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Haematological Disease
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
There are two types of acute leukaemia, defined by the lineage to which the blast cells belong: ALLAML
Neoplasia in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
The majority of pregnant women found to have leukemia are diagnosed during routine prenatal care. Signs and symptoms of acute leukemia include anemia, granulocytopenia, thrombocytopenia, splenomegaly, fatigue, fever, infection, and evidence of a bleeding diathesis. Physical exam may demonstrate pallor, petechiae, or ecchymoses. The diagnosis of leukemia oftentimes is confirmed by bone marrow examination. However, it can be initially suspected when a peripheral blood smear demonstrates a normocytic, normochromic anemia with a mild to severe thrombocytopenia. Blast cells are virtually always present despite a normal or low white blood cell count (238). Additionally, if the patient presents with a leukocytosis, flow cytometry and cytogenetics of a peripheral blood sample can be sufficient for diagnosis.
HLA-DR and -DQ Serotyping
Published in M. Kam, Jeffrey L. Bidwell, Handbook of HLA TYPING TECHNIQUES, 2020
Other Leukemic Cells. Cells from patients with chronic B lymphocytic leukemia (CLL) type normally for HLA-DR and -DQ even though their surface expression of DQ molecules is low.33 Blast cells from patients with chronic myeloid leukemia (CML) are completely class II negative.34 CML patients do not achieve full clinical remission with an absence of blast cells, but enough B lymphocytes are sometimes present in a blood sample for a class II typing to be obtained. Cells obtained from CML patients in blast crisis do express HLA-DR antigens.
Experimental drugs in clinical trials for acute myeloid leukemia: innovations, trends, and opportunities
Published in Expert Opinion on Investigational Drugs, 2023
Aleksandra Gołos, Joanna Góra-Tybor, Tadeusz Robak
For several years, much effort has been made to develop new, molecular-targeted drugs for AML. As far as genetically driven therapies have proved to be effective, the immune targets are still elusive. This may be because of the heterogeneity of the immune landscape between AML patients. Recent studies have revealed that different mutations in blast cells are characterized by other immune pathway alterations [98]. CD47, immune checkpoints: anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), programmed death-1 (PD1), the ligand for PD-1 (PD-L1), antibodies against T-cell receptors, and toll-like receptor 2 (TLR2) are the primary targets among immune therapies. In addition, bispecific T-cell engagers antibodies (BiTEs) and CAR-T cells have been of interest. The hallmark of most immune therapies in AML is their modest efficacy if used as a single agent. Therefore, the last clinical trials combine an immune–targeted agent with a hypomethylating or molecular-targeted one (Table 3).
Current and emerging pharmacotherapy for the treatment of childhood acute myeloid leukemia
Published in Expert Opinion on Pharmacotherapy, 2022
Branko Cuglievan, David McCall, Lindsay Robusto, M. Estela Mireles, Suzanne C. Gettys
Given the poor outcomes in relapsed/refractory AML, the development of targeted agents is desperately needed. Although adoptive immunotherapy using CD19-specific chimeric antigen receptor (CAR)-T cells has shown unprecedented results in other pediatric hematological malignancies [66–68], safe and effective CAR-T therapy for AML remains elusive. One reason is the difficulty in finding key antigens specific for leukemia populations that do not overlap with hematopoietic stem cells that would lead to prolonged myelosuppression [69]. Other challenges for immunotherapy is the innate ability of blast cells to resist treatment through augmenting the immune system response. Those evasion mechanisms include overexpressing T-cell ligands, promoting T-cell exhaustion, reducing their expression of antigen presentation molecules, and altering their cytokine milleu [70]. Blasts also alter the tumor microenvironment via secretion of inhibitory factors, altering production of CXCL12, increasing adipocyte metabolism and by vascular modification that can inhibit T-cell function [70].
Could COVID-19 induce remission of acute leukemia?
Published in Hematology, 2021
Eman Z. Kandeel, Lobna Refaat, Raafat Abdel-Fatah, Mohamed Samra, Ahmed Bayoumi, Mona S. Abdellateif, Hend Abdel-Hady, Mohamed Ali, Medhat Khafagy
This prompted further investigations in the form of: – Bone marrow aspirate (BMA) was normocellular with 53% blast cells, remarkable hemophagocytic features and dysplasia in the erythroid and myeloid series (Figure 1(A,B)).– Immunohistochemistry showed myeloid peroxidase positivity.– Immunophenotyping gating on CD45 dim population was positive for MPO, CD13, CD33, MHC class II, CD64, CD34, CD11C, CD14 and CD117. Blast cells were diagnosed as myeloid with a monocytic differentiation phenotype.– Cytogenetic findings were normal with no molecular findings as recurrent translocations, no mutation in FMS-like tyrosine kinase 3 internal tandem duplicate (FLT3-ITD) or nucleophosmin.