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De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.

ABSTRACT: The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1?, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.

SUBMITTER: Lopes MR

PROVIDER: S-EPMC5234038 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.

Lopes Matheus Rodrigues MR Pereira João Kleber Novais JK de Melo Campos Paula P Machado-Neto João Agostinho JA Traina Fabiola F Saad Sara T Olalla ST Favaro Patricia P

Scientific reports 20170113

The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a sign ...[more]

PMID: 28084439

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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.

Dataset Information

De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.

Publications

De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.

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