Search

Summary: The diagnosis of myeloproliferative neoplasms (MPN) requires the integration of clinical, morphological, genetic and immunophenotypic findings. Recently, there has been a transformation in our understanding of the cellular and molecular mechanisms underlying disease initiation and progression in MPN. This has been accompanied by the widespread application of high‐resolution quantitative molecular techniques. By contrast, microscopic interpretation of bone marrow biopsies by haematologists/haematopathologists remains subjective and qualitative. However, advances in tissue image analysis and artificial intelligence (AI) promise to transform haematopathology. Pioneering studies in bone marrow image analysis offer to refine our understanding of the boundaries between reactive samples and MPN subtypes and better capture the morphological correlates of high‐risk disease. They also demonstrate potential to improve the evaluation of current and novel therapeutics for MPN and other blood cancers. With increased therapeutic targeting of diverse molecular, cellular and extra‐cellular components of the marrow, these approaches can address the unmet need for improved objective and quantitative measures of disease modification in the context of clinical trials. This review focuses on the state‐of‐the‐art in image analysis/AI of bone marrow tissue, with an emphasis on its potential to complement and inform future clinical studies and research in MPN. [ABSTRACT FROM AUTHOR]

Despite much of the past 2 years being engulfed by the devastating consequences of the SAR‐CoV‐2 pandemic, significant progress, even breathtaking, occurred in the field of chronic myeloid malignancies. Some of this was show‐cased at the 15th Post‐American Society of Hematology (ASH) and the 25th John Goldman workshops on myeloproliferative neoplasms (MPN) held on 9th‐10th December 2020 and 7th‐10th October 2021, respectively. The inaugural Post‐ASH MPN workshop was set out in 2006 by John Goldman (deceased) and Tariq Mughal to answer emerging translational hematology and therapeutics of patients with these malignancies. Rather than present a resume of the discussions, this perspective focuses on some of the pivotal translational hematology and therapeutic insights in these diseases. [ABSTRACT FROM AUTHOR]

Keywords: Castleman disease; interleukins; POEMS; KSHV/HHV8; HIV; TAFRO EN Castleman disease interleukins POEMS KSHV/HHV8 HIV TAFRO 328 337 10 11/01/21 20211101 NES 211101 Methodology This "Good Practice Paper" was compiled according to the British Society for Haematology (BSH) process at (http://www.b-s-h.org.uk/guidelines). Despite the success of IL-6-signalling blockade, there remains a significant unmet clinical need not only for patients who are intolerant of anti-IL-6 therapy, but also for a reliable disease-modifying therapy.50 Tocilizumab is a monoclonal antibody that antagonises the IL-6 receptor (IL-6R) to block signal transduction.57 Tocilizumab is licensed in Japan, but not in the UK, for the treatment of iMCD-TAFRO. Survival rates for MCD are not clear given changes in in diagnostic criteria, reporting and therapy.7 Nevertheless, the 5-year OS rate for MCD have been estimated at ˜65%.4 Human herpesvirus 8-associated MCD (HHV8-MCD) A proportion of cases of MCD have been attributed to infection with HHV8. The choice of therapy in MCD depends on the presentation of the patient as well as identification of drivers of disease: HHV8-MCD, POEMS-MCD, iMCD (NOS and TAFRO). [Extracted from the article]

Assessing the impact of lockdown: Fresh challenges for the care of haematology patients in the COVID-19 pandemic Worldwide cases of confirmed COVID-19 are approaching three million, and citizens around the world are experiencing unprecedented changes to their lifestyles due to the measures implemented to slow the spread of the disease. New diagnoses of haematological malignancy There has been a 71% fall in the numbers of full blood counts performed from primary care in the four weeks since the lockdown was introduced, and 57% fewer patients referred by e-referral for specialist haematology review. [Extracted from the article]

