Sorting stem cells before transplant helps lower risk of graft-vs.-host disease, researcher reports at ASH

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'Back to normal life'

Sorting stem cells before transplant helps lower the risk of graft-vs.-host disease, researcher reports

Dec. 5, 2016
Dr. Curtis Mack

Dr. Curtis Mack, a radiation oncologist, was diagnosed in 2013 with leukemia and underwent a stem cell transplant. He participated in a clinical trial to investigate a way to lower the risk of graft-vs.-host disease.

Courtesy of Dr. Curtis Mack

[Editor's note: We've updated this story, originally published in June 2015, to reflect new findings about this clinical trial that were presented at the American Society of Hematology's annual meeting.]. 

For some leukemia patients, getting a blood stem cell transplant isn’t necessarily the biggest hurdle they face. In the first months after a transplant, up to 70 percent develop acute graft-vs.-host disease, an often-debilitating illness where the donor cells attack not just the disease but also the patient’s own healthy cells.

In about 50 percent of blood stem-cell recipients, it evolves into a long-term medical condition. When GVHD becomes chronic, patients typically need ongoing medical care, often develop disabilities and an impaired immune system, and can’t return to work or school. Some need frequent hospitalizations. Some die.

But now, researchers may have found a way to help lower the risk of GVHD.

On Monday, at the American Society of Hematology annual meeting in San Diego, Fred Hutch researcher Dr. Marie Bleakley reported that scientists have been able to drastically reduce the risk of GVHD in transplant patients by filtering fresh blood stem cells with magnets.

In a clinical trial at Fred Hutchinson Cancer Research Center, among 70 acute leukemia patients infused with specially filtered stem cells, less than 10 percent showed chronic GVHD, Bleakley reported. (Chronic GVHD symptoms can include joint pain, blurred vision, mouth sores, trouble breathing, rashes and other manifestations.) 

The paper updated findings Bleakley first reported in 2015 when the trial included 35 acute leukemia patients. 

They 'just got on with their lives'

"The big finding is that results from the first 35 seem to hold true with twice as many patients," said Bleakley, the paper’s first author and a Fred Hutch transplant specialist and immunology researcher. "We're seeing very low rates of chronic graft-vs.-host disease and no apparent compromise of any of the other important outcomes — no big increase in relapse or infection or any of the things that you hypothesize could be compromised if you did reduce GVHD.

"It’s great that (the low rates) have sustained" in more patients, Bleakley said. "It’s real."

In human terms, this means many trial patients quickly returned to their normal lives, or even notched big milestones, Bleakley said. 

"Some got married or got their master’s degrees, just got on with their lives and didn’t have that long period of ill health and disability. That’s a really significant development,” Bleakley said.

Researchers have long suspected that naïve T cells, a normally helpful component of the immune system, can cause severe GVHD after stem cell transplants. But another key piece of the body’s defenses, memory T cells, are unlikely to trigger severe GVHD. That’s because most memory T cells recognize fragments of proteins found on virally infected cells.

Bleakley and colleagues hypothesized that by weeding out the naïve T cells — but leaving in the memory T cells before giving leukemia patients stem cell transplants — it would cut the risk.

Here’s where they melded medicine with basic mechanics — on a miniscule scale. Naïve T cells contain, on their surfaces, a protein called CD45RA. That protein is not found on most memory T cells. The team used antibodies specific to CD45RA — antibodies, in fact, affixed to iron-dextran beads. 

The blood stem cells were then passed through a machine containing a magnet that grabbed and collected the iron-bead-wearing, naïve cells.

“The cells we want — stem cells and memory T cells — are collected on the bottom,” Bleakley said.

Dr. Marie Bleakley

Dr. Marie Bleakley

Fred Hutch file photo

Memory T cells are helpful to transplant recipients and others because they do just as their name describes. They remember when your body was exposed in the past to infections like the flu. They then help you resist those bugs if they come around again.

Beyond lower rates of chronic GVHD, the clinical-trial patients generally have had better health when compared to other leukemia patients, researchers noted.

