A New Stem Cell Therapy Provides Hope to Patients with Blood Cancer
Stacey Khoury felt more fatigued and out of breath than she was used to from just walking up the steps to her job in retail jewelry sales in Nashville, Tennessee. By the time she got home, she was more exhausted than usual, too.
"I just thought I was working too hard and needed more exercise," recalls the native Nashvillian about those days in December 2010. "All of the usual excuses you make when you're not feeling 100%."
As a professional gemologist, being hospitalized during peak holiday sales season wasn't particularly convenient. There was no way around it though when her primary care physician advised Khoury to see a blood disorder oncologist because of her disturbing blood count numbers. As part of a routine medical exam, a complete blood count screens for a variety of diseases and conditions that affect blood cells, such as anemia, infection, inflammation, bleeding disorders and cancer.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before."
While she was in the hospital, a bone marrow biopsy revealed that Khoury had acute myeloid leukemia, or AML, a high-risk blood cancer. After Khoury completed an intense first round of chemotherapy, her oncologist recommended a bone marrow transplant. The potentially curative treatment for blood-cancer patients requires them to first receive a high dose of chemotherapy. Next, an infusion of stem cells from a healthy donor's bone marrow helps form new blood cells to fight off the cancer long-term.
Each year, approximately 8,000 patients in the U.S. with AML and other blood cancers receive a bone marrow transplant from a donor, according to the Center for International Blood and Marrow Transplant Research. But Khoury wasn't so lucky. She ended up being among the estimated 40% of patients eligible for bone marrow transplants who don't receive one, usually because there's no matched donor available.
Khoury's oncologist told her about another option. She could enter a clinical trial for an investigational cell therapy called omidubicel, which is being developed by Israeli biotech company Gamida Cell. The company's cell therapy, which is still experimental, could up a new avenue of treatment for cancer patients who can't get a bone marrow transplant.
Omidubicel consists of stem cells from cord blood that have been expanded using Gamida's technology to ensure there are enough cells for a therapeutic dose. The company's technology allows the immature cord blood cells to multiply quickly in the lab. Like a bone marrow transplant, the goal of the therapy is to make sure the donor cells make their way to the bone marrow and begin producing healthy new cells — a process called engraftment.
"If approved, it will allow more patients to potentially receive a transplant than would have gotten one before, so there's something very novel and exciting about that," says Ronit Simantov, Gamida Cell's chief medical officer.
Khoury and her husband Rick packed up their car and headed to the closest trial site, the Duke University School of Medicine, roughly 500 miles away. There they met with Mitchell Horowitz, a stem cell transplant specialist at Duke and principal investigator for Gamida's omidubicel study in the U.S.
He told Khoury she was a perfect candidate for the trial, and she enrolled immediately. "When you have one of two decisions, and it's either do this or you're probably not going to be around, it was a pretty easy decision to make, and I am truly thankful for that," she says.
Khoury's treatment started at the end of March 2011, and she was home by July 4 that year. She say the therapy "worked the way the doctors wanted it to work." Khoury's blood counts were rising quicker than the people who had bone marrow matches, and she was discharged from Duke earlier than other patients were.
By expanding the number of cord blood cells — which are typically too few to treat an adult — omidubicel allows doctors to use cord blood for patients who require a transplant but don't have a donor match for bone marrow.
Patients receiving omidubicel first get a blood test to determine their human leukocyte antigen, or HLA, type. This protein is found on most cells in the body and is an important regulator of the immune system. HLA typing is used to match patients to bone marrow and cord blood donors, but cord blood doesn't require as close of a match.
Like bone marrow transplants, one potential complication of omidubicel is graft-versus-host disease, when the donated bone marrow or stem cells register the recipient's body as foreign and attack the body. Depending on the severity of the response, according to the Mayo Clinic, treatment includes medication to suppress the immune system, such as steroids. In clinical trials, the occurrence of graft-versus-host disease with omidubicel was comparable with traditional bone marrow transplants.
"Transplant doctors are working on improving that," Simantov says. "A number of new therapies that specifically address graft-versus-host disease will be making some headway in the coming months and years."
Gamida released the results of the Phase 3 study in February and continues to follow Khoury and the other study patients for their long-term outcomes. The large randomized trial evaluated the safety and efficacy of omidubicel compared to standard umbilical cord blood transplants in patients with blood cancer who didn't have a suitable bone marrow donor. Around 120 patients aged 12 to 65 across the U.S., Europe and Asia were included in the trial. The study found that omidubicel resulted in faster recovery, fewer bacterial and viral infections and fewer days in the hospital.
