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British Journal of Haematology Apr 2016Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases... (Review)
Review
Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30-40% of adults and 60-70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed.
Topics: Adult; Allografts; Cord Blood Stem Cell Transplantation; Graft vs Host Disease; Humans; Infant; Leukemia, Myeloid, Acute; Unrelated Donors
PubMed: 26766286
DOI: 10.1111/bjh.13926 -
British Journal of Haematology Aug 2015Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic... (Review)
Review
Deregulated Hedgehog (Hh) signalling activity may be associated with a broad range of cancer types and hence has become an attractive target for therapeutic intervention. Although initial haematological interest focused on the therapeutic targeting of this pathway in chronic myeloid leukaemia), small molecule inhibitors targeting the Hh pathway are now being tested in a range of other myeloid disorders, including myelofibrosis, myelodysplasia and acute myeloid leukaemia. In this review we will evaluate the rationale for targeting of the Hh pathway in myeloid diseases and discuss the novel agents that have entered the clinical arena. We will discuss pre-clinical models, emerging clinical trial data, and suggest how these targeted therapies may address current unmet medical needs. Finally, we will explore potential limitations of these therapies due to the emergence of secondary resistance mechanisms and speculate on future developments within this arena.
Topics: Animals; Antineoplastic Agents; Drug Delivery Systems; Hedgehog Proteins; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Neoplasm Proteins; Primary Myelofibrosis; Signal Transduction
PubMed: 25892100
DOI: 10.1111/bjh.13426 -
Frontiers in Immunology 2023In recent years, with the gradual advancement of haploidentical transplantation technology, the availability of donors has increased significantly, along with the... (Review)
Review
In recent years, with the gradual advancement of haploidentical transplantation technology, the availability of donors has increased significantly, along with the widespread use of reduced-intensity conditioning and the improvement of nursing techniques, giving more elderly acute myeloid leukemia (AML) patients the chance to receive allogeneic hematopoietic stem cell transplantation. We have summarized the classic and recently proposed pre-transplant assessment methods and assessed the various sources of donors, conditioning regimens, and post-transplant complication management based on the outcomes of large-scale clinical studies for elderly AML patients.
Topics: Humans; Aged; Graft vs Host Disease; Retrospective Studies; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Transplantation, Haploidentical
PubMed: 37207218
DOI: 10.3389/fimmu.2023.1102966 -
MedGenMed : Medscape General Medicine Mar 2005
Review
Topics: Acute Disease; Child; Humans; Leukemia, Myeloid, Acute
PubMed: 16369325
DOI: No ID Found -
British Journal of Haematology Feb 2014Novel therapies with increased efficacy and decreased toxicity are desperately needed for the treatment of acute myeloid leukaemia (AML). The anti CD33 immunoconjugate,... (Review)
Review
Novel therapies with increased efficacy and decreased toxicity are desperately needed for the treatment of acute myeloid leukaemia (AML). The anti CD33 immunoconjugate, gemtuzumab ozogamicin (GO), was withdrawn with concerns over induction mortality and lack of efficacy. However a number of recent trials suggest that, particularly in AML with favourable cytogenetics, GO may improve overall survival. This data and the development of alternative novel monoclonal antibodies (mAb) have renewed interest in the area. Leukaemic stem cells (LSC) are identified as the subset of AML blasts that reproduces the leukaemic phenotype upon transplantation into immunosuppressed mice. AML relapse may be caused by chemoresistant LSC and this has refocused interest on identifying and targeting antigens specific for LSC. Several mAb have been developed that target LSC effectively in xenogeneic models but only a few have begun clinical evaluation. Antibody engineering may improve the activity of potential new therapeutics for AML. The encouraging results seen with bispecific T cell-engaging mAb-based molecules against CD19 in the treatment of B-cell acute lymphobalstic leukaemia, highlight the potential efficacy of engineered antibodies in the treatment of acute leukaemia. Potent engineered mAb, possibly targeting novel LSC antigens, offer hope for improving the current poor prognosis for AML.
