoma (4.69%), Splenic Marginal Zone Lymphoma (4.69%) and T-cell NHL (4.69%). LPDs were more prevalent in males apart from Hodgkin's lymphoma. Discussion and Conclusion: LPDs is a group of many lymphoid neoplasms that vary in their prevalence. The prevalence observed in our population is greatly different form the cited literature. This could be explained by the low number of patients in our sample. [ABSTRACT FROM AUTHOR]

Progress in mantle cell lymphoma (MCL) has led to significant improvement in outcomes of patients even in the real world (RW) setting albeit to a lesser degree. In parallel to the demonstration of benefit using combination therapy with rituximab plus high-dose cytarabine (R-AraC) as well as dose intensive therapy-autologous stem cell transplantation (DIT-ASCT) consolidation and maintenance, it became clear over the last 2 decades that MCL is a highly heterogenous disease at the molecular level, explaining differences observed in clinical behavior and response to therapy. While clinical prognostic factors and models have helped stratify patients with distinct outcomes, they failed to help guide therapy. The identification of molecular high-risk (HR) features, in particular, but not only, p53 aberrations (including mutations and deletions [del]), as well as complex karyotype (CK), has allowed to identify subsets of patients with poorer outcomes (median overall survival [OS] <2 years) regardless of conventional therapies used. The constant pattern of relapse seen in MCL has fueled sustained and productive efforts, with 7 novel agents approved in the United States (US), showing high and durable efficacy even in HR and chemo-refractory patients and likely curing a subset of patients in the relapsed or refractory (R/R) setting. Progress in diagnostics, in particular next-generation sequencing (NGS), which is accessible in routine practice nowadays, can help recognize patients with HR features, well beyond MIPI or Ki-67 prognostication, although the impact on decision making is still unclear. The era of integrating novel agents into our prior standard of care (SOC) has begun with a confirmed benefit, for example, ibrutinib (Ib) in the TRIANGLE study, defining the first new potential SOC in younger patients in over 30 years. Expanding on novel agents, either in combination, sequentially or to replace chemotherapy altogether, using biological doublets or triplets has led to a median progression-free survival (PFS) in excess of 72 months, certainly competitive with prior SOC and will continue to reshape the management of MCL patients. Achieving minimal residual disease negative (MRD-ve) status is becoming a new endpoint in MCL, and customizing maintenance and/or de-escalation/consolidation strategies is within reach, although it will require prospective, built-in MRD-based approaches, with the goal of eliminating subclinical disease and not simply delaying time to relapse. Taking into account the biological diversity of MCL is now feasible in routine clinical practice and has already helped recognize what not to do for HR patients (i.e., avoid intensive induction chemotherapy and/or ASCT for p53 mutated patients) as well as identify promising novel options. Ongoing and future work will help expand on these dedicated approaches, to further improve the management and outcomes of all MCL patients., (Copyright © 2024. Published by Elsevier Inc.)

A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy.

Mantle cell lymphoma (MCL) is an aggressive B-cell neoplasm, but clinically indolent subtypes are also recognized. Data on the utility of mutation profiling in the context of routine workup and its role in risk-stratification of MCL patients are limited. In this study, we describe the mutational landscape and clinicopathologic correlates of a series of MCL cases at a single-institution setting. Samples from 26 patients with MCL were evaluated by NGS using DNA extracted from peripheral blood (PB) or bone marrow (BM). Evaluation of extent of PB or BM involvement was performed using flow cytometry immunophenotyping. The study group included 17 (65%) men and 9 (35%) women with a median age of 65 years (range, 50–94). Twenty-one (81%) patients had n odal MCL (N-MCL) and 5 (19%) had the " l eukemic variant" (L-MCL). Mutated genesincluded TP53 (35%), ATM (27%), CARD11 (10%); and FBXW7 , NOTCH1 , SPEN , BIRC3 (~5% each). Most mutations were clonal in nature. Ten unique TP53 mutations were identified in 9 samples, including 3 L-MCL cases. There was no difference in the frequency of TP53 mutations between L-MCL and N-MCL groups (p = 0.3), but TP53 mutations were subclonal in 2/3 L-MCL cases. Identification of clonal TP53 alterations in L-MCL patients prompted initiation of therapy despite low tumor burden. TP53 is commonly mutated in MCL. TP53 mutations may be clonal or subclonal. Seemingly indolent L-MCL may harbor subclonal TP53 mutations which may serve as a useful biomarker for prognostication, therapeutic planning, follow-up monitoring, and early detection of clonal expansion. • TP53 mutations are common in both the classical and leukemic non-nodal variant MCL. • TP53 mutations may be clonal or subclonal in MCL. • Subclonal TP53 mutations were more common in L-MCL. • In L-MCL it may serve as a useful biomarker for early detection of clonal expansion. [ABSTRACT FROM AUTHOR]

