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Bringing a leukemia treatment back to life with precision medicine

New research writes latest chapter in one drug's story

June 27, 2017 | by Susan Keown / Fred Hutch News Service

Art depicting an arrow hitting a tiny target, with larger target in the background

Researchers at Fred Hutch and around the world are zooming in on a specific group of patients who could benefit from a leukemia drug, called gemtuzumab ozogamicin (Mylotarg), that was pulled from the market seven years ago.

Illustration by Kimberly Carney / Fred Hutch News Service

Over its lifespan, the drug has starred in a drama with enough plot twists to rival a soap opera.

When gemtuzumab ozogamicin (Mylotarg) arrived on the scene in 2000, it was the first so-called “magic bullet” drug on the market, a targeted therapy that steers a cell-killing toxin to leukemia cells.

Then, 10 years later, it racked up another, more ignominious first. After a more extensive FDA-required clinical trial showed no clear evidence of the drug’s benefit to patient survival, it was the first medication to be withdrawn from the market after having been authorized through the FDA’s accelerated approval program, which is designed to speed urgently needed therapies to patients.

Now, new evidence may be bringing it back to life. Researchers are zooming in on a specific group of patients who could benefit from it in the latest example of the promise of precision medicine in cancer care. And its story offers important lessons about how we study new therapies, said one of the scientists whose research has helped lay the foundation for its reemergence.

“Our search for one drug that cures everything is really misplaced,” said pediatric leukemia specialist Dr. Soheil Meshinchi of Fred Hutchinson Cancer Research Center, where the drug was first developed more than two decades ago. “The drugs that failed in the past, [it] may not have been the drug’s failure but our failure to match them to the appropriate target.”

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What we can learn about global flu evolution from individual infections

Study of 10-year-old flu samples finds virus’s evolution in individual transplant patients partially mirrors later global trends

June 27, 2017 | By Rachel Tompa / Fred Hutch News Service

Illustration of a single person with stylized flu viruses standing in front of a global map with similar viruses

A new study using 10-year-old samples finds parallels between individual and global flu evolution patterns.

Illustration by Kim Carney / Fred Hutch News Service

A new study has found that flu evolution within some individuals can hint at the virus’s eventual evolutionary course worldwide.

Samples taken more than 10 years ago from people with unusually long flu infections — and analyzed recently using modern genome sequencing methods — revealed certain viral changes that matched global flu evolution trends several years later.

The study, published Tuesday in the journal eLife, tracked how flu evolved over time in four people who were especially vulnerable to unusually severe viral infections: bone marrow transplant patients. For people with healthy immune systems, a typical flu infection lasts about a week, said Fred Hutchinson Cancer Research Center evolutionary biologist and doctoral student Katherine Xue, first author on the study. So she and her colleagues at the Hutch, Seattle Children’s Research Institute and the University of Washington studied viruses that originated from patients who received transplants and developed severe flu infections that lasted two or more months.

These four patients were drawn from a group of nearly 500 transplant recipients who participated in a previous study led by Fred Hutch infectious disease researcher Dr. Michael Boeckh, also a co-author on Tuesday’s study. That large study began in 2005 to improve understanding about the sometimes-devastating impact of respiratory viruses in this vulnerable population — in fact, two of the four patients whose samples were analyzed in the current study went on to die of their infections.

Knowing what the flu virus does in a single infected person is important, Xue said, but it’s difficult to study because the typical flu infection is so short. Most research tracks how the virus changes on a global rather than on an individual level.

“We know that flu changes really quickly from year to year,” said Xue, who is also a student in the University of Washington’s Genome Sciences Department. “All that evolution has to start somewhere. It has to start with individual mutations that arise within people while they’re sick.”

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Understanding the night shift-cancer connection

New Fred Hutch study sheds more light on how shift work damages our health — and points toward a potential workaround

June 26, 2017 | By Diane Mapes / Fred Hutch News Service

Dr. Parveen Bhatti

Public health researcher Dr. Parveen Bhatti studies how night shift work (and day sleep) affects your body's ability to fight off cancer.

Photo by Robert Hood / Fred Hutch News Service

In 2006, just a year after graduating from nursing school, Nancy Krupienski took a position as a night nurse at a hospital near her home in Vernon, Connecticut. She worked 11 p.m. until 7 a.m. so she and her husband, who worked days, could grow their family and save on day care costs. Her sleep suffered “considerably” but the 31-year-old stuck it out, doing her best to catch up on sleep during her days off.

Three years and two babies later, her sleep was still bad — and so was her health, especially after her oldest child started school and began bringing home germs.

“I started getting sick,” said Krupienski, rattling off a host of ailments including respiratory infections, sinus infections, chronic stomach problems, acid reflux, gall bladder issues and more. “I could not catch a break.”

In 2014, Krupienski left nursing — and her onerous night shift — for a less stressful job at a high school. Her sleep returned to normal and her health improved dramatically. Then in November 2016, she learned she had breast cancer, a diagnosis that left her with a nagging suspicion.

“I always wonder if some sort of cell confusion occurs with night shift, reduced immunity and lack of sleep which could've had some sort of influence on me getting cancer,” said Krupienski, now 42. “I think my body was so worn out from so many years of lackluster sleep. Perhaps it triggered something that triggered the cancer.”

