HUTCH MAGAZINE 2015 / SUMMER

RIPPLE EFFECT Cord blood transplants,immunotherapy buildon BMT’s foundation

SECOND CHANCE Jenna Gibson, 12,owes her life to a

cord blood transplant

DECADES OF CHANGE BMT has evolved

dramatically in 40 years;one man has seen it all

THE

BONE MARROW

TRANSPLANT

ISSUE

FRED HUTCHINSON CANCER RESEARCH CENTERSUMMER 2015

BECAUSE OF ONE LIFE,

MILLIONS WERE CHANGED

Dr. E. Donnall Thomas pioneered bone marrow transplantation.

His work continues to shape the future of cancer care.

Q&A ‘The successes kept you going’Dr. Fred Appelbaum recounts 40 years of difficult and exhilarating advances in bone marrow transplantation. Photo by Robert Hood / Fred Hutch

BY MARY ENGEL / 4

BMT UNIVERSE

Bone marrow transplants and beyond Developed to treat leukemia, blood stem cell transplants gave rise to a universe of new therapies for an ever-growing number of patients and conditions.

BY DR. RACHEL TOMPA / 14

TABLE OF CONTENTS

ON CAMPUS

Letter from the directorBY DR. GARY GILLILAND / 3

PATIENT PROFILE

‘This little bag of cells is going to save her life’BY JENNA AND JULIE GIBSON, AS TOLD TO SUSAN KEOWN / 16

Dr. E. Donnall Thomas pioneered BMT at Fred Hutch. Photo by Susie Fitzhugh / Fred Hutch file

O N T H E C O V E R

Coming homeNearly 200 bone marrow / stem cell transplant survivors returned to Fred Hutchinson Cancer Research Center July 24-25, 2015, for the seventh Bone Marrow Transplant Survivor Reunion. Many of their donors, families and caregivers also attended the poignant gathering, held every five years. The survivors, shown below, were transplanted between five and 42 years ago. Photo by Robert Hood / Fred Hutch

FEATURE One life, a world of possibilitiesEach life saved since Dr. E. Donnall Thomas pioneered bone marrow transplantation decades ago offers untold promise. Meet Savanna Acosta, a toddler who now has a full life ahead of her thanks to a transplant. Photo by Bo Jungmayer / Fred Hutch

BY BILL BRIGGS / 6

GRAPHIC How transplants workOur step-by-step guide to the ins and outs of transplantation.

BY ANDREA DETTER AND JIM WOOLACE / 10

HUTCH MAGAZINE 2015 / SUMMER 5

Celebrating our transplant legacy, our patients’ courageTHIS IS A TRULY AMAZING TIME FOR CANCER RESEARCH AT FRED HUTCH. This is, after all, the

place where blood stem cell transplantation was pioneered, giving researchers the first clear

insights into the potential of the immune system to cure cancer.

This issue of our newly renamed Hutch Magazine looks back on this legacy. In the 40 years

since Fred Hutch officially opened its doors on Sept. 5, 1975, work by Dr. Don Thomas and

others in curing leukemia through transplantation has led directly to many other advances,

including today’s breathtaking progress in immunotherapy — harnessing the power of our

own immune system to treat cancer. We believe these innovations will lead to cures for many

cancers, including solid tumors, not in another 40 years but perhaps much sooner.

I wish Don were here to see all the excitement around these new modalities. He would not

only be excited himself, he would be helping us ride the crest of the wave.

You’ll read in these pages about the people who were here to help celebrate — all those

who attended our seventh BMT Survivor Reunion in July. The reunion honors the courage

of our transplant recipients and their families, who provide such incredible support. It also

celebrates the wonderful job Fred Hutch does building on Don’s legacy.

But mostly, the reunion is for the patients, for them to spend time with people who know,

like no one else, what they went through, what it’s like to face death and emerge with new life.

For me, and for all who participate, the reunion is an emotional event — seeing patients

celebrating with their donors, even while remembering the very difficult times. We also

remember with sadness those who didn’t survive despite heroic efforts. And we think of

those who may not survive long enough to benefit from the newest lifesaving medicines in

development.

The reunion reminds us that it is the people — those who have survived cancer and those

who haven’t — who send us back to our labs with renewed motivation and a real sense of

urgency. Hearing their stories reminds us of what we’re all working toward.

That’s why I’m glad we’ve started Share Your Story, where patients, caregivers and

researchers can talk about why what we do matters. You can see some of these stories in

Hutch Magazine and more at fredhutch.org/MyStory and at our new campus visitor center

that will open in September. We invite you to share your own story, to become part of this

exciting, extraordinary moment as we work together toward cancer cures.

Dr. Gary GillilandPresident and Director

FROM THE DIRECTOR

Dr. Gary GillilandPhoto by Robert Hood / Fred Hutch

Fred Hutch’s passionate researchers are changing lives with their breakthrough science.

