Stem cell transplant reverses Sickle Cell Disease in adults

There is no widely available cure for sickle cell disease. Some children with the disease have been successfully treated with blood, stem cell, or bone marrow transplants. This approach, though, was thought to be too toxic for use in adults. High doses of chemotherapy are used to destroy all of a child’s bone marrow, which is then replaced with marrow from a donor. Stem cell recipients typically need to take immunosuppressants for months to a few years. These medications can cause serious side effects.

In earlier studies, transplant recipients were found to have a mix of their own and the donor’s cells in their blood. Despite the mix, sickle cell disease was reversed. Based in part on these findings in children, as well as other preliminary work, a team at NIH’s Clinical Center in Bethesda, Md., set out to test a modified transplant procedure in adults with sickle cell disease. The clinical trial was conducted by researchers from NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Heart, Lung, and Blood Institute (NHLBI). Results appeared online on July 1, 2014, in the Journal of the American Medical Association.

Thirty patients, ages 16 to 65, with severe sickle cell disease enrolled in the study between 2004 and 2013. The patients first underwent a less toxic regimen to kill off some of their marrow cells. Next, they underwent a stem cell transplant, receiving cells donated by a healthy brother or sister.

The team found that the stem cell transplant reversed the disease in 26 of 30 patients (87%). The patients had normal hemoglobin, fewer hospitalizations, and lower use of narcotics to treat pain from the disease. The patients didn’t experience graft-versus-host disease—in which donor cells attack the recipient—after a median follow up of 3.4 years. Fifteen patients successfully stopped immunosuppression medications a year after the transplant. The treatment was unsuccessful in four patients, and some complications, such as infections, occurred.

“Side effects caused by immunosuppressants can endanger patients already weakened by years of organ damage from sickle cell disease,” says senior author Dr. John Tisdale. “Not having to permanently rely on this medication, along with use of the relatively less-toxic partial stem cell transplant, means that even older patients and those with severe sickle cell disease may be able to reverse their condition.”

The researchers continue to follow the patients to track the success of the approach.

Chicago native Ieshea Thomas, in 2012, was the first Midwest patient to receive a successful stem cell transplant to cure her sickle cell disease without chemotherapy in preparation for the transplant.

University of Illinois Hospital & Health Sciences System physicians performed the procedure using medication to suppress her immune system and one small dose of total body radiation right before the transplant.

The transplant technique is relatively uncommon and is a much more tolerable treatment for patients with aggressive sickle cell disease who often have underlying organ disease and other complications, says Dr. Damiano Rondelli, professor of medicine at UIC, who performed Thomas’s transplant.

The procedure initially allows a patient’s own bone marrow to coexist with that of the donor. Since the patient’s bone marrow is not completely destroyed by chemotherapy or radiation prior to transplant, part of the immune defense survives, lessening the risk of infection. The goal is for the transplanted stem cells to gradually take over the bone marrow’s role to produce healthy red blood cells.

Thomas, 33, had her first sickle cell crisis when she was just eight months old. Her disease became progressively worse as an adult, particularly after the birth of her daughter. She has spent most of her adult life in and out of hospitals with severe pain and has relied on repeated red blood cell transfusions. Her sickle cell disease also caused bone damage requiring two hip replacements.

“I just want to be at home with my daughter every day and every night,” said Thomas, who depends on family to help care for her daughter during her frequent hospitalizations.

This type of stem cell transplant is only possible for patients who have a healthy sibling who is a compatible donor.

Thomas’ sister was a match and agreed to donate blood stem cells through a process called leukapheresis. Several days prior to leukapheresis, Thomas’ sister was given drugs to increase the number of stem cells released into the bloodstream. Her blood was then processed through a machine that collects white cells, including stem cells. The stem cells were frozen until the transplant.

At transplant time, one by one, the bags were thawed and hung on an IV pole for infusion into Thomas. The procedure took approximately one hour. Her 13-year-old daughter, Miayatha, was at her bedside.

Six months after the transplant, Thomas was cured of sickle cell disease and no longer required blood transfusions.

“The donor cells have taken over completely, and blood tests show no sickle cell disease,” said Rondelli, director of the blood and marrow transplant program at UI Hospital. Thomas continues to take medication to prevent rejection of the donor stem cells.

About 30 adults have received a similar chemotherapy-free stem cell transplant for sickle cell disease in recent years at NIH. Approximately 85 percent have been cured.

“Sickle cell disease is devastating—both emotionally and physically,” said Dr. Dennis Levinson, a private rheumatologist in Chicago and clinical associate professor of medicine at UIC; he has taken care of Thomas for the past 16 years. “I’ve been terribly frustrated with Ieshea’s disease over the years, and I’ve cared for many other sickle cell patients who have died.”

Levinson says the stem cell transplant provides new hope for patients who often live day-to-day on painkillers and who are often misunderstood by clinicians.

Although these new developments should have patients all over jumping for joy, many are completely unaware of the procedure, are misinformed, or have doctors that haven’t recommended it.

Morgan Todd III, 34, has suffered with sickle cell his entire life, and like Thomas, was constantly in and out of the hospital and never truly able to carry on a normal life.

Todd goes to Synergy Medical Group in Los Angeles to undergo treatment—which includes replenishing his vital fluids and a constant dose of painkillers—from 9:30 a.m. to about 3:30 p.m., three times a week. He believes the treatment does its part, and notes, thankfully, that he hasn’t been hospitalized in three years.

Todd has heard about the new developments in sickle cell treatment, namely stem cell transplant. He says however, that he never looked into it because his doctor, who he has been with for 16 years, told him that he’d only have a 15 percent chance of surviving the procedure.

“That’s worse than playing Russian Roulette,” said Todd. “That’s like having a bullet in every chamber but one and testing fate. So now we don’t really talk about it. I don’t know anyone who has done it. I’d love to meet someone who has done it. I would ask so many questions,” he continued.

Todd admitted that when discussing the procedure with his doctor they never discussed any other options, cost or anything other than the risk. He also stated that because of the trust and familiarity he has with his doctor, he has never bothered to ask for a second opinion.

People with sickle cell disease interested in joining NIH blood stem-cell transplant studies may call or visit the NIH clinical trials registry at www.clinicaltrials.gov for more information.

Sources: Science Daily and NIH.gov.