Ann Hematol (2005) 84: 441446
DOI 10.1007/s00277-005-1026-4
ORIGINA L ARTICLE
Ashish Dixit . T. C. Chatterjee . Pravas Mishra .
Dharma R. Choudhry . M. Mahapatra . S. Tyagi .
Madhulika Kabra . Renu Saxena . V. P. Choudhry
Hydroxyurea in thalassemia intermediaa promising therapy
Received: 15 August 2004 / Accepted: 13 February 2005 / Published online: 19 April 2005
# Springer-Verlag 2005
Abstract Pharmacological agents such as hydroxyurea
(HU) have been known to cause induction of fetal hemo-
globin and possibly may alleviate the symptoms in thal-
assemia intermedia patients. Thirty-seven patients with
-thalassemia intermedia were enrolled to assess response
to HU therapy. Major response was defined as transfusion
independence or hemoglobin rise of more than 20 g/l and
minor response as rise in hemoglobin of 1020 g/l or re-
duction in transfusion frequency by 50%. The median age
was 10 years (range: 450 years) and median follow-up was
12 months (range: 436 months). Twenty-six patients
(70.2%) showed response to HU therapy. Seventeen pa-
tients (45.9%) were major responders, and nine patients
(24.3%) showed minor response. There was no correlation
of response with -thalassemia mutation or XmnI polymor-
phism; however, the presence of 3.7 deletion was asso-
ciated with major response in three patients. Mean fetal
hemoglobin (HbF) levels rose on HU therapy. Older age,
low baseline F cell percent, and low baseline HbF levels
(below 10%) were predictors of poor response. Response
was evident within 1 month of starting HU therapy in the
majority of responders. Thus, a short trial of HU therapy can
predict durable response.
Keywords Thalassemia intermedia . Hydroxyurea . HbF
induction
Introduction
Beta-thalassemia is the most commonly inherited blood
disorder in the world and results from a number of genetic
A. Dixit . T. C. Chatterjee . P. Mishra . D. R. Choudhry .
M. Mahapatra . S. Tyagi . M. Kabra . R. Saxena .
V. P. Choudhry (*)
Department of Haematology,
All India Institute of Medical Sciences,
New Delhi, India
e-mail: vedpchoudhry@yahoo.co.in
Tel.: +91-11-26594670
Fax: +91-11-26588663
defects in -globin gene expression [1]. It is a heteroge-
neous group of disorders resulting from decreased -globin
production and a subsequent imbalance in the /-globin
chain ratio. The excess chains precipitate within red blood
cells (RBCs) resulting in hemolysis and ineffective eryth-
ropoiesis. The phenotypic presentation varies in severity
based upon the imbalance of the /-globin chain ratio.
Thalassemia major presents early in life with anemia and is
generally transfusion dependent. On the other hand, het-
erozygous cases (thalassemia minor) are asymptomatic with
normal or only slightly reduced level of hemoglobin. Thal-
assemia intermedia is an intermediate condition between
the two extremes (10% of cases), can have a homozygous
or heterozygous inheritance pattern, is generally transfusion
independent or may require infrequent transfusion, and has
a clinically milder course than thalassemia major but severe
enough compared to thalassemia minor [2].
Enhancing -globin chain synthesis within the RBC
precursors will reduce the /non- chain imbalance and
could potentially lead to an improvement in RBC survival
resulting in rise of hemoglobin levels. Pharmacological
agents that increase -globin production, as evidenced by
an increase in fetal hemoglobin (HbF), have been evaluated
as therapeutic agents for patients with -thalassemia [3].
Response to hydroxyurea (HU) has been most promising
because of the oral route, relatively inexpensive cost, and
good experience with the use on a long-term basis in other
disorders [3]. Bradai et al. [8] used HU at 1520 mg/kg per
day in seven transfusion-dependent thalassemia major pa-
tients and found that six of them became transfusion inde-
pendent. The response persisted during the course of therapy
with median follow-up duration of 19 months. Drugs like
HU are expected to have more beneficial effects in thal-
assemia intermedia patients as the imbalance of the /-
globin chain is lesser. However, the studies published so far
have been on a limited number of patients [720]. Hoppe
et al. [16] treated five patients with thalassemia intermedia
with HU and found significant beneficial effect in four
cases, three of which became transfusion independent. We
present our data on response to HU in 37 patients with thal-
assemia intermedia.
