The role of low-dose cytosine arabinoside and aggressive chemotherapy in advanced myelodysplastic syndromes.
The efficacy of low-dose cytosine arabinoside (Ara-C) and aggressive chemotherapy was assessed in 67 patients with advanced myelodysplastic syndromes (MDS). In most cases, treatment was started because of worsening peripheral cytopenia, increase in bone marrow blasts, or transition of MDS to acute myeloid leukemia (AML). Of 51 patients (age range, 18-82 years) receiving low-dose Ara-C by subcutaneous bolus injection (10 mg/m2 every 12 hours) or continuous intravenous infusion (20 mg/m2/day), nine (18%) entered complete remission (CR) and four (8%) had a partial response (PR). Duration of CR varied from 4 to 25+ months. Overall survival of patients treated with Ara-C was not superior to that of a historical control receiving supportive care only. Hematologic toxicity of low-dose Ara-C was considerable, with 12 patients (24%) dying of hemorrhage or infection during the initial treatment course. Sixteen patients (age range, 17-65 years) who presented with a Karnofsky score of more than 80% were chosen for aggressive chemotherapy using standard AML protocols. In this group, nine CR and two PR were obtained. Early death from pneumonia occurred in two patients, and three patients had refractory disease. The factors most strongly associated with successful remission induction were (1) presence of Auer rods in granulocyte precursors, and (2) a comparatively low medullary blast count (less than 30%) at the start of treatment. Median duration of bone marrow aplasia for patients entering CR was 21 days (range, 6-51). Prolonged remissions (22+, 27+, and 29 months, respectively) could be achieved in three of four patients receiving consolidation and maintenance chemotherapy after induction of CR. From these data we conclude that aggressive chemotherapy should not generally be considered contraindicated in advanced MDS. In patients with a good Karnofsky score, this form of treatment may be more advantageous than the currently favored low-dose Ara-C, which is also myelotoxic, but induces remissions in only a minority of patients.
Aul
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C
Department of Internal Medicine, Heinrich Heine University, Düsseldorf, Federal Republic of Germany.
Schneider
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W
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012074:Remission Induction; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage
D003561:Cytarabine; D004317:Doxorubicin; D013866:Thioguanine