Novel Approach for Bone Marrow Transplantation Conditioning in Acute Myelogenous Leukemia not Responding to the Induction Therapy Using Etoposide Carried in Lipid Core Nanoparticles: A Pilot Clinical Study
| Autor: | Raul C. Maranhão, Débora F. Deus, Kelsy Catherina Nema Areco, Aleksandra Tiemi Morikawa, José Salvador Rodrigues de Oliveira, Thauany M Tavoni, Sandra Serson Rohr |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Oncology
Adult medicine.medical_specialty Transplantation Conditioning Platelet Engraftment Graft vs Host Disease Pilot Projects 03 medical and health sciences Myelogenous Young Adult 0302 clinical medicine Bone Marrow hemic and lymphatic diseases Internal medicine medicine Mucositis Humans Transplantation Homologous Etoposide Aged Transplantation business.industry Hematopoietic Stem Cell Transplantation Hematology Induction Chemotherapy Total body irradiation Middle Aged medicine.disease Lipids Leukemia Leukemia Myeloid Acute 030220 oncology & carcinogenesis LIPÍDEOS Nanoparticles business Whole-Body Irradiation 030215 immunology medicine.drug Chronic myelogenous leukemia |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1523-6536 |
| Popis: | Allogeneic hematopoietic cell transplantation (HCT) is the treatment of choice for acute myelogenous leukemia (AML) not responding to induction therapy. It is a therapeutic choice for the blast phase of chronic myelogenous leukemia (CML-BP) in patients failing to respond to tyrosine kinase inhibitors (TKIs). Lipid core nanoparticles (LDEs) concentrate severalfold more in blast cells than in corresponding normal cells. Incorporation of anticancer drugs to LDE formulations increases the pharmacologic action and decreases the toxicity. We tested a drug-targeting system, LDE-etoposide plus total body irradiation (TBI; 1200 cGy dose), in 13 patients with AML not responding to the induction therapy and in 2 patients with CML-BP refractory to second-generation TKIs. The mean patient age was 46.7 years (range, 22 to 66 years). The LDE-etoposide dose was escalated at 20, 30, 40, 50, and 60 mg/kg. No patients developed grade 4 or 5 toxicity; however, mucositis grade 3 occurred in 6 patients, 3 patients experienced diarrhea, and 1 patient had an elevated total bilirubin level. No deaths were related to conditioning. All patients were successfully engrafted. The median times to neutrophil and platelet engraftment were 20 ± 5 days and 16 ± 4 days, respectively. Five patients (33.4%) had acute graft-versus-host-disease (GVHD), including 4 grade I, and 1 with grade II, and 8 patients (57.1%) had moderate-to-severe chronic GVHD. This pilot study shows the potential of LDE-etoposide plus TBI as an HCT conditioning regimen in AML patients not responding to the induction and refractory therapies for CML-BP patient. These findings pave the way for subsequent larger clinical trials. |
| Databáze: | OpenAIRE |
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