In vitro and in vivo effects of deferoxamine in neonatal acute leukemia.
A six week old infant with acute leukemia failed to attain remission with chemotherapy. Because we previously demonstrated that the iron chelator deferoxamine (DFO) has antiproliferative properties and modulatory effects on cell differentiation, a protocol was designed for in vitro study and for clinical use in the patient. At diagnosis, blast cells were morphologically undifferentiated, had nondiagnostic cytochemistry, showed an abnormal karyotype (t[4;11]), expressed markers of B cell lineage, and demonstrated C mu gene rearrangement. Tissue culture of marrow or blood cells yielded colonies of leukemic blasts. Increasing concentrations of DFO produced a dose-dependent suppression of patient's blast colony growth in vitro, and blasts within colonies showed a marked change in surface antigen expression from lymphoid to myelomonocytic markers, became monocytic in appearance, and developed intense staining for nonspecific esterase. When DFO was given intravenously to the patient as a single agent for 48 hours, blasts no longer expressed lymphoid antigens and became strongly positive for myelomonocytic markers, identical to the in vitro findings. Intravenous DFO halted rising peripheral blood blast cell numbers and allowed a several-fold increase in normal hematopoietic progenitor colony growth. When combined with low-dose cytosine arabinoside in the treatment protocol, DFO caused striking leukemic cytoreduction. Our findings indicate that DFO has antileukemic properties by virtue of its effects on proliferation and differentiation, and they prompt further experimental and clinical studies with this agent.
D000951:Antigens, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002880:Chromosomes, Human, Pair 11 / Q000648:ultrastructure; D002894:Chromosomes, Human, Pair 4 / Q000648:ultrastructure; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D003676:Deferoxamine / Q000627:therapeutic use*; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007211:Indoles / Q000032:analysis; D007231:Infant, Newborn; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011241:Prednisone / Q000008:administration & dosage; D014178:Translocation, Genetic; D014750:Vincristine / Q000008:administration & dosage
D000951:Antigens, Neoplasm; D007211:Indoles; D003561:Cytarabine; C042610:5-bromo-4-chloroindoxyl acetate; D014750:Vincristine; D001215:Asparaginase; D003676:Deferoxamine; D011241:Prednisone; D003630:Daunorubicin