Azacitidine for myelodysplastic patients aged &gt; 65 years: a review of clinical efficacy

Breccia, Massimo; Molica, Matteo; Zacheo, Irene

doi:10.1517/14656566.2014.936849

Cited by 3 publications

(1 citation statement)

References 53 publications

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“…Primary endpoints for treatment of elderly MDS patients were maintaining a good quality of life rather than curative. Although MDS cannot be cured by HMAs, the emergence of hypomethylation treatment makes patients get better response, which is proved by stable blood count, transfusion independence and acceptable safety [6,[28][29][30]. In this sense, hypomethylation treatment is helpful for allo-HSCT, because it can obtain incalculable pre-transplant preparation time (donor seeking, financial support, etc.).…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes

et al. 2021

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Hypomethylating agents (HMAs) are effective therapies in myelodysplastic syndromes (MDS), but allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only way to cure MDS. According to the current literature, it is difficult to confirm whether HMAs bridging therapy is beneficial for MDS patients receiving allo-HSCT. Therefore, we tried to evaluate the effect of HMAs on long-term survival of the MDS patients. Databases, including PubMed, Embase Ovid, and the Cochrane Library, were searched for studies published up to January 10, 2021. Patients who accepted HMAs bridging to allo-HSCT were defined as experimental group, while patients who received the best supportive care (BSC) before allo-HSCT were control group. Overall survival (OS) was the primary end point. Seven studies were included in the final analysis. The final results showed no OS differences between patients accepted HMAs before allo-HSCT and those received BSC (HR = 0.86, 95% CI: 0.64–1.15, p = 0.32), indicating that MDS patients' long-term survival did not benefit from HMAs bridging therapy before allo-HSCT. This conclusion needs to be further verified by a large number of prospective randomized controlled trials, which have guiding significance for the treatment of MDS patients.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes

et al. 2021

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Yin and Yang of Cytidine Deaminase Roles in Clinical Response to Azacitidine in the Elderly: A Pharmacogenetics Tale

Fanciullino

Mercier

Serdjebi³

et al. 2015

Pharmacogenomics

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Azacitidine is a mainstay for treating hematological disorders. Azacitidine is metabolized by cytidine deaminase, coded by a highly polymorphic gene. Here, we present two elderly patients with opposite clinical outcomes after azacitidine treatment. First, an acute myeloid leukemia patient showed life-threatening toxicities, but outstanding complete remission, after a single round of azacitidine. Further investigations showed that this patient was cytidine deaminase 79A>C (rs2072671) homozygous with a marked deficient phenotype. Next, a chronic myelomonocytic leukemia patient displayed complete lack of response despite several cycles of azacitidine. This patient had a rapid-deaminator phenotype linked to the -31delC deletion (rs3215400). These polymorphisms lead to opposite clinical outcomes in patients with myelodysplastic syndromes treated with azacitidine, thus suggesting that determining cytidine deaminase status could help to forecast clinical outcome.

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Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo

Cooper

Choi

Karpova

et al. 2017

The Journal of Immunology

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Azacitidine (AzaC) mitigates Graft vs. Host Disease (GvHD) in both murine preclinical transplant models and in human clinical trials while maintaining a robust Graft vs. Leukemia (GvL) effect. Previous studies have failed to investigate the role of natural Tregs on the mitigation of GvHD by AzaC; instead focusing on the generation of suppressive regulatory T cells (Tregs, CD4+CD25+FOXP3+) through the in vivo conversion of alloreactive donor T effectors (Teff CD4+ CD25-, FOXP3-) and the direct anti-proliferative effects of AzaC on allogeneic T cells. Using B6.Foxp3DTR/GFP mice in which Tregs can be specifically ablated through administration of Diphtheria toxin, we demonstrate that nTregs are required in the donor graft for AzaC to optimally protect against GvHD and that nTregs, unlike T effs (Teffs, CD3+FOXP3-), are resistant to the anti-proliferative effects of AzaC. Gene expression analysis identified the potent cell cycle inhibitor, p21, was significantly upregulated in Teffs but not nTregs after treatment with AzaC. Furthermore, we demonstrate that Teffs deficient in p21 are less sensitive to the antiproliferative effects of AzaC. These results, demonstrate that nTregs are essential for AzaC to fully protect against GvHD and have important clinical implications for future clinical trials testing AzaC as a novel method of GvHD prophylaxis in man.

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Azacitidine for myelodysplastic patients aged > 65 years: a review of clinical efficacy

Cited by 3 publications

References 53 publications

Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes

Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes

Yin and Yang of Cytidine Deaminase Roles in Clinical Response to Azacitidine in the Elderly: A Pharmacogenetics Tale

Azacitidine Mitigates Graft-versus-Host Disease via Differential Effects on the Proliferation of T Effectors and Natural Regulatory T Cells In Vivo

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