Dataset Information

Isochromosome 7p, i(7)(p10): A rare AML, myelodysplasia-related entity.

ABSTRACT: We describe genomic findings in an AML case with isochromosome 7p, i(7)(p10), in which SNP array analysis uncovered an additional 7.07-Mb 20q deletion not detected by karyotyping. Several AML cases with i(7)(p10) as an isolated cytogenetic finding have been previously reported. Based on consequent loss of 7q, we propose that AML with i(7)(p10) represents a distinct entity belonging in the WHO group -7/7q-, which represents one of the genetic abnormalities defining AML, myelodysplasia-related. Additionally, the focal del(20q) identified here adds support for a specific common region of deletion in 20q in myeloid malignancies, implicating a small number of candidate genes.

SUBMITTER: Nejati R

PROVIDER: S-EPMC10493252 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Isochromosome 7p, i(7)(p10): A rare AML, myelodysplasia-related entity.

Nejati Reza R Neumann-Domer Ryan R Liu Zemin Z Koslosky Lori L Neumann-Domer Erin E Pei Jianming J Wang Y Lynn YL Testa Joseph R JR

Leukemia research reports 20230829

We describe genomic findings in an AML case with isochromosome 7p, i(7)(p10), in which SNP array analysis uncovered an additional 7.07-Mb 20q deletion not detected by karyotyping. Several AML cases with i(7)(p10) as an isolated cytogenetic finding have been previously reported. Based on consequent loss of 7q, we propose that AML with i(7)(p10) represents a distinct entity belonging in the WHO group -7/7q-, which represents one of the genetic abnormalities defining AML, myelodysplasia-related. Ad ...[more]

PMID: 37701905

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Project description:BackgroundCurrent national estimates for acute myelogenous leukemia (AML) indicate this disease accounts for 1.1% of new cancer diagnoses and 1.8% of cancer deaths in the United States. The 5-year overall survival rate for patients with AML was 27.4% between 2008 and 2014. The standard induction for patients with AML includes cytarabine, infused for 7 days, with 3 once-daily injections of an anthracycline, such as daunorubicin, known as the 7+3 regimen. Daunorubicin plus cytarabine liposomal encapsulation for injection was approved in the United States in 2017 for adults with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC).ObjectiveTo estimate the annual budget impact of introducing daunorubicin-cytarabine liposome as induction treatment for patients with tAML or AML-MRC in the United States over a 3-year period.MethodsThe model consisted of a simple decision analytic framework for a 1- to 3-year period. We used an incidence-based approach to estimate the annual number of patients newly diagnosed with tAML or AML-MRC in a hypothetical 1-million-member plan. Patients were allocated to 2 groups based on when daunorubicin-cytarabine liposome became available, with the base-case group allocated to the 7+3 regimen, and another group allocated to daunorubicin-cytarabine liposome treatment. The incidence of AML was estimated as 4.3 per 100,000 people. Efficacy measures included the proportion of complete responders, proportion of patients who had undergone transplantation, and survival at 180 and 365 days. Inpatient drug and hospitalization costs were based on diagnosis-related group rates, and outpatient drug costs on wholesale acquisition costs.ResultsBased on this hypothetical 1-million-member health plan, 15.1 members would receive intensive induction for newly diagnosed tAML or AML-MRC annually. Increasing the use of daunorubicin-cytarabine liposome (assumption of year 1, 20%; year 2, 50%; year 3, 80%) resulted in a 3-year incremental cumulative budget impact of $72,041 (1.7% increase for patients with tAML or AML-MRC), with a per-member per-month cost of $0.0032 at year 3. Over a 3-year period, the use of daunorubicin-cytarabine liposome would result in an estimated increase in the number of patients with a complete response to therapy by 2.72 (23.1%), which would lead to an incremental cost decrease of $179,956 per responding patient compared with the use of the 7+3 regimen in the base-case group.ConclusionsBased on these results, induction treatment with daunorubicin-cytarabine liposome for patients with tAML or AML-MRC instead of the 7+3 regimen may have a limited economic impact on the budget of commercial health plans and may result in cost offsets, particularly in patients who respond to therapy.

Project description:Tandem-duplication mutations of the UBTF gene (UBTF-TDs) coding for the upstream binding transcription factor have recently been described in pediatric patients with acute myeloid leukemia (AML) and were found to be associated with particular genetics (trisomy 8 (+8), FLT3-internal tandem duplications (FLT3-ITD), WT1-mutations) and inferior outcome. Due to limited knowledge on UBTF-TDs in adult AML, we screened 4247 newly diagnosed adult AML and higher-risk myelodysplastic syndrome (MDS) patients using high-resolution fragment analysis. UBTF-TDs were overall rare (n = 52/4247; 1.2%), but significantly enriched in younger patients (median age 41 years) and associated with MDS-related morphology as well as significantly lower hemoglobin and platelet levels. Patients with UBTF-TDs had significantly higher rates of +8 (34% vs. 9%), WT1 (52% vs. 7%) and FLT3-ITD (50% vs. 20.8%) co-mutations, whereas UBTF-TDs were mutually exclusive with several class-defining lesions such as mutant NPM1, in-frame CEBPAbZIP mutations as well as t(8;21). Based on the high-variant allele frequency found and the fact that all relapsed patients analyzed (n = 5) retained the UBTF-TD mutation, UBTF-TDs represent early clonal events and are stable over the disease course. In univariate analysis, UBTF-TDs did not represent a significant factor for overall or relapse-free survival in the entire cohort. However, in patients under 50 years of age, who represent the majority of UBTF-mutant patients, UBTF-TDs were an independent prognostic factor for inferior event-free (EFS), relapse-free (RFS) and overall survival (OS), which was confirmed by multivariable analyses including established risk factors such as age and ELN2022 genetic risk groups (EFS [HR: 2.20; 95% CI 1.52-3.17, p < 0.001], RFS [HR: 1.59; 95% CI 1.02-2.46, p = 0.039] and OS [HR: 1.64; 95% CI 1.08-2.49, p = 0.020]). In summary, UBTF-TDs appear to represent a novel class-defining lesion not only in pediatric AML but also younger adults and are associated with myelodysplasia and inferior outcome in these patients.

Dataset Information

Isochromosome 7p, i(7)(p10): A rare AML, myelodysplasia-related entity.

Publications

Isochromosome 7p, i(7)(p10): A rare AML, myelodysplasia-related entity.

Similar Datasets

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