Meta-analysis on effectiveness of hydroxyurea to treat transfusion-dependent beta-thalassemia

Abstract

Objective To determine the efficacy of hydroxyurea therapy on transfusion-dependent beta-thalassemia patients. Methods This study collected articles from databases, applied inclusion and exclusion criteria, and analyzed them for bias. The effects of hydroxyurea on transfusion requirements were categorized according to the following definitions. 'Good responders' were participants who became transfusion independent after treatment. 'Moderate responders' were participants who were still transfusion dependent, however, experienced a significant decline in their transfusion requirements. 'Poor responders' were defined as participants who did not respond to hydroxyurea. Results A total of 13 studies met all the inclusion and exclusion criteria providing a total of 1196 study participants. The weighted average of the odds ratio using the random effect model (P < 0.001) was determined to be 0.493 for good responders, 0.270 for moderate responders, and 0.229 for poor responders. Discussion Until now, there has not been any double-blinded placebo-controlled studies performed looking at the effectiveness of hydroxyurea with this regard, and this substantially limits this meta-analysis. More studies should be conducted to determine whether hydroxyurea preferentially treats particular type of mutations over others. Conclusion This study suggests that hydroxyurea provides some benefit to patients, and therefore, in certain clinical situations, it may be understandable to start a trial therapy of hydroxyurea to qualifying patients. However, a double-blinded placebo-controlled studies should be performed before its efficacy can be considered established.

Modifiers of γ-Globin Gene Expression and Treatment of β-Thalassemia

“…Cytotoxic compounds put an end to actively cycling progenitors and control cellular growth to trigger rapid erythroid-regeneration and the formation of F cells. Cytotoxic drugs such as vinblastine [89], busulfan [90], cytosine arabinoside [91], and hydroxyurea [92][93][94] are known inducers of HbF in humans through this mechanism. Rapid regeneration of erythroid cells allows progenitors with an active eHbF program to be selectively recruited for maturation.…”

Profiling of hydroxyurea‐treated β‐thalassemia/ serum proteome through nano‐LC–ESI–MS/ MS in combination with microsol‐isoelectric focusing

“…Patients with β ‐thalassemia are also frequently treated with HU because of the same genetic variants that contribute to the specific signal transduction pathways, which regulate γ ‐globin expression. Clinical benefits of the use of HU in β ‐thalassemia include better life quality, better growth and increased overall survival (Bayanzay & Khan, ). Despite the advantageous properties of HU in β ‐thalassemia, the mechanism of action is still unclear and needs to be explored at molecular level.…”

Discovery of Novel Fetal Hemoglobin Inducers through Small Chemical Library Screening

“…Currently, hydroxyurea (HU) is the only FDA-approved therapeutic treatment for the induction of HbF in SCD patients [ 13 , 23 ]. With respect to β -thalassemia, in spite of its verified benefits in certain cases, demonstrated by the reach of a transfusion-independent phenotype in patients with β -thalassemia intermedia [ 24 , 25 ], specific approvals for β -thalassemia are lacking. On the other hand, adverse effects and potential toxicity in the case of long-term treatment are expected, and have been described for HU [ 26 , 27 ].…”