The company plans to seek FDA approval this year. Simantov anticipates the therapy will receive FDA approval by 2022.
"Opening up cord blood transplants is very important, especially for people of diverse ethnic backgrounds," says oncologist Gary Schiller, principal investigator at the David Geffen School of Medicine at UCLA for Gamida Cell's mid- and late-stage trials. "This expansion technology makes a big difference because it makes cord blood an available option for those who do not have another donor source."
As for Khoury, who proudly celebrated the anniversary of her first transplant in April—she remains cancer free and continues to work full-time as a gemologist. When she has a little free time, she enjoys gardening, sewing, or maybe traveling to national parks like Yellowstone or the Grand Canyon with her husband Rick.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the stories covered this week:
- The eyes are the windows to the soul - and biological aging?
- What bean genes mean for health and the planet
- This breathing practice could lower levels of tau proteins
- AI beats humans at assessing heart health
- Should you get a nature prescription?
Two-and-a-half year-old Huckleberry, a blue merle Australian shepherd, pulls hard at her leash; her yelps can be heard by skiers and boarders high above on the chairlift that carries them over the ski patrol hut to the top of the mountain. Huckleberry is an avalanche rescue dog — or avy dog, for short. She lives and works with her owner and handler, a ski patroller at Breckenridge Ski Resort in Colorado. As she watches the trainer play a game of hide-and-seek with six-month-old Lume, a golden retriever and avy dog-in-training, Huckleberry continues to strain on her leash; she loves the game. Hide-and-seek is one of the key training methods for teaching avy dogs the rescue skills they need to find someone caught in an avalanche — skier, snowmobiler, hiker, climber.
Lume’s owner waves a T-shirt in front of the puppy. While another patroller holds him back, Lume’s owner runs away and hides. About a minute later — after a lot of barking — Lume is released and commanded to “search.” He springs free, running around the hut to find his owner who reacts with a great amount of excitement and fanfare. Lume’s scent training will continue for the rest of the ski season (Breckenridge plans operating through May or as long as weather permits) and through the off-season. “We make this game progressively harder by not allowing the dog watch the victim run away,” explains Dave Leffler, Breckenridge's ski patroller and head of the avy dog program, who has owned, trained and raised many of them. Eventually, the trainers “dig an open hole in the snow to duck out of sight and gradually turn the hole into a cave where the dog has to dig to get the victim,” explains Leffler.
By the time he is three, Lume, like Huckleberry, will be a fully trained avy pup and will join seven other avy dogs on Breckenridge ski patrol team. Some of the team members, both human and canine, are also certified to work with Colorado Rapid Avalanche Deployment, a coordinated response team that works with the Summit County Sheriff’s office for avalanche emergencies outside of the ski slopes’ boundaries.
There have been 19 avalanche deaths in the U.S. this season, according to avalanche.org, which tracks slides; eight in Colorado. During the entirety of last season there were 17. Avalanche season runs from November through June, but avalanches can occur year-round.
High tech and high stakes
Complementing avy dogs’ ability to smell people buried in a slide, avalanche detection, rescue and recovery is becoming increasingly high tech. There are transceivers, signal locators, ground scanners and drones, which are considered “games changers” by many in avalanche rescue and recovery
For a person buried in an avalanche, the chance of survival plummets after 20 minutes, so every moment counts.
A drone can provide thermal imaging of objects caught in a slide; what looks like a rock from far away might be a human with a heat signature. Transceivers, also known as beacons, send a signal from an avalanche victim to a companion. Signal locators, like RECCO reflectors which are often sewn directly into gear, can echo back a radar signal sent by a detector; most ski resorts have RECCO detector units.
Research suggests that Ground Penetrating Radar (GPR), an electromagnetic tool used by geophysicists to pull images from inside the ground, could be used to locate an avalanche victim. A new study from the Department of Energy’s Sandia National Laboratories suggests that a computer program developed to pinpoint the source of a chemical or biological terrorist attack could also be used to find someone submerged in an avalanche. The search algorithm allows for small robots (described as cockroach-sized) to “swarm” a search area. Researchers say that this distributed optimization algorithm can help find avalanche victims four times faster than current search mechanisms. For a person buried in an avalanche, the chance of survival plummets after 20 minutes, so every moment counts.
An avy dog in training is picking up scent
Sarah McLear
While rescue gear has been evolving, predicting when a slab will fall remains an emerging science — kind of where weather forecasting science was in the 1980s. Avalanche forecasting still relies on documenting avalanches by going out and looking,” says Ethan Greene, director of the Colorado Avalanche Information Center (CAIC). “So if there's a big snowstorm, and as you might remember, most avalanches happened during snowstorms, we could have 10,000 avalanches that release and we document 50,” says Greene. “Avalanche forecasting is essentially pattern recognition,” he adds--and understanding the layering structure of snow.
