Children with sickle cell disease often face severe pain, organ damage, recurrent strokes and repeated, prolonged hospital stays. Although there are medical interventions that can lessen the symptoms, there is no cure.
In an effort to change that, researchers at Washington University School of Medicine in St. Louis are leading a nationwide, multicenter clinical trial to determine the effectiveness of transplanting blood stem cells from unrelated donors into children with severe sickle cell disease.
The Phase II clinical trial is led by Shalini Shenoy, M.D., associate professor of pediatrics at Washington University School of Medicine in St. Louis and medical director of the pediatric bone marrow transplant program at St. Louis Children’s Hospital, and co-principal investigator Naynesh Kamani, M.D., of Children’s National Medical Center in Washington, D.C. Children with severe sickle cell disease who qualify will receive a blood stem cell transplant from either bone marrow or umbilical cord blood to replace their own red blood cells. The trial seeks to enroll 45 patients ages 3-16 with symptoms of severe sickle cell disease, such as strokes, frequent pain or repeated episodes of acute chest syndrome, a painful obstruction of the blood vessels in the lungs.
To prepare to receive blood stem cells from a donor, patients must go through an intense treatment called conditioning to reduce production of their own blood cells and prevent their immune system from rejecting donor cells. For this trial, patients will receive reduced-intensity conditioning that could help them better tolerate the transplant with fewer toxic side effects of conditioning, such as infertility. As part of the trial, researchers will determine if the reduced-intensity conditioning treatment will allow the healthy donor blood stem cells to grow successfully in the patient.
Sickle cell disease is an inherited blood disorder affecting red blood cells, which contain hemoglobin, the substance that carries oxygen from the lungs to all parts of the body. In patients with this disease, red blood cells contain an abnormal type of hemoglobin that causes the normally round, flexible red blood cells to become stiff and sickle- or crescent-shaped. The sickle cells can’t pass through tiny blood vessels, which can prevent blood from reaching some tissues and can result in tissue and organ damage, pain and stroke. In addition, sickle cells are short lived and lead to a shortage of red blood cells and anemia.
Sickle cell disease affects about 70,000 people in the United States and occurs in about 1 of every 500 African-American births and 1 of every 1,000 to 1,400 Hispanic-American births. Blood transfusions and bone marrow transplants have been shown to be effective treatments by replacing sickle cells with healthy red blood cells. However, blood transfusions have to be repeated regularly and can cause iron overload. Bone marrow transplants have a 10 percent mortality rate because of the possibility of infections, organ damage or graft-versus-host disease as donor cells work against the patient.
A healthy sibling who has the same tissue type as the patient is the best donor for a blood stem cell transplant, but few patients have such a suitable donor in their family. “So using unrelated donors who are close matches is the next best option if transplant is to be considered for this disease,” Shenoy says. “Though, the probability of finding a good match is lower for minorities due to fewer minority donors registered in the National Marrow Donor Program, we think we can certainly find a good match for several of our patients,” Shenoy says.
Physicians should only consider stem cell transplantation in children with severe cases of sickle cell disease and who have a closely matched donor, according to Shenoy.
“You only take a patient to transplant if the risk/benefit ratio is better by offering them the transplant,” she says. “Right now, blood stem cell transplant is the only potential curative therapy for severe sickle cell disease.”
In the preliminary trial, about 10 patients with sickle cell disease nationwide had successful blood stem cell transplants. The promising results generated interest in expanding the trial to a larger group of patients.
“For a successful outcome we need the red blood cells from the patient to be replaced by donor red cells without complications such as major graft-versus-host disease or organ damage,” Shenoy says. “We think we have a good chance. If the donor red cells are rejected, we expect that the patient will recover his or her own red cells and remain at baseline with the disease.”
The trial is supported by the Bone Marrow Transplant Clinical Trials Network of the National Heart, Lung, and Blood Institute, the National Marrow Donor Program, the Sickle Cell Disease Clinical Research Network and the Pediatric Blood and Marrow Transplant Consortium.
For more information about participating in the trial or about becoming a donor, contact Shenoy or Yvonne Barnes at (314) 454-6018 or visit the Bone Marrow Transplant Clinical Trials Network Web site at https://web.emmes.com/study/bmt.
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.