A subset of patients with high-risk acute myelogenous leukemia shows improved peripheral blood cell counts when treated with the combination of valproic acid, theophylline and all-trans retinoic acid.

Acute myelogenous leukemia (AML) patients (24 consecutive patients, median age 71 years, 17 high-risk disease) were treated with all-trans retinoic acid, theophylline and valproic acid. Among 22 evaluable patients 9 responded with increased normal peripheral blood cell counts. The responses could be classified as hematological improvement according to response criteria for patients with myelodysplastic syndromes (MDS) for four patients only. The nine patients with increased normal cell counts had a median survival from start of therapy of 147 days compared with 48 days for the other patients. Four patients fulfilling the MDS criteria had a survival ranging from 112 to 644 days. The treatment was associated with decreased in vitro cytokine-dependent AML cell proliferation and increased blood levels of Endocan and angiopoietin-2 both for responders and non-responders. We conclude that the therapy causes disease stabilization for a subset of AML patients.