Please select the eligibility criteria that correspond to the clinical trial below.
Title: Silent Cerebral Infarct Transfusion Multi-Center Clinical Trial
Brief Summary: The goal of this study is to determine the effectiveness of blood transfusion therapy for prevention of silent cerebral infarct (stroke) in children with sickle cell anemia.


Options:
A: Inclusion Criteria:

1. Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia,HbSOArab)
2. Age range of 4.0-15.99 years, inclusive, at the time of enrollment
3. Documented index (pre-treatment) abnormally high TCD Velocity by Transcranial Doppler ultrasonography. An abnormally high index TCD is defined as TCD V greater than or equal to 200 cm/sec, or abnormally high TCDi V greater than or equal to185cm/sec, or TCD maximum V greater than or equal to 250 cm/sec.
4. At least 12 months of chronic monthly erythrocyte transfusions since the index abnormal TCD examination
5. Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) for the past 6 months before enrollment
6. Parent or guardian willing and able to provide informed consent with verbal or written assent from the child
7. Ability to comply with study related treatments, evaluations, and follow-up

Exclusion Criteria:

1. Completed overt clinical stroke or TIA
2. Inability to obtain TCD velocities due to anatomical abnormalities such as a) Inadequate bone windows b) Previous revascularization procedures (e.g., EDAS)
3. Known severe vasculopathy or moya-moya disease on brain MRA
4. Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following: a) Multiple RBC alloantibodies making cross-matching difficult or impossible b) RBC autoantibodies making cross-matching difficult or impossible c) Religious objection to transfusions that preclude their chronic use d) Non-compliance with transfusions over the past 6 months before enrollment (temporary exclusion)
5. Inability to take or tolerate daily oral hydroxyurea, including a) Known allergy to hydroxyurea therapy b) Positive serology to HIV infection c) Malignancy d) Current lactation e) Previous stem cell transplant or other myelosuppressive therapy
6. Clinical and laboratory evidence of hypersplenism (temporary exclusions): a) Palpable splenomegaly greater than 5cm below the left costal margin AND b) Transfusion requirement greater than 250 mL/kg over the previous 12 months
7. Abnormal laboratory values at initial evaluation (temporary exclusions): a) Pre-transfusion hemoglobin concentration less than 8.0 gm/dL b) WBC count less than 3.0 x 10\^9/L c) Absolute neutrophil count (ANC) less than 1.5 x 10\^9/L d) Platelet count less than 100 x 10\^9/L e) Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL
8. Current participation in other therapeutic clinical trials
9. Current use of other therapeutic agents for sickle cell disease (e.g., arginine, decitabine, magnesium). Subjects must have been off hydroxyurea for at least 3- months prior to enrollment.
10. Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the CI makes participation ill-advised.
11. Inability or unwillingness to complete required screening and exit studies, including TCD ultrasonography, brain MRI/MRA, liver MRI and blood tests.
12. A sibling enrolled in TWiTCH
13. Pregnancy or unwillingness to use a medically acceptable form of contraception if sexually active (male OR female).
B: No eligibility criteria
C: Inclusion Criteria:

* Sickle cell anemia patients (SS/Sb0)
* \< 15 years old
* History of abnormal transcranial doppler (TCD) (≥ 200 cm/sec)
* Siblings from the same parental couple
* Parents amenable to Human Leucocyte Antigen (HLA) typing, SCT if an HLA-identical sibling is available or to long-term transfusion program

Exclusion Criteria:

* Sickle cell patients older than 15 years
* no history of abnormal transcranial doppler (TCD) (≥ 200 cm/sec)
* no sibling from the same parental couple
* parents averse to HLA typing, SCT if an HLA-identical sibling is available or to long-term transfusion program
D: INCLUSION:

* Patient must have sickle cell anemia (hemoglobin SS) or sickle beta thalassemia (hemoglobin SB) as confirmed at the local institution.
* Participating institutions must submit documentation of the diagnostic hemoglobin analysis to the Statistical and Clinical Coordinating Centers to confirm the diagnosis of sickle cell anemia prior to randomization.
* Patient must be 5 through 14 years of age.
* Patient must have a cerebral infarct documented by MRI scan as read by the neuroradiology panel.
* Informed consent with assent in accordance with the institutional policies (institutional Institutional Review Board approval) and Federal guidelines (approved by the United States Department of Health and Human Services) must be signed by the patient's legally authorized guardian acknowledging written consent to join the study. When suitable, patients will be requested to give their assent to join the study.

EXCLUSION:

* Patient with a history of a focal neurologic event lasting more than 24 hours with medical documentation or a history of prior overt stroke.
* Patients with a transcranial doppler (TCD) study with a time-averaged mean velocity greater than 200 cm/sec verified by the study radiologist.
* Patients with other neurological problems, such as neurofibromatosis, lead poisoning, or tuberous sclerosis.
* Patients with HIV infection.
* Pregnancy.
* Patients who received treatment with anti-sickling drugs or hydroxyurea within 3 months or anticipate receiving anti-sickling drugs or hydroxyurea during the course of the study.
* Abnormal kidney function (creatinine \> 2x upper limit of normal).
* Patients on chronic blood transfusion therapy for other reasons.
* Patients judged not likely to be compliant by his/her hematologist and local nurse coordinator based on previous compliance in clinic appointments and following advice. Specifically, families that have missed at least two appointments without notification within 12 months prior to the trial or parents of potential patients that have been reported for medical or education neglect are not eligible for this trial.
* Patients unable to receive blood transfusion because of alloimmunization.
* Patients with permanent or semi-permanent metallic (braces on teeth) structures attached to their body. Such patients cannot obtain a MRI of the head to assess the presence of silent cerebral infarcts.
* Siblings randomized in the trial.

Answer: D