Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia.
The pharmacokinetics of retinol palmitate were studied, and a therapeutic trial was performed in patients with ANLL. In the pharmacokinetics study, retinol was the only metabolite that was detected in plasma, and the peak concentration was 332 micrograms/dl (about 1.2 x 10(-5) M) 2.1 h after administration of retinol palmitate. Five patients with ANLL (4 with ANLL-M3 and one with ANLL-M2) were treated with retinol palmitate. In all patients with ANLL-M3, bone marrow suspension culture studies revealed that retinol induced both morphological and functional differentiation of immature leukemic cells. During the course of the treatment with retinol palmitate, morphological differentiation of bone marrow immature leukemic cells was observed in all patients with ANLL-M3 within 3-4 days after initiation of the therapy. In three of the four patients who underwent conventional chemotherapy, the sequential treatment with retinol palmitate resulted in a complete remission: controlling residual bone marrow leukemic cells. None of the patients showed any signs of aggravation of DIC in the coagulation parameters. These findings suggest the possibility that retinol palmitate functions as salvage therapy by inducing maturation and slowing proliferation, there by clearing out the residual leukemic cells following conventional chemotherapy.
Tsutani
H
H
First Department of Internal Medicine, Fukui Medical School, Japan.
Ueda
T
T
Uchida
M
M
Nakamura
T
T
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D004224:Diterpenes; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000084562:Retinyl Esters; D014407:Tumor Cells, Cultured; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology
D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate