Aplastic anemia is related to alterations in T cell receptor signaling

Xiao, Yankai; Zhao, Suwen; Li, Bo

doi:10.21037/sci.2017.09.07

Cited by 12 publications

(7 citation statements)

References 32 publications

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“…Large numbers of studies have proved that T lymphocytes have a close relationship with hematopoietic failure. [8] Based on this, the extensive application and good efficacy of immunosuppressive also confirmed the significance of immunopathology in the development of aplastic anemia. [9, 10]…”

Section: Aplastic Anemia In Tcm Theorymentioning

confidence: 70%

The progress of traditional Chinese medicine in the treatment of aplastic anemia

Zhu

2018

Journal of Translational Internal Medicine

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Aplastic anemia (AA) is a common hematologic disease that is characterized by hematopoietic failure of the bone marrow and pancytopenia of the peripheral blood, which can be divided into severe and non-severe aplastic ane-mia, or acute and chronic aplastic anemia according to the severity of the disease and the progress of the clinical course. During the past years, the advantages of Traditional Chinese Medicine (TCM) on the treatment of AA have been well clarified and its theory system has been improved as well. This review is mainly on representing the pathogenesis, therapeutic principle and method, research progression, and advantages of TCM on AA.

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Section: Aplastic Anemia In Tcm Theorymentioning

confidence: 70%

The progress of traditional Chinese medicine in the treatment of aplastic anemia

Zhu

2018

Journal of Translational Internal Medicine

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“…There are a number of known aberrancies that can contribute to the T cell-mediated destruction of hematopoietic progenitors, including oligoclonal expanded populations of autologous T cells, Th1 polarization leading to production of inhibitory cytokines, and Th17 immune responses [ 10 ]. More generally, the pathophysiology of AA can be attributed to aberrantly expressed T-cell receptor molecules, including the down-regulation of immune checkpoints CTLA-4 and PD-1 [ 11 ]. Therefore, in our patient case, the inappropriate modulation of T-cell activity secondary to treatment with nivolumab and ipilimumab could certainly have lead to the observed AA.…”

Section: Discussionmentioning

confidence: 99%

Aplastic anemia secondary to nivolumab and ipilimumab in a patient with metastatic melanoma: a case report

et al. 2018

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BackgroundImmune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of adverse events associated with these drugs will likely grow. Here we report a case of aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB therapy. To our knowledge, this is only the second case of AA secondary to dual ICB in the literature, and the first to have a positive patient outcome.Case presentationA 51-year old male with metastatic melanoma was started on dual immune checkpoint blockade, in the form ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Two weeks following the second cycle, he presented to the emergency department with profound polypipsia, polyuria and fatigue. The patient was diagnosed with diabetic ketoacidosis secondary to immune therapy induced type-1 diabetes and was admitted to the ICU. While in hospital the patient developed a symptomatic anemia and neutropenia. A bone marrow biopsy revealed a markedly hypocellular marrow with trinlineage hypoplasia with no evidence of myelodysplasia, neoplasm or excess blasts. Flow cytometry revealed an inverted CD4+:CD8+ ratio and an absence of hematogones. Taken together the presumed etiology was AA secondary to immunotherapy. The patient was subsequently started in IV methylprednisone 70 mg/day for 8 days, followed by a prednisone taper. This intervention rectified the bicytopenia and to date the patient has shown stable blood counts.ConclusionWith the use of ICBs becoming increasingly prevalent in the clinical arena, the number of patients presenting with immune-related adverse events will likely increase. The current case illustrates the need to be vigilant when managing cancer patients receiving ICB. The resolution of this patient’s AA with corticosteroids highlights the value of early detection and appropriate treatment of these rare immune-mediated adverse events.

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“…Typically, the oligoclonal T‐cell population decreases following IST and returns upon relapse, with the degree of V‐beta diversity predicting for response to IST . Altered T‐cell receptor signalling has also been demonstrated, contributing to abnormal T‐cell function . Subsequent production of myelosuppressive cytokines, including interferon gamma and tumour necrosis factor alpha, leads to apoptosis of HSC.…”

Section: Pathogenesismentioning

confidence: 99%

Revisiting acquired aplastic anaemia: current concepts in diagnosis and management

Clucas

Fox

Wood

et al. 2019

Internal Medicine Journal

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Acquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti-thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and lifethreatening condition.

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Aplastic anemia is related to alterations in T cell receptor signaling

Cited by 12 publications

References 32 publications

The progress of traditional Chinese medicine in the treatment of aplastic anemia

The progress of traditional Chinese medicine in the treatment of aplastic anemia

Aplastic anemia secondary to nivolumab and ipilimumab in a patient with metastatic melanoma: a case report

Revisiting acquired aplastic anaemia: current concepts in diagnosis and management

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