Get the latest news at fredhutch.org.

3

Dr. E. Donnall Thomas and his wife, Dottie, pioneered bone marrow transplantation,

saving countless lives. By including Fred Hutch in their estate plans,

they fueled more lifesaving research.

Be part offuture cures

with a giftthrough your estate.

206.667.3396 / fredhutch.org/plannedgiving

Help us discover future cures by including Fred Hutchinson Cancer Research Center

in your will or trust or as a charitable beneficiary of a retirement account or insurance policy.

Fred Hutch file

HUTCH MAGAZINE 2015 / SUMMER 5

BY MARY ENGEL

Write to Mary Engel atmengel@fredhutch.org

Dr. Fred Appelbaum recounts 40 years of difficult and exhilarating advances in

bone marrow transplantation

The successeskept you going

‘’

4

Can you tell us about the early days of transplantation?

DR. FRED APPELBAUM: In the early- to mid-1970s, the first patients being transplanted were patients whose life expectancy was measured in weeks to months. These end-stage patients were already very sick, they had very advanced leukemia, and so the cure rates were very low, in the range of 15 percent. That meant that eight or nine out of 10 patients would not be cured. That was really, really hard. But we had some patients who went into remission — there was no leukemia there. And they came back [to the Hutch] in six months, they came back in a year, and they came back at two years. Oh my God, this patient was really cured. That was incredibly exhilarating. They’d been brought back literally from the jaws of death.

How did you stay optimistic when so many patients didn’t survive?

It was hard because you failed so many times in a row, but the successes just pumped you up and kept you going. And of course Don Thomas was just a giant of a man in both his personality and his vision, and having a leader like that was absolutely instrumental.

How did advances in controlling nausea, infections and pain help?

You might think of an antiemetic — a medicine that keeps you from vomiting — as trivial. But the drugs we were using were so nauseating and the vomiting was so severe that people would aspirate some of the vomitus and bring it back into their lungs, which would set them up for pneumonias. Just a thing that seems a minor advance really made a huge difference in the ability of people to tolerate the transplant procedure.

Also [Dr. Robert] Hickman [a founding member of the Hutch transplant team] figured out a way to place catheters so you could give intravenous alimentation [nutrition] throughout the procedure. People would lose so much weight until Bob

figured out a way to allow us to give those fluids through a central vein. All these things added up to much better supportive care that allowed people to get through this very difficult procedure.

What has changed in terms of how you screen stem cell donors?

Before 1980, the only people who could donate were essentially brothers and sisters who matched. Only about a third of the population has a matched sibling. Then we did the first matched unrelated transplant [for a patient with leukemia] in the late 1970s. Today there are over 21 million individuals worldwide who have been HLA-typed [human leukocyte antigens used for determining a match] to serve as unrelated donors.

Tell us about the first unrelatedtransplant.

A 10-year-old girl, Laura Graves, had acute lymphocytic leukemia and had already failed first-line chemotherapy. Her dad was [Dr. Robert] Graves [from Fort Collins, Colorado.] Bob had done enough reading that he knew that Laura’s HLA type was a common one. He came here and said, “You know, I’ll bet you could find a donor for my daughter.” [There were no matches within the family.]

Lo and behold, one of our technicians matched Laura Graves. So we then talked to the Institutional Review Board, and everyone said to go ahead. We did the transplant. Laura went into complete remission and did very well for about two years. Unfortunately, her leukemia came back, and she did eventually die. But the transplant itself, the nuts and bolts of the transplant, actually went very, very well.

Bob Graves realized that HLA typing is so variable that you’d need a really large registry if you’re going to make this more generally available. So Bob developed the Laura Graves Foundation to help support development of such a registry. And eventually, Bob Graves and Don Thomas met Admiral Elmo R. Zumwalt Jr., whose son came here for a transplant. Elmo helped get funding for the National Marrow Donor Program [now called Be The Match] that provides all these unrelated donors.

How did transplantation lead to today’s advances in immunotherapy?

When you do a transplant, you’re putting a new immune system into the patient, and this new immune system from the donor can see the leukemia cells as being foreign and reject them. And then our task became, OK, can we, in fact, identify the cells that are doing that and can we augment that effect?

One of the problems with transplantation is that, yes, the new immune system can come in and see the leukemia and get rid of it. But that new immune system also could react against other tissues in the patient’s body. When that happens it is called graft-vs.-host disease. Our task over the last 30 years has been to try and segregate the graft-vs.-leukemia effect from the graft-vs.-host effect. The trick in doing that is to find targets that are expressed by the leukemic cells but not by other tissues in the body.

The second thing you have to do is find cells from the donor that can see those targets and react against them. We can find some of them but oftentimes there are too few or they react too weakly or they survive for too short a period of time. So now we’re able to take cells from the donor and genetically manipulate them to specifically see that target on the leukemic cell. And we can expand them into large numbers and watch as they go back into the patient, see the leukemia, react against it, kill the leukemic cells and watch those patients go into remission or stay in remission and potentially be cured.

