Treatment of preleukemic syndromes with continuous intravenous infusion of low-dose cytosine arabinoside.
Preleukemic syndromes compose a group of acquired bone marrow disorders characterized by dysplastic maturation of hematopoietic cells and peripheral blood cytopenias. These syndromes have been generally considered untreatable. We administered low doses of cytosine arabinoside by continuous infusion for 14 to 21 days (20 mg/m2/d) to 16 patients with preleukemia in various stages of evolution to acute leukemia. Steady state plasma cytosine arabinoside levels ranged from 41.8 to 64.2 nmol/L. Eleven patients demonstrated marked improvement in hematopoiesis and loss of transfusion requirements for periods ranging from two to 27 + months. All but one responding patient developed recurrent pancytopenia, but additional responses to low-dose cytosine arabinoside were achieved in five of five retreated patients. Median overall survival time is 12 months for the 11 responding cases, and nine months for nonresponders. The major toxicity of low-dose cytosine arabinoside is myelosuppression, and most patients required platelet transfusion support and administration of antibiotics. Chromosome analyses demonstrated evolution to a new clone of hematopoietic cells in three patients, and persistence of the same abnormal clone in another patient. These results suggest that low-dose cytosine arabinoside therapy may result in improved hematopoiesis by promoting maturation or by selecting new stem cell clones. Low-dose cytosine arabinoside therapy thus deserves further evaluation both as a single agent and in combination with other agents in the treatment of myelodysplastic syndromes.
D000328:Adult; D000368:Aged; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D002869:Chromosome Aberrations; D003114:Colony-Forming Units Assay; D003561:Cytarabine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D004341:Drug Evaluation; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D011289:Preleukemia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D013577:Syndrome; D013997:Time Factors
D003561:Cytarabine