Dataset Information

Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

ABSTRACT: Transcranial Doppler (TCD) detects stroke risk in patients with sickle cell anemia (SCA). Hydroxyurea therapy has the ability to induce increased levels of fetal hemoglobin in sickle cells thus decreasing tendency for red cell sickling. This study aimed to evaluate TCD findings in SCA patients on hydroxyurea and correlate the time-averaged mean velocity (TAMV) with their hematological parameters. Forty SCA patients of both sexes, aged 16-22 years with no history of stroke were screened with TCD for an elevated TAMV, divided into: Group T (20 patients on blood transfusion); and Group H (20 patients on daily hydroxyurea). For all, full medical history, clinical examination, hemoglobin, hematocrit, leukocytes, platelets, fetal hemoglobin and sickling test, in addition TCD to describe the pattern of cerebral blood flow abnormalities were done. TAMV in all cerebral arteries were significantly higher in Group T than Group H, the highest TAMV (147.5 ± 57.09 cm/s) was found in the right middle cerebral artery and correlated negatively with hematocrit in Groups H (P < 0.001). There were 2 (10%) abnormal TAMV results and 5 (25%) conditional in Group T, while all results were normal in Group H. Hydroxyurea therapy may lower TCD velocities and prevent the risk of primary stroke in SCA patients.

SUBMITTER: Moeen SM

PROVIDER: S-EPMC5786611 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

Moeen Sawsan M SM Thabet Ahmad F AF Hasan Hosam A HA Saleh Medhat A MA

Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 20170408 1

Transcranial Doppler (TCD) detects stroke risk in patients with sickle cell anemia (SCA). Hydroxyurea therapy has the ability to induce increased levels of fetal hemoglobin in sickle cells thus decreasing tendency for red cell sickling. This study aimed to evaluate TCD findings in SCA patients on hydroxyurea and correlate the time-averaged mean velocity (TAMV) with their hematological parameters. Forty SCA patients of both sexes, aged 16-22 years with no history of stroke were screened with TCD ...[more]

PMID: 29398806

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Project description:ImportanceIn children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown.ObjectiveTo determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA.Design, setting, and participantsNonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor.ExposuresMSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching.Main outcomes and measuresThe primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years.ResultsSixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001).Conclusions and relevanceAmong children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up.Trial registrationClinicalTrials.gov Identifier: NCT01340404.

Project description:For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions.TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4-16 years and had abnormal TCD flow velocities (? 200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307.Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140-146) in children who received standard transfusions and 138 cm/s (135-142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10-8·98). Non-inferiority (p=8·82?×?10(-16)) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions).For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke.National Heart, Lung, and Blood Institute, National Institutes of Health.

Dataset Information

Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

Publications

Lower Transcranial Doppler Flow Velocities in Sickle Cell Anemia Patients on Hydroxyurea: Myth or Fact.

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