U doctors pioneer in sickle cell treatment

Craig Gustafson

An 8-year-old girl from Buffalo, N.Y., was given the opportunity to lead a normal life by University physicians, becoming the first person in the world to receive a new treatment for sickle cell disease.
University physicians used an experimental bone marrow treatment to cure Nina Herrera of sickle cell disease, ending years of aching joints and blood transfusions.
The procedure, completed Aug. 27, was the first transplant of its type in the world and deemed a success by the doctors last week.
Sickle cell disease is a genetic disorder — found primarily in African-Americans and Hispanic Americans — that distorts the shape of red blood cells in the body. The cells that deliver oxygen become misshapen and begin to clog blood vessels. In effect, the disease ceases blood flow to certain parts of the body.
Dr. Lakshmanan Krishnamurti, who conducted the bone marrow transplant with Dr. John Wagner, said the disease lowers a person’s life expectancy by an average of 30 years.
He added that the typical method of handling sickle cell disease was painful and arduous.
First, patients receive chemotherapy to totally eradicate the patient’s bone marrow. On average, the chemotherapy lasts 40 days.
Marrow from a donor is then placed into the patient. Krishnamurti said the procedure ends in death 5 percent to 10 percent of the time.
“It is 40 days of unreal pain,” he said.
With the new treatment, chemotherapy lasts only nine days and radiation one day.
In the process, a majority of the patient’s bone marrow is destroyed before a donor’s marrow is implanted. The two marrows mix in a process called engraftment. The new marrow should produce healthy red blood cells.
Like any pioneering treatment, there was uncertainty regarding the success of this new procedure.
“We knew the bone marrow transplant showed promise, but there is risk in any type of surgery,” Krishnamurti said.

An existence of pain
In her eight years of life, Nina Herrera has known more than her fair share of unreal pain.
Nina’s serious problems began when she was 4 years old; blood clots rendered her legs temporarily paralyzed.
When she was 5, a clot appeared close to her brain, causing a severe stroke. Afterward, she could no longer use the left side of her body.
The shy, young girl went through two years of rehabilitation treatment at Robert Warner’s Rehabilitation Hospital in Buffalo, N.Y.
She was able to regain use of her legs and left arm, but experts there said she would never recover use of her left hand.
Nina can walk again, though she becomes fatigued easily.
Since the stroke, Nina has needed a blood transfusion every 30 days.
Her parents said they took Nina to the hospital about four times a year for different sickle cell crises.
“She would be in the swimming pool and come out complaining of pain in her feet,” said Melvin Herrera, Nina’s father. “Her joints would just swell up from the water, and we’d have to take her to the hospital.”
After the stroke, things became unbearable.
“It was devastating going in (the hospital) and seeing her strapped down with tubes in her with a team of doctors working on her,” he said. “She would try to make facial expressions, but even that was hard because the stroke made the left side of her face numb.”
A new hope
Iris Herrera, Nina’s mother, looked everywhere for hope.
She finally found it in a People magazine article about a young boy with the disease who had a bone marrow transplant and was cured. She cut his picture out and put it on her bulletin board.
“I looked at that boy every day,” she said. “I thought, ‘Someday Nina’s going to be sickle cell free.'”
As luck would have it, Nina’s doctor in Buffalo attended a conference in San Francisco where Wagner was giving a presentation on bone marrow transplants for severe cases of sickle cell disease. Wagner spoke of a new technique that would reduce the amount of pain associated with the process.
Once the Herreras found out about the treatment, they contacted the University. They were informed that although the procedure was less taxing for the patient than typical treatments, there was no guarantee of success. There would still be the distinct possibility Nina could die before the procedure was completed.
“It was one of the hardest decisions I’ve ever had to make,” Iris said.

The treatment
The University competed with many of the top research institutions in the country four years ago for a $850,000 grant from the National Institutes of Health to find a better treatment for sickle cell disease.
The goal was to make bone marrow transplants safer and more accessible to older patients.
Once a patient is 16 years old, the disease is too advanced for treatment.
Bruce Blazar, a University pediatrician, was in charge of the pre-clinical and clinical studies to develop new approaches.
“We broke down each of the components of the (previous) method,” he said. “We thought we should work with modifying the current principles.”
They examined a process used with older adults suffering from cancer, in which bone marrow was only partially destroyed instead of being totally eliminated.
“This is some cool stuff,” Krishnamurti said. “This could potentially be applied to so many diseases. We’ve really lowered the bar.”

Afraid to live and die
In June, the Herreras met with Wagner to discuss the risks and benefits of the procedure.
“He answered all my questions,” Melvin said. “We decided to go with it.”
Nina was filled with trepidation when decision time came.
She would say, “Mommy, don’t let them do this to me.”
“It broke my heart,” Iris said. “I hoped I was making the right decision.”
Both parents then received extended leaves of absence from their employers. Since the family arrived in Minnesota on Aug. 9, they have been living at the Ronald McDonald House on Ontario Street.
Doctors used nine days of chemotherapy to destroy a majority of Nina’s bone marrow. The 10th day of treatment — radiation day — was the worst.
Nina’s temperature shot to 105.3 degrees, she vomitted numerous times and her father said he couldn’t make out a word she was saying.
“Thank God it was just one day,” he said. “I was so scared. I thought she would have seizures … luckily, the fever went down.”
Nina recalled her harrowing day and said she felt “sicky-poo.”
The next morning, doctors took bone marrow from Nina’s 12-year-old brother, Christian, and ran tests to make sure it would work. By the afternoon, the transplant was complete.
“Whatever is going to heal her, I’ll do for her,” Christian said. “I don’t think any brother wants to see his sister like that.”
A successful transplant occurs when the donor’s marrow is producing 5 percent to 10 percent of the cells. Thus far, Christian’s marrow has taken over 71 percent of the blood cell-producing, which is better than anyone could have hoped for.
So far, the pain Nina once endured has subsided and might be absent for good.
“I am happy not just for my daughter but for all the people that can be cured,” Melvin said. “Five years from now, hopefully a child won’t have to go through a stroke like Nina. Maybe they can get cured before they get to that stage.”
The family is slated to stay at the Ronald McDonald house until November or December, depending on Nina’s condition.
University physicians emphasized that this was merely a first step, although a significant one, toward curing all sickle cell disease sufferers.

Craig Gustafson covers the Medical School and welcomes comments at [email protected] He can also be reached at (612) 627-4070 x3233.