Marrow transplants promising as cure for sickle cell

Courtesy by: Post-gazette

When Austin Jones would get a fever, it almost always meant a trip to UPMC Children’s Hospital in Pittsburgh.

But today, thanks to a life-altering bone marrow transplant he got from his older brother five years ago, a fever just means the 10-year-old has to “take some Tylenol, eat some chicken soup and go lie down,” said his father, Anthony Jones Sr. of Indiana, Pa.

Austin Jones was born with sickle cell anemia, a hereditary blood disorder that disproportionately affects African-Americans, can cause pain, organ damage, high blood pressure and strokes, and shortens life spans by 25 to 30 years.

He is one of seven patients cited in a new study by doctors at Children’s and three other institutions that could pave the way for wider use of bone marrow transplants to cure sickle cell anemia.

Doctors have known for years that bone marrow transplants are the only way to cure sickle cell for now, but the key to the new study is that it uses a much less intensive regimen of chemotherapy and radiation to prepare patients for the transplant.

In conventional marrow transplants, doctors use heavy doses of chemo and radiation to completely wipe out the patient’s blood-producing marrow, in hopes the transplanted cells will take over that function.

The risk, though, is that some patients will die from infections or an attack on their bodies by the transplanted cells known as graft-vs.-host disease.

For cancer patients, such risks are usually an acceptable trade-off if the only other option is dying from the malignancy, said Dr. Lakshmanan Krishnamurti, a Children’s cancer specialist and lead author of the study appearing in the November issue of Biology of Blood and Marrow Transplantation.

Sickle cell patients don’t face the same risk of dying from their disease, Dr. Krishnamurti said, but when they are told a typical marrow transplant will keep them in the hospital for weeks and make them very sick, many decline to go through with it.

By using less chemo and radiation, the approach taken by Dr. Krishnamurti and his colleagues stops short of wiping out the patient’s own bone marrow, though, and he believes “if you can make the transplant less toxic, people are more likely to go forward with it.”

Six of the seven patients described in the study no longer have sickle cell, which gets its name from the shape the red blood cells assume, which causes them to jam up in people’s capillaries, triggering intense pain and the other complications.

Instead, they now produce healthy, ovoid red blood cells that come from the bone marrow donated by one of their siblings.

Because their own marrow wasn’t obliterated, though, their white blood cells are a mixture of their own and their siblings’, which could even give them an advantage in fighting off infections, Dr. Krishnamurti said.

Besides being less toxic, the new procedure costs less and means less time in the hospital, he said, all of which could be especially persuasive for African-American patients, who sometimes have less health insurance and more distrust of the health care system.

For the Jones family, the less-toxic treatment protocol wasn’t a major factor, partly because Austin’s symptoms had been so severe, said his father.

Austin had his first fever and trip to Children’s when he was 9 months old, Mr. Jones said, and over the next five years, he was back in the hospital repeatedly, including for “silent strokes” — bleeding in the brain that showed no outward symptoms.

So when Dr. Krishnamurti suggested that Austin get a bone marrow transplant from his older brother Anthony Jr., the Joneses didn’t hesitate.

“When we found out Austin was diagnosed with this” after he was born, Mr. Jones said, “our prayer was ‘Lord, not only heal Austin, but Lord, eradicate this disease from the earth.’ So that prayer went forth when he was an infant, and now, when he was 5, we were hearing about transplantation, and it was an answer.”

Austin went into the hospital in the summer of 2003 and had 45 days of chemo, radiation and other preparatory treatment.

“We watched his hair fall out, watched him go down to nothing [in weight], but he was fine with it, because he had gone through a lot of procedures already in his life.

“Needles were not an issue for him. Taking pills was not an issue for him. You know, you never miss something you never had, so he was like, ‘OK, this is the way it is.’ ”

The day of the transplant, doctors took marrow from brother Anthony’s pelvis and infused it into Austin over about four hours from an IV bag.

Life was actually more challenging for the Joneses after they left the hospital, Mr. Jones said. Austin was put on immunosuppressant drugs so his body wouldn’t reject the transplant, “so you’re talking about a child who doesn’t have an immune system, and you’re trying to make your home dust-free and germ-free and you still have an 11-year-old and 9-year-old at home.”

Eventually, though, he was weaned off the immunosuppressants, just as the other patients in the study were, and his new, hybrid immune system kicked into gear.

The only patient whose transplant didn’t work, Dr. Krishnamurti said, stopped taking her immunosuppressants too soon, and even though she recovered, her sickle cell anemia returned.

An outside expert who was not part of the study agreed that the less-intense procedure might pave the way for more bone marrow transplants in sickle cell anemia.

Mary Fabry, a sickle cell researcher at Albert Einstein College of Medicine in New York, said that in Europe, where another red blood cell disorder called beta thalassemia is more prevalent, transplants are more common, because most of those patients are otherwise fated to die in their 20s or 30s.

New treatments have allowed many sickle cell patients in America to live into their 50s and longer, she said, so there has been less urgency to get marrow transplants. “The really big problem with transplantation in sickle cell disease is that the outcome of the disease has been so unpredictable.”

Seeing how it has changed his son’s life, though, Anthony Jones Sr. is a believer.

“Without reservation I would encourage anyone to pursue this,” he said. If sickle cell families were to ask his advice, “I would say, ‘You cannot not do it.’ “

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