The advent of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of several hematological malignancies. Although the initial benefit was mainly observed in aggressive leukemias and lymphomas, recent data have resulted in the approval of multiple CAR-T therapies in indolent lymphomas, with ongoing research showing great promise for further improvements and therapeutic optimizations. In this article, we review the published data and approved therapies for CAR-T cell therapy for indolent lymphomas focusing on mantle cell lymphoma and follicular lymphoma while describing the work in chronic lymphocytic leukemia and future strategies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective To study the clinical features,therapeutic effects, prognostic factors of 140 patents with mantle cell lymphoma (MCL). Methods Clinical data of 140 MCL patients admitted from June 2009 to January 2016 in our hospital were retrospectively analyzed. Results The median age of 140 patients was 59 years with a ratio of 6 : 1 for men and women. There were 134 cases (95.7%) in Ann-Arbor stage III - IV, 37 cases (26.4%) with B symptoms, 61 cases (43.6%) with bone marrow involvement and 38 cases (27. 1%) with enlarged spleen. The overall response rate (ORR), 3-year survival rate and progression-free survival rate in the treatment group with rituximab were 87. 1%, 68. 1% and 59.5% respectively, which were significantly higher than those in the rituximab-free treatment group (66.6%, 51.5% and 31.7%, respectively). The difference was statistically significant (all P<0.05). Among patients treated with rituximab, the complete remission rates (70.8% and 77.8%) of R-HyperCVAD/MA and VcR-CAP regimens were higher than those of R-CHOP regimen (39.0%, both P<0.05). However, there was no significant difference in the overall response rate, overall survival rate and progression-free survival rate (all P>0.05). Univariate analysis showed that age, Ki-67 index, B symptoms, bone marrow invasion, platelet count, LDH, β2-MG and MIPI scores were associated with overall survival (all P<0.05). Multivariate analysis showed that age (HR= 4.940, 95% CI-. 2.347 to 10.397), B symptom (HR = 2.900, 95% CI-. 1.517-5.544), β2-MG (HR= 2.945, 95% CI: 1.656-5.238), Ki-67 index (HR = 4.915, 95% CI: 2.554-9.456) and treatment with rituximab-containing regimen (HR = 2.450, 95% CI: 1.352-4.440) were independent factors for OS. Conclusions Most patients with MCL were older adults and usually had bone marrow involvement and spleen involvement. Rituximab combined with chemotherapy (especially R-HyprCVAD/MA and VcR-CAP) had better clinical efficacy than conventional chemotherapy. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a malignant B-cell neoplasm, which comprises monomorphic and small- to medium-sized mantle zone-derived lymphoid cells. It is characterized by chromosomal translocation t(11;14)(q13;q32) and CCND1 truncation, resulting in cell cycle deregulation. It is an aggressive type of non-Hodgkin lymphoma with a propensity to present with extranodal involvement. This study shows the case of an 80-year-old Caucasian male who complained of a 2-month progressive swelling on the right side of his face. The magnetic resonance imaging exam showed multifocal involvement of the head and neck, including oral manifestations, bilateral parotid glands, palate, tongue, and floor of the mouth. An incisional biopsy of the tumor mass was performed. The morphological and immunophenotypic findings were consistent with the diagnosis of MCL. The patient died 4 months later, without any chance of undergoing a therapeutic approach. Although MCL is a rare condition, it should be subjected to a differential diagnosis when affecting the maxillofacial area. Imaging exams and both immunohistochemical and morphological analyses are needed to reach the correct diagnosis. Here, we present an unusual MCL with multifocal involvement of the head and neck

