Premium
Desensitization to hydroxycarbamide following long‐term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients
Author(s) -
Rigano Paolo,
Pecoraro Alice,
Calzolari Roberta,
Troia Antonio,
Acuto Santina,
Renda Disma,
Pantalone Gaetano Restivo,
Maggio Aurelio,
Marzo Rosalba Di
Publication year - 2010
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2010.08397.x
Subject(s) - in vivo , hydroxycarbamide , medicine , haematopoiesis , fetal hemoglobin , immunology , gastroenterology , hematology , hemoglobinopathy , pharmacology , disease , stem cell , endocrinology , fetus , biology , pregnancy , genetics , microbiology and biotechnology
Summary Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of β‐thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short‐ (1 year) and long‐term (mean follow‐up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo . Our results confirm a good response to HC after a short‐term follow‐up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow‐up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long‐term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the ‘ in vivo ’ response. The mechanism of this loss of response to HC remains to be determined.