JOHNS HOPKINS (US) — Even partially matched bone marrow transplants can eliminate sickle cell disease in some patients, ridding them of debilitating symptoms and the need for pain medication and blood transfusions.
After a preliminary clinical trial, scientists say the use of bone marrow that is not fully matched to the recipient could potentially help make marrow transplants available to a majority of sickle cell patients who need them.
As reported online in the journal Blood, after a median follow-up of two years, transplants successfully eliminated sickle cell disease in 11 of 17 patients. Three were fully matched to their donors and eight received half-matched donor marrow. All 11 patients are free of painful sickle cell crises and 10 no longer have anemia. There were no deaths and no unexpected toxicities.
Six of the 11 successful patients (all half-matched) have been able to stop taking immunosuppressive drugs, although some still require narcotics for chronic pain because of sickle cell-related organ damage. Blood tests on the six patients show that their red cells are now completely derived from donor marrow.
Patients with severe sickle cell disease suffer from intractable pain, organ damage and shortened life spans. The inherited disorder is caused by a genetic mistake in oxygen-carrying hemoglobin molecules in red blood cells. The flaw stiffens red cells, shaping them into pronged “sickles” that clump and stick into blood vessel walls, cutting off blood and oxygen to tissues and organs throughout the body.
SCD occurs in approximately one in 400 African Americans and in Caucasians, though rarely. An estimated 100,000 people in the United States currently live with the disease. Most patients die before age 50; many suffer poor quality of life with frequent episodes of “off-the-charts” pain and an increased risk for kidney failure, stroke, deep-vein thrombosis, and lung disease.
Treatments include blood transfusions and a drug, hydroxyurea. Many patients use narcotics to control severe pain and have repeat hospitalizations. Bone marrow transplants have cured some cases, but matching donors are rare and the procedure itself poses risk.
“We’re trying to reformat the blood system and give patients new blood cells to replace the diseased ones, much like you would replace a computer’s circuitry with an entirely new hard drive,” says Robert Brodsky, director of hematology at Johns Hopkins University and one of the study’s investigators.
“While bone marrow transplants have long been known to cure sickle cell disease, only a small percentage of patients have fully matched eligible donors.”
National registries often are of little help in finding donors for sickle cell patients, because most of those in need are African American or members of other minorities who are vastly underrepresented in registries, researchers say.
Seeking to overcome the shortage of donors, investigators at Johns Hopkins have developed techniques, recently tested in leukemia and lymphoma patients, to transplant with bone marrow that is half-identical—”haploidentical”—to the patient’s tissue type. Half-matched bone marrow can be obtained from parents, children, and most siblings and is extracted by needle from the hip bone.
For the SCD study, the team screened patients to find bone marrow donors with either half-identical or fully matched tissue. Each transplant candidate had experienced many severe pain crises or significant organ problems or had failed to improve with hydroxyruea. The team found donors for 17 patients: 14 were half-identical and three were fully matched siblings. The youngest patient was 15, the oldest 46.
Four of the investigators are listed as inventors on a patent application related to the procedure. One has served on a scientific advisory board for Hemaquest Pharmaceuticals Inc., a company developing a drug for sickle cell disease.
Funding was provided by the National Cancer Institute and Sistema Nacional de Investigadores in Mexico.
Source: Johns Hopkins University