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Blood, 1 June 2002, Vol. 99, No. 11, pp. 3905-3908
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Maintenance of elevated fetal hemoglobin levels by
decitabine during dose interval treatment of sickle cell
anemia
Joseph DeSimone,
Mabel Koshy,
Louise Dorn,
Donald Lavelle,
Linda Bressler,
Robert Molokie, and
Nasrin Talischy
From the University of Illinois at Chicago and the
Veterans Administration Chicago West Side Division, IL.
We have previously demonstrated that 5-aza-2'-deoxycytidine
(decitabine) augments fetal hemoglobin (HbF) levels in patients with
sickle cell anemia (SS) who did not respond to hydroxyurea (HU). The
present study was designed to determine the effect of repeated
decitabine dosing on HbF levels and hematologic toxicity over a 9-month
treatment period. Seven patients (5 HU nonresponders) were entered. One
patient had  -thalassemia sickle cell anemia. Decitabine was
administered by intravenous infusion at a starting dose of 0.3 mg/kg
per day, 5 days a week for 2 weeks, followed by a 4-week
observation period. If the absolute neutrophil count dropped below
1000, the dose was reduced by 0.05 mg/kg per day in the next
cycle. A drug dose was obtained for each patient, and it resulted in an
elevated HbF without neutropenia (absolute neutrophil count
nadir greater than 1500) or evidence of cumulative toxicity. Average
HbF and average maximal HbF levels attained during the last 20 weeks of
treatment for the 6 SS patients increased to 13.93% ± 2.75% and
18.35% ± 4.46%, respectively, from a pretreatment mean of
3.12% ± 2.75%. Mean and mean maximal hemoglobin (Hb) levels increased from 7.23 ± 2.35 g/dL to 8.81 ± 0.42 g/dL and
9.73 ± 0.53 g/dL, respectively. Individual maximal F-cell
number observed during the trial was 69% ± 10.12%. The absence of
cumulative toxicity may allow shorter intervals between drug
treatments, which may lead to higher hemoglobin and HbF levels after
several treatment cycles and, therefore, to greater clinical improvement.
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