Do alpha deletions influence hydroxyurea response in thalassemia intermedia?

Abstract

Thalassemia intermedia patients show variable phenotypes. Hydroxyurea (HU) may benefit some of the thalassemia intermedia cases (1), however, the parameters influencing the response to HU have not been reported. In this study, the molecular parameters, alpha-globin and beta-globin genotype and the Xmn I polymorphism, were correlated with the HU response. Twenty patients with thalassemia intermedia were given HU (10-20 mg/kg) and responses were evaluated over a one year period. Twelve patients (60%) showed a good response to therapy with a significant increase in Hb and HbF levels and with elimination of the transfusion requirement in four patients. Four out of the twelve (33%) patients were positive for -alpha(3.7) deletions whereas none of the 8 non-responders were positive for alpha deletions. One each of the responders and non-responders were positive for alpha alpha alpha(anti-3.7) triplication. Three (25%) responsive and one non-responsive patients were homozygous for the IVS1-1 (G-->T) mutation. Three of the responsive patients with alpha deletions were also homozygous positive for Xmn I polymorphism. Thus, in addition to acting in synergy with the XmnI polymorphism, alpha deletions may be an independent factor predicting good response to HU in thalassemia intermedia, although this needs to be confirmation in larger studies.

Optimal management of β thalassaemia intermedia

“…Hydroxycarbamide may also have a more general role in increasing globin synthesis (Atweh & Loukopoulos, 2001). Large series of TI patients have been reported from Iran (Karimi et al, 2005) and India Panigrahi et al, 2005). The results were impressive, especially in the first study, where most patients were reported to have become transfusion independent.…”

“…Previous studies from Europe had documented a constant increase of the erythrocyte volume and in HbF, but only a modest effect on total Hb concentration. Co-inheritance of a thalassaemia, the Xmn-1 HBG2 polymorphism (Panigrahi et al, 2005) and the underlying b globin genotype may be predictive of a good response to hydroxycarbamide; Hb E/b thalassaemia patients generally have a good response (Singer et al, 2005). However, one study from Italy reported a decrease in the efficacy of hydroxycarbamide in TI patients after a longterm follow-up (Mancuso et al, 2006).…”

Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia

“…50,61,90 Of note, several reports confirm that the effects of hydroxyurea in patients with hemoglobin S/b-thalassemia may be better than those even reported for homozygous hemoglobin S disease, because the synthesized g-chains not only inhibit the sickling process, but they also neutralize the noxious effects of the excess a-chains and cut down on ineffective erythropoiesis. [91][92][93][94][95] Co-inheritance of a-thalassemia was described as a predictor of good response in some studies, 44,77,96 but it was found to have no effect in others. 49,68,85 Homozygosity for the XmnI polymorphism (2158C.…”

-Thalassemia Intermedia: A Clinical Perspective

“…Clinical experience suggests that induction of fetal hemoglobin production using hydroxycarbamide is associated with increases in total hemoglobin levels of 1 g/dL, a decrease in transfusion demand, and amelioration of certain disease complications like PHT, although a decrease in efficacy on long-term therapy is noted (Panigrahi et al 2005;Karimi et al 2010bKarimi et al ,c, 2011Rigano et al 2010;Taher et al 2010c;Amoozgar et al 2011b). Treatment with hydroxycarbamide may also reduce the incidence of thrombotic events including silent strokes (M Karimi, S Haghpanah, MH Bagheri, et al, unpubl.).…”