Somatic mutations as markers of outcome after azacitidine and allogeneic stem cell transplantation in higher-risk myelodysplastic syndromes

Falconi, Giulia; Fabiani, Emiliano; Piciocchi, Alfonso; Criscuolo, Marianna; Fianchi, Luana; Rossi, Elisa; Finelli, Carlo; Cerqui, Elisa; Ottone, Tiziana; Molteni, Alfredo; Parma, Matteo; Santarone, Stella; Candoni, Anna; Sica, Simona; Leone, Giuseppe; Voso, Maria Teresa

doi:10.1038/s41375-018-0284-9

Cited by 35 publications

(35 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a previous study, mutations in CBL, IDH2, DNMT3A, ASXL1, and TP53 were associated with poor prognosis in patients with MDS 26 . Among them, TP53 mutation was reported to affect response to decitabine or azacitidine treatment [27][28][29] . Although several studies have shown an association between TP53 mutations and poor survival outcomes in patients treated with azacitidine [27][28][29] , some studies have reported an association between TP53 mutations and higher decitabine sensitivity 30 .…”

Section: Discussionmentioning

confidence: 99%

“…Among them, TP53 mutation was reported to affect response to decitabine or azacitidine treatment [27][28][29] . Although several studies have shown an association between TP53 mutations and poor survival outcomes in patients treated with azacitidine [27][28][29] , some studies have reported an association between TP53 mutations and higher decitabine sensitivity 30 . In addition, compared with azacitidine, decitabine is known to be a more potent hypomethylating agent, and therefore, drug-specific loci or gene-specific DNA methylation might explain the differences in their therapeutic effects 31,32 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Lee

Kang

Jeon

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Numerous studies have analysed the clinical efficacies of hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS). However, reports that compare the two HMAs, decitabine and azacitidine, in patients with lower-risk (low and intermediate-1) MDS are limited. We compared 5-day decitabine and 7-day azacitidine regimens in terms of treatment responses, survival outcomes, and adverse events in patients with lower-risk MDS with poor prognostic features. The overall response rates (ORRs) were 67.2% and 44.0% in the patients treated with decitabine and azacitidine, respectively (P = 0.014). While the median progression-free survival (PFS) was significantly better in the patients treated with decitabine than in those treated with azacitidine (P = 0.019), no significant differences in event-free and overall survival rates were observed between the two groups. Multivariate analysis revealed that compared with azacitidine treatment, decitabine treatment is significantly associated with a higher ORR (P = 0.026) and longer PFS (P = 0.037). No significant differences were observed in the incidence of grade 3 or higher haematologic adverse events in response to the two HMAs. In conclusion, in lower-risk MDS, especially with poor prognostic features, ORR and PFS were significantly better with 5-day decitabine treatment than with 7-day azacitidine treatment, with comparable safety. Myelodysplastic syndromes (MDS) are clonal haematologic disorders characterised by ineffective and dysplastic haematopoiesis that causes cytopenia, leading to the development of acute leukaemia 1,2. Previously, MDS was generally divided into lower-risk (low and intermediate-1) and higher-risk (intermediate-2 and higher) categories on the basis of the International Prognostic Scoring System (IPSS) 3 , and treatment decisions were usually made based on the risk group. The treatment for higher-risk MDS aims to modify the natural course of the disease using hypomethylating agents (HMAs), chemotherapy, or stem cell transplantation, whereas the treatment for lower-risk MDS aims to improve cytopenia, reduce transfusion requirements, and provide the best supportive care 4. However, lower-risk MDS patients with poor prognostic features were known to be associated with progression to acute myeloid leukaemia or severe cytopenia 4. Hence, more active treatments are needed for this group of patients. Currently, two types of HMAs (decitabine or azacitidine) are available for the treatment of MDS 5. Several previous studies reported the efficacy of HMAs in different clinical settings. In higher-risk MDS, a 7-day azacitidine regimen (75 mg/m 2 daily every 4 weeks) was reported to result in higher response rates and better overall survival

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Lee

Kang

Jeon

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…This process is catalyzed by epigenetic regulatory enzymes, including DNA methyltransferases, methylcytosine dioxygenases and isocitrate dehydrogenases. Epigenetic regulatory enzymes have been recognized as mutated in various types of cancer, and mutations of these enzymes have been closely related to the malignant phenotype [80,81,82,83,84].…”

Section: Forkhead Box Proteins In Idhs Mutated Acute Myeloid Leukamentioning

confidence: 99%

The Role of Forkhead Box Proteins in Acute Myeloid Leukemia

Gurnari

Falconi

Bellis

et al. 2019

Cancers

Self Cite

View full text Add to dashboard Cite

Forkhead box (FOX) proteins are a group of transcriptional factors implicated in different cellular functions such as differentiation, proliferation and senescence. A growing number of studies have focused on the relationship between FOX proteins and cancers, particularly hematological neoplasms such as acute myeloid leukemia (AML). FOX proteins are widely involved in AML biology, including leukemogenesis, relapse and drug sensitivity. Here we explore the role of FOX transcription factors in the major AML entities, according to “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia”, and in the context of the most recurrent gene mutations identified in this heterogeneous disease. Moreover, we report the new evidences about the role of FOX proteins in drug sensitivity, mechanisms of chemoresistance, and possible targeting for personalized therapies.

show abstract

“…Although DNMT3A mutations have been reported a lot in MDS, the prognostic significance still remains controversial. Many studies have reported the clinical impact of DNMT3A mutations in MDS, most of which indicated that the DNMT3A mutations were associated with poor prognosis [17][18][19][20][21][22], while other studies showed they had no significant effect on overall survival [23][24][25][26][27][28][29]. Thus, to further illustrate the prognostic effect of DNMT3A mutations in patients with MDS, we performed this meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of DNMT3A mutations in myelodysplastic syndromes: a meta-analysis

et al. 2019

View full text Add to dashboard Cite

2019) Prognostic value of DNMT3A mutations in myelodysplastic syndromes: a meta-analysis, Hematology, 24:1, 613-622, ABSTRACTObjectives: Although DNA (cytosine-5)-methyltransferase 3 alpha (DNMT3A) gene mutations have been widely reported in myelodysplastic syndromes (MDS), the prognostic significance of DNMT3A mutations is still controversial. In this study, we conducted a meta-analysis to determine the prognostic effect of DNMT3A mutations in patients with MDS. Methods: Eligible studies from PubMed, Embase, Web of Science, Clinical Trials and the Cochrane Library were searched. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS) and leukemia-free survival (LFS) were pooled to assess the effect of DNMT3A mutations on the prognosis in MDS patients. Results: A total of 12 studies with 2236 patients were included in this meta-analysis. The pooled HRs for OS and LFS revealed that MDS patients with DNMT3A mutations had a significantly poor prognosis as compared with those without mutations (OS: HR = 1.654, 95% CI = 1.387-1.973, p < 0.001; LFS: HR = 4.624, 95% CI = 3.121-6.851, p < 0.001). Discussion and Conclusion: This meta-analysis showed an adverse prognostic effect of DNMT3A mutations in patients with MDS, which will contribute to risk stratification and prognostic assessment in the disease.

show abstract

Somatic mutations as markers of outcome after azacitidine and allogeneic stem cell transplantation in higher-risk myelodysplastic syndromes

Cited by 35 publications

References 13 publications

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study

The Role of Forkhead Box Proteins in Acute Myeloid Leukemia

Prognostic value of DNMT3A mutations in myelodysplastic syndromes: a meta-analysis

Contact Info

Product

Resources

About