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A boy, his chicken and a bone marrow transplant

An experimental treatment — and an unconventional pet — offered both hope and healing for Andrew Adams’ rare and debilitating genetic disorder

June 23, 2017 | By Rachel Tompa / Fred Hutch News Service

Andrew Adams with his pet chicken on his shoulder

Andrew Adams with one of his pet chickens, Daisy Duke, in his home in Redmond, Washington. Andrew is five years out from a lifesaving bone marrow transplant.

Photo by Robert Hood / Fred Hutch News Service

If you drive by the Adams’ house — tucked at the end of a cul-de-sac in Redmond, Washington — there’s a decent chance you’ll spot Andrew Adams sitting on his front porch, quietly snuggling a chicken.

Andrew, who is 23, does many things quietly — he’s autistic and has little use for small talk. He also does many things with a chicken by his side. When Andrew is home, if he’s not sitting on the porch, he’s often playing video games in his room with his favorite bird — Daisy Duke — on his lap.

Daisy Duke is a stately, rotund Buff Orpington chicken with feathers the color of light caramel. She and her three fellow coop-mates act more like housecats than hens.

“They’ve been handled since they were chicks,” said Kristin Adams, Andrew’s mother.

Andrew calls them his “chickadees” and sometimes shares more with the birds than with his human family, Kristin said. In turn, the hens talk to him in a series of soft chirps and burbles. He’s been a chicken owner since the age of 8, when he instantly bonded with a little brown Araucana chick at a feed store that he named Frightful, after a hawk in a favorite book.

A few months after Frightful came into their lives, Kristin overheard her son telling his beloved pet that he thought his body was trying to kill him. Since birth, Andrew had experienced bouts of severe abdominal pain, high fevers and painful ulcers in his mouth that made eating impossible 

It would be months more before the family got anywhere close to understanding what was causing the symptoms. And it would be many more years before he finally received an experimental stem cell transplant at age 18 in a last-ditch effort to stop the ravages his immune cells were inflicting on his body.

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Lynann Bradbury joins Fred Hutch as vice president of Communications & Marketing

June 22, 2017 | By Andrea Detter / Fred Hutch News Service

Lynann Bradbury

“The prospect of elevating our brand and our great work nationally and internationally is an incredibly exciting challenge. And it’s an important one,” said Lynann Bradbury, Fred Hutch's new vice president of Communications & Marketing.

Photo courtesy of Lynann Bradbury

“Be purpose-conscious, not self-conscious.”

Over the years, this favorite phrase of her father’s became a maxim for Lynann Bradbury. It’s one she’ll continue to embrace in her new role as Fred Hutchinson Cancer Research Center’s vice president of Communications & Marketing, which she began June 19.

Clarity of purpose has always been paramount for Bradbury — as a communications strategist working with Microsoft and other technology companies, and through decades of community service in Seattle and around the world. Now tasked with building awareness and support for Fred Hutch, she will use purpose to align her skills and her team’s strategies with the goals of the organization.

“Lynann is a consummate communications and marketing professional who brings experience and connectivity that will enable us to promote the Hutch’s mission,” said Fred Hutch President and Director Dr. Gary Gilliland.

That mission proved magnetic for Bradbury.

“Clarity of purpose drew me to Fred Hutch,” she said. “No matter where you sit in the organization or what role you play, you know the ultimate purpose here is to cure cancer.”

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Good News at Fred Hutch

Celebrating faculty and staff achievements

June 22, 2017

Dr. Philip Bradley

"Our study is aimed at developing tools that would allow us to decode T-cell receptor sequences, which could improve diagnosis and treatment of a variety of human diseases and cancers," said Fred Hutch computational biologist Dr. Philip Bradley.

Photo by Stefanie Felix / Fred Hutch News Service

Researchers create a ‘Rosetta Stone’ to decode immune recognition

Scientists from Fred Hutch and St. Jude Children’s Research Hospital have developed an algorithm that functions like a Rosetta Stone to help decipher how the immune system recognizes and binds antigens. The study, published online Wednesday in the journal Nature, should aid development of more personalized cancer immunotherapy, and advance diagnosis and treatment of infectious diseases.

The immune system depends on molecules called T-cell receptors on the surface of T cells to recognize and respond to foreign antigens from virus-infected cells, tumors and other threats. Genomic rearrangement means that a large number of different T-cell receptors are possible. Each person can have about 100 million different receptors, referred to as their T-cell repertoire, with little overlap even in identical twins. Each receptor in the repertoire is capable of recognizing a different antigen and rallying the immune response to address that threat.

“Our immune repertoires contain detailed information on pathogen exposures, autoimmune diseases and cancer, but this information is encoded in the protein sequences of immune receptors and we don't currently have the ability to interpret these sequences, said Fred Hutch computational biologist Dr. Philip Bradley, co-corresponding author on the study along with St. Jude immunologist Dr. Paul Thomas. “Our study is aimed at developing tools that would allow us to decode T-cell receptor sequences, which could improve diagnosis and treatment of a variety of human diseases and cancers.”

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