High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes after ASCT. For all patients the 5-year overall survival (OS) was 71% (95% confidence interval [CI], 63% to 77%) and progression-free survival (PFS) was 53% (95% CI, 45% to 60%). The 5-year cumulative incidence of relapse was 41% (95% CI, 34% to 48%) with a continuous pattern of relapse events occurring at a median of 2.1 years (range, .2 to 13.4) after ASCT. In multivariate analysis, post-transplant maintenance rituximab was the factor most significantly associated with both OS (relative risk [RR], .17; 95% CI, .07 to .38) and PFS (RR, .25; 95% CI, .14 to .44). For the subset of patients who had positron emission tomography (PET) data available and were in a PET-negative first complete remission at ASCT (n = 105), maintenance rituximab was significantly associated with superior OS (RR, .17; 95% CI, .05 to .59) and PFS (RR, .20; 95% CI, .09 to .43). These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is an uncommon B-cell lymphoma that prototypically expresses CD5, but a small subset is CD5 negative. The clinical significance of CD5 negativity is not yet well-elucidated. This case series aims to contribute to the understanding of CD5-negative MCL by looking at specific markers and outcome in our cases with long-term follow-up. Eight cases of CD5-negative MCL were identified in the case files at the Massachusetts General Hospital from 1978 to 2016. Clinicopathological characteristics were evaluated, including immunohistochemical stains for cyclin D1, SOX11, Ki67, and p53. Patients initially presented with involvement of lymph nodes and spleen ( n = 4), sinonasal or oral mucosa ( n = 2), orbital soft tissue ( n = 1), and salivary gland ( n = 1). On histology, the cases all showed classic MCL morphology, with a monotonous population of medium-sized cells with irregular nuclear contours. The cases were positive by immunohistochemistry for cyclinD1 (8/8 cases), essentially negative for p53 staining (8/8 cases), and mostly positive for SOX11 (5/8 cases). All cases had a low Ki67 proliferation rate (<5%). Long-term clinical follow-up on five cases showed that four patients had a clinical course complicated by multiple relapses to the skin, soft tissue, liver, and bone marrow. Seven cases with available follow-up showed an average survival of 121 months (SD 86 months), with no detectable survival difference between the SOX11 positive and negative cases. CD5-negative MCL is an uncommon subtype of MCL that overall appears to have a better prognosis and longer overall survival than classic MCL, despite SOX11 expression. The cases also show little p53 expression and a low Ki67 proliferation index. [ABSTRACT FROM AUTHOR]

Aggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto- HCT) is effective for younger patients with mantle cell lymphoma ( MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyper CVAD/ MTX/ ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) ( RH) versus rituximab plus bendamustine ( RB) in a randomized phase II trial to select a pre-transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto- HCT. Fifty-three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2-year progression-free survival ( PFS) was 81% vs. 82% and overall survival ( OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi-centre transplant trials in MCL. RB achieved a 2-year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL. [ABSTRACT FROM AUTHOR]

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given.

A 66-year-old man developed a slowly enlarging, bilateral, painless, periorbital, and orbital swelling with ptosis, nonaxial proptosis, chemosis, exposure keratopathy, and decreased vision in both eyes. He had fever, night sweats, and weight loss (B-symptoms), along with lymphadenopathy and elevated serum lactate dehydrogenase, with no prior history of lymphoma. A transpalpebral incisional biopsy revealed a rare case of mantle-cell lymphoma of blastoid variant, stage IVB. The main immunophenotype characteristics were cyclin D1+, CD5+, CD10−, CD23−, Bcl-6−/+, and a high (up to 80%) Ki-67 proliferation index. Following an excellent response to the immune-chemotherapy treatment plan, all ocular adnexal lymphoma manifestations disappeared completely; however, 13 months after the initial presentation, there was a recurrence of the disease with rapid worsening and death. The blastoid variant of mantle cell lymphoma, a rare subtype of mantle-cell lymphoma, is a highly aggressive neoplasm, ultimately having a fatal outcome. As the initial manifestation of the disease, ocular adnexal region blastoid variant of mantle-cell lymphoma is an exceptional event, with only one previous case reported. [ABSTRACT FROM AUTHOR]

Introduction: Retrospective analysis was performed at a single institution to assess the responsiveness of mantle cell lymphoma (MCL) to involved-field radiotherapy (IFRT).Methods: All patients treated with IFRT to at least one site of MCL between 1998 and 2012 were included. There were 25 patients who received radiotherapy to 60 disease sites. Primary endpoint was overall response rate (ORR) infield for the first site of MCL treated per patient. Predictors of ORR were analysed for the primary endpoint. Time to local progression (TLP) infield and progression-free survival were calculated from the start of the first treatment course. Analysis of all sites collectively was also undertaken. Survival analysis was conducted by the Kaplan-Meier method.Results: ORR rate was 84% for the first site treated per patient. Complete response and partial response rates were 68% and 16% respectively. Median TLP following radiotherapy to the first site was not reached. Infield control rate was 91% at 12 months (95% confidence interval 69-97%). When analysis was performed on all 60 sites, ORR was 85%. Symptomatic improvement occurred after IFRT to 93% of all sites. Systemic progression outside the radiotherapy field was the predominant form of failure following IFRT.Conclusion: Radiotherapy generally induced a clinical response at all levels of dose administered, ranging from 3 to 36 Gy. However, increased durability of local control was suggested with higher doses. Radiotherapy is an effective treatment for palliation of MCL with objective and symptomatic responses seen over a range of radiotherapy doses. [ABSTRACT FROM AUTHOR]

