Bridging-to-Transplant with Azacitidine for Myelodysplastic Syndrome and Acute Myeloid Leukemia, Reduces the Incidence of Acute Graft-versus-Host Disease

Murakami, Koichi; Ueno, Hironori; Okabe, Takashi; Kagoo, Toshiya; Boku, Saigen; Yano, Takahiro; Yokoyama, Akihiro

doi:10.4081/hr.2017.7114

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…After first-line azacitidine application in high-risk MDS and AML patients, HSCT was feasible in the majority of patients with a pre-transplant CR rate of 24% and a median overall survival of 20.9 months after HSCT [ 60 ]. Interestingly, pre-transplant azacitidine application appears to decrease the risk of severe GvHD and to reduce the risk of relapse after HSCT compared to standard induction [ 61 , 62 ].…”

Section: Bridging Strategiesmentioning

confidence: 99%

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Hecker

Miller

Götze

et al. 2018

Cancers

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Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and lack of a suitable donor. With the higher availability of suitable donors as well as of reduced intensity conditioning regimens, novel low intensity treatments prior to transplantation and optimized supportive care, the number of older AML patients being successfully transplanted is steadily increasing. Against this background, we review current treatment strategies for older AML patients planned for allogeneic stem cell transplantation based on clinical trial data, discussing differences between approaches with advantages and pitfalls of each. We summarize pre-treatment considerations that need to be taken into account in this highly heterogeneous older population. Finally, we offer an outlook on areas of ongoing clinical research, including novel immunotherapeutic approaches that may improve access to curative therapies for a larger number of older AML patients.

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Section: Bridging Strategiesmentioning

confidence: 99%

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Hecker

Miller

Götze

et al. 2018

Cancers

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“…Clinical studies have shown that patients with intermediate-and high-risk MDS or elderly old AML receive HMA treatment preferentially. HMAs have also been widely used in low-risk MDS (116), in combination with other chemotherapies to enhance the activity of cytotoxic drugs in leukemia, lymphoma and other solid tumors (117)(118)(119), as maintenance therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and as part of conditioning regimens before allo-HSCT (120)(121)(122). Researchers have been exploring how to predict the response, cause, and outcome of resistance because of nonresponsiveness in some patients.…”

Section: Discussionmentioning

confidence: 99%

Resistance to Hypomethylating Agents in Myelodysplastic Syndrome and Acute Myeloid Leukemia From Clinical Data and Molecular Mechanism

Zhao

Wang

et al. 2021

Front. Oncol.

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The nucleoside analogs decitabine (5-AZA-dC) and azacitidine (5-AZA) have been developed as targeted therapies to reverse DNA methylation in different cancer types, and they significantly improve the survival of patients who are not suitable for traditional intensive chemotherapies or other treatment regimens. However, approximately 50% of patients have a response to hypomethylating agents (HMAs), and many patients have no response originally or in the process of treatment. Even though new combination regimens have been tested to overcome the resistance to 5-AZA-dC or 5-AZA, only a small proportion of patients benefited from these strategies, and the outcome was very poor. However, the mechanisms of the resistance remain unknown. Some studies only partially described management after failure and the mechanisms of resistance. Herein, we will review the clinical and molecular signatures of the HMA response, alternative treatment after failure, and the causes of resistance in hematological malignancies.

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“…38 ICT can be used as a bridge to transplantation for patients failing 5-azacytidine (AZA). 39 Venetoclax, is an orally selective inhibitor of the B-cell lymphoma 2 protein that, when acting synergistically with AZA, increases both response and prolonged survival as it was observed in a phase III trial. 40,41 Indeed, prior trials trying to evaluate the efficacy of their combination comparing to venetoclax alone in AML patients, showed promising results.…”

Section: Targeting Genetic Abnormalities In Mds and Amlmentioning

confidence: 97%

PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome

et al. 2021

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Poly (ADP-ribose) polymerase-1 (PARP1) is a key mediator of various forms of DNA damage repair and plays an important role in the progression of several cancer types. The enzyme is activated by binding to DNA single-strand and double-strand breaks. Its contribution to chromatin remodeling makes PARP1 crucial for gene expression regulation. Inhibition of its activity with small molecules, leads to the synthetic lethal effect by impeding DNA repair in the treatment of cancer cells. At first PARP1 inhibitors (PARPi) were developed to target BRCA mutated cancer cells. Currently, PARPi are being studied to be used in a broader variety of patients either as single agents or in combination with chemotherapy, antiangiogenic agents, ionizing radiation, and immune checkpoint inhibitors. Ongoing clinical trials on olaparib, rucaparib, niraparib, veliparib and the most recent talazoparib show the advantage of these agents in overcoming PARPi resistance and underline their efficacy in targeted treatment of several hematologic malignancies. In this review, focusing on the crucial role of PARP1 in physiological and pathological effects in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), we give an outline of the enzyme's mechanisms of action and its role in the pathophysiology and prognosis of MDS/AML and we analyze the available data on the use of PARPi, highlighting their promising advances in clinical application.

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Bridging-to-Transplant with Azacitidine for Myelodysplastic Syndrome and Acute Myeloid Leukemia, Reduces the Incidence of Acute Graft-versus-Host Disease

Cited by 5 publications

References 16 publications

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Resistance to Hypomethylating Agents in Myelodysplastic Syndrome and Acute Myeloid Leukemia From Clinical Data and Molecular Mechanism

PARP1 as a therapeutic target in acute myeloid leukemia and myelodysplastic syndrome

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