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Keywords: ambiguous lineage leukaemia; bilineal; monocytic; paediatric EN ambiguous lineage leukaemia bilineal monocytic paediatric e34 e39 6 01/28/22 20220201 NES 220201 Ambiguous lineage leukaemia (ALAL) is a rare sub-type of paediatric acute leukaemia. There are four main subgroups according to the lineage of differentiation, namely: (i) mixed phenotype acute leukaemia (MPAL), (ii) bilineal acute leukaemia, (iii) undifferentiated acute leukaemia, and (iv) acute leukaemia with early switch to a different lineage.1-4 MPAL accounts for 1-2% of paediatric leukaemia.3 The World Health Organization (WHO) classifications (2008 and 2016) have established strict criteria for diagnosis of MPAL, emphasising myeloperoxidase for myeloid lineage, cytoplasmic cluster of differentiation 3 (CD3) for T lineage, and CD19 and other B markers for B lineage.1,4 Flow cytometry has been pivotal in diagnosis, treatment response and minimal residual disease (MRD) assessment in MPAL. Acute lymphoblastic leukemia-like treatment regimen provides better response in mixed phenotype acute leukemia: a comparative study between adults and pediatric MPAL patients. A provisional diagnosis of AML with monocytic differentiation was considered and commenced on AML treatment as per UK national guidelines due to rising white blood cell counts (Table I). [Extracted from the article]

Background: Autologous bone-marrow-derived cells are currently employed in clinical studies of cell-based therapy in multiple sclerosis (MS) although the bone marrow microenvironment and marrow-derived cells isolated from patients with MS have not been extensively characterised. Objectives: To examine the bone marrow microenvironment and assess the proliferative potential of multipotent mesenchymal stromal cells (MSCs) in progressive MS. Methods: Comparative phenotypic analysis of bone marrow and marrow-derived MSCs isolated from patients with progressive MS and control subjects was undertaken. Results: In MS marrow, there was an interstitial infiltrate of inflammatory cells with lymphoid (predominantly T-cell) nodules although total cellularity was reduced. Controlling for age, MSCs isolated from patients with MS had reduced in vitro expansion potential as determined by population doubling time, colony-forming unit assay, and expression of β-galactosidase. MS MSCs expressed reduced levels of Stro-1 and displayed accelerated shortening of telomere terminal restriction fragments (TRF) in vitro. Conclusion: Our results are consistent with reduced proliferative capacity and ex vivo premature ageing of bone-marrow-derived cells, particularly MSCs, in MS. They have significant implication for MSC-based therapies for MS and suggest that accelerated cellular ageing and senescence may contribute to the pathophysiology of progressive MS. [ABSTRACT FROM AUTHOR]

Background: Haematological malignancy is an important cause of pleural effusion. Pleural effusions secondary to haematological malignancy are usually lymphocyte predominant. However, several other conditions such as carcinoma, tuberculosis, and chronic heart failure also cause lymphocytic effusions. Lymphocyte subset (LS) analysis may be a useful test to identify haematological malignancy in patients with lymphocytic effusions. However, research into their utility in pleural effusion diagnostic algorithms has not yet been published. Objectives: We aimed to determine the clinical utility of pleural fluid LS analysis and whether it can be applied to a diagnostic algorithm to identify effusions secondary to haematological malignancy. The secondary aim was to evaluate the diagnostic value of pleural fluid differential cell count. Methods: Consecutive consenting patients presenting to our pleural service between 2008 and 2013 underwent thoracentesis and differential cell count analysis. We proposed an algorithm which selected patients with lymphocytic effusions (>50%) to have further fluid sent for LS analysis. Two independent consultants agreed on the cause of the original effusion after a 12-month follow-up period. Results: A total of 60 patients had samples sent for LS analysis. LS analysis had an 80% sensitivity (8/10) and a 100% specificity for the diagnosis of haematological malignancy. The positive and negative predictive values were 100 and 96.1%, respectively. Overall 344 differential cell counts were analysed; 16% of pleural effusions with a malignant aetiology were neutrophilic or eosinophilic at presentation. A higher neutrophil and eosinophil count was associated with benign diagnoses, whereas a higher lymphocyte count was associated with malignant diagnoses. Conclusions: LS analysis may identify haematological malignancy in a specific cohort of patients with undiagnosed pleural effusions. A pleural fluid differential cell count provides useful additional information to streamline patient pathway decisions. [ABSTRACT FROM AUTHOR]

