Efficacy of Hydroxyurea in Transfusion-Dependent Major β-Thalassemia Patients: A Meta-Analysis

Abstract

The present meta-analysis was conducted to determine the efficacy of hydroxyurea in patients with transfusion dependent major β-thalassemia. The present meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines. A systematic search was carried out to evaluate the efficacy of hydroxyurea in patients with transfusion-dependent B-thalassaemia using electronic databases, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. The keywords used to search for relevant studies included "hydroxyurea", "thalassemia", "transfusion-dependent", and "efficacy". Outcomes assessed in the present meta-analysis included transfusion in one year and intervals between transfusions (in days). Other outcomes assessed in the present meta-analysis were fetal hemoglobin (%), hemoglobin (%), and ferritin levels (ng/dl). Total of five studies were included in the analysis enrolling 294 patients with major B-thalassemia. The pooled analysis reported that the mean interval between transfusions was significantly higher in patients receiving hydroxyurea compared to those not receiving hydroxyurea (mean deviation {MD}: 10.07, 95% CI: 2.16, 17.99). Hemoglobin was significantly higher in patients receiving hydroxyurea compared to its counterparts (MD: 1.71, 95% CI: 0.84, 2.57). Patients receiving hydroxyurea had significantly lower ferritin levels compared to those not receiving hydroxyurea ). These findings suggest that hydroxyurea may be a promising and cost-effective alternative to blood transfusions and iron chelation therapies for betathalassemia patients. However, the authors noted that further randomized controlled trials are needed to validate these findings and to determine the optimal dosages and treatment regimens for hydroxyurea in this patient population.

New Synthetic Isoxazole Derivatives Acting as Potent Inducers of Fetal Hemoglobin in Erythroid Precursor Cells Isolated from β-Thalassemic Patients

“…In order to verify the possible impact of c4 in the development of therapeutic approaches for β-thalassemia, we examined the HbF inducing activity of c4 (a) in ErPCs from patients with different genotypes ( Figure 9 A) and (b) in comparison with inducers presently employed in clinical trials ( Figure 9 B). We selected hydroxyurea and rapamycin; hydroxyurea is employed in several clinical trials, such as NCT03183375 and NCT00809042 [ 38 , 39 , 40 , 41 , 42 , 43 ], while rapamycin (sirolimus) is employed in two clinical trials (NCT03877809 (A Personalized Medicine Approach for β-thalassemia Transfusion Dependent Patients: Testing sirolimus in a First Pilot Clinical Trial) and NCT04247750 (Treatment of β-thalassemia Patients with Rapamycin (Sirolimus): From Pre-clinical Research to a Clinical Trial) [ 44 ].…”

“…Currently, hydroxyurea (HU) is the only one approved drug able to induce fetal hemoglobin [ 14 , 18 , 38 , 39 , 40 , 41 ]. However, the side effects (as leukopenia and neutropenia) of the HU treatment, and the fact that it is active only in some patients, attracts limited enthusiasm for the use of this molecule [ 42 , 43 ].…”

“…These cells, isolated from patients with different genotypes ( Figure 3 ), represent an excellent model system for screening HbF inducers that are to be considered in pre-clinical studies for developing therapeutic protocols for β-thalassemia. For this reason, in our study, the biological effects of the isoxazole derivatives were compared with those of two well-known HbF inducers, HU and rapamycin, which are both employed in clinical trials for β-thalassemia [ 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ].…”

Unraveling Impact of Hemoglobin F and A2 Levels: Correlation With Disease Severity and Treatment Response in Transfusion-Dependent Beta-Thalassemia

“…Hence, there is a need for an alternative treatment capable of alleviating symptoms associated with transfusion dependence and therefore iron overload [25]. HU and thalidomide, identified as potent Hb inducers, have been subjected to numerous trials, all of which have demonstrated their effectiveness in increasing Hb levels and reducing transfusion requirements in patients with TDT, whether administered individually or in combination [17,[23][24][25][26][27]. Our findings align with the aforementioned studies, as we observed an overall response rate of 90.1% to treatment (12.9% with HU alone, 0.8% with thalidomide alone, and 86.4% with the combination).…”

Pharmacologic Therapies in Beta Hemoglobinopathies: Fetal Globin Gene Induction in the First Molecular Diseases

“…[59][60][61] Pharmacologic Therapies in Beta Hemoglobinopathies: Fetal Globin Gene Induction in the First Molecular Diseases In some subjects with β-thalassemia intermedia, HU increases HbF, reduces ineffective erythropoiesis, and reduces anemia and marrow fibrosis. [73][74][75][76] In a few patients with thalassemia intermedia treated with low doses of ≤10 mg/kg per day, four days per week, HU increased total Hb levels by preferentially increasing β-globin biosynthesis. 77 Interestingly, the presence of the Xmn-I T/T genotype or the BCL11A rs766432 C allele correlates strongly with response to HU (p <0.001), allowing for targeted selection of patients who are most likely to benefit.…”