Stem cell transplant cures children with sickle cell anemia, says Alberta hospital

7 girls, 2 boys cured in what lead doctor considers unprecedented treatment

By Lisa Monforton,

Cardelia Fox has a tattoo on the inside of her right forearm with the words "Set free." 

It's a reminder of how a cutting-edge transplant at the Alberta Children's Hospital cured her of sickle cell anemia and a life of hospital stays and blood transfusions.

The chronic genetic blood disorder caused Fox to have three childhood strokes — the first when she was only six months old. She would have two more at age six and 10.

Until the age of 17, she had been in and out of hospital and previously needed to have monthly life-saving blood transfusions.

The year Fox turned 17 she was one of the first patients to undergo the stem cell transplant procedure at the Alberta Children's Hospital.

The success of the procedure has captured interest from around the world, says Dr. Greg Guilcher, a pediatric oncologist who leads the sickle cell blood and marrow transplant program in Calgary.

Dr. Greg Guilcher is the lead doctor for the stem cell transplant procedure at Alberta Children's Hospital.

"To our knowledge, no one else is offering this protocol in children with sickle cell anemia," said Guilcher, who is also an assistant professor in the departments of oncology and pediatrics at the University of Calgary's Cumming School of Medicine.

What sets the Calgary procedure apart from other sickle cell anemia cures in young children is the lead up to the transplant. 

"​This protocol uses the 'lightest' doses of medication — no chemotherapy but immune suppressing drugs only, with a low dose of radiation," said Dr. Guilcher in a statement. 

While the protocol was developed and is used in the U.S., Dr. Guilcher said he's not aware of any other hospital using it on children.

More exciting is the fact that there have been no incidents of stem cell rejection. 

"We're getting phone calls and emails from around the world from interested parents and other doctors. We think we're ahead of the curve in offering this curative therapy as a standard of care."

Sickle cell anemia is a chronic illness where blood vessels can become blocked when blood cells change into a sickle shape, potentially affecting every organ and causing strokes, lung disease heart strain and spleen and bone damage. With advanced drug therapy treatment, life expectancy is 55- to 60-years-old.

The success of the procedure, which was first performed in Calgary in 2009, has cured seven girls and two boys to date.

Life-changing, says patient

"Before the stem cell transplant I felt like I was trapped," says Fox, whose sister Tamika Allen was a perfect match — a rare one in five occurrence within families. "Without this treatment I would likely still be at Foothills getting blood transfusions every month."

Tamika Allen, left, was a perfect stem cell match to her sister Cardelia Fox, which allowed her to have a procedure curing her of sickle cell anemia. (CBC)

Once Allen found out she was a full match, she didn't think twice about helping her sister.

Without a family match, the transplant procedure is generally considered too risky to perform.

"When we learned I was a match there was never any question of whether or not I'd do it," said Tamika, now 22. "Of course I'm going to do this for my sister. It was such a good feeling to be able to help make her life better — now I call her my mini-me."

Rising incidence in Canada

People of African descent are most often affected by sickle cell anemia. One parent can pass on the mutation and not cause the illness, but the illness results when both parents pass it on.

Fox's grandmother died at the age of 35 because of complications from the disease.

In 2008, the Sickle Cell Clinic at the children's hospital regularly treated 16 children.

Now there are more than 80, primarily because of immigration, says Dr. Mike Leaker. He is the head of the clinic, which sees patients from Alberta, Saskatchewan and eastern B.C.

"We now have some excellent medications that can change the course of the illness for many patients," said Leaker. "But a drug is still a treatment, not a cure. For families the word 'cure' is incredibly powerful."

Guilcher is expecting continued interest in the procedure from around the world

Sickle Cell Anemia: From Basic Science to Clinical Practice

Age No Longer Should Be A Barrier To Stem Cell Transplantation For Older Patients With Blood Cancers

Age alone no longer should be considered a defining factor when determining whether an older patient with blood cancer is a candidate for stem cell transplantation. That's the conclusion of the first study summarizing long-term outcomes from a series of prospective clinical trials of patients age 60 and over who were treated with the mini-transplant, a "kinder, gentler" form of allogeneic (donor cell) stem cell transplantation developed at Fred Hutchinson Cancer Research Center. The findings are published Nov. 2 in JAMA, The Journal of the American Medical Association.

"Age is no longer a barrier to allogeneic transplant," said Mohamed Sorror, M.D., M.Sc., an assistant member of the Hutchinson Center's Clinical Research Division and corresponding author of the paper.

