Summer 2015 PDF - Fred Hutchinson Cancer Research Center

FRED HUTCHINSON CANCER RESEARCH CENTER
SUMMER 2015
THE
BONE MARROW
TRANSPLANT
ISSUE
RIPPLE EFFECT
Cord blood transplants,
immunotherapy build
on 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
HUTCH MAGAZINE 2015 / SUMMER
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.
Coming home
Nearly 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
TABLE OF
CONTENTS
FEATURE
Q&A
Each 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
Dr. Fred Appelbaum recounts 40 years of difficult and
exhilarating advances in bone marrow transplantation.
Photo by Robert Hood / Fred Hutch
One life, a world of possibilities
‘The successes kept you going’
BY MARY ENGEL / 4
BY BILL BRIGGS / 6
GRAPHIC
How transplants work
Our step-by-step guide to the ins and outs of transplantation.
BY ANDREA DETTER AND JIM WOOLACE / 10
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
ON CAMPUS
Letter from the director
BY 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
O N THE COVER
Dr. E. Donnall Thomas pioneered BMT
at Fred Hutch. Photo by Susie Fitzhugh /
Fred Hutch file
Fred Hutch’s passionate researchers are
changing lives with their breakthrough science.
Get the latest news at fredhutch.org.
FROM THE DIRECTOR
Celebrating our transplant
legacy, our patients’ courage
THIS 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.
Be part of
future cures
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
with a gift
through your estate.
Dr. Gary Gilliland
Photo by Robert Hood / Fred Hutch
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
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.
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.
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.
Dr. Gary Gilliland
President and Director
206.667.3396 / fredhutch.org/plannedgiving
Fred Hutch file
HUTCH MAGAZINE 2015 / SUMMER
3
5
Q&A
Dr. Fred Appelbaum recounts
40 years of difficult and
exhilarating advances in
bone marrow transplantation
‘The successes
kept you going ’
BY MARY ENGEL
DR. FRED APPELBAUM was a medical student in
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.
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.
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,
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.
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.
4
Dr. Fred Appelbaum
Photo by Robert Hood / Fred Hutch
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
HUTCH MAGAZINE 2015 / SUMMER
Tell us about the
first unrelated
transplant.
A 10-year-old girl, Laura Graves, had acute
lymphocytic leukemia and had already failed firstline 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.
Write to Mary Engel at
mengel@fredhutch.org
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.
5
ONE LIFE – AND A WORLD OF POSSIBILITIES
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
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.
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.
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
SHARE
YOUR STORY
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.
Nearly 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.
“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
***
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
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
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
“[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.”
Tanisha King, Houston
Transplant: 1994
Kim Murphy, Victoria, Texas
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.”
Darrell Barstow, Puyallup, Wash.
Transplant: 1998
“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
8
“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.”
FEATURE
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-ofout-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
Read more at
fredhutch.org/MyStory
Write to Bill Briggs at
bbriggs@fredhutch.org
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.”
9
BONE MARROW TRANSPLANT INS AND OUTS
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.
Steps in the transplant process
Apheresis
machine
1 Preparation
Bone
marrow
2 Stem Cell
Marrow contains
blood stem cells
Allogeneic transplant
Someone other than the patient
donates stem cells. Most commonly
used for patients with leukemias,
blood disorders like aplastic anemia
and immunodeficiencies.
A SIGN OF SUCCESS
The number of transplants performed has grown
dramatically as Hutch research and training boosted
the procedure's success and availability.
Allogeneic
Autologous
Types
of blood
cells
320,000 transplants in
the U.S. alone as of 2013
100,000
50,000
0
1980
infection-fighting
white blood cells,
oxygen-carrying
red blood cells
and platelets,
which help
blood clot.
1975
Thomas publishes first
indication that BMT could
cure some patients
1990
2000
2010 2013
Learn more or consider becoming a bone marrow donor. Go to:
bethematch.org or giftoflife.org.
Design: Jim Woolace; Reporting: Andrea Detter
Photos: 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
1976
Hutch establishes
first pediatric BMT
program
1978
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.
200,000
150,000
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.
Blood stem cells are
collected from one of
three sources:
Blood
stem cells
that generate the
components of
the blood and
immune system:
4 Stem Cell Infusion
Hickman
catheter
Collection
Doctors conduct a thorough exam to
confirm the best type of transplant.
Autologous transplant
Patient serves as their own stem cell
donor. Most commonly used for
patients with lymphomas.
THE ROLE OF
BONE MARROW
TRANSPLANT’S
YIN AND YANG
Hutch teams recognize that the transplanted
immune system can eliminate the patient’s
cancer, laying the foundation for modern cancer
immunotherapy
Conditioning
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.
1979
Pelvic
bone
1986
1990
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
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.
FINDING
A MATCH
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.
Hutch researchers first treat
GVHD with methotrexate and
cyclosporine, now the gold
standard
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.
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.
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
Cord blood
for future
unit
use.
Successful transplant from a
matched, unrelated donor at Fred
Hutch opens door to registries
of volunteer marrow donors
5 Engraftment
3 Pre-Transplant
Roughly 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.
1991
Marrow with almost no
functioning stem cells
After transplant, healthy
cells repopulate the marrow
6 Recovery
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.
Hutch is first to use
peripheral blood stem
cells, simplifying donation
and speeding engraftment
1997
Hutch researchers introduce
regimens of reduced intensity
for older patients and those
with medical complications
2005
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.
Hutch scientists develop new method
for multiplying stem cells to make cord
blood transplants an option for more
patients with no matched adult donor
2012
World’s
1 millionth
transplant
performed
Grateful
survivors
gather at
BMT 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
NEARLY 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.
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: 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
VIEW MORE
PHOTOS ONLINE AT
FREDHUTCH.ORG/
REUNION
BOTTOM LEFT: Molly Horton’s “grateful” card.
Photo by Robert Hood / Fred Hutch
12
HUTCH MAGAZINE 2015 / SUMMER
13
Write to Rachel Tompa at
rtompa@fredhutch.org
A pioneering procedure’s
expanding influence
Infectious disease
Cord blood
transplants
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.
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.
Developed to treat leukemia, stem cell transplants
gave rise to new therapies for an ever-growing
number of patients and conditions
BY DR. RACHEL TOMPA
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
14
Gene therapy
Mini-transplants
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.
Developed 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.
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.
Broadening
transplantation’s reach
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.
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.
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.
Immunotherapy
This 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.
PATIENT PROFILE
Write to Susan Keown at
skeown@fredhutch.org
Jessie Quinn with her
husband, Brett Williams,
their daughter Luna Williams
and dog Topo.
‘This little bag of
cells is going to
save her life’
Double your
gift
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.
through your
employer’s
match program.
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
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.
Your support helps patients like Jessie Quinn, whose life was saved
by a treatment pioneered by Dr. Colleen Delaney at Fred Hutch.
Maximize your support for lifesaving treatments today
by asking your employer to match your gift.
fredhutch.org/matchmygift
16
Photo courtesy of the Quinn family
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Summer 2015
Vol. 38, No. 3