SCD-Haplo: A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease

Sickle cell anemia is an inherited form of anemia, a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout the body. These patients are at increased risk of death, stroke, frequent pain crises, acute chest syndrome as well as chronic conditions including: lung damage, retinopathy, kidney damage, leg ulcers, and pulmonary hypertension.

There's no cure for most people with sickle cell anemia. However, treatments can relieve pain and help prevent co-morbid conditions associated with sickle cell anemia. Hydroxyurea is the only FDA approved drug to help alleviate symptoms associated with sickle cell disease. The mortality rate is still high in patients using hydroxyurea and a significant percentage of patients still have aggressive disease despite the hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of many of the complications of sickle cell disease such as pulmonary hypertension.

Historically, stem cell transplantation in sickle cell disease was mainly done in the pediatric population. The options were more limited for adults with sickle cell disease with aggressive disease despite hydroxyurea. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Alloimmunization refers to the production of antibodies which occurs in up to 50% of patients with sickle cell disease who are on chronic transfusion therapy making further transfusions difficult with a high potential for hemolytic transfusion reactions.

Recently the use of a non-myeloablative stem cell transplantation regimen (relying on immunotherapy instead of chemotherapy) for sickle cell disease in adults showed 88% engraftment rates (30 out of 34 patients) with no GVHD and 0% mortality. However, these transplants used only fully HLA-matched siblings, which are unavailable to all but approximately 14-28% of patients who could benefit from such a transplant at UIC.

A recent study at Johns Hopkins carried out a similar haploidentical (half matched) transplant with 14 sickle cell patients who lacked fully HLA-matched donors. Approximately two years following transplant, 57% of patients successfully engrafted (8 or 14 patients). There were no deaths and only one episode of acute GVHD of the skin which resolved without therapy.