scholarly journals Recent advances of targeted therapy in relapsed/refractory acute myeloid leukemia

2021 ◽  
Author(s):  
Jiale Ma ◽  
Zheng Ge
Keyword(s):  
Acute Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Leukemic Cells ◽  
Bone Marrow Transplants ◽  
Future Directions ◽  
Recent Advances ◽  
Refractory Acute Myeloid Leukemia ◽  
Low Toxicity ◽  
Acute Myeloid

Despite advances in the understanding of disease pathobiology, treatment for relapsed or refractory acute myeloid leukemia (R/R AML) remains challenging. The prognosis of R/R AML remains extremely poor despite chemotherapy and bone marrow transplants. Discoveries on recurrent and novel genetic mutations, such as FLT3-ITD and IDH1/IDH2, critical signaling pathways, and unique molecular markers expressed on the surface of leukemic cells have been under investigation for the management of R/R AML. Other than monoclonal antibodies, diabodies and triabodies are new targeted therapies developed in recent years and will be the new direction of immunotherapy. Targeted agents combined intensive regimens can be viable options for salvage therapy and as bridges to allogeneic transplant. Future directions will focus on novel, efficient and targeted combinations, low-toxicity maintenance, and individualized precision strategies. Here, we review the major recent advances of targeted therapies in the treatment of R/R AML.

scholarly journals Current challenges in clinical development of “targeted therapies”: the case of acute myeloid leukemia

Blood ◽  
2015 ◽  
Vol 125 (16) ◽  
pp. 2461-2466 ◽  
Author(s):  
Elihu Estey ◽  
Ross L. Levine ◽  
Bob Löwenberg
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Targeted Therapies ◽  
Myeloid Leukemia ◽  
Residual Disease ◽  
Leukemic Cells ◽  
Newly Diagnosed ◽  
Preclinical Models ◽  
First Choice ◽  
Acute Myeloid

Abstract A fundamental difficulty in testing “targeted therapies” in acute myeloid leukemia (AML) is the limitations of preclinical models in capturing inter- and intrapatient genomic heterogeneity. Clinical trials typically focus on single agents despite the routine emergence of resistant subclones and experience in blast-phase chronic myeloid leukemia and acute promyelocytic leukemia arguing against this strategy. Inclusion of only relapsed-refractory, or unfit newly diagnosed, patients risks falsely negative results. There is uncertainty as to whether eligibility should require demonstration of the putative target and regarding therapeutic end points. Although use of in vivo preclinical models employing primary leukemic cells is first choice, newer preclinical models including “organoids” and combinations of pharmacologic and genetic approaches may better align models with human AML. We advocate earlier inclusion of combinations ± chemotherapy and of newly diagnosed patients into clinical trials. When a drug plausibly targets a pathway uniquely related to a specific genetic aberration, eligibility should begin with this subset, including patients with other malignancies, with subsequent extension to other patients. In other cases, a more open-minded approach to initial eligibility would facilitate quicker identification of responsive subsets. Complete remission without minimal residual disease seems a particularly useful short-term end point. Genotypic and phenotypic studies should be prespecified and performed routinely to distinguish responders from nonresponders.

scholarly journals Acute myeloid leukemia with leukemic pleural effusion and high levels of pleural adenosine deaminase: A case report and review of literature

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 387-396
Author(s):  
Sing-Ting Wang ◽  
Chieh-Lung Chen ◽  
Shih-Hsin Liang ◽  
Shih-Peng Yeh ◽  
Wen-Chien Cheng
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pleural Effusion ◽  
Adenosine Deaminase ◽  
Myeloid Leukemia ◽  
Diagnostic Yield ◽  
Leukemic Cells ◽  
Pleural Effusions ◽  
Diagnostic Dilemma ◽  
True Incidence ◽  
Acute Myeloid

Abstract Pleural effusions are rarely observed in association with acute myeloid leukemia (AML), and their true incidence remains unknown. Given the low diagnostic yield from cytopathologic analysis of malignant pleural effusions and the fact that patients with leukemia are often thrombocytopenic and unable to tolerate invasive procedures, the incidence of leukemic effusions may be underestimated. Here, we report a rare case of pleural effusion in a patient with newly diagnosed AML. Initial analysis revealed an exudative, lymphocyte-predominant effusion. High levels of adenosine deaminase (ADA) were detected in pleural fluid, consistent with a diagnosis of tuberculosis. However, the analysis of pleural cytology revealed leukemic cells, permitting the diagnosis of leukemic effusion to be made. The patient underwent induction chemotherapy and pleural effusion resolved without recurrence. This case emphasizes the diagnostic dilemma presented by high levels of ADA in a leukemic pleural effusion, as this association has not been previously considered in the literature.

Sign in / Sign up

Export Citation Format

Share Document