Blood, 1 January 2002, Vol. 99, No. 1, pp. 1-1
Who should get HU? ... And how?
Sickle cell anemia is a cruel and disheartening disease that
can be ameliorated by treatment with hydroxyurea (HU). HU can also
cause life-threatening marrow depression. It probably can cause
leukemia and skin cancer in patients with myeloproliferative disease,
and it may be embryotoxic, teratogenic, and mutagenic in humans.
Because of those risks, HU should be prescribed for those most likely
to "benefit" from it. "Benefit" is hard to quantitate, and in
this study Ware and colleagues (page 10) used an easily measured
surrogate, the percentage of fetal hemoglobin in hemolysates (% HbF).
They looked for predictors of high HbF in children treated with HU. As
in a French trial of young patients and a study of American
adults, they found maximum HbF during treatment
(Fmax) to be significantly associated with
pretreatment % HbF. Fmax was also related to
maximum tolerated dose of HU and to an estimate of compliance. Problems
with compliance may have been responsible for failure of at least one
other study to show such a dose response relationship.
Patients with really high levels of % HbF usually don't
need HU, for they often have mild disease. Ware and colleagues tell us
to select those with relatively high % HbF from among our
sickest patients, although some patients with low HbF also respond
well. Beyond that selection, they tell us how to treat. We
should push the HU dose to just below toxicity, but we'd best be
cautious in what we tell our patients and their parents. We can hold
out hope of improvement, but we should not promise it. Patients must be
sure they understand our instructions, and we must be clear in the
instructions we give if we expect patients to comply with them.
Samuel Charache
Johns Hopkins University School of
Medicine