Of course there’s no reason you can’t take [these T cells] from the patients themselves [instead of from donors]. So you can get rid of the whole idea of the transplant now and do these so-called adoptive immunotherapies, where we’re taking out these T cells from the patient and giving them back to the patient, eradicating their leukemia. These are still clinical trials. We have a long way to go, but it is really incredibly exciting.

Impressively, we also have data that what we’re doing may not be restricted to leukemia and lymphoma, that we may be able to do this in the common solid tumors — including diseases like breast cancer and lung cancer and melanoma — and even the deadliest of the diseases like pancreatic cancer. If that happens, then the legacy of transplantation will be absolutely astounding.

Dr. Fred Appelbaum Photo by Robert Hood / Fred Hutch

DR. FRED APPELBAUM was a medical student in

1970 when he stumbled upon Dr. E. Donnall Thomas’

initial description of bone marrow transplantation in

a medical journal. He was transfixed.

“I thought it was so cool that this was even

possible,” said Appelbaum, now deputy

director and executive vice president of

Fred Hutchinson Cancer Research Center.

In 1978, he leapt at the chance to work

alongside Thomas at Fred Hutch,

helping to refine the pioneering

technique that transformed

leukemia and related cancers,

once thought incurable, into

highly treatable diseases.

Today more than 1 million

people around the globe have

received blood stem cell transplants

to treat dozens of different diseases,

and researchers at Fred Hutch continue

to build on that work to find innovative new

treatments. Recently, Appelbaum sat down to talk

about 40 years of transplants at Fred Hutch, from

the early, heart-wrenching challenges to the latest

innovations in immunotherapy, which harnesses

the body’s own immune system to fight cancer.

Q&A

BY BILL BRIGGS

THE NUMBERS ARE SO VAST,

the hope and healing they

embody seem difficult to

grasp. Globally, doctors have

performed more than 1 million

bone marrow / stem cell

transplants — a procedure

pioneered at Fred Hutchinson

Cancer Research Center. A

national marrow donor registry

inspired by a Fred Hutch patient

has facilitated more than

68,000 transplants. And, since

1975, more than 14,000 people

have received transplants at the

Hutch. Yet to truly fathom the

depth of all those lives restored,

sometimes it requires one

patient’s story: Savanna Acosta

was going to die. But she didn’t.

Dr. E. Donnall Thomas’ pioneering work in

bone marrow transplantation has allowed countless people

to have futures full of rich promise — including little

Savanna Acosta.

ONE LIFE – AND A WORLD OF POSSIBILITIES

Savanna Acosta, 23 months old, meets Pam Dicaire, her stem cell donor, during

Fred Hutch’s Bone Marrow Transplant Survivor Reunion on July 25, 2015. Also

on stage were, left to right, Savanna’s mother, Athena Gomez, Pam’s daughter,

Shaelynn, and Pam’s husband, Kevin. Photo by Robert Hood / Fred Hutch

98

“I feel like I’ve been very blessed with the

opportunity to see my children be raised to adulthood, and now they’re in school and starting to

be productive in society — it gives me great satisfaction.”

Dana Smith, Spokane, Wash.Transplant: 1996

“[Cancer] has given me an appreciation for life — how short it

is, and how beautiful it can be — and for the people who spend their lives committed to research and helping people with deadly

diseases. When that [diagnosis] moment arrives … It’s like falling off a ladder or a traffic accident. Your life changes in an instant and you know it’s never

going to be the same again.”

Kim Murphy, Victoria, TexasTransplant: 1998

“I couldn’t imagine

being anywhere else [than Fred Hutch] ... It’s so very therapeutic.

Just opening the window and catching the breeze, or hearing the seagulls — it’s

very Zen like. It’s a very healing environment. The little things helped me turn the

corner and helped me move forward with myself.”

Tanisha King, HoustonTransplant: 1994

SHE WAS BORN AUG. 28, 2013, seemingly healthy. Her genes, however, hid a fatally flawed immune system that left her body defenseless against even the most common germs. The first symptom surfaced when she was 2 months old and began developing toe-to-head rashes.

Initially, doctors believed she had cradle cap. But when her third rash flared, physicians also spotted swollen lymph nodes and abnormalities in Savanna’s blood work. The diagnosis: severe combined immunodeficiency (SCID). Her body did produce T cells — the so-called “generals” of the immune system — but those cells didn’t function. In layman’s terms, she had “bubble boy disease” — the affliction made famous by David Vetter, a Texas boy who had SCID and inspired the making of the 1970s movie “The Boy in the Plastic Bubble.”

Savanna had one chance — a stem cell transplant. With an infusion of a donor’s healthy stem cells, her body could grow a new immune system built on the donor’s DNA. Without a transplant, she would likely suffer multiple organ infections and not survive beyond her first or second birthday, doctors familiar with the disease said.

