The goal of this study is to see if women with sickle cell disease (SCD) experience any difference in their pain while using the birth control injection, Depo-Provera, as compared to when not using this method. Depo-Provera is FDA-approved.

The duration of the study is 6 months with 6-7 in-person visits at the University of Pennsylvania that include a urine pregnancy test, blood draw, and surveys. The study duration is divided into a 3-month "baseline" period, where you would not use any hormonal contraception, and 3 months with the Depo-Provera injection. You would also complete weekly messages that ask about pain and menstrual cycle.

We are seeking women who are between the ages of 18 and 50 who have been diagnosed with SCD, have a regular menstrual cycle, and experience at least one vaso-occlusive pain episode per month.

Individuals with severe sickle cell disease, who are between 18 and 50 years old, may be able to participate. A number of screening tests will be done to determine if subjects can participate. These include review of your past medical history, physical exam, blood and urine tests, pregnancy test, heart ultrasound, electrocardiogram, pulmonary function test, kidney function test, questionnaires, and magnetic resonance imaging (MRI) of the heart and liver. If eligible, blood stem cells will be collected by apheresis.A gene in thesestem cells will thenbe edited to help the stem cells make more fetal hemoglobin. Higher levels of fetal hemoglobin can improve red blood cell sickling. You will then be hospitalized and chemotherapy will be given to empty out the bone marrow. The stem cells, with themodifiedgene, will then be given back to you. You will be followed for side effects and to see if themodifiedgene helps you make healthyred blood cells.

The study will enroll male and female patients between 2 years to 25 years of age with sickle cell disease or beta thalassemia major, who do not have a matched related donor, and their doctor feels their condition should be treated with hematopoietic stem cell transplantation (HSCT).

-For Sickle Cell Disease, individuals must have significant disease.We would consider you for transplant if you have had severe neurologic symptoms including stroke, frequent vaso-occlusive events (examples include pain episodes requiring pain management or acute chest syndrome), or administration of regular and frequent red blood cell transfusions to prevent disease complications.

-For Beta-Thalassemia Major, you would be considered a candidate for transplant if you have genetic test confirming Beta Thalassemia and have required 8 or more transfusions per year in the past two years.

The purpose of this research study is to test a new method of cell processing for stem cell transplants with a closely matched unrelated donor. The new method is called alpha/beta T cell and B cell depletion using a device called CliniMACs. We want to see if this method can reduce some of the complications of the transplant and decrease the time it takes for the new stem cells to establish a new immune system. The use of the CliniMACs device for alpha/beta T and B cell depletion is experimental and is considered research.