442
Patients and methods
Thirty-seven consecutive patients attending the outpatient
department (OPD) of the Department of Hematology, All
India Institute of Medical Sciences (AIIMS), from Decem-
ber 2001 to July 2003 were enrolled for the study. Written
informed consent was obtained before the enrollment.
Inclusion criteria: diagnosis of thalassemia was based on
quantification of HbF and HbA2 by high-performance
liquid chromatography (HPLC) including family studies.
Thalassemia intermedia included cases of homozygous or
heterozygous -thalassemia and was defined as patients
who were:
1. Transfusion independent but had persistent anemia of
more than 6 months duration with or without organo-
megaly in the absence of intercurrent illness
2. Transfusion dependent but with a transfusion require-
ment of less than four units per year to maintain hemo-
globin above 80 g/l
3. Transfusion dependent and requiring more than four
units per year; however, the transfusions started
after the age of 5 years and/or were associated with
hypersplenism
Exclusion criteria:
1. Cases of thalassemia intermedia with other than -
thalassemia genotype (for example, -thalassemia,
-thalassemia heterozygous with structural hemoglo-
binopathies)
2. Cases with preexisting renal or hepatic diseases
3. Cases with positive serology for human immunodefi-
ciency virus (HIV), hepatitis B or C, or with chronic
infections (such as tuberculosis)
The median age of the patients was 10 years (range: 4
50 years). History of an affected family member was avail-
able in nine cases (24.3%). The majority of the patients
(17) were Punjabis of whom 14 were migrants from Pakistan
Sindh province. Hemolytic facies was present in 23 patients
(62%). All patients except one had some organomegaly with
mean palpable liver span below the costal margin of 3.0
1.9 cm (range: 012 cm) and mean palpable spleen size
of 5.22.6 cm (range: 012 cm) palpable below the left
costal margin.
Table 1 Distribution of -thal- -Thalassemia mutation
assemia mutations among var-
ious groups on HU
IVS 1-1(G-T)/IVS 1-1(G-T)
IVS 1-5(G-C)/IVS 1-5(G-C)
IVS 1-1(G-T)/619-bp deletion
IVS 1-1(G-T)/codon 8/9 (+G)
IVS I-5(G-C)/
619-bp deletion/
IVS 1-1(G-T)/IVS 1-5(G-C)
No mutations identified
Mean hemoglobin before starting therapy was 6512 g/l
(range: 4092 g/l). Fifteen cases (40%) were transfusion
independent, seven of which (18.9%) had never received
any transfusion. Two cases did not require transfusion after
splenectomy, and the remaining six cases required transfu-
sion at presentation only, had stable hemoglobin of >60 g/l
on folic acid supplementation, and refused further transfu-
sions for personal reasons. The median age at receiving
the first transfusion was 6 years (range: 250 years). Of
the transfusion-dependent patients, the median transfu-
sion requirement was 4 units per year (range: 112 units)
with four patients requiring >10 units a year, whereas the
transfusion requirement started after 5 years of age only.
The median number of transfusions received before starting
therapy was 4 units (range 1100 units). Mean serum ferritin
level was 694.5773.7 ng/ml (range: 803,600 ng/ml).
Three patients were on chelation therapy with oral deferi-
prone, and one patient refused chelation therapy for finan-
cial reasons. Six patients (16.2%) had elevated HbA2 also
along with HbF, and two patients (5.4%) had raised HbA2
alone without raised HbF (heterozygous -thalassemia).
Red blood cell survival studies were performed in 20
patients using 99Tc-labeled RBCs. The median RBC sur-
vival was 12.5 days (range: 822 days). Three patients had
evidence of hypersplenism by nuclear scan two of whom
were enrolled after splenectomy and one patient refused
splenectomy. Two more splenectomized patients where
RBC survival studies were not available were also enrolled.
In all, four (10.5%) splenectomized patients entered the
study.
Mutation analysis for five common -thalassemia genes
prevalent in the country and responsible for >90% of total
mutations was performed in 27 cases. Three patients (11.1%)
were negative for the five common mutations tested. Ten
patients (37%) were homozygous, eight (29.6%) were com-
pound heterozygous, and six cases (22.2%) were heterozy-
gous for these mutations. Distribution of various mutations
and XmnI polymorphism is given in Tables 1, 2.
Dose: hydroxyurea (Hydrea, Sarabhai) was given at
10-mg/kg per day starting dose and increased by 5-mg/kg
per day increments at 4-weekly intervals to a maximum of
20 mg/kg per day or until the myelotoxicity appeared.