The mantle cell lymphoma (MCL) is a non-Hodgkin's lymphoma in which initial presentation in the palate is particularly rare. Only six cases have been reported in the literature. We present the case of a 70-year-old man was referred to the department of oral surgery with a chief complaint of denture instability. On clinical examination, a sessile and ulcerated mass was noted on the posterior portion of the right hard palate. An incisional biopsy was performed and the diagnosis of MCL was confirmed. The patient underwent multiple chemotherapy treatment and expired several years later from other medical complications. Lymphomas of the oral cavity are rare, and because the prognosis of such tumor is generally poor, a high degree of suspicion should be kept. [ABSTRACT FROM AUTHOR]

Obatoclax, a BH3 mimetic inhibitor of anti-apoptotic Bcl-2 proteins, demonstrates synergy with bortezomib in preclinical models of mantle cell lymphoma (MCL). This phase I/II study assessed obatoclax plus bortezomib in patients with relapsed/refractory MCL. Twenty-three patients received obatoclax 30 or 45 mg plus bortezomib 1.0 or 1.3 mg/m2, administered intravenously on days 1, 4, 8 and 11 of a 21-day cycle. In phase I, the combination was feasible at all doses. Obatoclax 45 mg plus bortezomib 1.3 mg/m2 was selected for phase II study. Common adverse events were somnolence (87%), fatigue (61%) and euphoric mood (57%), all primarily grade 1/2. Grade 3/4 events included thrombocytopenia (21%), anemia (13%) and fatigue (13%). Objective responses occurred in 4/13 (31%) evaluable patients (three complete and one partial response). Six patients (46%) had stable disease lasting ≥ 8 weeks. Obatoclax plus bortezomib was feasible, but the synergy demonstrated in preclinical models was not confirmed. [ABSTRACT FROM AUTHOR]

Patients with mantle cell lymphoma (MCL) have an adverse outcome after relapse. Bendamustine has demonstrated a good efficacy and toxicity profile in previously reported trials. In this study, we present a retrospective analysis of the Spanish experience in relapsed/refractory MCL treated with bendamustine in combination or alone with the objective of knowing the efficacy and toxicity profile of this treatment in our current clinical practice. Fifty eight patients were registered: 67 % male with median age of 71 years, and 2 is the median number of previous lines. The most frequent bendamustine regimen was bendamustine plus rituximab (83 %). The median number of cycles was 5 (range 1-8). The overall response rate was 84 % with 53 % of complete response/unconfirmed complete response (CR/uCR). Median progression-free survival (PFS) was 16 months (95 % confidence interval (CI) 13.3-18.8), and for patients who achieved CR/uCR, it was 33 months (95 % CI 11.1-54.2). Median overall survival (OS) was 30 months (95 % CI 25.6-34.9). For PFS, only blastoid histology and not achieving CR after bendamustine had a significant negative impact on the univariate and multivariate analyses ( p < 0.05). Nevertheless, for OS, only an elevated lactate dehydrogenase (LDH) had negative impact on both, univariate and multivariate analyses ( p < 0.05). Only one case of treatment-related mortality in a 79-year-old patient with very bad performance status was reported. In 280 cycles, 12 (4 %) hospitalizations for febrile neutropenia were reported. In our population, bendamustine has been a good salvage treatment with a favorable toxicity profile in a non selected and heavily pretreated population of patients with MCL. [ABSTRACT FROM AUTHOR]

