User barriers: Table 1
Adherence to therapy: Ninety-five (88.8%) patients reported
taking hydroxyurea daily. Among defaulters, six (50%) reported failing
to take for 3 months (poor compliance). Table 1 summarizes
compliance with doctor’s appointments and laboratory tests.Only 26 patients (22.8%) complied with 13 doctor’s appointments in 1
year. Twenty patients (17.5%) and 37 patients (32.5%) completed
expected hematologic and organ function tests respectively.
Safety : Starting dose : Most patients (96.5%) received
15 mg/kg /day of HU. Four patients (3.5%) with Hb <6gm/dl
received 10 mg/kg/day. Dose escalation: Escalation of dose was
not consistent for logistic reasons and many patients were on the
starting dose for over 6 months. Routine escalation did not go above 20
mg/kg/day for about 90% of the patients. Side effects:Reported side effects are shown in Table 2. Therapy was stopped for 3
months in a patient with persistent abdominal pain and was later resumed
at a lower dose and gradually escalated. One child had accidental
overdosage of HU suspension (about 105mg/kg/dose) and therapy was
suspended because of transient marrow suppression. Changes in mean serum
alanine transaminase and serum creatinine at baseline and 18 months are
not statistically significant (p=0.312; p=0.122) respectively. Table 3.
No patient had dose-limiting toxic effects regarding thrombocytopenia,
alanine transaminase or serum creatinine. Mild, transient neutropenia
(ANC of 1.34 to 1.5x 109/l) occurred in 5 patients
(5.6%) that resolved with dose adjustment.
Hematologic : Baseline values showed anemia (mean of
7.1±1.3g/dl), low Hb F (mean of 8.2±0.6%) and leukocytosis (mean of
13.7±0.5 x109/l). After 24 months of therapy (n=40),
there was significant increase from baseline in Hb (1.6g/dl, 95% CI 1.1
to 1.7), the mean corpuscular volume (9 fl, 95% CI 5.2 to 11.4), foetal
hemoglobin (5.3%, 95% CI 2.4 to 8.2). Significant increases were also
documented at 6 months, 12 months and 18 months of therapy (Table 3).
There was a progressive and significant reduction in white cell count (
-4.1x109/l, 95% CI -4.8 to-2.4), absolute neutrophil
count ( -2.3 x 109/l, 95% CI -2.1 to -2.9) from
baseline through 24 months. Table 4. There was a progressive decline in
total bilirubin (TB) over the 2-year period.
Clinical effects: Majority 104 (91.2%) of the patients
reported an improved general well-being and symptomatic relief Table 2.Parental satisfaction: Most 102 (89.5%) of the parents
expressed satisfaction with use of hydroxyurea and would like to
continue its use. Table 5 summarizes parental concerns about hydroxyurea
which includes cost of laboratory tests, availability and cost of drugs.