Many older patients with acute myeloid leukaemia ( AML) that receive standard intensive chemotherapy fail to achieve complete remission ( CR). Upfront identification of patients unlikely to benefit from standard induction chemotherapy would be important for exploration of novel therapies. This study evaluated if a flow cytometric assay measuring pre-treatment CD34+ CD38low blast frequency could predict therapeutic-resistance in 736 AML patients entered into the UK National Cancer Research Institute AML16 trial. High peripheral blood CD34+ CD38low blast frequency (>7% of leucocytes), present in 18% of assessable patients, conferred significantly reduced CR rates (38% vs. 76%, P < 0·0001) and poor survival, and was independently prognostic for all endpoints of treatment resistance by multivariate analysis. [ABSTRACT FROM AUTHOR]

Flow cytometry has had an impact upon all areas of clinical pathology and now, in the 21st century, it is truly coming of age. This study reviews the application of flow cytometry within clinical pathology with an emphasis upon haematology and immunology. The basic principles of flow cytometry are discussed, including the principles and considerations of the flow-cell and hydrodynamic focusing, detector layout and function, use of fluorochromes and multicolour flow cytometry (spectral overlap and colour compensation), alongside the strategies available for sample preparation, data acquisition and analysis, reporting of results, internal quality control, external quality assessment and flow sorting. The practice of flow cytometry is discussed, including the principles and pitfalls associated with leukocyte immunophenotyping for leukaemia and lymphoma diagnosis, immune deficiency, predicting and monitoring response to monoclonal antibody therapy, rare event detection and screening for genetic disease. Each section is illustrated with a case study. Future directions are also discussed. [ABSTRACT FROM AUTHOR]

Background: Patients with primary antibody deficiency often have delayed diagnosis. Very low IgE, found during investigations for allergy, may be a marker for other immunodeficiency. Methods: We introduced a new laboratory policy of testing cases with very low IgE levels for possible linked antibody deficiency. The data represent an audit of routine results collected over two years. Results: Very low IgE (≤2 IU/mL) was identified in 85/2622 (3.2%) routine patient samples. Two children and four adult patients were found to have one or more classes of immunoglobulin below the reference range for age. In 2/6, the initiative of the laboratory led to a new unsuspected diagnosis of antibody immunodeficiency. Conclusions: Common variable immunodeficiency continues to be overlooked as a primary cause of lung disease in adults. Very low serum IgE should trigger appropriate investigation (immunoglobulin quantification and serum electrophoresis). [ABSTRACT FROM AUTHOR]

Background: Radiological monitoring of malignant pleural mesothelioma (MPM) using modified RECIST criteria is limited by low sensitivity and inter-observer variability. Serial serum mesothelin measurement has shown utility in the assessment of treatment response during chemotherapy but has never been assessed in the longer term follow up of patients.Methods: This is a single centre study of consecutive patients diagnosed with MPM who received chemotherapy or best supportive care (BSC). Serum mesothelin measurements with paired 6 monthly CT scans were performed following the completion of chemotherapy, or from baseline in the BSC group. Changes in mesothelin were correlated with radiological progression and overall survival.Results: Forty-one patients with MPM were recruited and followed up for a minimum of 12 months (range 12-21 months). The majority of patients (n = 23) received chemotherapy with pemetrexed and cisplatin. Across the cohort a 10% rise in serum mesothelin could predict radiological progression with a sensitivity of 96% (IQR; 79-100) and specificity of 74% (IQR; 50-91). Sensitivity fell to 80% in sarcomatoid only disease. Patients with a rising mesothelin at 6 months had significantly worse overall survival (175 days) compared to stable/falling levels (448 days) (p = 0.003).Conclusions: This is the first study to assess serum mesothelin's ability to detect progression of MPM following chemotherapy or during BSC. A 10% rise in serum mesothelin level showed excellent sensitivity at predicting progressive disease. Mesothelin measurement has several advantages over serial CT imaging including reducing hospital visits and cost. [ABSTRACT FROM AUTHOR]

Focuses on issues related to immunophenotyping of leukemia and lymphoma. Assessment of dendritic cell analysis; Appraisal of immunophenotypic diagnosis of T cells; Overview of research in this field.