Abstract: A phase I/II trial was designed to evaluate the safety and efficacy of adding bortezomib to standard BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous hematopoietic stem cell transplantation (ASCT). Eligible patients had relapsed/refractory indolent or transformed non-Hodgkin lymphoma or mantle cell lymphoma (MCL) that was relapsed/refractory or in first partial (PR) or complete remission (CR). Patients received bortezomib on days −11, −8, −5, and −2 before ASCT. Phase I had 4 dose cohorts (.8, 1, 1.3, and 1.5 mg/m2) and 3 patients were accrued to each. Any nonhematological ASCT-related toxicity >2 on the Bearman scale occurring between day −11 and engraftment defined the maximum tolerated dose (MTD). After the MTD has been reached, another 20 patients were enrolled at this dose to determine a preliminary overall response rate (ORR). Patients who were in CR or PR at day +100 were considered responders. The study enrolled 42 patients through August 14, 2009. The median age was 58 (range, 34 to 73) years, with 33 males and 9 females. The most common diagnoses were MCL (23 patients) and follicular lymphoma (7 patients). The median number of prior therapies was 1 (range, 0 to 6). The median follow-up was 4.88 (range, 1.07 to 6.98) years. Thirteen patients were treated in phase I and 29 patients were treated in phase II. The MTD was initially determined to be 1.5 mg/m2 but it was later decreased to 1 mg/m2 because of excessive gastrointestinal toxicity and peripheral neuropathy. The ORR was 95% at 100 days and 87% at 1 year. For all 38 evaluable patients at 1 year, responses were CR 84%, PR 1%, and progressive disease 13%. Progression-free survival (PFS) was 83% (95% CI, 68% to 92%) at 1 year, and 32% (15% to 51%) at 5 years. Overall survival (OS) was 91% (95% CI, 79% to 96%) at 1 year and 67% (50% to 79%) at 5 years. The most common National Cancer Institute grade 3 toxicities were neutropenic fever (59%), anorexia (21%), peripheral neuropathy (19%), orthostatic hypotension/vasovagal syncope (16%), and 1 patient failed to engraft. Compared with 26 MCL in CR1 historic controls treated with BEAM and ASCT, PFS was 85% and 43% for the BEAM group versus 87% and 57% for those who received bortezomib in addition to standard BEAM (V-BEAM) at 1 and 5 years, respectively (log-rank P = .37). OS was 88% and 50% for the BEAM group versus 96% and 72% for V-BEAM at 1 and 5 years, respectively (log-rank P = .78). In conclusion, V-BEAM and ASCT is feasible. The toxicities were manageable and we did not observe any treatment-related mortalities; however, we did observe an excess of autonomic dysfunction and ileus, which is concerning for overlapping toxicity with BEAM conditioning. Determining relative efficacy of V-BEAM compared to BEAM would require a randomized trial. [Copyright &y& Elsevier]

Primary lymphomas arising in the large intestine are less frequent than either gastric or small bowel lymphomas. Primary colorectal lymphomas account for about 0.2% of all neoplasm. Mantle cell lymphoma in form of multiple lymphomatous polyposis is less frequent in colorectum than in the small bowel.2 We present a case of 68 year-old man suffered from abdominal pain and diarrhoea for one year with complain of blood in stool for last 15 days. Multiple polypoid masses were found in the entire colon and caecum on colonoscopic examination. Computerized tomography of the abdomen revealed a large soft tissue mass lesion in caecum and ascending colon with diffuse polypoidal wall thickening involving the transverse colon, sigmoid colon, descending colon with mesenteric lymph node enlargement. Colonoscopic excision of polyp from ascending colon and transverse colon was done. The histological diagnosis was Non-Hodgkin lymphoma with multiple lymphomatous polyposis. In immunohitochemistry, there was positive staining for CD20, CD 5 and cyclin D1 and suggestive of mantle cell lymphoma B cell type. MCL is an aggressive lymphoma, which typically presents in advanced stage; there is often involvement of mesenteric and peripheral lymph nodes, spleen, bone marrow and peripheral blood 6.

Mantle cell lymphoma is a type of no-Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and gland as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of stablishing multidisciplinary relationships for a global approach has been shown by this clinical case.

A case of primary prostate involvement by mantle-cell lymphoma diagnosed at the time of transvesical adenomectomy is reported. Diagnostic difficulties and clinical outcome are also presented. The possibility of prostate involvement by malignant lymphomas, albeit rare, should be considered in any case of histological evidence of dense prostate lymphoid infiltrate in patients with lower urinary tract obstruction, and should be highly suspected in patients with prior history of systemic lymphoma. Immunohistochemical analysis is essential for a correct diagnosis. Both urologists and pathologists should be aware of the existence of such a rare clinical condition. [ABSTRACT FROM AUTHOR]

Background Rituximab-hyper-CVAD alternating with rituximab-high-dose methotrexate and cytarabine is a commonly utilized regimen in the United States for mantle cell lymphoma (MCL) based on phase II single institutional data. To confirm the clinical efficacy of this regimen and determine its feasibility in a multicenter study that includes both academic and community-based practices, a phase II study of this regimen was conducted by SWOG. Patients and methods Forty-nine patients with advanced stage, previously untreated MCL were eligible. The median age was 57.4 years (35–69.8 years). Results Nineteen patients (39%) did not complete the full scheduled course of treatment due to toxicity. There was one treatment-related death and two cases of secondary myelodysplastic syndrome (MDS). There were 10 episodes of grade 3 febrile neutropenia, 19 episodes of grade 3 and 1 episode of grade 4 infection. With a median follow-up of 4.8 years, the median progression-free survival was 4.8 years (5.5 years for those ≤65 years) and the median overall survival (OS) was 6.8 years. Conclusions Although this regimen is toxic, it is active for patients ≤65 years of age and can be given both at academic centers and in experienced community centers. [ABSTRACT FROM AUTHOR]