Toxicity: myelotoxicity was defined by absolute neutro-
phil count (ANC) less than 1.5109/l or platelet count less
than 100109/l. Hepatotoxicity and renal toxicity were de-
Patients (n=27) Major responders Minor responders Nonresponders
(n=14) (n=7) (n=6)
9 (33.3%) 4 4 1
1 (3.7%) 1 0 0
3 (11.1%) 3 0 0
3 (11.1%) 2 1 0
(5 18.5%) 1 0 4
1 (3.7%) 0 0 1
2 (7.4%) 1 1 0
3 (11.1%) 2 1 0

Table 2 Distribution of XmnI polymorphism among various groups
on HU therapy
XmnI Patients Major Minor Nonresponders
polymorphism (n=24) responders responders (n=5)
(n=12) (n=7)
+/+ 12 (50%) 5 5 2 2 g/l in transfusion-independent patients
+/ 8 5 2 1
(33.3%)
/ 4 2 0 2
(16.6%)
fined as more than twofold rise in alanine aminotransferase
(ALT) or aspartate aminotransferase (AST) and as a >50%
increase in serum creatinine concentration, respectively. If
toxicity occurred, treatment was stopped until blood counts
returned to normal and then reintroduced at a lower dose
which, if tolerated, was considered the maximum tolerated
dose.
Duration of follow-up: minimum of 6 months of trial
before considering a failure of response. Patients were
assessed earlier if a major response had already occurred
and hemoglobin had stabilized for at least 2 months.
The median follow-up duration was 12 months (range: 4
36 months). Two patients required dose adjustments for
myelotoxicity, and in one of them, the dose could be in-
creased to 15 mg/kg per day. One patient developed mild
diarrhea, which subsided by itself after 2 weeks. The re-
maining patients tolerated the therapy well.
Laboratory monitoring: baseline hemoglobin and RBC
indices were derived from the mean of three to four values
over at least 6 months preceding the initiation of HU. Eval-
uation of baseline HbF, HbA2, and F cells was done at least
4 weeks after the last transfusion. All cases were screened for
hepatitis B and C and HIV before starting the therapy. Other
studies for enzymopathies [glucose-6-phosphate dehydro-
genase (G6PD), pyruvate kinase (PK) deficiency], parox-
ysmal nocturnal hemoglobinuria, and hereditary spherocytosis
were done wherever indicated.
Follow-up: complete blood counts (CBC) at 2-weekly
intervals until the maximum dose was reached and then
once in 4 weeks; renal and liver function tests once every
4 weeks until maximum dose and then every 8 weeks; HbF,
443
HbA2, and F cell estimation at the end of 6 months or after
the major response.
Response criteria:
Major response: transfusion independent with final Hb
>80 g/l in transfusion-dependent patients and a rise of
Minor response: transfusion independent with rise in
Hb >20 g/l but final Hb <80 g/l or >50% decrease in
transfusion requirement in transfusion-dependent pa-
tients and rise in Hb between 10 and 20 g/l in trans-
fusion-independent patients
No response: rise in Hb <10 g/l in transfusion-inde-
pendent patients and decrease in transfusion require-
ment by <50% in transfusion-dependent patients
Laboratory methods: hemoglobin (Hb) estimation and
total blood counts were done using an electronic counter
(Sysmex K-4500, Kobe, Japan). Peripheral smear exami-
nation was done for red cell morphology and presence of
nucleated RBCs. Reticulocyte count, serum iron studies,
and other hematological tests were done as per standard
methods [4]. Serum ferritin was measured by immunomet-
ric enzyme immunoassay using a standard kit (ORG 5FE,
ORGENTEC Diagnostika GmbH, Mainz, Germany). HbF
and HbA2 estimation was done by HPLC (Bio-Rad Variant,
Hercules, Calif., USA). F cell estimation was done by the
method of Kleihauer-Betke et al. [4], and the percentage
of F cells (number of F cells/100 RBCs on a smear) was
calculated.
Results
Twenty-six patients (70.2%) showed response to HU
therapy. Seventeen patients (45.9%) showed major re-
sponse, and nine patients (24.3%) showed minor response.
The median time to achieve first response was 2 months
(range: 14 months), and the median time to reach peak
response was 5 months (range: 28 months).
Major responders Of the major responders (17 patients)
(45.9%), the median age was 10 years (range: 431 years).