Topics: Animals; Antibodies, Monoclonal; Humans; Leukemia, Myeloid, Acute
PubMed: 24321020
DOI: 10.1111/bjh.12691 -
Bioscience Reports Apr 2022Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to... (Review)
Review
Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to treat AML are reaching the limits of their efficacy, necessitating the urgent development of novel targeted therapies. Canonical Wnt signalling is an evolutionary conserved cascade heavily implicated in normal developmental and disease processes in humans. For over 15 years its been known that the central mediator of this pathway, β-catenin, is dysregulated in AML promoting the emergence, maintenance, and drug resistance of leukaemia stem cells. Yet, despite this knowledge, and subsequent studies demonstrating the therapeutic potential of targeting Wnt activity in haematological cancers, β-catenin inhibitors have not yet reached the clinic. The aim of this review is to summarise the current understanding regarding the role and mechanistic dysregulation of β-catenin in AML, and assess the therapeutic merit of pharmacologically targeting this molecule, drawing on lessons from other disease contexts.
Topics: Humans; Leukemia, Myeloid, Acute; Wnt Signaling Pathway; beta Catenin
PubMed: 35352805
DOI: 10.1042/BSR20211841 -
British Journal of Haematology Feb 2018
Topics: Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Transplantation Conditioning
PubMed: 29193005
DOI: 10.1111/bjh.15031 -
Journal of Clinical Pathology Jun 2016Transforming growth factor α (TGFα) is a peptide growth factor known to be expressed in normal haemopoiesis. It is also expressed in a range of epithelial neoplasms...
BACKGROUND
Transforming growth factor α (TGFα) is a peptide growth factor known to be expressed in normal haemopoiesis. It is also expressed in a range of epithelial neoplasms but has not been assessed in haemopoietic malignancies. We have performed an immunohistochemical evaluation of TGFα in acute and chronic myeloid malignancies.
METHODS
TGFα expression was semiquantitatively assessed in 69 normal bone marrow trephines and 157 cases of myeloid malignancy using an immunohistochemical approach.
RESULTS
Blast cells of myeloid origin in acute myeloid leukaemia (AML), myelodysplasia and accelerated and blast phases of chronic myeloid leukaemia (CML) were TGFα positive. In acute promyelocytic leukaemia the neoplastic cells had significantly weaker TGFα expression than seen in other forms of AML. The blast cells in CML-accelerated and blast phases were positive with similar expression to AML.
CONCLUSIONS
TGFα is expressed in neoplastic myeloblasts and could, therefore, be used as blast cell biomarker in diagnostic haematopathology. In addition, TGFα immunohistochemistry may be of use in identifying a therapeutic target.
Topics: Biomarkers; Bone Marrow; Hematopoiesis; Humans; Immunohistochemistry; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Leukocytes; Myelodysplastic Syndromes; Myeloproliferative Disorders; Transforming Growth Factor alpha
PubMed: 26984929
DOI: 10.1136/jclinpath-2015-203526 -
Journal of Clinical Pathology Jun 2020Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone... (Review)
Review
Paraneoplastic leukemoid reaction (PLR) is the extreme leukocytosis that occurs due to a non-haematolymphoid cytokine-secreting tumour (CST) in the absence of bone marrow infiltration by that solid tumour. The clinical presentation is widely variable, and therefore challenging. If the underlying malignancy is not clinically apparent, PLR could be mistaken for myeloproliferative neoplasms, altering the patient's management. CSTs are highly aggressive tumours associated with a poor prognosis due to multiple mechanisms. Localising and treating the underlying malignancy is the mainstay of treatment. Both the treating clinician and the pathologist should keep a high level of suspicion for this entity in patients having unexplained leukocytosis. We herein discuss the underlying mechanisms, clinical presentation, pathological features, differential diagnosis and prognosis of this rare entity. An emphasis on the role of the pathologist is provided since the lack of knowledge on this entity can lead to dramatic effects on the patient, including unnecessary diagnostic testing and treatments.
Topics: Cytokines; Diagnosis, Differential; Humans; Leukemia, Myeloid; Leukemoid Reaction; Leukocytes; Myeloproliferative Disorders; Neoplasms; Prognosis
PubMed: 31941653
DOI: 10.1136/jclinpath-2019-206340 -
British Journal of Haematology Jan 2017
Topics: Adult; Child; Drug Resistance, Neoplasm; Genomics; Humans; Leukemia, Myeloid, Acute; Remission Induction
PubMed: 27766614
DOI: 10.1111/bjh.14415