Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Multicenter Study Comparing the Results of Allogeneic Stem Cell Genoidentical in Children With Sickle Cell Anemia and Cerebral Vascular Disease Detected by Transcranial Doppler
Brief Summary: The aim of this study is to demonstrate that cerebral velocities assessed by transcranial doppler (TCD) are more significantly decreased by SCT than by long-term transfusion program A multicenter, national, non-randomized, prospective study of paired cohort will be conducted, with 2 groups of exposed (SCT) and non-exposed (TP) patients.


Options:
A: Inclusion Criteria:

* Pediatric subjects with severe forms of sickle cell anemia (HbSS, HbSβ0 thalassemia, HbSOArab)
* Age range of 5.0-18.9 years, inclusive, at the time of study entry
* Initial (primary) completed overt clinical stroke after the age of one year (12 months) with documented infarction on brain computed tomography (CT) or magnetic resonance imaging (MRI)
* At least 18 months of chronic monthly erythrocyte transfusions since primary stroke
* Transfusional iron overload, defined as a previously documented liver iron concentration (LIC) greater than or equal to 5.0 mg Fe per gram of dry weight liver or serum ferritin greater than or equal to 500 ng/mL on two independent measurements
* Adequate monthly erythrocyte transfusions with average HbS less than or equal to 45% (the upper limit of the established academic community standard) in the 6 months prior to study entry
* Parent or guardian willing and able to provide informed consent with verbal or written assent from the child (less than 18 years of age) or subject willing and able to provide informed consent (older than 18 years of age)
* Ability to comply with study-related treatments, evaluations, and follow-up

Exclusion Criteria:

* Inability to receive or tolerate chronic red blood cell (RBC) transfusion therapy, due to any of the following:

  1. Multiple RBC alloantibodies making cross-matching difficult or impossible
  2. RBC autoantibodies making cross-matching difficult or impossible
  3. Religious objection to transfusions that preclude their chronic use
  4. Non-compliance with transfusions in the 6 months prior to study entry (temporary exclusion)
* Inability to take or tolerate daily oral hydroxyurea, due to any of the following:

  1. Known allergy to hydroxyurea therapy
  2. HIV infection
  3. Cancer
  4. Pregnant or breastfeeding
  5. Previous stem cell transplant or other myelosuppressive therapy
* Clinical and laboratory evidence of hypersplenism, due to any of the following:

  1. Palpable splenomegaly greater than 5 cm below the left costal margin and
  2. Transfusion requirement greater than 250 mL/kg in the 12 months prior to study entry
* Abnormal laboratory values at initial evaluation (temporary exclusion):

  1. Pre-transfusion hemoglobin concentration less than 7.0 gm/dL
  2. White blood cell (WBC) count less than 3.0 x 109/L
  3. Absolute neutrophil count (ANC) less than 1.5 x 109/L
  4. Platelet count less than 100 x 109/L
  5. Serum creatinine more than twice the upper limit for age OR greater than or equal to 1.0 mg/dL
* Current participation in other therapeutic clinical trials
* Current use of other therapeutic agents for SCA (e.g., arginine, decitabine, magnesium)
* Any condition or chronic illness, such as a positive tuberculin (PPD) test, which in the opinion of the study physician makes study participation ill-advised
* Inability or unwillingness to complete required screening studies, including blood tests, brain MRI/magnetic resonance angiography (MRA), and liver biopsy
* A sibling enrolled in SWiTCH
B: 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
C: Inclusion Criteria:

* Majority fetal and sickle (FS or SF) hemoglobin pattern confirmed centrally by electrophoresis (screening may begin at 7 months of age)

Exclusion Criteria:

* Chronic transfusion therapy
* Cancer
* Less than 5th percentile (10th percentile for the pilot study) height, weight, or head circumference for age
* Severe developmental delay (e.g., cerebral palsy or other mental retardation, Grade III/IV intraventricular hemorrhage)
* Stroke with neurological deficit
* Surgical splenectomy
* Participating in other clinical intervention trials
* Probable or known diagnosis of Hemoglobin S-Hereditary Persistence of Fetal Hemoglobin
* Known hemoglobin S-beta plus thalassemia (hemoglobin A present)
* Any condition or chronic illness, which in the opinion of the principal investigator, makes participation unadvised or unsafe
* Inability or unwillingness to complete baseline (pre-enrollment) studies, including blood or urine specimen collection, liver-spleen scan, abdominal sonogram, neurological examination, neuropsychological testing, or transcranial Doppler ultrasound (interpretable study not required, but confirmed velocity greater than 200 cm/sec results in ineligibility)
* Previous or current treatment with hydroxyurea (HU) or another anti-sickling drug
* The following exclusion criteria are transient; patients can be re-evaluated for eligibility:

  1. Hemoglobin less than 6.0 gm/dL
  2. Reticulocyte count less than 80,000/cu mm if hemoglobin is less than 9 gm/dL
  3. Neutrophil count less than 2,000/cu mm
  4. Platelet count less than 130,000/cu mm
  5. Blood transfusion in the 2 months prior to study entry unless HbA is less than 10%
  6. ALT greater than twice the upper limit of normal
  7. Ferritin less than 10 ng/ml
  8. Serum creatinine greater than twice the upper limit of normal for age
  9. Bayley standardized mental score below 70
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: B