Jeffrey S. Wisch

Response of Preleukemic Syndromes to Continuous Infusion of Low-Dose Cytarabine

Preleukemic syndromes are a group of acquired bone-marrow disorders characterized by dysplastic maturation of hematopoietic cells and peripheral-blood cytopenias. Although the clinical course is variable, most patients succumb to hemorrhage, infection, or acute leukemia. These syndromes are generally considered untreatable. We administered low doses of cytarabine by continuous intravenous infusion for 7 to 21 days in eight patients with preleukemia or with preleukemia in evolution to acute leukemia. Eight of 13 courses were associated with marked increases in peripheral-blood granulocyte, platelet, and red-cell counts, with the result that six of the eight patients needed no transfusions for 2 to over 14 months. These preliminary results demonstrate that continuous infusion of low-dose cytarabine can offer patients with preleukemic syndromes hematologic improvement with limited toxicity.

Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase.

OBJECTIVES The incidence and severity of growth retardation in children with type 1 Gaucher disease and the response to enzyme replacement therapy with alglucerase were studied. STUDY DESIGN A retrospective analysis of growth in 99 children and adolescents with type 1 Gaucher disease before treatment, and in 54 of those subjects during treatment, was done. Growth was compared with gender, age, and dosage of replacement enzyme. RESULTS Linear growth was normal in the first 1 to 2 years of life and then decelerated. Height was at or below the 5th percentile in 50% of all subjects immediately before treatment. The mean z score was -1.49 (95% confidence interval, -1.83 to -1.16), corresponding to the 6.8th percentile for height. Seventy-two percent were below the 50th percentile and 50% were at or below the 5th percentile for mid-parental height (p <0.001). One and one-half years after treatment was started, the estimated mean z score for all subjects was -1.01, which corresponds to the 16th percentile for height. Normal growth was achieved within 4 to 30 months in eight of nine subjects who were at or below the 5th percentile. It occurred only in those receiving higher doses (60 to 120 U/kg per 4-week period) of alglucerase. There was a significant association between z scores for height before treatment and liver enlargement (r= 0.57; p < 0.01). CONCLUSIONS Half of the subjects who manifest type 1 Gaucher disease in childhood have growth retardation. Treatment with adequate amounts of modified enzyme replacement was effective in normalizing linear growth.

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.