For her family, the choice was simple.“She’s my life,” said Savanna’s mother, Athena

Gomez, a certified nursing assistant who lives in Lakewood, Washington. “It was the only way to fix it.”

Savanna’s family members were tested for possible matches of white blood cell proteins

called human leukocyte antigens (HLA). A perfect match is key to reducing serious post-transplant complications. No familial matches were found.

Time was critical. If Savanna received a transplant before she fell

ill with a life-threatening infection, her physician said, the chances of survival were well above 95 percent.

* * *

IN THE MID-1970S, BMTs were considered radical. The first successful transplant was done in Cooperstown, New York, in the late 1950s involving two identical twins, one with leukemia. Dr. E. Donnall Thomas performed the procedure. In 1975, Thomas moved his research to Fred Hutch, then a new facility with a new clinical focus: refining Thomas’ promising groundwork. The first patients being transplanted had advanced leukemia.

“We had some [BMT] patients who went into remission — there was no leukemia there,” recalled Dr. Fred Appelbaum, who joined the Hutch in 1978. Today, he serves as the center’s deputy director and executive vice president.

Those first lives saved still stir Appelbaum. In early 2015, a woman who underwent a transplant at the Hutch 30 years ago returned to see him. She brought a photo album.

“These pictures through the years. … Her kids were really small then, now they’re grown. And you see the family pictures and the grandkids. That’s really nice.”

In 1979, Fred Hutch doctors hit another milestone, performing the first successful transplant with HLA-matching cells harvested from a donor who was not in the patient’s family. The recipient was Laura Graves, a 10-year-old girl with acute lymphocytic leukemia. Her matched donor was a Hutch laboratory technician.

* * *

AFTER SAVANNA’S DIAGNOSIS, doctors allowed her to go home with her mom — with crucial caveats. Given her defective immune system, the baby had to be kept out of crowds, and only her family was allowed physical contact.

Gomez, 33, decided to confine herself and her daughter to a recreational vehicle outside her

Mother-donor moment: Savanna’s mom, Athena Gomez, left, shares pictures with Pam Dicaire, Savanna’s stem cell donor, moments after meeting for the first time at Fred Hutch’s Bone Marrow Transplant Survivor Reunion. Photo by Bo Jungmayer / Fred Hutch

SHARE YOUR STORYNearly 200 transplant survivors attended the seventh Bone Marrow Transplant Survivor Reunion at Fred Hutch. Every survivor has an incredible story. Here are just a few.

parents’ home. It became their temporary cocoon. “You know the movie ‘The Boy in the [Plastic]

Bubble’? She had to be [the] girl in a bubble,” Gomez said.

Their stay lasted just one week. On the Monday before Thanksgiving 2013, Gomez awoke and thought her daughter looked seriously ill. She drove Savanna to Tacoma General Hospital. The baby’s condition rapidly worsened.

“Her temp went down to 96.5 [degrees]. She was going into hypothermia. She turned purple. She was starting to shut down,” Gomez said.

An ambulance transported Savanna to Seattle Children’s Hospital where she was stabilized with IV fluids and antibiotics. Doctors told Gomez her daughter would remain hospitalized until the transplant.

But the donor hunt wasn’t going perfectly. At Seattle Cancer Care Alliance, Fred Hutch’s

treatment arm, search specialist Laurie Corner had found about 30 potential donors by combing bone marrow registries around the world. From their genetics, Corner determined some were only “suitable matches” for Savanna, meaning they matched nine out of 10 antigens, raising the odds of post-transplant complications. Some were not available to donate.

With time short and Savanna hospitalized, Corner asked one of the suitable matches to donate. Then, fresh information surfaced about a registered donor in New Brunswick, Canada. Pam Dicaire, a former flight attendant, was a 10-out-of-out-10 match to Savanna. She agreed to donate.

“The woman who called said it was an urgent case,” Dicaire recalled. “It felt like the lottery. I mean, how in the world could I be a match for someone when her own relatives aren’t? … Once I made the decision to do it, there was no turning back because [the recipient] could die.”

* * *

THE NOTION OF A BONE MARROW REGISTRY in North America grew out of that first successful unrelated donor transplant, performed at Fred Hutch in 1979.

Laura Graves’ family was so inspired by the potential of unrelated transplants that it led an effort to launch a donor database. That list grew into the National Marrow Donor Program’s Be The Match, which has managed the largest marrow

registry in the world, spanning nearly 12.5 million potential donors, the organization states.

The early discoveries about bone marrow transplants, pioneered by Hutch scientists, provided the first definitive evidence that the immune system could fight cancer — that a healthy donor’s stem cells could cure a transplant recipient of blood cancer. Researchers also discovered that non-cancerous diseases, like SCID, could be reversed.

Those gains helped spark the modern age of immunotherapy — a family of cancer treatments that harnesses the disease-fighting power of a patient’s own immune system, said Dr. Gary Gilliland, Fred Hutch’s president and director.