Background: There is no consensual first-line chemotherapy for elderly patients with mantle cell lymphoma (MCL). The GOELAMS (Groupe Ouest-Est des Leucémies Aiguës et Maladies du Sang) group previously developed the (R)VAD+C regimen (rituximab, vincristine, doxorubicin, dexamethasone and chlorambucil), which appeared as efficient as R-CHOP (rituximab, cyclophosphamide, doxorubicine, vincristine, prednisone) while less toxic. Based on this protocol, we now added bortezomib (RiPAD+C: rituximab, bortezomib, doxorubicin, dexamethasone and chlorambucil) given its efficacy in relapsed/refractory MCL patients. The goal of the current phase II trial was to evaluate the feasibility and efficacy of the RiPAD+C regimen as frontline therapy for elderly patients with MCL. Patients and methods: Patients between 65 and 80 years of age with newly diagnosed MCL received up to six cycles of RiPAD+C. Results: Thirty-nine patients were enrolled. Median age was 72 years (65–80). After four cycles of RiPAD+C, the overall response rate was 79%, including 51% complete responses (CRs). After six cycles, CR rate increased up to 59%. After a 27-month follow-up, median progression-free survival (PFS) is 26 months and median overall survival has not been reached. Four patients (10%) discontinued the treatment because of a severe toxicity and seven patients (18%) experienced grade 3 neurotoxicity. Conclusion: The bortezomib-containing RiPAD+C regimen results in high CR rates and prolonged PFS with predictable and manageable toxic effects in elderly patients with MCL. [ABSTRACT FROM PUBLISHER]

Abstract: The zebrafish provides a useful experimental system for investigations of aural development. To permit the controlled expression of transgenes in developing hair cells, we isolated the genomic control regions of the parvalbumin 3a (pvalb3a) and parvalbumin 3b (pvalb3b) genes. Deletion analysis and somatic-cell transgenesis restricted the cis-acting control regions for hair cells to as little as 484base pairs for pvalb3a and 650base pairs for pvalb3b. Using both meganuclease-mediated and standard methods, we produced transgenic animals that transmit transgenes through their germ lines. These fish express GFP in hair cells in the inner ear and lateral line. Two stable transgenic lines express GFP prior to hair-bundle formation, so the associated promoter constructs are suitable for manipulating gene expression during bundle development. We additionally identified a transgenic line that offers variable labeling of supporting cells. [Copyright &y& Elsevier]

Described herein is an unusual case of mantle cell lymphoma (MCL) histologically mimicking marginal zone lymphoma (MZL). An 83-year-old man presented with multiple adenopathies and a hilar mass encroaching on the right lung. A transbronchial biopsy showed small blue cells suspicious for small cell carcinoma. On further analysis the cells were predominantly small cleaved and CD20 positive, suggesting follicular lymphoma, grade 2. An axillary lymph node biopsy showed germinal centers surrounded by monocytoid B cells. Flow cytometry was negative for CD5 and CD23 and the diagnosis of MZL was considered. Because of the aggressive clinical behavior, including extensive necrosis on imaging studies, immunohistochemistry for cyclin D-1 was performed and was positive. Bone marrow was extensively involved and it showed t(11;14), in addition to other complex cytogenetic abnormalities. Differentiating MCL from MZL has prognostic and therapeutic implications, particularly when considering the potential role of targeted therapy and cell cycle modulators. [ABSTRACT FROM AUTHOR]

Introduction: Mantle cell lymphoma (MCL) is rare and very aggressive form of lymphoma. It is a subtype of B-cell non Hodgkn lymphoma. MCL are mostly advanced in stage at diagnosis and this is associated with poorer prognosis. The extranodal sites that are commonly involved are gastrointestinal tract, spleen, liver, bone marrow, Waldeyer's ring, skin, lacrimal glands and central nervous system. Case Report: Here we present a 70 year old lady with complaint of dysphagia over 2 months without voice change. There was no B symptom. Clinically, a pedunculated mass was seen to arise from her base of tongue. There was no palpable nodes, liver or spleen. Patient had chemotherapy following the diagnosis of mantle cell lymphoma concluded through an excision biopsy. She is now on surveillance. She has no recurrence at 1 year following completion of treatment. Conclusion: Mantle cell lymphoma should always be considered at initial presentation of a patient presenting with dysphagia despite no other apparent abnormalities in view of its aggressive behaviour. [ABSTRACT FROM AUTHOR]