Table 3 shows the comparative parameters for the various
variables before and after therapy. Mean rise in Hb was 25
7.1 g/l, and the difference between previous Hb and post-

Table 3 Comparative data of major responders (n=17). NRBCs/100 cell hemoglobin concentration, RDW red cell distribution width and
WBC nucleated red blood cells per 100 WBCs, Ret reticulocytes, standard deviation (SD)
MCV mean cell volume, MCHb mean cell hemoglobin, MCHC mean
Mean Hb NRBCs/100 Ret MCV MCHb MCHC RDW F cells HbF
(g/l) WBC (%) (fl) (pg) (g/l) (SD) (%) (%)

Pre- 659 14.627.7 3.12.3 71.71.7 22.12.8 31117 59.59.4 72.418.4 67.025.7
therapy (4585) (1105) (19.1) (58.990.8) (18.528.6) (284335) (46.680.6) (4592) (13.696)
Post- 9110 4.28.5 2.31.4 74.09.2 23.73.9 32118 60.99.4 81.718.2 76.022.2
therapy (80119) (036) (16) (57.588.7) (17.031.0) (290352) (42.682.5) (5599) (25.694.6)
p value <0.001 <0.05 <0.05 <0.05 <0.01 <0.05 >0.05 <0.01 <0.01
444
Table 4 Comparative data of minor responders (n=9). NRBCs/100 cell hemoglobin concentration, RDW red cell distribution width and
WBC nucleated red blood cells per 100 WBCs, Ret reticulocytes, standard deviation (SD)
MCV mean cell volume, MCHb mean cell hemoglobin, MCHC mean
Mean Hb (g/l) NRBCs/100 Ret (%) MCV (fl) MCHb (pg) MCHC (g/l) RDW (SD) F cells (%) HbF (%)
WBC

Pre- 6316 4.23.0 1.91.3 70.64.7 22.62.6 31631 57.112.0 74.326.1 70.228.5
therapy (4090) (110) (0.34.0) (62.779.0) (19.827.1) (248350) (41.877.2) (3599) (22.695.2)
Post- 8112 3.01.5 1.60.8 73.63.0 23.32.3 31623 60.19.0 84.017.9 78.720.6
therapy (6.310.0) (05) (13) (68.878.8) (19.026.0) (260338) (48.572.8) (58100) (30.792.7)
p value <0.001 >0.05 >0.05 <0.05 >0.05 >0.05 >0.05 >0.05 >0.05

therapy Hb was statistically significant (p<0.001). Mean
cell volume (MCV), mean cell hemoglobin (MCH), and
mean cell hemoglobin concentration (MCHC) increased
on HU therapy, and this increment reached statistical sig-
nificance. Mean reticulocyte count and nucleated red blood
cell (NRBC) count also decreased significantly on therapy.
There was a rise in HbF levels and F cell percent during
the therapy period, which was of statistical significance (p<
0.01); however, this response was not uniform, and all pa-
tients with a baseline HbF >85% showed a poor or no rise in
HbF value despite a rise in total Hb levels. There was no
significant difference in serum bilirubin levels and red cell
distribution width (RDW) during therapy.
Three patients had a decrease in Hb levels with infec-
tion, and one of them required transfusion once. Response
to HU was restored after control of infection and was main-
tained thereafter. Eight patients witnessed a regression in
the degree of organomegaly after a median of 12 months of
therapy.
Minor responders Nine patients (24.3%) were minor
responders to HU therapy. Of these, two became transfusion
independent with rise of Hb of >20 g/l; however, the Hb
remained below 80 g/l (73 and 75 g/l, respectively). The
comparative data in this group are depicted in Table 4.
The mean rise in Hb was 189 g/l, which was of statis-
tical significance (p<0.001). Mean nucleated RBCs and
reticulocyte count decreased, and MCV and MCHb rose
during the course of therapy; however, the difference reached
statistical significance for MCV only. There was no signif-
icant change in MCHC and RDW during therapy. Mean F
cell count and HbF levels rose after starting HU therapy;
however, unlike the major responders, the difference here
did not reach statistical significance. There was a poor cor-
relation of HbF rise with total Hb rise in patients with base-
line HbF of >85%, similar to major responders. One of the
patients was a major responder to begin with; however, Hb
decreased soon after the initial rise and was maintained
below 80 g/l subsequently.