“We are on the threshold of amazing advances in the treatment of cancer,” Gilliland said.

“The thing that I’m so excited about,” Appelbaum said, “is to see if we really can take what now appears to be our ability to engineer T cells and combine it with things that take the brakes off the immune system to make a difference in solid tumors. … Some of the responses that we’re seeing in melanoma — and in some cases of lung cancer and bladder cancer — are truly enduring.”

* * *

SAVANNA WAS TRANSPLANTED ON JAN. 20, 2014. Her body rallied. In late April, she was

discharged from Seattle Children’s. “She wasn’t crawling yet when we left. But when

we got home, from the end of April to November [2014], she learned how to crawl, walk and run,” Gomez said.

By July 2015, Savanna had been weaned off of her post-transplant medications. Doctors were vaccinating her new immune system. She even met Dicaire, her donor, at Fred Hutch’s seventh Bone Marrow Transplant Survivor Reunion, which drew close to two hundred survivors.

Savanna is so energetic she rarely naps, her mother said. She smiles while playing in the dirt outside with her cat, Tigger. She loves dancing. She enjoys car rides.

“She likes to help. If you’re folding clothes, she’ll try to fold with you. If she makes a mess on the floor, she’ll get a towel to clean it up. She’s pretty much a happy baby,” Gomez said.

“If you look at her now, you wouldn’t even know what she went through.”

Read more at fredhutch.org/MyStory

Write to Bill Briggs atbbriggs@fredhutch.orgFEATURE

“I do feel [my blood cancer diagnosis] gave

me the opportunity, after my treatment and cure, to be able to give

back and pay it forward and help others in need, and try to motivate people

to help others by becoming bone marrow donors.”

Jay Feinberg, Boca Raton, Fla.Transplant: 1995

Darrell Barstow, Puyallup, Wash. Transplant: 1998

“In some ways, I’m almost glad I had the cancer. It’s easy

for me to say that because I had a very good outcome, but because of

what I’ve gone through, I appreciate and enjoy things so much more now than I

otherwise would have.”

1975 1986 1990 2012

BONE MARROW TRANSPLANT INS AND OUTS

1 Preparation

Steps in the transplant process

2 Stem CellCollection

3 Pre-TransplantConditioning

6 Recovery

Hickmancatheter

Apheresismachine

Pelvicbone

Cord bloodunit

bethematch.org or giftoflife.org.

Autologous Allogeneic

A SIGN OF SUCCESS

Learn more or consider becoming a bone marrow donor. Go to:

4 Stem Cell Infusion

5 Engraftment

A few days after conditioning, patients receive stem cells intravenously, which then flow through the bloodstream and settle in the marrow. The infusion can last several minutes to several hours depending on the volume of cells delivered.

For the next 100 days, patients get daily or weekly check-ups to track their progress and monitor for infections and other complications. It can take a year or more for blood counts to normalize and the new immune system to work well.

Engraftment is when the donated cells (the graft) take root in the bone marrow and begin to make healthy new red blood cells, white blood cells and platelets. It can take 10 days to several weeks and eventually changes the patient’s blood type to that of his or her donor.

TRANSPLANT’SYIN AND YANGRoughly half of

allogeneic transplant patients experience

graft-vs.-host disease, a potentially

life-threatening complication that

arises when donated cells attack the

patient’s healthy tissues.

A related phenomenon, called

the graft-vs.-leukemia effect,

occurs when donated immune cells recognize the

patient’s cancer as foreign and attack it. The discovery of this

effect is a cornerstone of modern cancer

immunotherapy since it revealed that the

human immune system has the ability to eliminate tumors.

FINDINGA MATCH

Transplant success hinges on finding the

right donor. Allogeneic transplant patients and donors

are matched by immune molecules

called human leukocyte antigens.

HLA matching minimizes graft

rejection and GVHD.If a patient has no matching relative, specialists search

national and international

registries to find a volunteer donor.

If no match can be identified, patients may be able to use

cord blood stem cells, which don’t need to be

as closely matched.

The number of transplants performed has grown dramatically as Hutch research and training boosted

the procedure's success and availability.

Blood stem cells are collected from one of three sources:

Circulating, or peripheral, blood: Donors get an injection to make — and release into the blood — more stem cells. A few days later, an apheresis machine sifts 12 ounces of stem cells from the donor’s blood and returns the rest to the donor through another vein. Cells can be used immediately or frozen until the patient is ready.

Bone marrow: 1-2 quarts of marrow, which the body replaces in a month, are drawn out of the pelvic bones with a needle.

Umbilical cord blood: About 5 teaspoons of stem cells are collected from an umbilical cord donated after a baby is born. The cells are then frozen for future use.

