A recurring nightmare
More than 30 years after Crystal Gully was declared cancer free, the disease came back. So she returned to MD Anderson where she beat the odds once before.
When 9-year-old Crystal Gully twisted her arm during school recess, the pain was intense.
“I thought the ache would subside,” says Gully, now 44, “but it got worse each day.”
Gully’s parents took her to the family doctor, who ordered X-rays. The result? No fractures. The third-grader’s arm was likely sprained, the doctor said, and would heal with time.
But her pain persisted, and Gully’s parents sought a second opinion. This time, the doctor ordered a blood test.
“He opened the results and his face just fell,” Gully recalls. “He told my parents, ‘This is not what we expected.’”
Gully was diagnosed with acute lymphoblastic leukemia, or ALL, the most common childhood cancer. The disease originates in the bone marrow where blood cells are made, and bone pain is a hallmark symptom.
The family was stunned. After leaving the doctor’s office, they stopped at a roadside diner for refreshments and to gather their thoughts.
“We decided MD Anderson was my best hope,” Gully says.
That evening, they boarded a plane and flew from her hometown of McAllen, at the southern-most tip of Texas, to Houston.
Three little words
At MD Anderson, more bad news followed. Gully’s disease had advanced. She wasn’t expected to live more than a few more weeks.
But a young doctor named Lawrence Frankel offered a glimmer of hope. A new trial for pediatric leukemia patients was launching, and he invited Gully to participate.
Children who enrolled in the study would receive three powerful chemotherapy drugs injected directly into the spine, in addition to traditional chemo delivered through an arm vein.
Frankel offered no guarantees, but said it was worth a shot.
It worked. After two years of treatment, Gully was declared cancer free at age 11.
“I went home to south Texas, and picked up where I left off,” she says. “Life became normal again.”
Gully grew up, married, and gave birth to three healthy children, defying doctors’ predictions that harsh cancer treatments might leave her unable to conceive.
Life was good, and cancer was a distant memory until December 2015, when Gully, then 42, was awakened by excruciating chest pain at 2 a.m.
“I thought surely I was having a heart attack,” she recalls.
Doctors at her local hospital found that Gully hadn’t suffered a heart attack, but instead a pulmonary embolism — a potentially deadly condition that occurs when a blood clot becomes wedged inside an artery in the lungs. Blood flow is restricted, and the heart pumps harder and faster in a futile effort to get blood to the lungs. Sometimes a heart attack occurs.
The emergency room doctor recited a number of reasons pulmonary embolisms arise, including cancer.
“He explained that tumor cells increase clotting substances in blood,” Gully says, “so blood clots may signal cancer.”
To rule out the disease, the doctor ordered a blood test. A normal white blood cell count is 10,000. Gully’s was 48,000.
“I instantly knew what that meant,” Gully says. “I’d seen those numbers when I fought leukemia as a child.”
The doctor confirmed what Gully already knew.
“You have cancer,” he said.
“Those three little words are no less terrifying the second time around,” Gully says. “I was shocked.
Fighting cancer again wasn’t in my plans.”
Remembering how she beat the odds 33 years ago, Gully headed back to MD Anderson, where a bone marrow test confirmed she had acute lymphoblastic leukemia, the same diagnosis as last time. Once again she was poised at the starting line of another cancer marathon.
“Wouldn’t it be nice if cancer were a one-time experience?” asks Christopher Benton, M.D., who became Gully’s leukemia specialist after she was admitted two years ago. “When your treatment is finished, you can say you’d been there, done that and you’ll never do it again.”
Unfortunately, compared with someone who has never had cancer, a person who survives the disease once is more likely to get sick again, says Benton, an assistant professor of Leukemia.
Some people experience a recurrence of their original cancer when a rogue cancer cell escapes detection and re-emerges from hiding months, years or even decades later. Others survivors are dealt a second cancer down the road, unrelated to their first.
Benton’s challenge was to figure out if Gully’s second leukemia was a recurrence of her first, or a totally different cancer.
Knowing the answer to this question would guide her treatment the second time around.
Like a medical detective, he ordered Gully’s 1982 medical file from a warehouse where MD Anderson’s archived records are stored. The 500-plus page document was assembled long before the days of computerized records. It contained hundreds of handwritten notes by teams of doctors that meticulously documented every detail of Gully’s pediatric treatment.
Benton read the well-worn chart cover to cover, seeking similarities that might prove Gully’s two cancers were related.
But the one piece of information he most hoped to find was missing. Benton wanted to know if Gully’s childhood cancer contained a genetic rearrangement called the Philadelphia chromosome, where parts of chromosomes 9 and 22 break off and switch places. The changed chromosome 22, named for the city where it was first discovered, is linked to a particularly aggressive form of ALL.