Kojima M, Nakamura S, Iijima M, Murayama K, Sakata N, Masawa N. Lymphoid variant of hyaline vascular variant of Castleman's disease containing numerous mantle zone lymphocytes with clear cytoplasm. APMIS 2005;113:75–80.We report two unusual cases of hyaline vascular type Castleman's disease showing a pale clear cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had medium-sized round or slightly indented nuclei and a moderate amount of clear cytoplasm. The histopathologic findings in our cases were similar to those of nodal marginal zone B-cell lymphoma. However, immunohistochemistry demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, CD79a+, sIgM+, sIgD+, CD5-, CD10-, CD43-, CD45RO-, Bcl-2+, Bcl-6- and cyclin D1-. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. Reactive lymph node lesions only rarely show mantle cell hyperplasia with clear cytoplasm. This unusual mantle cell hyperplasia with clear cytoplasm associated with a hyaline vascular type of Castleman's disease should be differentiated from nodal marginal zone B-cell lymphoma, mantle cell lymphoma and follicular lymphoma. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and furthermore careful attention should be paid to the morphologic examination. [ABSTRACT FROM AUTHOR]

Aims Assessment of the expression of antigens CD5, CD10 and CD23 can be of value in the differential diagnosis of small B-cell lymphoma. Correct subclassification is important since optimal treatment regimes differ between the subtypes. The aim of this study was to generate monoclonal antibodies recognizing these antigens in paraffin-embedded tissue and to assess their efficacy using a panel of cases of small B-cell lymphoma of various subtypes. Methods and results For each antibody synthetic recombinant protein and conventional murine hybridoma technology was employed. Monoclonal antibodies effective in formalin-fixed, paraffin-embedded tissue were successfully generated, designated NCL-CD5-4C7, NCL-CD10-270 and NCL-CD23-1B12, respectively. A series of 58 cases of small B-cell lymphoma including examples of each subtype (lymphocytic, follicle centre cell, mantle cell, marginal zone and lymphoplasmacytoid) was assembled and immunostaining for the respective antigens carried out using the monoclonal antibodies produced. Our results indicate that the antibodies are specific for their respective antigens and give the predicted phenotypic profile in the small B-cell lymphoma subtypes. Conclusions These novel monoclonal antibodies may be of value in routine diagnostic practice. [ABSTRACT FROM AUTHOR]

We present a case of a pleural space malignancy masked by an atypical presentation of mantle cell lymphoma. Our patient presented with a large pleural effusion and right sided pleural studding, initially attributed to a new diagnosis of mantle cell lymphoma. Rare atypical epithelial cells were also seen amongst the clonal population of lymphocytes. The patient lacked systemic manifestations of mantle cell lymphoma and did not improve with chemotherapy. A pleural biopsy ultimately revealed the presence of an undifferentiated carcinoma, favoring a lung primary. A discussion of synchronous pleural space malignancies involving lymphomas is given. [ABSTRACT FROM AUTHOR]

A 73-year-old man presented with multiple lymphadenopathy. He had a 20-year history of palmoplantar psoriasis evolved to a diffuse erythrodermic picture in the last two years. Topic and systemic medications including prednisolone, acitretin, anti-IL17 (ixekizumab), TNF inhibitor (adalimumab), anti-IL23 (guselkumab), methotrexate, cyclosporine, and phosphodiesterase 4 inhibitor (apremilast) were ineffective. Repeated skin biopsies excluded mycosis fungoides, confirming psoriasis; molecular analysis of T-cell receptor genes ruled out clonality. The axillary lymph node histology documented a dermatopathic lymphadenitis, often associated with chronic cutaneous inflammatory diseases. At an accurate morphological evaluation, features of HHV8-positive multicentric Castleman disease were observed. Moreover, in a few follicles, in situ mantle cell neoplasia was identified. The translocation t(11;14)(q13;q32), characteristic of mantle cell lymphoma, and the monoclonal IGH gene rearrangement were present. HHV8 DNA was identified on plasma sample. Multicentric Castleman disease in psoriatic patients is a rare event and it might be favored by the immunomodulatory treatment in longstanding psoriasis. Multicentric Castleman disease patients are predisposed to developing simultaneous or subsequent lymphoma. In situ mantle cell neoplasia often behaves indolently, although it may progress to overt mantle cell lymphoma. Rituximab achieved a good control of psoriasis. Unfortunately, the patient developed Staphylococcus aureus sepsis for which he is currently on antibiotic therapy. [ABSTRACT FROM AUTHOR]