Bone marrow and blood stem cell transplantation is one of the greatest success stories in cancer care. Pioneered at Fred Hutch by Dr. E. Donnall Thomas, who won the 1990 Nobel Prize in physiology or medicine for his work, and steadily refined by Hutch teams over four decades, the treatment has transformed survival rates for some leukemias and other blood disorders from zero to upwards of 90 percent. For patients with certain diseases, it remains the only therapy available with the potential to cure.

Doctors conduct a thorough exam to confirm the best type of transplant.

Autologous transplantPatient serves as their own stem cell donor. Most commonly used for patients with lymphomas.

Allogeneic transplantSomeone other than the patientdonates stem cells. Most commonly used for patients with leukemias, blood disorders like aplastic anemia and immunodeficiencies.

Thomas publishes first indication that BMT could cure some patients

1976Hutch establishes first pediatric BMT program

1978Hutch teams recognize that the transplanted immune system can eliminate the patient’s cancer, laying the foundation for modern cancer immunotherapy

1979Successful transplant from a matched, unrelated donor at Fred Hutch opens door to registries of volunteer marrow donors

Hutch researchers first treat GVHD with methotrexate and cyclosporine, now the gold standard

Hutch team is first to use non-invasive method to detect cytomegalovirus, and ganciclovir to prevent CMV-related pneumonia, boosting survival and launching new era in infectious disease research

1991Hutch is first to use peripheral blood stem cells, simplifying donation and speeding engraftment

1997Hutch researchers introduce regimens of reduced intensity for older patients and those with medical complications

2005Hutch scientists develop new method for multiplying stem cells to make cord blood transplants an option for more patients with no matched adult donor

World’s1 millionth transplant performed

Next, the patient’s body is prepared to receive the new cells.

A Hickman catheter — developed at Fred Hutch by Dr. Robert Hickman — is surgically implanted to administer drugs and take blood samples without repeated needle sticks.

Over the course of a week, patients receive high doses of chemotherapy, total body irradiation or both to eliminate as much of the cancer (or other disease-causing cells) as possible and reduce the chances an allogeneic transplant will be rejected. This preparative regimen leaves patients highly vulnerable to infections.

Some patients undergo regimens of reduced intensity. Pioneered by Fred Hutch’s Dr. Rainer Storb, these regimens use lower doses of chemotherapy and radiation that aren’t as toxic. They have extended transplantation to patients who are older or have additional medical complications.

Design: Jim Woolace; Reporting: Andrea DetterPhotos: Bo Jungmayer, iStock, Dr. Cecilia Yeung

Sources: Fred Hutch, SCCA, Be The Match, Center for International Blood and Marrow Transplant Research, Appelbaum FR. N Engl J Med 2007;357:1472-5

200,000

150,000

100,000

50,000

019901980 2000 2010 2013

320,000 transplants in the U.S. alone as of 2013

THE ROLE OF BONE MARROW

Bonemarrow

Typesof blood

cells

Bloodstem cells

that generate thecomponents ofthe blood and

immune system:

infection-fightingwhite blood cells,oxygen-carryingred blood cellsand platelets,

which helpblood clot.

Marrow containsblood stem cells

After transplant, healthy cells repopulate the marrow

Marrow with almost no functioning stem cells

HUTCH MAGAZINE 2015 / SUMMER 1312

TOP: Bina Sugumar, a research tech in the Susan Parkhurst Lab, shows fruit flies to Bone Marrow Transplant Reunion attendees on July 24 at Fred Hutch. Photo by Bo Jungmayer / Fred Hutch

BOTTOM RIGHT: Jessica Horton, right, reads her daughter Molly’s “I am grateful for” card. Linda Horton, Jessica’s mother and Molly’s grandmother, looks over her shoulder. Molly, 13, is a seven-year BMT survivor. The Hortons are from Gig Harbor, Wash. Photo by Robert Hood / Fred Hutch

BOTTOM LEFT: Molly Horton’s “grateful” card. Photo by Robert Hood / Fred Hutch

Grateful survivors gather at BMT reunionNEARLY 200 FORMER PATIENTS attended the seventh Bone Marrow Transplant Survivor Reunion at Fred Hutch on July 24-25, 2015. Transplant recipients and their donors, families and caregivers shared stories, heard presentations about new advances in treatment, saw labs where groundbreaking research is taking place and celebrated with a reception at Seattle’s Museum of History & Industry. “This weekend is to honor all of you,” said Dr. Fred Appelbaum, Fred Hutch deputy director and executive vice president.