Benton already knew Gully’s adult cancer contained the Philadelphia chromosome. A test named FISH (fluorescence in situ hybridization), which detects chromosome rearrangements, confirmed its presence in her bone marrow.
But the FISH test didn’t exist when Gully first had cancer in 1982. A less-sophisticated technique was used to identify the Philadelphia chromosome back then, but in Gully’s case, it didn’t work.
“I wanted to perform the FISH test on her childhood tumor if we could locate her original biopsy slides,” Benton says.
“DNA is very robust. It doesn’t easily degrade over time, so I had every reason to believe the test would work.”
But where should Benton look for the 33-year-old, longforgotten slides? Were they discarded years ago, or did they still exist? Benton searched the Internet for Dr. Frankel, Gully’s pediatric oncologist. He found the now-retired doctor living in North Carolina, and called him.
Frankel clearly recalled that patients’ slides were archived during his tenure at MD Anderson, but he couldn’t remember where. Benton queried Leukemia Chair Hagop Kantarjian, M.D., who’s worked at MD Anderson since 1983, along with other veteran faculty members. With their help, he tracked Gully’s slides to a warehouse in west Houston where tumor samples from MD Anderson patients dating back to the 1950s are housed.
Historical slides aren’t in demand, Benton says, so the warehouse has largely fallen from memory. He’s delighted to know it exists.
“I feel like I’ve uncovered an archaeological treasure,” he says.
Lightning and lasers
With Gully’s slides in hand, Benton consulted Carlos Bueso-Ramos, M.D., Ph.D., an MD Anderson professor who specializes in hematopathology – the branch of pathology that studies diseases of the blood and bone marrow.
Bueso-Ramos is an expert in using a laser to precisely cut cancer cells away from the slides on which they’re mounted – a technique known as laser microdissection technology. The cells are then dropped into a collection tube for DNA sequencing, which can distinguish one type of cancer from another and identify cancers that are related. Before the development of this technology, there was no way to get cancer cells off slides, or to separate them from surrounding cells.
“Tumors are a complex mix of cancer cells and noncancerous ones. Laser capture microdissection uses a laser to cut out pure cancer cells from each tumor,” Bueso-Ramos explains. “The technique also allows researchers to analyze each cancer cell in unprecedented detail, measuring the genetic changes that occur during the development of the disease.”
Using this technique, MD Anderson scientists sequenced Gully’s childhood tumor and her adult tumor to see if they were related. They were not. Benton will confirm the initial findings with another test, but says, “We now suspect Crystal
Gully had two unrelated cancers. Lightning struck twice.”
God and good medicine
Gully’s story is not uncommon. Of the 1.6 million people diagnosed with cancer this year in the United States, one in six will have already battled a different cancer, according to the National Cancer Institute.
It’s a cruel encore, like surviving a hurricane, only to be swept away in a flash flood. It’s also becoming more common. The odds of developing a new cancer are double what they were 25 years ago, Benton says. The blame is mostly pinned on better treatments keeping survivors alive longer to run the risk of getting cancer again. Not to mention that, in general, the older a person gets, the greater their risk of cancer.
“Most survivors will never get a second cancer,” Benton says.
“Research suggests that, in general, a survivor’s risk of getting a new cancer diagnosis is 14 percent greater than the risk for someone who has never had cancer.”
Today, Gully is in complete remission, with the aid of targeted therapy drugs like Gleevec, Sprycel and Iclusig, which block the growth of the aggressive cancer cells that are the hallmark of Philadelphia chromosome-positive leukemia.
Such drugs didn’t exist when Gully fought cancer the first time.
“My survival is a miracle of God,” she says, “and good medicine.”
“When I was little, I was terrified of needles. This time, I was terrified I wouldn’t live to see my children grow up.”
Reunited, after 33 years
Amous Jones was working in MD Anderson’s Laboratory Services Department when the phone rang.
“You may not remember me,” said the voice on the other end of the line. “It’s been a long time.”
Instantly, Jones knew it was Crystal Gully.
The pair first met in 1982, when Jones was a young phlebotomist newly trained in the art of drawing blood, and Gully was a 9-year-old undergoing leukemia treatment.
The two formed an immediate bond, so strong that Gully would allow only Jones to draw her blood.
“We just clicked,” Gully says. “Amous was always upbeat and happy, like a ray of sunshine.”
Jones remembers Gully’s dazzling smile and zeal for life.
“That precious child had such a sweet spirit and outgoing personality. She never complained, even when she wasn’t feeling well.”
After Gully beat cancer and was discharged, the two remained pen pals for years.
The pair reunited 33 years later when Gully called Jones from an upstairs hospital room after she was re-admitted with a second cancer diagnosis.
“I bolted out of my chair and ran upstairs to see her,” says Jones, who now heads MD Anderson’s phlebotomy training program. “What a reunion we had!”
They hugged and cried and reminisced, and vowed to never lose touch again.