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Lipid Core Nanoparticles Plus Etoposide With Transplantation for AML

By: Kelly M. Hennessey, PhD
Posted: Wednesday, October 14, 2020

The treatment of choice for patients with acute myeloid leukemia (AML) who do not respond to induction therapy is hematopoietic cell transplantation. Myeloablative conditioning prior to transplantation may improve outcomes in some patients; however, reducing regimen-related toxicity is necessary. Oliveira et al, of Escola Paulista de Medicina da Universidade Federal de São Paulo, Brazil, used artificial lipid core nanoparticles to deliver etoposide to patients with high-risk AML or chronic myeloid leukemia in the blast phase in a hematopoietic cell transplantation conditioning regimen. These results were reported in the journal Biology of Blood and Marrow Transplantation.

Low-density lipoproteins (LDL), which carry most of the cholesterol of plasma in humans, are mimicked by lipid core nanoparticles. LDL receptors are overexpressed in the cells of patients with AML, likely due to the added need for cholesterol for cell membranes in response to accelerated mitotic rate. Lipid core nanoparticles can be taken up by cells along with LDLs and, when combined with anticancer drugs, increase the efficacy of chemotherapy and drastically reduce toxicity to normal cells and tissues. 

A total of 15 patients were enrolled in this pilot study (13 with AML). These patients had not responded to induction therapy with tyrosine kinase inhibitors. Lipid core nanoparticles plus etoposide were escalated at 20 to 60 mg/kg.

No grade 4 or 5 toxicities occurred even in the highest-dose levels, no grade III or IV graft-versus-host disease occurred, and the incidence of grade I or II graft-versus-host disease was minimal. “Our results show that the use of lipid core nanoparticles-etoposide plus radiation therapy was well-tolerated and safe,” confirmed the researchers. “Higher lipid core nanoparticles-etoposide doses can be tested for hematopoietic cell transplantation conditioning in future studies.

Disclosure: For full disclosures of the study authors, visit www.sciencedirect.com.



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