VIEW MORE PHOTOS ONLINE ATFREDHUTCH.ORG/

REUNION

TOP: Bone marrow transplant reunion attendees acknowledge Dr. Rainer Storb as his professional accomplishments are read during his introduction at the BMT reunion on the Fred Hutch campus in Seattle on July 24. Photo by Robert Hood / Fred Hutch

MIDDLE LEFT: Cindi Cervone and her husband, David, a 30-year transplant survivor from Sterling Heights, Mich., listen to Dr. Fred Appelbaum speak during the welcome reception. Photo by Robert Hood / Fred Hutch

BOTTOM LEFT: Kate Pittman, from Lilburn, Ga., hugs a fellow survivor at the BMT reunion at Fred Hutch. Photo by Bo Jungmayer / Fred Hutch

BOTTOM RIGHT: Fred Hutch President and Director Dr. Gary Gilliland thanks BMT survivors and their families for helping to push cancer research forward during his speech at the BMT reception July 25 at Seattle’s Museum of History & Industry. Photo by Robert Hood / Fred Hutch

WHEN DR. E. DONNALL THOMAS first pioneered bone marrow transplantation in the 1960s and 1970s, his goal was to treat patients with advanced leukemia — at the time, a nearly universal death sentence. Today, thousands of patients with blood cancers around the world are cured every year thanks to modern forms of transplantation, and the procedure is also used for dozens of other diseases besides leukemia, with many more in the research pipeline.

Most importantly for the future of cancer therapies, it was Thomas and his colleagues’ work developing bone marrow transplantation at the newly founded Fred Hutchinson Cancer Research Center that revealed the potential for the human immune system to eliminate cancer.

Although the researchers originally aimed to cure leukemia by eradicating patients’ malignant white blood cells with high doses of chemotherapy and radiation, and then replacing them with healthy donor cells, they found something unexpected — when a cancer patient received a transplant from an identical twin, their disease often roared back within mere months of the transplant.

But patients who received cells slightly different from their own — from donors such as siblings who were not genetically identical matches or even unrelated individuals — had much lower relapse rates. For these patients, the researchers

found that the unrelated donated immune cells were better able to recognize their cancer as “foreign” and attack it.

That observation launched decades of intense exploration by research teams at the Hutch and around the world into the immune system’s tumor-fighting potential. Ultimately, it laid the groundwork for the now-burgeoning field of immunotherapy, which uses a variety of techniques to harness or enhance the power of immune cells or molecules to precisely target malignant cells, sparing healthy cells the toxic side effects associated with traditional cancer treatments.

Immunotherapies represent just one of the families of treatments that continue to ripple out of transplantation, extending the reach of this landmark approach and its cousins to more and more patients. Researchers (many of whom trained under Thomas early in their careers) have built upon the foundation of transplantation new houses of treatment and cures for other diseases also once thought incurable. Thanks to one man’s dedication and stubborn pursuit of a technique many believed unachievable, scientists are now working to reverse disease-causing genetic mutations, offer curative transplants to every blood cancer patient in need and cure most cancers with a single infusion of disease-fighting immune cells or molecules.

A pioneering procedure’s expanding influenceDeveloped to treat leukemia, stem cell transplants gave rise to new therapies for an ever-growing number of patients and conditions

BY DR. RACHEL TOMPA THE BMT UNIVERSE

Bone marrow transplants

Pioneering work by Dr. E. Donnall Thomas and his colleagues at Fred Hutch made bone marrow transplantation a curative therapy for patients with certain blood cancers. Over the

years, their unique approach to refining the procedure and steadily building on discoveries has rippled into many other spheres of treatment — and continues to drive

new ideas that could translate into therapies for many more patients in need.

Supportive care

Methods developed to support transplant patients through the difficult procedure — like

food safety guidelines for immunocompromised patients and the Hickman line, an extended-use

catheter developed at the Hutch to deliver IV nutrition or chemotherapy and draw blood samples without

requiring patients to undergo hundreds of individual needle sticks — have helped shape the standard

of care for patients undergoing many other forms of treatment beyond transplantation.

Cord blood transplants

Using stem cells from donated umbilical cords, which don’t need to be

as stringently matched to the recipient as adult stem cells, cord blood transplantation

broadens options for the thousands of cancer patients every year who can’t find a

matched adult donor.

Mini-transplantsDeveloped at Fred Hutch, these gentler

versions of bone marrow transplantation brought the procedure’s curative power

to an older population not previously eligible for the more toxic preparations

of the traditional transplant.

ImmunotherapyThis collection of techniques developed at the Hutch

and at many other research centers around the world harnesses and boosts the body’s own ability to eliminate cancer

cells and is based on Thomas’ original observations of the immune system’s power to fight cancer. Whether through immune

molecules known as antibodies that can precisely recognize tumors, killer immune cells known as T cells engineered or

selected for their ability to home directly to and destroy cancer cells, or vaccines that can trigger the patient’s immune

system to prevent or treat cancer, immunotherapeutic approaches are already being used to treat certain

cancers. And many more techniques currently being tested are poised to change how we treat — and

cure — nearly all cancers.

Gene therapy What researchers have learned about both

transplantation and stem cells has broadened the possibilities for modern gene therapy.