Introduction : While there has been an improvement in the treatment of mantle cell lymphoma (MCL) in both median progression-free survival (PFS; >7-8 years) and overall survival (OS; >10-12 years), patients with high-risk features such as high risk MIPI (mantle cell international prognostic index), high Ki-67 (≥30%), or blastoid variants still carry poor outcome with a median OS of 3 years. Furthermore, patients with high-risk molecular features, such as TP53 mutations, show dismal outcome, with a median OS of 1.8 years, regardless of therapy used. Further studies have led to the development of six novel drugs approved for the treatment of relapse/refractory (R/R) MCL, leading to improved survival even in refractory or high-risk patients. Areas covered : This review covers clinical biological and molecular features that impact MCL outcome with current standards. Beyond the recognition of separate subentities, we review how high-risk molecular features have paved the way toward a new paradigm away from chemoimmunotherapy. Expert opinion : Progress in novel therapies and in routine diagnostics, particularly next-generation sequencing (NGS), support the development of new treatment strategies, not based on the dose intensity/age dichotomy, which may prevent the need for chemotherapy and improve outcome across MCL including in high-risk subsets.

Abstract Background Mantle cell lymphoma (MCL) is a rare variety of non-Hodgkin's lymphoma which originates from CD5+ B-cell population in the mantle zones of lymphoid follicles. Coexistence of such tumours in the axillary lymph nodes with invasive breast cancers without prior history of adjuvant chemotherapy or radiotherapy has not been previously reported in literature. Case report We report a rare case of breast cancer co-existing with stage I mantle cell lymphoma of the ipsilateral axillary lymph node detected fortuitously by population screening. Conclusion Though some studies have tried to prove breast carcinomas and lymphomas to share a common molecular or viral link, more research needs to be done to establish whether such a link truly exists.

Primary mantle cell lymphoma (MCL) is a controversial entity. It is difficult to diagnose MCL in a single organ without lymph node involvement. However, with the advent of PET-CT scans and large panels of immunohistochemistry markers, there have been increasing reports of primary MCL detected in various organs of which the GI tract is the most common. In this case report, we describe the diagnosis and clinical course of a patient who presented with 'B symptoms' and respiratory distress. On further investigation, he was found to have a mass in his trachea, which was diagnosed as primary MCL. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma is a type of non- Hodgkin lymphoma that affects extranodal areas, especially, bone narrow, digestive tract and Waldeyer ring. Here we report a case of mantle cell lymphoma IV Ann Arbor stage with cutaneous lesions on nasal dorsum and glans penis as the first manifestations. Skin involvement is a very rare manifestation and less than 20 cases have been reported in the literature. The importance of establishing multidisciplinary relationships for a global approach has been shown by this clinical case. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of CLL/SLL relies on flow cytometric immunophenotyping. Increasing emphasis is being placed on precise detection of the minimal residual disease. Following antigen recommendations of ERIC and ESCCA's Harmonization Project, we validated a 14-color assay for the characterization CD5+ lymphoproliferative neoplasms and CLL MRD with a sensitivity of at least 10 -4 ., Methods: The assay was designed based on ERIC/ESCCA recommended antigens with the addition of CD40 for alternate gating when CD19 expression is reduced. Lower limit of quantitation/lower limit of detection, assay procedural precision, linearity, and limit of blank were established. Then, 52 CD5+ B-cell lymphoproliferative neoplasms (41 CLL/11 non-CLL) and 29 normal samples were used for parallel evaluation. Automated cluster identification and quantitation of CLL clones in MRD setting was performed using Barned-Hutt SNE. Separation analysis between CLL and non-CLL phenotypes was performed by PCA and bh-SNE., Results: Separation ratios for each antigen exceeded ERIC/ESCCA guidelines. Precision was <20% at LLOQ (0.01%). The limit of blank was <10/500,000 cells. Concordance between the 14-color and legacy assay (Deming regression y = 1.01x, r 2  = .99) was seen. All 20 samples with MRD levels 0.5%-0.006% (median 0.04%) showed an abnormal cell cluster by bh-SNE, with concordant results between manual and automated quantitation (y = x, r 2  = 1). CLL cases clustered together and away from mantle cell lymphoma by bh-SNE and PCA with outlier atypical phenotype CLL cases posing diagnostic challenges by both manual and automated analysis., Conclusion: The 14-color CD5+ LPD assay provides a robust standardization platform for MRD and disease characterization using both manual and automated analysis., (© 2020 International Clinical Cytometry Society.)