For example, their one- and two-year estimates of overall survival were 82 and 79 percent, Bleakley said. 

Historically, “the ballpark is 40 to 60 percent survival,” Bleakley said.

Among 78 leukemia patients who have enrolled in the trial to date, 14 have died.

As the trial has expanded, researchers successfully treated some patients who received blood stem cells from matched, unrelated donors, which would make the procedure available to many more people, Bleakley said. (The original 35 patients were transplanted via matched donors to whom they were related).

In addition, the researchers have now successfully treated seven of the trial patients with lower amounts of pre-transplant radiation, part of the standard process to prepare a body for the procedure, Bleakley said. Called "intermediate intensity conditioning," or a "midi-transplant," the regimen involves 4 Gray, the unit that measures absorbed radiation in the body. Most blood stem cell transplants use high-intensity radiation, 13 Gray. This gentler therapy is easier on the body, making the life-saving procedure suitable for 50- to 60-year-olds and for patients with other medical complications. 

'It was my time to give back'

For one of the original 35 trial patients, Dr. Curtis Mack, the science cut, ironically, close to home.

Mack felt sluggish and in pain while running a half marathon in June 2013. During a July 4th weekend training run, he needed to walk — a glaring clue something was amiss. Hours later, while reading a medical journal, he noticed his fingers were bleeding. Mack got a blood test. The diagnosis was leukemia. He was admitted to a hospital that same week.

His profession: radiation oncologist. He practices in Tucson, Arizona.

“I tried to be a patient,” said Mack, 52. “Because leukemia is not in the daily realm of a radiation oncologist. It’s cancer, yes. But leukemia, in general, is not handled by us.

“Probably, I asked less questions than most folks would.”

Mack also works as an investigator for the Radiation Therapy Oncology Group, or RTOG. The national clinical cooperative, funded by the National Cancer Institute, performs clinical trials of new treatments, learning how to boost survival rates and improve quality of life for cancer patients.

Soon, Mack flew to Seattle and met with Dr. Fred Appelbaum, deputy director and executive vice president of Fred Hutch, and an oncologist. The decision was made to perform a blood stem cell transplant for Mack. He heard about Bleakley’s clinical trial and agreed to participate.

On Oct. 28 of that year, Mack loaded up his dogs, and he and his partner returned to Seattle. They rented a townhouse near downtown, staying five months.

“As an investigator for the RTOG, we participate in several [clinical] trials here — esophageal, head and neck, breast, prostate. So I tell my private story to try and practice what we preach: If we can learn something and treat you, and be better next time, it’s a bonus,” Mack said. “That’s why I try to talk folks into trials, when they’re appropriate and they qualify.

“This seemed like it was my time to give back.”

Today, three years out from his transplant, Mack does a CrossFit workout — a mix of weight lifting, gymnastics and exercise — five days a week. Back in Tucson, he lives with his partner, Darrell Leetham, and three Weimaraners. The dogs go to work with him, and on weekends he runs with the dogs. "I used to tire easily, but then one day I realized, 'Hey, I feel normal,' " he recalled. "It kinda sneaks up on you."

His running pace is still slower than before his illness. But that may simply be due to having less time and older dogs, he said. And when he compares his body today to his body before illness, he is still struck by his rejuvenation. 

“It’s amazing to think how far I degenerated, to the point where I was barely carrying a bag of groceries. And I had to sit down. Holy crap, I couldn’t stand for more than a couple of minutes. It was crazy. I thought: ‘Oh my God, am I ever going to be able to be normal?’

“Now, I forget all about that.”

To read more about Fred Hutch at ASH 2016, visit our page here.

Bill Briggs is a former Fred Hutch News Service staff writer. Follow him at @writerdude. Previously, he was a contributing writer for NBCNews.com and TODAY.com, covering breaking news, health and the military. Prior, he was a staff writer for The Denver Post, part of the newspaper's team that earned the Pulitzer Prize for coverage of the Columbine High School massacre. He has authored two books, including "The Third Miracle: an Ordinary Man, a medical Mystery, and a Trial of Faith." 

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