Hexamethylene bisacetamide in myelodysplastic syndrome and acute myelogenous leukemia: a phase II clinical trial with a differentiation-inducing agent.
Hexamethylene bisacetamide (HMBA) is a potent inducer of differentiation of a number of transformed cell lines in vitro. We report results of a phase II clinical trial in 41 patients with myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) to whom HMBA was administered by continuous infusion for 10 days and repeated after an interval of 18 to 75 days. HMBA induced a complete remission (CR) in three patients and a partial remission (PR) in six patients. The median duration of CR was 6.8 months (range 1.3 to 16 months) and 3.7 months for PR (range 1 to 7 months). No significant difference was observed between responders and nonresponders with respect to the mean HMBA plasma levels, which were 0.86 +/- 0.04 mmol/L and 0.87 +/- 0.12 mmol/L, respectively. In certain patients morphologic and chromosome analyses provided evidence that HMBA induced differentiation of transformed hematopoietic precursors. The most prominent toxicity was thrombocytopenia, generally reversible on cessation of administration of HMBA.
Andreeff
M
M
Department of Molecular Pharmacology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Stone
R
R
Michaeli
J
J
Young
C W
CW
Tong
W P
WP
Sogoloff
H
H
Ervin
T
T
Kufe
D
D
Rifkind
R A
RA
Marks
P A
PA
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000473:pathology; D002454:Cell Differentiation; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D007958:Leukocyte Count; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D009504:Neutrophils / Q000473:pathology; D010976:Platelet Count; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced
D000081:Acetamides; C014026:hexamethylene bisacetamide