Sorror and colleagues found that the five-year rates of overall and disease-progression-free survival among mini-transplant patients were 35 percent and 32 percent, respectively. Patients in three age groups 60 to 64, 65 to 69 and 70 to 75 had comparable survival rates, which suggested that age played a limited role in how patients tolerate the mini-transplant. Increased medical problems unrelated to cancer (comorbidities) and a higher degree of cancer aggressiveness were the two factors that affected survival among those older patients. For example, patients who had less-aggressive cancer and fewer comorbidities had a five-year survival rate of 69 percent, while patients with more aggressive cancer and a significant number of comorbidities had a survival rate of 23 percent, regardless of age.

Although a long-term survival rate of one-third of patients may seem low, these patients all would have died of their diseases within a matter of months without a transplant. "The majority of patients were referred for a transplant after they had exhausted all forms of conventional therapy," said Sorror, who works in the research group led by Rainer Storb, M.D., who developed the mini-transplant.

"While there is much room for improvement, particularly with regard to relapse, these results are encouraging given the poor outcomes with non-transplantation treatments, especially for patients with high-risk AML (acute myeloid leukemia), fludarabine-refractory CLL (chronic lymphocytic leukemia) or progressive lymphoma," the authors wrote.

The mini-transplant, known in medical circles as nonmyeloablative transplantation, was developed by researchers at the Hutchinson Center for older and medically sicker patients who otherwise could not tolerate the standard, more-toxic, high-dose regimens used to prepare patients for transplantation.

Bone Marrow Stem Cells Reverse Sickle Cell Disease

By Drew Halley
A revolutionary new procedure for stem cell transplant is reversing the effects of severe adult sickle cell disease. For years, adults suffering from sickle cell anemia have relied on consistent blood transfusions and drug treatments to combat the disorder. Bone marrow transplants can reverse sickle cell, but have so far been restricted to children in the early stages of the disease. That is, until now.
Sickle cell anemia is a congenital blood disorder that affects all races, but is most common to persons with African ancestry, affecting about 72,000 in the US and millions worldwide. Red blood cells normally take the shape of a doughnut without its hole; in the blood of sickle cell patients, the cells assume an abnormal sickle shape. Sickle cells block small blood vessels and inhibit blood flow, which causes debilitating pain, damages organs and increases the risk of stroke. Many of the risks of sickle cell can be mediated through early diagnosis, dietary supplements, and drug treatment. But even with modern treatment, life expectancy for sickle cell patients is 42 in males, 48 in females. Some severe cases are resistant to existent therapies and can cut life even shorter.
Because red blood cells are produced in bone marrow, some high-risk children qualify for marrow transplants from a suitable sibling donor. Like all organ transplants, the procedure carries the danger of immune rejection, and so requires immunosuppressant drugs in addition to radiation therapy to kill diseased marrow. Transplants have been traditionally restricted to children, whose organs are comparably stronger than adults who suffer from the disease. Transplants are rare – there have been about 200 in the past few decades – and are attempted only in children whose disorders are life-threatening.
But a new procedure developed by the National Institute of Health (NIH) and Johns Hopkins University has successfully transplanted marrow to adults, reversing the disorder in 9 out of 10 patients. The new treatment uses significantly less radiation (about one fourth) to kill the patient’s existent marrow, combined with the immunosuppressant drug Sirolimus to reduce the likelihood of transplant rejection. By allowing more of the patient’s own marrow to remain, recovery from the transplant is faster and healthier (patients could previously spend months in germ-free isolation while their immune systems recovered). Thirty months after the transplant, the nine patients with successful transplants are healthy and show no side effects.
Many adults with sickle cell anemia take the drug hydroxyurea to treat the disorder. Hydroxyurea works by stimulating the body to produce a form of hemoglobin normally only found during development in the womb. The production of this hemoglobin type helps to balance the proportion of healthy vs. sickle cells in the blood, and reduces the damage done to lungs, kidneys, and liver (not to mention the risk of stroke). But hydroxyurea doesn’t work for all adult patients, making the prospect of adult marrow transplant a much-needed form of alternative therapy.

Kelly Halloway, the first half-match donation recipient at the National Institute of Health
So far, most adult patients who have received marrow transplants have had “full match” donors – siblings with a fully compatible genetic makeup. The chances of a sibling being fully matched are only 25%. But new procedures are expanding the pool of potential donors to “half match” donors, which includes parents and improves the likelihood of a compatible sibling to 75%. That means more sources of transplant marrow, and a better shot at a successful reversal of the disease.

Future research will aim to expand marrow transplants beyond sickle cell patients. Several other congenital blood diseases could conceivably be treated with marrow transplants, including such debilitating disorders as beta-thalassemia.Researchers are currently exploring the emerging possibilities of adult marrow transplants, and will doubtless yield more amazing treatments in coming years