However, determining where the hazards lie can be tricky. While a dense layer of snow over a softer, weaker layer may be a recipe for an avalanche, there’s so much variability in snowpack that no one formula can predict the trigger. Further, observing and measuring snow at a single point may not be representative of all nearby slopes. Finally, there’s not enough historical data to help avalanche scientists create better prediction models.
That, however, may be changing.
Last year, an international group of researchers created computer simulations of snow cover using 16 years of meteorological data to forecast avalanche hazards, publishing their research in Cold Regions Science and Technology. They believe their models, which categorize different kinds of avalanches, can support forecasting and determine whether the avalanche is natural (caused by temperature changes, wind, additional snowfall) or artificial (triggered by a human or animal).
With smell receptors ranging from 800 million for an average dog, to 4 billion for scent hounds, canines remain key to finding people caught in slides.
With data from two sites in British Columbia and one in Switzerland, researchers built computer simulations of five different avalanche types. “In terms of real time avalanche forecasting, this has potential to fill in a lot of data gaps, where we don't have field observations of what the snow looks like,” says Simon Horton, a postdoctoral fellow with the Simon Fraser University Centre for Natural Hazards Research and a forecaster with Avalanche Canada, who participated in the study. While complex models that simulate snowpack layers have been around for a few decades, they weren’t easy to apply until recently. “It's been difficult to find out how to apply that to actual decision-making and improving safety,” says Horton. If you can derive avalanche problem types from simulated snowpack properties, he says, you’ll learn “a lot about how you want to manage that risk.”
The five categories include “new snow,” which is unstable and slides down the slope, “wet snow,” when rain or heat makes it liquidly, as well as “wind-drifted snow,” “persistent weak layers” and “old snow.” “That's when there's some type of deeply buried weak layer in the snow that releases without any real change in the weather,” Horton explains. “These ones tend to cause the most accidents.” One step by a person on that structurally weak layer of snow will cause a slide. Horton is hopeful that computer simulations of avalanche types can be used by scientists in different snow climates to help predict hazard levels.
Greene is doubtful. “If you have six slopes that are lined up next to each other, and you're going to try to predict which one avalanches and the exact dimensions and what time, that's going to be really hard to do. And I think it's going to be a long time before we're able to do that,” says Greene.
What both researchers do agree on, though, is that what avalanche prediction really needs is better imagery through satellite detection. “Just being able to count the number of avalanches that are out there will have a huge impact on what we do,” Greene says. “[Satellites] will change what we do, dramatically.” In a 2022 paper, scientists at the University of Aberdeen in England used satellites to study two deadly Himalayan avalanches. The imaging helped them determine that sediment from a 2016 ice avalanche plus subsequent snow avalanches contributed to the 2021 avalanche that caused a flash flood, killing over 200 people. The researchers say that understanding the avalanches characteristics through satellite imagery can inform them how one such event increases the magnitude of another in the same area.
Avy dogs trainers hide in dug-out holes in the snow, teaching the dogs to find buried victims
Sarah McLear
Lifesaving combo: human tech and Mother Nature’s gear
Even as avalanche forecasting evolves, dogs with their built-in rescue mechanisms will remain invaluable. With smell receptors ranging from 800 million for an average dog, to 4 billion for scent hounds, canines remain key to finding people caught in slides. (Humans in comparison, have a meager 12 million.) A new study published in the Journal of Neuroscience revealed that in dogs smell and vision are connected in the brain, which has not been found in other animals. “They can detect the smell of their owner's fingerprints on a glass slide six weeks after they touched it,” says Nicholas Dodman, professor emeritus at Cummings School of Veterinary Medicine at Tufts University. “And they can track from a boat where a box filled with meat was buried in the water, 100 feet below,” says Dodman, who is also co-founder and president of the Center for Canine Behavior Studies.
Another recent study from Queens College in Belfast, United Kingdom, further confirms that dogs can smell when humans are stressed. They can also detect the smell of a person’s breath and the smell of the skin cells of a deceased person.
The emerging avalanche-predicting human-made tech and the incredible nature-made tech of dogs’ olfactory talents is the lifesaving “equipment” that Leffler believes in. Even when human-made technology develops further, it will be most efficient when used together with the millions of dogs’ smell receptors, Leffler believes. “It is a combination of technology and the avalanche dog that will always be effective in finding an avalanche victim.”