Researchers at the Hutch and elsewhere are developing cutting-edge gene therapies that aim

to reach directly into patients’ genomes and correct disease-causing mutations or snip out hidden

viral DNA, thus curing genetic or viral diseases such as HIV, sickle cell disease, thalassemia, severe

combined immunodeficiency (SCID) and Fanconi anemia.

Broadeningtransplantation’s reach Today, blood stem cell transplants are used

for numerous forms of leukemia and lymphoma as well as dozens of other diseases, including myelodysplastic syndromes (MDS), multiple

myeloma, Wiskott-Aldrich syndrome, anemias and more, as well as for children with blood cancers.

Researchers are also testing transplantation to treat autoimmune disorders

such as Crohn’s disease.

Infectious disease

Because transplantation destroys much of their immune systems, patients are especially susceptible to infections, many of which can be

dangerous or even deadly. In an effort to improve transplant safety, Hutch teams have made seminal

contributions to understanding how to detect, prevent and treat many of the viruses and fungi

that can cause disease — work that also kicked off research that has impacted care for other immunocompromised people, including

organ transplant recipients and patients with HIV.

14

Write to Rachel Tompa at rtompa@fredhutch.org

16

‘This little bag of cells is going to save her life’ A girl and her mom remember a lifesaving transplant BY JENNA AND JULIE GIBSON, AS TOLD TO SUSAN KEOWN

JENNA GIBSON WAS DIAGNOSED with acute myeloid leukemia when she was 9 years old. She was treated with a cord blood transplant. She and her mother, Julie, shared their story.

JULIE: We took Jenna in to her pediatrician — it was March 5, 2012 — and her doctor looked at her, just one look, and said, “Huh, Jenna, something’s just not right.”

As soon as the doctor got the blood results back — it was just two hours — she was calling us and telling us to go to the ER at Seattle Children’s Hospital, immediately.

The word “surreal” gets overused. This, this was surreal, to have this moment. I can remember calling my husband, and telling him, “Hey, we’re on our way to Seattle Children’s,” and I’m using this voice that doesn’t match what I’m saying. I didn’t want to get Jenna all nervous if we didn’t have to. But when your pediatrician says, “The ER will see you immediately,” you know that’s not good.

JENNA: I took the diagnosis of leukemia pretty hard, just like anyone would, and I broke down in tears. I was really nervous to see what would happen to me.

JULIE: She went on one round of chemo, and it was after that round that they knew that chemotherapy alone was not going to be enough, she was labeled “high risk.” And it was at that point that they knew that she was going to have to have a bone marrow transplant.

One reason we were so devastated when we found out she was going down the transplant road is that you need a matched donor, and the first place they look is siblings. Jenna happens to be adopted, so we knew a sibling donor match was not an option. And secondly, the percentage of donors that are non-Caucasian is tiny. Jenna’s non-Caucasian.

When a matched bone marrow donor could not be found for Jenna, she got a cord blood transplant under the care of Fred Hutch’s Dr. Colleen Delaney. Cord blood is a lifesaving option for the thousands of patients every year who, like Jenna, need a transplant of blood stem cells but cannot find a matched adult donor.

It was amazing to watch those cells go into her. It’s just this little bag, and it’s so nonchalant. Because by then she’d had so many blood and platelet transfusions, for Jenna it was no different than any other type of transfusion, procedurally. But this is what was going to save her life. Going back to that word “surreal,” this is what that word is used for. Because it’s unbelievable: This little bag of cells is going to save her life.

In the end, she walked away from cancer treatment with just three rounds of chemo plus full-body radiation. There are kids that go rounds and rounds and rounds and rounds and rounds of chemo. So, hindsight’s 20/20 and we were devastated then [when we found out she would need a transplant], but we’ve praised God every day since.

We’re almost at three years, but at the five-year mark we can finally feel pretty confident that it’s not coming back. We’re looking forward to that.

Jenna Gibson, 13, and her mom, Julie, in their Maple Valley, Wash., home on March 20, 2015. Jenna survived leukemia when she was 9 years old. Photo by Robert Hood / Fred Hutch

Write to Susan Keown atskeown@fredhutch.orgPATIENT PROFILE

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Jessie Quinn with her husband, Brett Williams,

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FRED HUTCHINSON CANCER RESEARCH CENTER

Summer 2015 Vol. 38, No. 3

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DESIGNERS: Victoria Comfort, Sophia Kuo, Amy Lin, Kim Westphal and Jim Woolace

PHOTOGRAPHERS: Robert Hood and Bo Jungmayer

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At Fred Hutch, we tell the world about the incredible, life-changing science happening here, and we know the importance of being part of our community. To that end, and for the first time ever, we are opening the doors to a visitor center to showcase our research, tell our stories and give everyone who visits an opportunity to connect with us on a personal level. Starting in September 2015, you can visit our campus, learn how Fred Hutch continues to change lives and share your own story. Come with questions and leave inspired. Cures Start Here.

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EDITORS: Linda Dahlstrom, Andrea Detter, Joe Myxter and Kristen Woodward