Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ<sup>+</sup> thalassemia with IVS1‐5(G→C) mutation

Dehury, Snehadhini; Purohit, Prasanta; Patel, Siris; Meher, Satyabrata; Kullu, Bipin Kishore; Sahoo, Lulup Kumar; Patel, Neel; Mohapatra, Anjali; Das, Kunal; Patel, Dilip Kumar

doi:10.1002/pbc.25391

Cited by 19 publications

(23 citation statements)

References 40 publications

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“…Significant decreases in LDH, TB, DB, and IB were seen among SCA-HU + patients, suggesting an improvement in the hemolytic profile. These findings are supported by results reported by Dehury et al, who also observed reduced levels of LDH and TB in association with HU use in HbS β + thalassemia [ 37 ].…”

Section: Discussionsupporting

confidence: 88%

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

et al. 2018

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This study investigated associations between SNPs in genes encoding metabolizing drug enzymes and laboratory parameters in sickle cell anemia patients under hydroxyurea (SCA-HU+). We evaluated hematologic and biochemical parameters by electronic methods and SNPs by PCR-RFLP and multiplex PCR in 35 SCA-HU+ patients and 67 SCA-HU− patients. The HbS, total cholesterol, lactate dehydrogenase, aspartate aminotransferase, total bilirubin and fractions levels, and leukocyte, eosinophil, monocyte, and erythroblast counts were reduced in SCA-HU+ patients (p < 0.05). Moreover, they presented higher HbF, C-reactive protein, and ferritin levels and elevated MCH and MCV values (p < 0.05). Genotype frequencies of variants GA + AA of MPO −463G>A and c1c2 + c2c2 of CYP2E1 −1293G>C/−1053C>T were higher in SCA-HU+ patients (p < 0.05). Independent associations were found between the variant A allele and lower total cholesterol, between c2 allele and low alpha-1 antitrypsin and between the null GSTT1 variant and high indirect and total bilirubin in SCA-HU+ patients. In SCA-HU− patients, independent associations were found between the variant A allele and high uric acid and between c2 allele and high urea. Our results suggest that SNPs MPO −463G>A, CYP2E1 −1293G>C/−1053C>T, and GSTT1 can be associated with alterations in lipid, inflammatory, renal, hemolytic, and hepatic profiles. However, further studies are needed to elucidate these associations.

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Section: Discussionsupporting

confidence: 88%

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

et al. 2018

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“…The use of hydroxyurea in SCA is especially attractive for low‐resource settings because of its ease of oral administration, potential for reducing medical cost, and safety profile . In the SCATE study, toxicities from hydroxyurea were uncommon and no different than reported in other pediatric populations (<10% severe neutropenia and reticulocytopenia) . Other adverse events during the study (neurological and non‐neurological) were also rare and not observed in any greater frequency than prior studies .…”

Section: Discussionmentioning

confidence: 81%

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

et al. 2015

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Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was an NHLBI-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0-thalassemia (1), and HbSD (1), median age 5.4 years (range, 2.7-9.8)]. Due to slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI 0 to 35%) in the hydroxyurea arm and 47% (95% CI 6 to 81%) in observation arm at 15 months (p=0.16). In post-hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities, compared to observation (0% versus 50%, p=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 versus +10.2 cm/sec, p=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities.

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“…Currently, more than 200 causative molecular defects have been described so far in the β-globin gene causing β-thalassemia and also relation of some mutations have been found which respond to hydroxyurea 23 – 25 . Previously it was identified that the metabolite profile of β-thalassemia patients significantly differs from healthy 26 .…”

Section: Introductionmentioning

confidence: 99%

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern

Iqbal

Ansari

Parveen

et al. 2018

Sci Rep

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Augmentation of fetal hemoglobin (HbF) production has been an enduring therapeutic objective in β-thalassemia patients for which hydroxyurea (HU) has largely been the drug of choice and the most cost-effective approach. A serum metabolomics study on 40 patients with β-thalassemia prior to and after administration of HU was done along with healthy controls. Treated patients were divided further into non-responders (NR), partial (PR) and good (GR) per their response. 25 metabolites that were altered before HU therapy at p ≤ 0.05 and fold change >2.0 in β-thalassemia patients; started reverting towards healthy group after HU treatment. A prediction model based on another set of 70 HU treated patients showed a good separation of GR from untreated β-thalassemia patients with an overall accuracy of 76.37%. Metabolic pathway analysis revealed that various important pathways that were disturbed in β-thalassemia were reverted after treatment with HU and among them linoleic acid pathway was most impactfully improved in HU treated patients which is a precursor of important signaling molecules. In conclusion, this study indicates that HU is a good treatment option for β-thalassemia patients because in addition to reducing blood transfusion burden it also ameliorates disease complications by shifting body metabolism towards normal.

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Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ⁺ thalassemia with IVS1‐5(G→C) mutation

Abstract: In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ(+) -thalassemia in resource poor setting.

Cited by 19 publications

References 40 publications

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern

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Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ+ thalassemia with IVS1‐5(G→C) mutation

Abstract: In view of easy affordability, better acceptability, minimal toxicity, the need of infrequent monitoring and its potential effectiveness, low and fixed dose of hydroxyurea is suitable for treatment of patients with HbSβ(+) -thalassemia in resource poor setting.

Cited by 19 publications

References 40 publications

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Sickle Cell Anemia Patients in Use of Hydroxyurea: Association between Polymorphisms in Genes Encoding Metabolizing Drug Enzymes and Laboratory Parameters

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

Hydroxyurea Treated β-Thalassemia Children Demonstrate a Shift in Metabolism Towards Healthy Pattern

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Low and fixed dose of hydroxyurea is effective and safe in patients with HbSβ⁺ thalassemia with IVS1‐5(G→C) mutation