Treatment of Adult Patients With Hemoglobin SC Disease (SCYTHE)
Treatment of Adult Patients With Hemoglobin SC Disease (SCYTHE)
Sickle cell disease (SCD), specifically hemoglobin SC disease (HbSC), is a subtype of sickle
 cell disease with typically higher hemoglobin and milder or later disease complications.
 Sickle cell disease is a disorder in which red blood cells (RBCs) are abnormally shaped. This
 can result in painful episodes, serious infections, and damage to body organs. One medication
 used to treat sickle cell disease is hydroxyurea.

 Hydroxyurea therapy offers significant benefits for infants, children, and adolescents with
 sickle cell anemia. These include a reduction in the frequency of pain crises and acute chest
 syndrome (inflammation of the lungs). Hydroxyurea has been given to many HbSC patients but
 HbSC patients were not included in the large clinical trials used to test hydroxyurea in SCD,
 so less is known about how HbSC patients respond to hydroxyurea.

 The purpose of this research study is to see if hydroxyurea, a medication given to many
 patients with the most common type of sickle cell, those who are homozygous for the sickle
 mutation (HbSS), helps individuals who have HbSC. The investigators will see if it helps by
 giving a questionaire when the medication is started, and then every two months at a clinic
 visit. The questionaire, called the AdultsQLTM 3.0 Sickle Cell Disease Module, measures
 quality of life. The investigators will also see how hydroxyurea changes laboratory test
 numbers, and blood thickness.
Patients will be recruited from the patient population followed at the Texas Children's
 Cancer and Hematology Centers (TCC/HC)/Baylor College of Medicine (BCM) and the University of
 Texas Houston Hematology Center. To be eligible to participate in this study, patients must
 have HbSC disease, have experienced a sickle cell disease related complication, or have a
 score of 80 or lower on the AdultQLTM Sickle Cell Disease Module 3.0. This questionnaire will
 be offered to all patients with HbSC seen in our clinic that consent to this study. Patients
 must also agree to clinic visits every two months, and to phlebotomy, or blood removal after
 6 months on the study if they meet criteria for phlebotomy.

 If the patient is a sexually active female, they will be offered birth control. If the
 patient chooses not to initiate effective birth control, they will be tested at their
 scheduled visit with a urine pregnancy test. If the patient becomes pregnant they will be
 removed from the study.

 Patients will be assessed in clinic every two months after starting treatment. Hydroxyurea
 will be started at 10 mg/kg/day, and increased by 5 mg/kg/day if needed to a maximum
 tolerated dose (MTD) of 35/mg/day. The most common side effect of the drug is a drop in
 infection fighting cells, or white blood cells, so the medication will be started at a low
 dose and the dose will be increased only if it is safe to do so. After 6 months at MTD on the
 study, patients will be evaluated for their response to hydroxyurea. If they have not reached
 their MTD after 6 months their time on the study will be increased to allow for 6 months
 observation at MTD. The minimum time the patients will be on the study is 12 months after
 starting hydroxyurea therapy with an option to participate in a 2 year observation study
 following the end of the study.

 If the patients have had minimal or no benefit from the medication, monthly phlebotomy will
 be added to their treatment regimen, at 7-10 ml/kg. The first phlebotomy volume will be 7
 ml/kg, but may be increased to 10 ml/kg to obtain the target Hb of 9-10 g/dL. Patients will
 remain on hydroxyurea and phlebotomy for six months. If their Hb is less than or equal to 9.0
 g/dL on their phlebotomy visit, phlebotomy will not be performed and their phlebotomy visits
 will be spaced every 2 months. Patients time on the study will be increased to allow for 6
 months observation to ensure that there is no late harmful effects. The minimum time patients
 will be on the study is 18 months after starting phlebotomy with an option to participate in
 a 2 year observation study following the end of the study.

 Patients will be asked to allow the investigators to review information from their medical
 records at the start of the study, and throughout the study. If the patient would like to
 participate in the two year follow-up, their records will be reviewed during that period as
 well.
Inclusion Criteria:

 -  Diagnosis of HbSC disease

 -  Score of 80 or lower on the AdultQLTM 3.0 Sickle Cell Disease Module, or any disease
 related complication, including, but not limited to, one or more pain events per year,
 proliferative sickle retinopathy, avascular necrosis, cholelithiasis, or any
 thrombotic event. If the subject has a score >80, they may still enroll on the trial,
 and be analyzed for secondary endpoints. They will be excluded from analysis of the
 primary endpoint.

 Exclusion Criteria:

 -  Failure to meet inclusion criteria

 -  Hydroxyurea usage in the last 3 months.

 -  Chronic RBC transfusion therapy

 -  Packed red blood cell transfusion in the last 3 months (temporary exclusion).

 -  Pregnancy, or refusal to use medically effective birth control if female and sexually
 active.

 -  Current phlebotomy therapy