From the Archives of Iranian Medicine, Volume 12, Number 3, May 2009
http://www.ams.ac.ir/AIM/09123/0013.pdfResults
Forty-nine patients (28 women and 21 men)
enrolled in the study. The mean age of the patients
was 18.38 years (range: 10 – 40 years). The mean
packed red cell transfusions in one year before
starting of HU was 22.75 units, which decreased to
6.02 after treatment (P< 0.01, t-test). The mean Hb
levels was 8.52 g/dL and 8.45 g/dL during one
year before and after HU therapy, respectively; this
difference was not significant (P=0.543, t-test).
Before initiation of HU, the patients required blood
transfusion every three to four weeks, but only
three to four months after treatment, transfusion
stopped in 12 patients, spaced out in 32 patients
(once every three to four months instead of once
every month), and continued in five patients. The
mean ferritin level during one year before the
starting of HU was 2751.44 ng/mL, but decreased
to 1594.20 ng/mL after one year of HU therapy
(P<0.001, t-test). The mean deferoxamine injection
decreased from 84.83 to 49.46 (P<0.001, t-test)
(Table 1). We had only one hematologic
complication (platelet<100,000/mm3). Thrombocytopenia
was transient, which resolved with
discretion of HU dose. Eight patients suffered from
nausea at the beginning of treatment, which
resolved spontaneously.
There were no hepatic,
renal, or other complications during the treatment.Discussion
The mainstay of treatment in major β-
thalassemia still relies on regular blood
transfusions and the use of iron chelators.
Pharmacologic reactivation of γ-globin genes holds
great promise for the treatment of thalassemia
syndromes as well as of sickle cell disease.
Hydroxyurea has been demonstrated to up regulate
γ-chain synthesis and HbF production. This drug
has been used successfully in the treatment of
sickle cell anemia by increasing HbF levels and
reducing clinical complications,8 although there is
limited experience with this agent in betathalassemic
patients.9,10
We described the results of the treatment of 49
splenectomized, transfusion-dependent major betathalassemic
patients with HU. The effects on total
Hb, transfusion requirements, and the level of
ferritin were the most significant observation of
this study.
We observed a significant decrease in blood
transfusion. The response to HU was equal in
males and females. Decrease of transfusion
requirement began in the first three to four months
of HU therapy. Our findings show that the effects
of HU therapy can occur after a short period of
time.The significant decrease of serum ferritin in the
responder group is clinically very important as iron
overload is the main hazard to these patients. The
serum ferritin decrement is due to decrease of
blood transfusion and to a lesser extent due to
increased iron utilization by increased Hb
production and also suppression of ineffective
erythropoiesis.HU treatment was well-tolerated and it did not
cause any hematologic toxicity except in one
patient who developed transient thrombocytopenia
which resolved after a short period of HU
cessation.
Although the carcinogenic effect of long-term
use of HU remains a matter of serious concern,
we
did not encounter any malignancies including
leukemia in the five-year follow-up. This study
shows that HU can be an effective and safe
treatment for major thalassemia in long-term
therapy.This corroborates the report from several years ago from Algeria that showed positive results using hydroxyurea in thal majors. This was a bigger study and the positive results suggest that hydroxyurea therapy should be considered one of the tools in decreasing transfusion frequency in thalassemia major. The lack of serious side effects is also quite encouraging.
The report is attached to this post as a pdf file.