Survival and hospitalization among patients with acute myeloid leukemia treated with azacitidine or decitabine in a large managed care population: a real-world, retrospective, claims-based, comparative analysis

Smith, B. Douglas; Beach, C. L.; Mahmoud, Dalia; Weber, Laura; Henk, Henry J.

doi:10.1186/2162-3619-3-10

Cited by 34 publications

(32 citation statements)

References 15 publications

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“…While the median OS in our study appears short in comparison with that reported by Fenaux et al from the comparison of azacitidine and BSC only (median, 19.1 vs 13.4 months), the studies are not directly comparable due to differences in the patient cohorts, as displayed by the OS of patients in the BSC arms [6]. The few retrospective studies that compared decitabine and azacitidine did not specifically assess the survival among patients with RAEBt and/or 20-30 % blasts [18][19][20][21][22]. Importantly, we also observed that the favorable impact of decitabine on the outcome of RAEBt patients was similar among various patient subgroups and significantly differed from that among RAEB patients.…”

Section: Survival In Subgroups Of Raebt Patientscontrasting

confidence: 56%

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

et al. 2015

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In the European Organisation for Research and Treatment of Cancer (EORTC)/GMDSSG phase III trial 06011, we compared decitabine (15 mg/m 2 every 8 h for 3 days) with best supportive care (BSC) in patients ≥60 years with myelodysplastic syndromes (MDS) by FrenchAmerican-British (FAB) criteria. Here, we reinvestigate trial 06011 for the activity and efficacy specifically in patients with refractory anemia with excess blasts in transformation (RAEBt). Response rates in the decitabine arm (N=40) were as follows: complete or partial remission, 15 %; hematologic improvement, 15 %; resistant disease, 30 %. RAEBt patients in the decitabine arm had longer progression-free survival (PFS; hazard ratio (HR) 0.30, 95 % confidence interval (CI) 0.18-0.51; median, 6.2 vs 2.8 months) and overall survival (OS; HR 0.68, 95 % CI 0.42-1.11; median, 8.0 vs 6.0 months) than in the BSC arm (N=35). Censoring at allogeneic hematopoietic stem cell transplantation, the OS difference between the treatment groups increased, particularly among patients Electronic supplementary material The online version of this article (doi:10.1007/s00277-015-2489-6) contains supplementary material, which is available to authorized users.

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Section: Survival In Subgroups Of Raebt Patientscontrasting

confidence: 56%

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

et al. 2015

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“…DNMT inhibitor 5‐aza‐dC has been approved by the National Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome and acute myeloid leukemia . It is also tested in various clinical trials of cancer treatment, including breast cancer, liver cancer, colon cancer, lung cancer, bladder cancer, prostate cancer and so on.…”

Section: Discussionmentioning

confidence: 99%

Dust induces lung fibrosis through dysregulated DNA methylation

Zhang

Liu

Wang

et al. 2019

Environmental Toxicology

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Pneumoconiosis is a serious occupational disease that often occurs to coal workers with no early diagnosis and effective treatment at present. Diffuse pulmonary fibrosis is the major pathological change of pneumoconiosis, and its mechanism is still unclear. Epigenetics is involved in the development of many diseases, and it is closely associated with fibrosis. In this study, we investigated whether DNA methylation contributes to the pathogenesis of pulmonary fibrosis in pneumoconiosis. By exposure to coal dust or silica dust, we established the models of coal worker's pneumoconiosis (CWP), which showed an increased expression of COL‐I, COL‐III. We further found that DNMT1, DNMT3a, DNMT3b, MBD2, MeCP2 protein expression changed. Pretreatment with DNMT inhibitor 5‐aza‐dC reduced expression of COL‐I, COL‐III, and reduced pulmonary fibrosis. In summary, our results showed that DNA methylation contributes to dust‐induced pulmonary fibrosis and that it may serve as a theoretical basis for testing DNA methyltransferase inhibitors in the treatment of CWP.

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“…Epigenetic silencing via methylation has been implicated in human cancer, including the development of hematopoietic malignancies. Irreversible DNA methyltransferase inhibitors, such as 5‐azacytidine and decitabine, seem to represent promising therapeutic options for myeloid malignancies, including AML (Szmigielska‐Kaplon and Robak, ; Muller‐Thomas et al, ; Smith et al, ). CHFR , localized to 12q24, has been reported to delay entry into mitosis at the G2 to M entry site, and has been proposed as a candidate tumor‐suppressor gene.…”

Section: Discussionmentioning

confidence: 99%

CHFR hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome

Gao

Liu

Zhang

et al. 2015

Genes Chromosomes & Cancer

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The CpG island of the promoter region of the checkpoint with fork-head associated and ring finger gene (CHFR), a mitotic checkpoint gene with tumor-suppressor functions, is hypermethylated in various human cancers. The objective of this study was to evaluate the frequency of aberrant CHFR promoter methylation in acute myeloid leukemia (AML) patients in an attempt to improve prognostication. CHFR promoter methylation levels were analyzed in 358 newly diagnosed AML cases and 30 healthy donors by the use of quantitative methylation-specific polymerase chain reaction. In addition, we analyzed possible association between CHFR hypermethylation and hematological characteristics, chromosome abnormalities, genetic mutations, and survival. Hypermethylation of the CHFR promoter was observed in 24% (85 of 358) AML patients, but not in healthy individuals. CHFR hypermethylation correlated significantly with SRSF2 and DNMT3A mutations. Patients with hypermethylation exhibited lower overall survival and shorter relapse-free survival than nonmethylated cases. In multivariate analysis, CHFR hypermethylation was an independent factor predicting poor overall survival but not relapse-free survival. In conclusion, hypermethylation of the CHFR promoter, frequent in AML, is associated with adverse outcome, and can thus be used for risk stratification.

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Survival and hospitalization among patients with acute myeloid leukemia treated with azacitidine or decitabine in a large managed care population: a real-world, retrospective, claims-based, comparative analysis

Cited by 34 publications

References 15 publications

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) - results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG)

Dust induces lung fibrosis through dysregulated DNA methylation

CHFR hypermethylation, a frequent event in acute myeloid leukemia, is independently associated with an adverse outcome

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