{"title":"Myeloma and MGUS","authors":"Matthew J Streetly","doi":"10.1016/j.mpmed.2025.02.010","DOIUrl":"10.1016/j.mpmed.2025.02.010","url":null,"abstract":"<div><div>Plasma cell disorders result from a clonal proliferation of bone marrow plasma cells and range from benign monoclonal gammopathy of undetermined significance (MGUS) to malignant myeloma. Serum or urine monoclonal protein is usually detectable. MGUS is asymptomatic but can progress to myeloma or lymphoma. Myeloma is generally a disease of elderly individuals and presents with variable problems including anaemia, bone pain, fractures, spinal cord compression, renal failure, hypercalcaemia, recurrent infections and hyperviscosity. Diagnosis is based on bone marrow examination, and prognosis is influenced by specific acquired genetic abnormalities. Treatment is required after the development of, or to reduce the risk of developing, myeloma-related organ or tissue impairment. Myeloma is incurable, and treatment combines anti-myeloma chemoimmunotherapy with supportive therapies. Younger, medically fit patients are treated with intensive regimens combining chemotherapy with an autologous stem cell transplant, whereas older patients with co-morbidities and poorer performance status are generally offered less intensive treatment. It has a responding–relapsing disease course with eventual development of drug resistance. However, newer therapy options alone or in combination have improved outcomes in myeloma.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 325-330"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CAR-T cells – the future for cancer therapy","authors":"Reuben Benjamin, Francesco Restuccia","doi":"10.1016/j.mpmed.2025.03.002","DOIUrl":"10.1016/j.mpmed.2025.03.002","url":null,"abstract":"<div><div>Chimeric antigen receptor T cells (CAR-T) are a novel form of immunotherapy in which T cells from individuals with cancer are genetically modified to express a chimeric receptor enabling them to target cancer cells, with profound anti-tumour effects. CAR-T cells have shown highly impressive results in the treatment of B cell haematological malignancies, with several CD19-targeted CAR-T cells products now approved for routine clinical use. The main adverse effects of CAR-T cells treatment include cytokine-release syndrome, neurotoxicity and cytopenias; these require prompt treatment in specialist centres. Future developments related to CAR-T cells are likely to see products with improved efficacy, newer indications such as solid tumours and autoimmune disease and more affordable and easier access to this promising therapy.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 340-342"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Chronic lymphocytic leukaemia","authors":"Anita Sarma, Piers EM Patten","doi":"10.1016/j.mpmed.2025.03.003","DOIUrl":"10.1016/j.mpmed.2025.03.003","url":null,"abstract":"<div><div>Chronic lymphocytic leukaemia is a common subtype of non-Hodgkin lymphoma often diagnosed incidentally through the finding of a lymphocytosis on a routine blood count. Key diagnostic tests are peripheral blood morphology and immunophenotyping. At all stages of disease patients are vulnerable to infections and other malignancies. Treatment is only indicated in individuals who show progression by developing symptoms such as fatigue, lymphadenopathy or splenomegaly, or cytopenias. An increasing number of prognostic biomarkers are now available to assess likely disease outcome and response to different types of treatment. Use of newer agents such as Bruton tyrosine kinase inhibitors and BCL2 inhibitors have largely replaced more traditional chemo-immunotherapy and significantly improved outcomes.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 298-303"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hodgkin lymphoma","authors":"David Wrench","doi":"10.1016/j.mpmed.2025.02.013","DOIUrl":"10.1016/j.mpmed.2025.02.013","url":null,"abstract":"<div><div>Hodgkin lymphoma typically presents as a painless mass and can be subclassified into classical and nodular lymphocyte-predominant forms, each with characteristic age of incidence peaks. Most patients who develop Hodgkin lymphoma can now be cured. In view of this, initial treatment can be adapted to disease response demonstrated on interim positron emission tomography/computed tomography. This enables patients with good-risk disease to benefit from early attenuation of therapy (to limit the risks of long-term treatment-associated complications) while maintaining treatment efficacy, and patients with poor-risk disease to benefit from early treatment escalation. A minority of patients are either refractory to or relapse after first-line therapy, but novel agents are overcoming chemotherapy resistance. Furthermore, the incorporation of these new treatments in the initial therapy heralds improvements in tolerability of treatment and reductions in risk of early progressive disease.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 312-318"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Non-Hodgkin lymphoma","authors":"James Paterson, Jonathan Lambert","doi":"10.1016/j.mpmed.2025.02.011","DOIUrl":"10.1016/j.mpmed.2025.02.011","url":null,"abstract":"<div><div>Non-Hodgkin lymphoma (NHL) is the seventh most common cancer in the UK and represents a heterogenous group of malignancies. This article gives a brief overview of the current classification of B and T cell NHL, the molecular and cytogenetic abnormalities associated with their pathogenesis, and principles for managing them. Although advances in immuno-chemotherapy and supportive care have resulted in better patient outcomes, many challenges remain, especially for individuals with relapsed and refractory disease.