Phase I trial of plerixafor combined with decitabine in newly diagnosed older patients with acute myeloid leukemia
Autor: | Danielle C. Marshall, Cindy Ippoliti, Monica L. Guzman, Hsiao-Ting C. Hsu, Nicole M. Cruz, Linda Lam, Duane C. Hassane, Ellen K. Ritchie, Yulia Dault, Gail J. Roboz, Joseph M. Scandura, Paul J. Christos |
---|---|
Rok vydání: | 2018 |
Předmět: |
Acute Myeloid Leukemia
Male 0301 basic medicine Oncology Benzylamines Receptors CXCR4 medicine.medical_specialty Myeloid Maximum Tolerated Dose Decitabine Cyclams Article 03 medical and health sciences 0302 clinical medicine Cell Movement Heterocyclic Compounds Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Aged Aged 80 and over CXCR4 antagonist business.industry Plerixafor Hazard ratio Myeloid leukemia Hematology Middle Aged medicine.disease 3. Good health Leukemia Myeloid Acute Leukemia Treatment Outcome 030104 developmental biology medicine.anatomical_structure Hypomethylating agent 030220 oncology & carcinogenesis Female business medicine.drug |
Zdroj: | Haematologica |
ISSN: | 1592-8721 0390-6078 |
Popis: | Acute myeloid leukemia carries a dismal prognosis in older patients. The objective of this study was to investigate the safety and efficacy of decitabine combined with the CXCR4 antagonist plerixafor in newly diagnosed older patients with acute myeloid leukemia and to evaluate the effects of plerixafor on leukemia stem cells. Patients were treated with monthly cycles of decitabine 20 mg/m2 days 1–10 and escalating doses of plerixafor (320–810 mcg/kg) days 1–5. Sixty-nine patients were treated, with an overall response rate of 43%. Adverse karyotype did not predict response (P=0.31). Prior hypomethylating agent treatment was the strongest independent predictor of adverse overall survival (hazard ratio 3.1; 95%CI: 1.3–7.3; P=0.008) and response (14% in previously treated patients, 46% in treatment naïve; P=0.002). As expected, the most common toxicities were myelosuppression and infection. Plerixafor induced mobilization of leukemia stem and progenitor cells, but did not cause clinically significant hyperleukocytosis. Reduction in leukemia stem cells appeared to correlate with duration of response. Plerixafor can be safely added to decitabine in poor-prognosis, elderly acute myeloid leukemia patients. The maximum tolerated dose of the combination was 810 mcg/kg. While mobilization of leukemia stem cells was observed in some patients, the clinical benefit of adding plerixafor was uncertain. This trial was registered at clinicaltrials.gov identifier: 01352650. |
Databáze: | OpenAIRE |
Externí odkaz: |