Response to hydroxyurea therapy in β‐thalassemia

Abstract

Although a relatively small number of previous studies suggest a modest response to hydroxyurea (HU) therapy in b-thalassemia, more recent investigations have revealed that some transfusion-dependent patients can become transfusion-independent following HU therapy. Patients with Gc XmnI polymorphism, several b-globin mutations, and a-thalassemia deletions were inconsistently reported to have significant responses to HU therapy. To better predict who may respond, we retrospectively evaluated the clinical response and the molecular background of 18 b-thalassemia patients treated with HU for a mean of 46 months. The majority of transfusion-dependent patients responded to HU therapy with 9 out of 11 (82%) becoming transfusion-independent. Five thalassemia intermedia (TI) patients receiving occasional blood transfusion did not require any additional transfusions following therapy and two TI patients who had never received transfusions had a 2 g/dl increase in their hemoglobin level. The majority of b-thalassemia major patients who became transfusion-independent (7/9) were either homozygous (5) or heterozygous (2) for the XmnI polymorphism. No correlation was identified between response to therapy and the presence of specific b-thalassemia mutations or a-globin deletions. We conclude that further analysis of the degree of response of transfusion-dependent b-thalassemia patients to HU therapy, as well as, the impact of their genetic background on this response is required to identify patients likely to have significant response. Am. J. Hematol. 83:366-370, 2008. V

Fetal hemoglobin chemical inducers for treatment of hemoglobinopathies

“…These findings have been confirmed in large studies carried out on Iranian, Indian, and Algerian β-thalassemic patients, showing good responses in a significant proportion (i.e., >50%) of β-thalassemic patients, without any major toxicity related to HU administration [194][195][196][197][198][199][200].…”

“…Koren et al [198] β-thal intermedia 7 100% (all patients became transfusion-free). 11±3 mg kg −1 day −1…”

“…Koren et al [198] β-thal intermedia 18 61% (responding patients had a total Hb increase of >1.5 g/dL). Bradai et al [199] β-thal major 20 80% (reduction of transfusion requirement) 16 mg kg −1 day −1…”

Pluripotent Stem Cells in Research and Treatment of Hemoglobinopathies

“…In severe thalassemia (major), patients require regular transfusion, which comes with the risk of antibody sensitization and the complications of iron overload. Treatments like hydroxyurea, which increase fetal hemoglobin (HbF) levels, reduce the severity of b-thalassemia because they decrease the number of unpaired a-globin chains (Platt et al 1984;Weatherall 2001;Koren et al 2008). However, hydroxyurea is not effective in b-thalassemia patients because they need higher levels of HbF than SCA patients to ameliorate their symptoms (Alebouyeh et al 2004;Yavarian et al 2004).…”

Hydroxycarbamide‐induced dermopathy

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Hydroxycarbamide (hydroxyurea) is an agent administered orally for the treatment of chronic myelogenous leukemia, myeloproliferative disorders, thalassemias, erythrocytosis, and sickle cell anemia [1][2][3]. An estimated 13% of patients with chronic myelogenous leukemia have mucocutaneous changes with long-term hydroxycarbamide therapy [4].

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