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 319-324"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Acute leukaemia","authors":"Aditya Tedjaseputra, Richard Dillon, Kavita Raj","doi":"10.1016/j.mpmed.2025.03.004","DOIUrl":"10.1016/j.mpmed.2025.03.004","url":null,"abstract":"<div><div>The acute leukaemias consist of acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL), which typically present in older adults and childhood, respectively. Uncontrolled proliferation of abnormal, immature blasts leads to bone marrow failure and cytopenias, which may present as medical emergencies (e.g. leukostasis, catastrophic coagulopathy). Approximately 90% of children with ALL are cured. The outcomes of AML patients are more heterogenous but have improved significantly in recent years through optimization of supportive care and incorporation of targeted therapies. Lineage distinction (AML vs ALL) is attained first through morphology and flow cytometry. Exclusion of acute promyelocytic leukaemia, an AML subtype with a very high early death rate without appropriate treatment, must occur within hours of presentation of a patient with suspected acute leukaemia. Cytogenetics and comprehensive molecular testing further delineate specific subtypes, prognosis and therapeutic targeting. Treatment of acute leukaemias is centred around three aims: (1) attainment of complete remission (CR) via induction; (2) maintenance of CR via consolidation and/or maintenance therapy, including consideration of allogeneic stem cell transplant for high-risk patients; and (3) early detection of impending relapse through measurable residual disease monitoring, affording early pre-emptive therapy. Cumulatively, these approaches have improved the outlook of patients with acute leukaemias.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 288-297"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Approach to the investigation of lymphadenopathy and splenomegaly","authors":"Catherine A Cox","doi":"10.1016/j.mpmed.2025.02.008","DOIUrl":"10.1016/j.mpmed.2025.02.008","url":null,"abstract":"<div><div>Lymphadenopathy and splenomegaly, alone or in combination, are common presentations with a diverse range of causes. These can range from a normal physiological response to a simple, acute infection, to the first presentation of malignancy. As such, timely diagnostics is crucial. Understanding the function of these organs is a necessary step to forming a differential diagnosis. This article breaks down the roles of the lymph nodes and spleen within the immune system and common causes of lymphadenopathy and splenomegaly. It then provides a structure to history-taking and examination. An algorithm for a diagnostic approach is presented into which this information can be fed. It highlights important red flag symptoms and critical tests that should be performed to lead to timely diagnosis and treatment.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 308-311"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Haematological emergencies","authors":"Shahira Butt, Merrina Gregory, Priya Sriskandarajah, Natalia Curto-Garcia","doi":"10.1016/j.mpmed.2025.03.006","DOIUrl":"10.1016/j.mpmed.2025.03.006","url":null,"abstract":"<div><div>This article provides an overview of the management of common haematological emergencies. Individuals with haematological disorders often present with co-morbidities and/or undergo chemotherapy, which can pose challenges to clinicians who are unfamiliar with these conditions. Accurate interpretation of laboratory data, in-depth knowledge of disease-related complications and strong clinical skills are critical for diagnosing and managing haematological emergencies. This review focuses on the key principles involved in diagnosing and managing the most frequently encountered emergencies in these patients.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 343-350"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myelodysplastic neoplasms","authors":"Jiexin Zheng","doi":"10.1016/j.mpmed.2025.02.007","DOIUrl":"10.1016/j.mpmed.2025.02.007","url":null,"abstract":"<div><div>Myelodysplastic neoplasms (MDSs) are rare clonal haematological neoplasms that result from disordered haematopoiesis. MDSs typically present in elderly individuals with cytopenia in one or more blood cell lineages. MDSs are diagnosed based on clinical, morphological, cytogenetic and genetic changes, with the latest international MDS classifications in 2022 incorporating these disease features into different MDS subtypes. Prognostic scoring systems can be used in individuals with MDS at presentation, to confer an estimated overall survival as well as guide appropriate treatment; this should be tailored based on the prognostic score as well as individual clinical factors.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 278-281"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Myeloproliferative neoplasms","authors":"Laura Li Gagnon, Claire N Harrison","doi":"10.1016/j.mpmed.2025.02.006","DOIUrl":"10.1016/j.mpmed.2025.02.006","url":null,"abstract":"<div><div>Myeloproliferative neoplasms (MPNs), polycythaemia vera, essential thrombocythaemia and myelofibrosis – are uncommon clonal haematological malignancies generally diagnosed from late middle age onwards, although they can occur in children and young adults. They should be suspected in patients with elevated blood counts, atypical thrombosis or splenomegaly. Their clinical courses share similarities, including thrombosis, haemorrhage and a tendency to progress to myelofibrosis or acute myeloid leukaemia. Myelofibrosis has a poorer prognosis and significant disease burden affecting quality of life. Advances in diagnostics and genomics have recently been used to stratify risk more accurately. Furthermore, the development of treatment modalities aimed at targeting specific molecular pathways, such as Janus kinase inhibitors, has resulted in a therapeutic paradigm shift. Several ground-breaking studies have proved the efficacy of the first such agents and they are now licensed as first-line therapy in myelofibrosis and as second line in polycythaemia vera. Additional targets, such as <em>CALR</em>, are under evaluation in clinical trials. However, the mainstay of treatment for polycythaemia vera and essential thrombocythaemia remains aggressive management of thrombotic risk factors, antiplatelet therapy for most patients, and cytoreductive agents such as hydroxycarbamide and interferon for patients at high risk of thrombosis. This is, nevertheless, a rapidly evolving landscape.</div></div>","PeriodicalId":74157,"journal":{"name":"Medicine (Abingdon, England : UK ed.)","volume":"53 5","pages":"Pages 282-287"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143924650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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