Evidence regarding hydroxyurea (HU) effectiveness in thalassemia patients is variable and largely comes from observational studies. We suspect inconsistency in its efficacy may affect roles of HU in clinical practice worldwide. We undertook a survey of hematologists to explore the usage, effectiveness, side effects and barriers towards use of HU in clinical practice.


Adult and pediatric hematologists from Canada, USA, India and Thailand were surveyed by non-random sampling (snow balling). A web based survey was distributed through the Canadian hemoglobinopathy organization, ASPHO listserv, Hematology India contacts and the author’s contacts.


Total 112 hematologists responded [North America(82), India(24), Thailand(4), Australia(2)]. In last five years, 23% of respondents did not come across any literature regarding HU use in thalassemia. Only 18% felt that HU is effective in reducing blood transfusion (BT) requirements by ≥30% in thalassemia major(TM) in contrast to literature showing 30-80% response. Just over half of the hematologists felt HU is effective in reducing BT requirement in thalassemia intermedia(TI) and hemoglobin E/b thalassemia(HbE/bthal), in comparison to reported response of 50-100%. Drug’s ability to cause transfusion independence in TM, TI and HbE/β thal was believed by 6%, 66.3% and 46.3% of respondents, respectively, compared to literature reports of 30-70%(TM), 60-100%(TI) and 50%(HbE/β thal) transfusion independence rates with HU use(Musallam KM, et al. Blood. 2013).

Half of the respondents had never tried HU in thalassemia. Major barriers towards HU use were: 1) patient refusal/fears(23%), 2)non-support by colleagues(16.8%), 3)physician concerns about side effects/cancer(14.1%), 4)compliance(11.5%), 5)funding(11.5%), 6)poor evidence(10.6%), and 7)poor physician knowledge(7%). Majority believed baseline HbF, Xmn1 polymorphism, unknown factors and β mutations to be responsible for HU effectiveness which have not been consistently reported in literature.

Views regarding HU carcinogenicity were: 60%-unproven, 19%-no idea, 14%-confident about safety and 7%-proven risk. We know only 2 cases of leukemia in thalassemics on HU (a 58 year old TI patient with myeloproliferative syndrome developing AML, and a child developing leukemia within 3 months of starting HU) though a causal association could not be determined in either case. Long term data in thalassemia(13 year) and SCA(17.5 year) do not show increased risk of malignancy.

Perceived monthly cost of HU therapy for an adult was $100-300 and $50-100 (40% responses each), whereas actual cost is $50-75 in Canada, $35-40 in Thailand (subsidized) and $25 in India. Of note, the approximate cost of a BT is $700 and of chelation(deferasirox) is $1400/month in Canada.

Major reasons for HU discontinuation were: non-response(54%), unknown factors(37.5%), poor compliance(28.1%), cytopenias(25%), pregnancy(15.6%), hepatotoxicity(9.4%), and nephrotoxicity (7.8%). The last two have not been reported in thalassemia literature. Around 60% of physicians felt inability to adequately assess HU response.


There is a disconnection between evidence and perceived HU response and side effects, with most hematologists underestimating the response. This could be explained by reporting bias, low utilization of HU with poor response assessment, and poor physician awareness. These factors may influence physician counselling and eventually patient’s choice and compliance, major barriers against HU use. Inconsistencies in HU use creates confusion among patients, trainees and affects comparison of disease outcomes. Improved access to HU, physician education with more acceptances of HU trials in thalassemia may increase its use. This along with systematic studies, with objective tools for functional outcomes (e.g. growth, quality of life) may help understand the true potential of HU and promote the formulation of guidelines. Being a generic drug, HU lacks commercial interest to get support for a large scale studies. If we can identify a subgroup of thalassemia patients where HU is effective, the positive effects on quality of life and the cost savings could be significant.


Off Label Use: Hydroxyurea is used in thalassemia for over two decades to reduce transfusion requirements and other purposes but its indications in thalassemia are not well recognized and accepted.. Viprakasit:Novartis: Honoraria, Research Funding; Shire co.: investigator in clinical trials, investigator in clinical trials Other.

Author notes


Asterisk with author names denotes non-ASH members.