Nonresponders Amongst the 11 nonresponders (29.7%), the
median age was 16 years (range: 450 years) with four
patients >30 years of age. Two patients aged 31 and 50 years,
respectively, had raised HbA2 levels only without rise in
HbF levels at presentation; one of them was requiring
repeated transfusions. Another two patients had raised HbA2
along with raised HbF. Of the 11 patients, 4 had HbF below
10%. The comparative parameters before and after therapy
are depicted in Table 5.
Even in these patients, mean Hb rose from 6515 g/l
(range: 4092 g/l) to 7014 g/l, which was of statistical
significance for the transfusion-independent patients only.
However, it was still below the set criteria for a meaningful
response and could have been a part of fluctuations in Hb in
these patients. There was a rise in MCV in transfusion-
independent patients, which was statistically significant.
The nucleated RBCs did come down (statistically insignif-
icant), but there was no change in any other parameter.
There was no significant difference in HbF levels and F
cell count before and after therapy; however, in one of the
patients, HbF rose from 12.2 to 27.7% without a rise in
total Hb.

Table 5 Comparative data of nonresponders (n=11). NRBCs/100 cell hemoglobin concentration, RDW red cell distribution width and
WBC nucleated red blood cells per 100 WBCs, Ret reticulocytes, standard deviation (SD)
MCV mean cell volume, MCHb mean cell hemoglobin, MCHC mean
Mean Hb (g/l) NRBCs/100 Ret (%) MCV (fl) MCHb (pg) MCHC (g/l) RDW (SD) F cells (%) HbF (%)
WBC

Pre- 6515 7.210.1 2.81.4 68.82.5 21.52.0 31423 54.312.4 36.240.8 40.941.1
therapy (4092) (030) (1.05.0) (63.372.6) (18.925.8) (270365) (30.670.8) (290) (0.389.6)
Post- 7014 5.16.6 2.71.3 71.24.2 21.82.4 31117 53.710.7 36.240.8 41.939.3
therapy (47100) (023) (1.05.0) (65.079.4) (19.026.0) (268328) (33.367.9) (290) (0.588.5)
p value <0.05a >0.0.5 >0.0.5 <0.0.5a >0.0.5 >0.0.5 >0.0.5 >0.0.5 >0.0.5
a
Only in transfusion-independent patients
 445
Table 6 - and -thalassemia Patient mutation mutation XmnI Response to Hydrea
mutations in thalassemia inter-
media on HU
1 3.7 del heterozygous IVS 1-1(G-T)/IVS 1-1(G-T) +/+ Major
2 3.7 del heterozygous IVS 1-1(G-T)/Fr 8-9(+G) +/ Major
3 3.7 del heterozygous IVS 1-1(G-T)/619 bp del +/ Major
4 triplication Negative +/ Minor
5 triplication Not done Not done Nonresponder

There was no significant difference amongst the three
groups in terms of sex, transfusion dependence, number of
transfusions, age at first transfusion, and degree of orga-
nomegaly or RBC survival. No significant difference was
found amongst the groups for baseline average hemoglobin,
leukocyte count, nucleated RBCs, reticulocyte count, MCV,
MCH, MCHC, RDW, and unconjugated bilirubin either.
Both responding groups were comparable with regards to all
of the parameters. However, there was a significant dif-
ference in the age of patients in responding groups when
compared to the nonresponding group (p<0.05), which con-
tained older patients (4 of 11 above 30 years of age). Mean
baseline HbF and F cell count was also higher in the re-
sponding groups (both major and minor) when compared
individually with the nonresponding group, which was sta-
tistically significant (p<0.05). Two patients who had raised
HbA2 alone in the absence of raised HbF (heterozygous -
thalassemia) did not show any response to HU therapy.
No mutation was predictive of positive response to HU
therapy. However, IVS,1-5(G-C) in a heterozygous state
was more frequently associated with the nonresponding
group. Presence of XmnI polymorphism, though seen more
commonly in the responding groups than the nonrespond-
ing group, did not reach statistical significance.
In 14 of 46 cases, both - and -thalassemia mutations
were studied: -thalassemia mutations were found in five
cases and the remaining were negative. Three patients were
heterozygous for 3.7 deletion, and two had triplication of
the gene. In one of the patients with triplication of the
gene, -thalassemia mutation was not available; however,
this was a heterozygous thalassemia (with only raised HbA2),
and the association with triplication might have been re-
sponsible for the intermedia phenotype. He had jaundice
with low Hb (82 g/l) but was transfusion independent and
did not respond to HU therapy. The other patient with trip-
lication of the gene was negative for five common -
thalassemia mutations and was a minor responder to HU
therapy. Table 6 shows the interaction of these mutations.