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are unfit for or relapsed postautologous stem-cell transplantation have poor outcomes. Historically, mTORC1 inhibitors have produced responses in approximately 30% of patients in this setting. mTORC1 inhibitor efficacy may be limited by resistance mechanisms including AKT activation by mTORC2. To date, dual mTORC1/2 inhibitors targeting both the TORC1 and TORC2 complexes have not been investigated in DLBCL. This phase II trial investigated the oral dual mTORC1/2 inhibitor vistusertib in an intermittent dosing schedule of 125 mg b.d. for 2 days per week. Thirty patients received vistusertib and six received vistusertib-rituximab for up to six cycles (28-day cycles). Two partial responses were achieved on monotherapy. Durations of response were 57 and 62 days, respectively, for these patients. 19% had stable disease within six cycles. In the monotherapy arm, the median progression-free survival was1.69 (95% confidence interval [CI] 1.61-2.14) months and median overall survival was 6.58 (95% CI 3.81-not reached) months, respectively. The median duration of response or stable disease across the trial duration was 153 days (95% CI 112-not reached). Tumour responses according to positron emission tomography/computed tomography versus computed tomography were concordant. There were no differences noted in tumour volume response according to cell of origin by either gene expression profiling or immunohistochemistry. Vistusertib ± rituximab was well tolerated; across 36 patients 86% of adverse events were grade (G) 1-2. Common vistusertib-related adverse events were similar to those described with mTORC1 inhibitors: nausea (47% G1-2), diarrhoea (27% G1-2, 6% G3), fatigue (30% G1-2, 3% G3), mucositis (25% G1-2, 6% G3), vomiting (17% G1-2), and dyspepsia (14% G1-2). Dual mTORC1/2 inhibitors do not clearly confer an advantage over mTORC1 inhibitors in relapsed or refractory DLBCL. Potential resistance mechanisms are discussed within. [ABSTRACT FROM AUTHOR]

The invasion of lymphatic vessels by colorectal cancer (CRC) and its subsequent spread to draining lymph nodes is a key determinant of prognosis in this common and frequently fatal malignancy. Although tumoural lymphangiogenesis is assumed to contribute to this process, review of the current literature fails to support any notion of a simple correlation between lymphatic vessel density and CRC metastasis. Furthermore, attempts to correlate the expression of various lymphangiogenic growth factors, most notably VEGF-C and VEGF-D, with the lymphatic metastasis of CRC have provided contradictory results. Recent evidence from animal and human models of tumour metastasis suggests that complex functional and biochemical interactions between the microvasculature of tumours and other cell types within the tumour microenvironment may play a pivotal role in the behaviour of commonly metastasizing tumours. Indeed, previous insights into tumoural blood vessels have provided candidate markers of tumoural angiogenesis that are currently the subject of intense investigation as future therapeutic targets. In this review article we survey the current evidence relating lymphangiogenesis and lymphangiogenic growth factor production to metastasis by CRC, and attempt to provide some insight into the apparent discrepancies within the literature. In particular, we also discuss some new and provocative insights into the properties of tumoural lymphatics suggesting that they have specific expression profiles distinct from those of normal lymphatic vessels and that appear to promote metastasis. These findings raise the exciting prospect of future biomarkers of lymphatic metastasis and identify potential targets for new generation anti-tumour therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary Diagnosis of essential thrombocythaemia (ET) is challenging in patients lacking JAK2/CALR/MPL mutations. In a retrospective evaluation of 320 patients with ‘triple‐negative thrombocytosis’, we assessed utility of bone marrow histology (90.9% of patients) and myeloid gene panel (MGP, 55.6%). Supportive histology (‘myeloproliferative neoplasm‐definite/probable’, 36.8%) was associated with higher platelet counts and varied between centres. 14.6% MGP revealed significant variants: 3.4% JAK2/CALR/MPL and 11.2% other myeloid genes. Final clinical diagnosis was strongly predicted by histology, not MGP. 23.7% received cytoreduction (17.6% under 60 years). Real‐world ‘triple‐negative’ ET diagnosis currently depends heavily on histology; we advocate caution in MGP‐negative cases and that specific guidelines are needed. [ABSTRACT FROM AUTHOR]