Epigenetic Therapy in a Patient With Down Syndrome and Refractory Acute Myeloid Leukemia

Becktell, Kerri; Houser, Kerri; Burke, Michael J.

doi:10.1097/mph.0000000000001158

Cited by 17 publications

(13 citation statements)

References 20 publications

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“…To date, only single case reports describing treatment with demethylating agents or histone deacetylase inhibitors have been published in patients with DS and refractory or relapsed AML. [ 38 , 39 ]…”

Section: Discussionmentioning

confidence: 99%

Outcomes of patients with Down syndrome and acute leukemia

Schmidt¹,

Coliţă

Ivanov

et al. 2021

Medicine

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Children with Down syndrome (DS) have a higher risk of developing acute leukemia than do those without DS. There are few studies in the literature about outcome, survival, and difficulties of treating patients with DS and acute leukemia in a developing country. This study aimed to analyze the outcome, response to treatment, survival, treatment complications, and causes of death in patients with DS and acute leukemia compared with those in patients with acute leukemia without DS diagnosed in the same period of time. We conducted a retrospective observational analysis including a cohort of 21 patients with DS and acute leukemia diagnosed between 2009 and 2018 in 3 hemato-oncology centers (2 pediatric centers and 1 adult hematology center). A group of patients with DS-acute lymphoblastic leukemia (DS-ALL) was analyzed and compared with a group of 165 patients with acute lymphoblastic leukemia without DS, and a group of patients with DS-acute myeloid leukemia (DS-AML) was analyzed and compared with a group of 50 patients with acute myeloid leukemia without DS, which was diagnosed during the same period of time (2009–2018) and treated under similar conditions in terms of both treatment protocols and economic resources. The overall survival rates in children with DS-ALL and DS-AML were 35.7% and 57.1%, respectively ( P = .438). The overall survival rate was significantly worse in children with DS-ALL than in those with acute lymphoblastic leukemia without DS (35.71% vs 75.80%, P = .001). We noted that treatment-related mortality in the patients with DS-ALL was high (50%) (infections and toxicities related to chemotherapy); this result was significantly different from that for patients with leukemia without DS ( P < .0001). The relapse rate was higher in patients with DS-ALL but not significantly higher than that in patients without DS ( P = .13). In contrast, the overall survival rate was better for patients with DS-AML than for those with acute myeloid leukemia without DS (57.1% vs 45.1%, P = .47). Because of the particularities of the host, we suggest that DS-ALL and DS-AML should be considered as independent diseases and treated according to specific protocols with therapy optimization per the minimal residual disease.

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Section: Discussionmentioning

confidence: 99%

Outcomes of patients with Down syndrome and acute leukemia

Schmidt¹,

Coliţă

Ivanov

et al. 2021

Medicine

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“…The first step is a genome-wide hypomethylation directly related to the additional copy of chromosome 21. The second step, detected in TL-DS cells which presented GATA1 mutation, consists in aberrant hypermethylation that affects genes responsible for hematological development and regulation of cell processes such as growth, proliferation, cell cycle regulation and death [23,93,94] (Fig. 10).…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

MicroRNA-155-5p Plays a Critical Role in Transient Leukemia of Down Syndrome by Targeting Tumor Necrosis Factor Receptor Superfamily Members

Sas

Pașca

Jurj

et al. 2020

Cell Physiol Biochem

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“…Whole‐exome sequencing revealed that 46% and 33% of ML‐DS blasts contain mutations in cohesin complex genes and epigenetic regulators, respectively . Although these findings suggest potential benefit of epigenetic targeted therapies, the use of demethylating agents or histone deacetylase inhibitors in children with DS has only been reported in anecdotal cases to date and has not been evaluated systematically in clinical trials. As a result, an efficacious or even agreed‐upon standard of care for the treatment of children with relapsed ML‐DS is lacking.…”

Section: Aml In Dsmentioning

confidence: 99%