Experimental bone marrow transplant could be cure for sickle cell disease

Wearing protective garb to wards off germs, Kelly Holloway greets one of her pets "Nick" after arriving home from receiving a stem cell transplant to battle sickle cell disease. Photo by Jon C. Lakey, Salisbury Post.

Kelly Holloway speaks about her battle with sickle cell disease and being one of first in nation to get half-match stem cell transplant to battle the desease. Photo by Jon C. Lakey, Salisbury Post.

Kelly Holloway speaks about her battle with sickle cell disease and being one of first in nation to get half-match stem cell transplant to battle the desease. Holloway keeps a portfolio from her modeling in the early 1990's. Photo by Jon C. Lakey, Salisbury Post.

Kelly Holloway speaks about her battle with sickle cell disease and being one of first in nation to get half-match stem cell transplant to battle the desease. Photo by Jon C. Lakey, Salisbury Post.

Kelly Holloway speaks about her battle with sickle cell disease and being one of first in nation to get half-match stem cell transplant to battle the desease. Holloway keeps a portfolio from her modeling in the early 1990's. Photo by Jon C. Lakey, Salisbury Post.

Kelly Holloway speaks about her battle with sickle cell disease and being one of first in nation to get half-match stem cell transplant to battle the desease. Photo by Jon C. Lakey, Salisbury Post.

By Shavonne Potts

spotts@salisburypost.com

Kelly Holloway reaches out for her cat, Jax, a rescued Persian with long cream-colored fur, but she's not quite able to connect with him.

It could be the mask, gloves or the hospital gown she wears over her clothes. Holloway is almost completely covered from head-to-toe. It's the best way to protect herself and her immune system.

Holloway, who grew up in Cleveland, recently underwent a procedure that she hopes will completely cure her of the inherited blood disorder, sickle cell disease.

At 6 months old, Holloway was diagnosed with sickle cell, which causes red blood cells to contort and causes them to block blood vessels.

"Her blood count was low and the doctors did another test," said Alice Holloway, Kelly's mother.

That second test confirmed doctors' suspicions that the infant had sickle cell.

Sickle cell is caused by abnormal hemoglobin, a protein in red blood cells that transports oxygen and gives blood its red color. Normal red blood cells look like doughnuts without holes and move easily through the blood vessels. Sickle cells form a "C" or sickle shape and clump in the blood vessels.

In the United States, more than 80,000 people are affected by sickle cell disease, mainly people of African ancestry and to a lesser extent people of Hispanic, Middle Eastern, Asian and white ancestry.

Kelly, now in her 40s, is a part of a study at the National Institutes of Health in Betheseda, Md., where she's received an experimental bone marrow transplant that researchers believe is a possible cure for sickle cell disease.

Living with sickle cell

As a child, Kelly's blood count was constantly monitored because sickle cells break up easily and survive for only 10 to 20 days. Normal red blood cells survive 120 days, which can make blood transfusions pretty routine. Transfusions increase the number of normal red blood cells in the body.

Kelly was given penicillin frequently since sickle cell disease makes it harder to fight infections because of decreased immune function.

"They put so much penicillin in her she became allergic," Alice said.

Kelly could have a common cold one day, bronchitis the next and eventually double pneumonia. She had several bouts of pneumonia as a child. She also had to stay hydrated since blood can thicken and cause blockages in blood vessels when it's dehydrated.

Although Kelly has been affected with the disease her entire life, she's still led a pretty normal existence. She graduated from West Rowan High and went on to graduate from Livingstone in 1996 with degrees in sociology and business. She has modeled and appeared on the cover of magazines.

Awaiting a kidney

When cells become hard and pointed like the sickle they're named for, they often get stuck and block the vessels. This blockage can lead to pain, stroke and damage to major organs. Kelly now needs a kidney transplant.

In the meantime, she has daily kidney dialysis, and without this, toxic wastes build up in her blood and tissues. She also has gallstones, injections in her left eye to stop bleeding and pulmonary arterial hypertension (which is high blood pressure in the lung arteries that make it harder for blood to flow through).

A new treatment

During a visit with her cardiologist, Kelly was referred to the National Institutes of Health, where researchers were doing a study on pulmonary hypertension. Kelly went through a week of testing.

"I told them, 'I think I need a stem cell transplant,' " she said, sort of joking.

But her casual comment was taken seriously and she was enrolled in a modified blood adult stem-cell transplant regimen study.

Bone marrow transplants have been used to treat sickle cell disease for 20 years, but almost all of the 200 cured have been children.

The process began with Kelly's sister, Nieda, who had a procedure that stimulates the bone marrow to produce stem cells. The stem cells are collected and the rest of the cells are infused back into the body.

"They were hoping to get 5,000 cells and they got 15,000," Alice said.

The "new" red blood cells from the donor allows the healthy cells to outlast and replace the disease-causing cells.

"The bone marrow transplant is the only cure that can be offered to treat sickle cell where traditionally a brother or sister is a match," said Dr. Courtney Fitzhugh.

Fitzhugh co-authored a paper about full-matched stem cell transplantation in sickle cell disease, which appeared in the December 2009 edition of the New England Journal of Medicine. She's written a protocol for a half-matched person who can serve as a donor. It took the better part of six months to write the protocol for this study.

Johns Hopkins University has conducted similar research, but Kelly is the first and only half-matched recipient at the National Institutes of Health.

Repeated attempts to contact researchers at Johns Hopkins University's Sickle Cell Center for Adults were unsuccessful.

The decision to become the first half-matched recipient wasn't a hard one, Kelly said.

"It was all worth it. I would do it again," she said.

The trial was conducted in Maryland by National Institutes of Health researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases.

A sibling is usually the best match because it ensures the patient's body does not reject the new marrow. In other studies, stem cells donated from parents often are rejected in their new environment.

In Kelly's case, her younger sister was the half match she needed. Currently, 72 percent of Nieda's blood cells have taken over Kelly's blood.

"We can tell what percentage of those cells come from the donor. We've found that we don't have to completely replace the recipient's cells," Fitzhugh said.

Levels as much as 10 percent could reverse sickle cell disease, she said.

"A parent should be a half match to a child and every sibling has a 50 percent chance of being a half match, a 25 percent chance of being a full match and 25 percent chance of not being a match at all," Fitzhugh said.

The patient's body can reject the cells and the sickle cell can return. What researchers do is give the patient medication and radiation to prevent rejection.

A week before the procedure, Kelly was given low-dose chemotherapy and full-body radiation. After Kelly received a treatment, she had an unexpected side effect that left her hair matted. Her hair was so fused together she had to cut it.

Most participants who were full-matched were completely bald, Kelly said.

She's been in isolation for the last month and was released May 4.

In the December study, nine of 10 adults who received full matched stem cell transplants had effective reversal of sickle cell disease.

"We should start to get some idea around three to six months if it (half-matched) worked for Kelly," Fitzhugh said.

Now Kelly must wait. She has faith that this procedure will be a definite cure.

"I have to have faith. That's what all the prayers are for — a cure," she said.

Her mother hopes this will be the answer to many others' prayers.

"There is a cure for sickle cell and people don't have to suffer," Alice said.

"It's important for people to be aware of sickle cell and know that bone marrow is an option. We are really trying to help improve the lives of patients," Fitzhugh said.

It will be years before the treatment is applied on a larger scale, she said.

Health care providers and sickle cell patients, or their family members, who may be interested in joining the study should call 301-402-6466 for more information.