A recent study conducted at the Hopkins School of Medicine provides renewed optimism for the treatment of sickle cell disease. Researchers have demonstrated that bone marrow transplants only partially matched to a patient’s tissues can successfully eradicate the disease and the need for lifelong treatment.
Sickle cell disease is characterized by red blood cells that adopt a sickle, or crescent-like shape instead of being rounded and hollow. Red blood cells are normally tasked with carrying oxygen throughout the body via the hemoglobin protein. However, a mutation in the hemoglobin gene creates abnormal red blood cells that are inefficient at transporting oxygen.
The mutation that affects hemoglobin in sickle cell disease is known as a point mutation, where only one amino acid is wrong throughout the extensive sequence that comprises the protein chain. Specifically, the amino acid valine is present in position six instead of glutamic acid.
Hemoglobin is made up of four protein chains—two alpha two beta. The mutation that causes sickle cell disease occurs on the beta chain. If only one of the beta chains is affected with the mutation, a person is considered a carrier. In the event that both chains are affected, a person develops the disease.
Sickle cell disease is a painful and debilitating condition because it affects the body’s overall ability to function. Without enough oxygen to circulate, sickle cell patients often experience pain, anemia, and organ damage. Furthermore, the pointy shape of sickle cells causes them to get stuck in the blood vessels, which can cause bleeding and restricted blood flow to the tissues. Most patients with the disease can live up to age 50 and have a considerably low quality of life.
Sickle cell patients often receive blood transfusions, but one of the most effective treatments against the disease is a bone marrow transplant. Red blood cells are formed in the bone marrow, so a healthy marrow equips sick patients with the machinery to form healthy cells.
When the body and transplant are incompatible, a patient develops graft versus host disease, which causes an immune response. It can be severe and ultimately fatal.
Because of the risk of organ rejection in any transplant procedure, healthcare professionals have thus far been keen on finding perfect matches for sickle cell patients.
However, the shortage of bone marrow matches inspired researchers at Hopkins to try to use bone marrow transplants that are only half matched to the sickle cell patient’s tissues. Such bone marrow is termed “haploidentical,” meaning that it can be obtained from one’s parents, children and most siblings.
The Hopkins team screened 19 patients with severe sickle cell disease in order to find a proper half match. They were able to find donors for 17 out of the 19 patients, 14 of which were half matched and three of which were complete matches.
Before they proceeded with the transplants, the team administered a regimen of immunosuppressant drugs, low toxicity chemotherapy and low dose total body irradiation, in order to decrease the risk of organ rejection.
Following the transplant, the patients received high doses of chemotherapy in order to kill their remaining sickle cells. The specific chemotherapeutic agent that the team used is called cyclophosphamide, and it is unique because it can kill patients’ old , diseased cells without harming the healthy blood cells from the transplant.
Of all the patients, aged 15 to 46, the majority had successful transplants. Specifically, 11 out of 17 were successful, meaning that these patients no longer experience sickle cell related crises. Furthermore, 10 of the patients no longer have anemia and six of the patients are off the immunosuppressant drugs. These six patients were all half matched, and tests on their blood indicate that their blood cells are completely produced from the donor marrow.
The researchers are optimistic that this new transplant method will significantly improve the health of patients who are afflicted with sickle cell disease. They are currently working on different ways to increase the number of stem cells during transplantation and to use other immunosuppressant drugs.