Stroke With Transfusions Changing to Hydroxyurea (SWiTCH)

Ware, Russell E.; Helms, Ronald W.

doi:10.1182/blood-2011-11-392340

Cited by 334 publications

(263 citation statements)

References 32 publications

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“…However, concerns for the burden associated with chronic blood transfusion therapy led hematologists to consider hydroxyurea therapy as an alternative to periodic blood transfusions. For secondary stroke prevention, the Stroke With Transfusions Switching to Hydroxyurea (SWiTCH) trial randomly allocated children with SCA and stroke to receive either standard treatment (transfusions coupled with chelation) or alternate treatment (hydroxyurea coupled with phlebotomy) [76]. The primary endpoint was a composite of recurrent stroke and liver iron concentration.…”

Section: Stroke Prevention In Scamentioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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Over the past 40 years, public health measures such as universal newborn screening, penicillin prophylaxis, vaccinations, and hydroxyurea therapy have led to an impressive decline in sickle cell disease (SCD)-related childhood mortality and SCD-related morbidity in high-income countries. We remain cautiously optimistic that the next 40 years will be focused on meeting current challenges in SCD by addressing chronic complications of SCD to reduce mortality and improve quality of life in a growing population of adults with SCD in high-income countries, while simultaneously decreasing the disparity of medical care between high and low-income countries.

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Section: Stroke Prevention In Scamentioning

confidence: 99%

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

2015

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“…Stem cell transplantation has a role in the secondary prevention of strokes while preliminary results on hydroxyurea are unfavourable. 34 However, the role of both modalities in the primary prevention of strokes is yet to be determined.…”

Section: Discussionmentioning

confidence: 99%

Discontinuing prophylactic transfusions increases the risk of silent brain infarction in children with sickle cell disease: data from STOP II

Abboud

Yim

Musallam

et al. 2011

Blood

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In the STOP II trial, discontinuation of prophylactic transfusions in high risk children with sickle cell disease (SCD) resulted in a high rate of reversion to abnormal blood-flow velocities on transcranial Doppler (TCD) ultrasonography and strokes. We analyzed data from STOP II to determine the effect of discontinuing transfusions on the development or progression of silent brain infarcts on magnetic resonance imaging (MRI). At study entry, 21 of 79 (27%) patients had evidence of silent infarcts. There were no statistically significant differences in baseline characteristics between patients with normal brain MRI or silent infarcts at study entry. At study end, 3 of 37 (8.1%) patients in the continued-transfusion group developed new brain MRI lesions compared with 11 of 40 (27.5%) in the transfusion-halted group (P ‫؍‬ .03). The total number of lesions remained essentially unchanged decreasing from 25 to 24 in the continuedtransfusion group while increasing from 27 to 45 in transfusion-halted patients. Thus, discontinuation of transfusions in children with SCD and abnormal TCD who revert to low-risk increases the risk of silent brain infarction. Together with data from STOP, these findings demonstrate that transfusions prevent the development of silent infarcts in patients with SCD and abnormal TCD but normal MRA. (Blood. 2011;118(4):894-898) IntroductionEstimates of the prevalence of silent brain infarcts, in children with sickle cell disease (SCD) range from 17% to 35%. [1][2][3][4] Despite the terminology, 'silent infarcts' are clinically significant given their association with subsequent overt stroke and neurocognitive deficits in school-aged children. 2,[5][6][7][8][9] Better understanding of the associated risk factors and efforts to optimize prevention remain essential. Reported risk factors for silent infarction are raised white blood-cell count, anemia, severe vasculopathy, and the SEN ␤-globin haplotype. 4,[10][11] Transfusions have been successfully used to prevent initial or recurrent strokes in SCD. [12][13][14][15][16] To prevent first strokes, the Stroke Prevention Trial in Sickle Cell Anemia (STOP) used prophylactic red-cell transfusions in children who were identified by transcranial Doppler (TCD) ultrasonography as being at high risk for stroke. This strategy reduced the incidence of stroke among such children from 10% per year to Ͻ 1% per year. 15 The STOP study led to recommendations for TCD screening and prophylactic transfusion for children with abnormal velocities on ultrasonography. 17 Among patients with MRI evidence of silent infarction and raised velocities by TCD enrolled in STOP, transfusion also diminished the risk of new silent infarcts. 18 Despite the reduced risk of stroke, the potentially indefinite duration of transfusion aroused concern about adverse effects, especially iron overload. In the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP II) Trial, discontinuation of transfusions in patients whose TCD velocities had normalized (normal TCD) resulted in a hig...

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“…Hydroxyurea was not equivalent to transfusion in the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) trial based on a composite end point ( Table 1). 31 In a cohort of children with SCA, hydroxyurea decreased the rate of recurrent stroke compared with no therapy (Table 2). 21 In adults with HbSb 0 -and HbSb 1 -thalassemia, new ischemic neurologic events occurred on hydroxyurea despite effectively reducing VOC and hospitalizations ( Table 2).…”

Section: Clinical Outcomesmentioning

confidence: 99%

“…Thirteen studies 6, [21][22][23][24][25][26][27][28][29][30][31][32] indicated a goal to increase to maximum tolerated dose (limited by mild myelosuppression), 5 studies increased until clinical or laboratory improvement was observed, [33][34][35][36][37] and 5 studies used fixed dosing at 10 or 20 mg/kg per day. 15,[38][39][40][41] When stated, all studies used a maximum dose of 30 to 35 mg/kg per day.…”

Section: Hydroxyurea Administrationmentioning

confidence: 99%