All patients with 3.7 del were major responders to HU
therapy. All patients with a response to HU and -thalas-
semia mutations also had XmnI polymorphism either homo-
zygous or heterozygous.
Discussion
Patients with thalassemia intermedia are usually well com-
pensated for their disease and pay the price in terms of in-
creased morbidity from organomegaly, osteoporosis, and
other effects of exuberant extramedullary erythropoiesis.
Hence, the decision to start these patients on a regular trans-
fusion regimen is always difficult. Even a small rise in he-
moglobin would be of immense value to suppress the high
turnover of erythroid tissue and provide gratifying results.
Hydroxyurea produces fetal hemoglobin production via a
reactivation of genes as a result of some unknown mole-
cular mechanisms. The clinical benefits of using this drug in
sickle cell anemia have already been demonstrated [5]. Sig-
nificant benefit is also expected in severe -thalassemia
patients because the increased production of chains can
balance the lack of chains, can neutralize excess of
chains, and provides improvement. The beneficial results in
thalassemia major patients have not been very encouraging
[611]; however, many studies have documented good
response in thalassemia intermedia patients [1219]. Most
of these studies included very small numbers of patients,
and there was a need for a bigger study to prove the efficacy
of HU in this group of patients.
We studied the response to HU in 37 patients and found
encouraging results. Overall, 26 patients (70.2%) showed
response to HU therapy. Of these, 17 patients (45.9%)
showed a major response. The response to HU therapy was
evident within 1 month of starting HU therapy in the ma-
jority of patients. Only one patient had a delayed onset of
response at 4 months, and this patient was a minor re-
sponder. Hence, response to HU can be predicted by a short
trial (3 months) of therapy directly. Although most of the
patients showed stabilization of hemoglobin after 6 months
of therapy, in some of the patients, peak effect was delayed
until 8 months of therapy. There was no significant side
effect other than myelotoxicity in two patients requiring
dose adjustments. Most of the patients maintained their Hb
on HU therapy (maximum follow-up up to 36 months);
however, in three patients, Hb decreased after suffering an
intercurrent illness, and in all of them, the response to HU
was restored after controlling the infection.
Table 7 Comparison of results of HU therapy with other published
series
Study Patients Response Response Overall
(n) (major) (minor) response
Hoppe et al. 5 2 2 4 (80.0%)
[16]
de Paula et al. 7 2 1 3 (42.8%)
[9]
Present study 37 17 9 26 (70.2%)
446
No correlation of response to HU was found with -
thalassemia mutation; however, an increased association was
seen with XmnI polymorphism (statistically insignificant).
Association with 3.7 deletion in the heterozygous state was
a predictor of good response to HU therapy; however, all
cases with this mutation also had the presence of XmnI
polymorphism, suggesting a combination of variables af-
fecting the final response. None of the patients with het-
erozygous -thalassemia who had raised HbA2 alone with
thalassemia intermedia phenotype responded to HU, making
this group of patients poor responders to HU therapy. One of
these cases also had triplication as a causative factor. An
interesting observation was that the older age, low baseline
F cell percent, and low HbF levels (particularly below 10%)
were predictors of a poor response. In fact, none of the pa-
tients with baseline HbF <10% showed any significant
response to HU therapy. Mean HbF level rose on HU ther-
apy significantly; however, there was no direct correlation of
degree of response with the rise in HbF value in patients
with baseline HbF of >85%, suggesting that possibly there
are other mechanisms of action for HU as well. In fact,
Zeng et al. [20] demonstrated that HU can increase -, -
and -globin levels and hence may promote reduction in
ineffective erythropoiesis.
Our results are significant in terms of the strict definition
of response categorized as major or minor. In many studies,
even a marginal rise in Hb was taken as evidence of re-
sponse [1219]. Table 7 shows the comparative data with
other studies. Our study is the largest series of patients with
thalassemia intermedia on HU therapy.
HU is a promising drug in the treatment of thalassemia
intermedia patients. A short trial of drug may determine the
likely responders to treatment and may improve the quality
of their life. However, its potential to cause leukemogenesis
is still of concern. With more experience from the sickle cell
patients, this issue will also be addressed sooner or later.
Studies on larger numbers of patients for longer duration
of therapy are needed to evaluate its long-term safety and
efficacy.
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