retinol-palmitate and Leukemia--Myeloid--Acute

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.

Topics: Adult; Aged; Bone Marrow; Diterpenes; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Retinyl Esters; Tumor Cells, Cultured; Vitamin A

Twenty-one children with AML, who achieved complete remission with cytostatics, were treated with high doses of retinoids after remission was achieved. They were given 52 mumol retinyl palmitate/m2 (50,000 International Units/m2) daily for at least 2 years thereafter. Thirteen of the children are still in complete remission with a mean observation time of 103 months. Due to the positive effects of retinoids seen in the treatment of AML, we have studied uptake of lipoprotein-associated retinyl esters in bone marrow cells and peripheral leukocytes in vivo. An oral load of 104 mumol/m2 (100,000 International Units/m2) retinyl palmitate resulted in a doubling of the concentration of total retinol in bone marrow cells and peripheral leukocytes after 5 hours. However, in the fasting state no significant difference was observed between the content of total retinol in bone marrow cells from controls and from patients receiving retinyl palmitate daily for years. Our study suggests that bone marrow cells take up retinyl esters postprandially, but do not store retinoids.

Topics: Anticarcinogenic Agents; Bone Marrow; Child; Diterpenes; Humans; Leukemia, Myeloid, Acute; Leukocytes; Metabolic Clearance Rate; Retinyl Esters; Time Factors; Vitamin A

Topics: Antineoplastic Combined Chemotherapy Protocols; Child; Cytarabine; Diterpenes; Humans; Leukemia, Myeloid, Acute; Retinyl Esters; Vitamin A

Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Central Nervous System Diseases; Child; Child, Preschool; Cytarabine; Diterpenes; Doxorubicin; Female; Humans; Infant; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Male; Pancytopenia; Recurrence; Retinyl Esters; Vitamin A; Vomiting