The goal of hydroxyurea therapy is to increase the percent hemoglobin F in red blood cells. An increase in hemoglobin F is associated with:
(1) fewer painful, vasocclusive events
(2) fewer episodes of acute chest syndrome
(3) reduced early mortality.
In children treated with hydroxyurea the quartile with the highest response had a mean hemoglobin F percentage of 26%, with an absolute increase from baseline of +16% (indicating a mean baseline level of 10% hemoglobin F).
Mild myelosuppression (as manifested by reductions in white blood cells and reticulocytes while minimizing anemia) is associated with maximal hemoglobin F response.
Factors associated with optimum hemoglobin F response:
(1) maximum tolerated dose of hydroxyurea in mg per kg per day
(2) excellent compliance
(3) low reticulocyte count, decreased from baseline
(4) low white blood cell count, decreased from baseline
(5) high hemoglobin level, increased from baseline
(6) high MCV (macrocytosis), increased from baseline
Although response data is shown in Table 2 (page 13), it shows the mean response for quartiles, which makes implementation difficult. The following will be used to guestimate cutoffs for the implementation.
|
Factor
|
Mean Values for Highest Quartile
|
|
maximum tolerated daily dose
|
26.9 mg/kg
|
|
compliance
|
excellent
|
|
absolute reticulocyte count with therapy
|
135,000 per µL
|
|
change in reticulocyte count from baseline
|
decrease by 272,000 per µL
|
|
absolute WBC count with therapy
|
7,400 per µL
|
|
change in WBC count from baseline
|
decrease by 7,400 per µL
|
|
hemoglobin level with therapy
|
10.2 g/dL
|
|
change in hemoglobin from baseline
|
increase by 2 g/dL
|
|
MCV with therapy
|
107 fL
|
|
change in MCV from baseline
|
increase by 21 fL
|
