Meet the Girl with Gene NUP214-ABL1
When Myrrah Shapoo arrived at Columbia University Medical Center last year with a form of cancer that wouldn’t respond to chemotherapy, a team of physicians and scientists working on a new precision-medicine initiative faced their ultimate test.by David J. Craig Published Summer 2016
By the time they landed at Kennedy International Airport on the morning of January 26, 2015, nine-year-old Myrrah Shapoo was already suspicious. Her father had promised her the trip would be fun — that they would sit in the fancy seats at the front of the plane and watch cartoons. But her mother had been crying as she rushed to pack their suitcases, and it seemed strange that all her aunts and uncles had suddenly shown up at the family’s New Delhi home to hug and kiss Myrrah goodbye.
Now Myrrah was wondering why her father insisted on pushing her through the airport terminal in a wheelchair when, really, she could have walked. And why did she have to wear a silly paper mask? Finally, when a distant relative greeted them outside the baggage claim and asked her father in hushed tones about “her condition,” Myrrah figured it out.
“Papa,” she said, “am I sick again?”
In the summer of 2012, after countless doctor’s appointments, dozens of tests, and months spent watching their six-year-old daughter suffer from unexplained fevers, achy bones, and deep and persistent tiredness, Sajid and Rubina Shapoo got the awful diagnosis. Their daughter Myrrah had acute lymphoblastic leukemia (ALL).
ALL is a cancer of the blood — specifically of the white blood cells. Typically those cells work with the immune system to fight infection and protect the body against disease, but in children with ALL, an uncontrollable proliferation of cancerous white blood cells upsets the delicate constitution of the bloodstream, crowding out normal white blood cells, as well as red blood cells and platelets. This makes it impossible for the body to properly fight infection, absorb oxygen, or heal wounds.
Acute lymphoblastic leukemia is the most common form of cancer in children. It is also one of the most treatable; nearly 90 percent of children diagnosed with the condition are cured. Myrrah’s parents, after getting over their initial shock, were optimistic that she would survive.
“The doctors told us that if you had to get cancer, this was the one with the best prognosis,” says Sajid, who works as a police official in India. “And, clearly, when you’re told that your daughter has a disease that most kids recover from, you expect her to be among the fortunate ones.”
Myrrah was initially treated at New Delhi’s Indraprastha Apollo Hospital, which boasts a state-of-the-art cancer clinic, considered among the best in India. Her doctors there followed the same diagnostic and treatment protocols that physicians at most hospitals in the US or Europe recommend. Within hours of determining that her white blood cells were cancerous, they sent a sample of Myrrah’s blood to a laboratory for karyotyping, a form of genetic analysis that involves examining a cell’s nucleus through a microscope to see if any of its forty-six chromosomes are missing or misshapen. The scientists who examined Myrrah’s blood were looking at those X-shaped bundles of coiled-up DNA for clues. For instance, if a particular section of chromosome 9 was lopped off and fused onto the end of chromosome 22, it would indicate a mutation commonly called the “Philadelphia chromosome.” This would suggest that Myrrah had a subtype of leukemia that is treatable with Gleevec, one of a handful of cancer drugs that have been designed to target specific genetic aberrations. But there was no Philadelphia chromosome and no other hints as to what was driving Myrrah’s illness.
Without a clear road map for treatment, her doctors did what any other oncologists would do in the situation: they prescribed a cocktail of four common chemotherapy drugs — dexamethasone, vincristine, daunomycin, and PEG-asparaginase — to be administered every day for a month through a port that would be implanted in Myrrah’s neck. The physicians at Apollo Hospital would subsequently give her several additional chemotherapy cocktails — typically administered for a month or so at a time — in order to maximize the chances that any cancer cells that withstood one drug would be destroyed by another. If leukemia cells migrated to her spinal column or brain, where chemotherapy drugs couldn’t penetrate the blood-brain barrier, they would also bombard Myrrah with radiation.
To understand the suffering that Myrrah would go through in those first arduous months of treatment, it helps to know how chemotherapy works. These drugs, most of which were developed in the 1940s, ’50s, and ’60s, an era of aggressive chemical experimentation on human cancer patients, attack various molecules in the body that are necessary for cell growth and cell division. The idea is that since cancer cells grow and divide at a maniacal pace, they are preferentially affected and die off before the rest of the body breaks down. But these drugs take a severe toll on all cells that divide rapidly. They kill those found in hair follicles, which makes patients go bald; they attack the lining of the digestive tract, which causes severe nausea and diarrhea; and they annihilate the mucous membranes, which can lead to painful sores in the mouth and on the lips. Myrrah experienced all of these side effects and more: the drugs made her mentally foggy and weakened her immune system so badly that she developed repeated infections; on one occasion, she nearly died of meningitis. During this period Myrrah lived at the hospital for weeks at a time, and her parents took turns sleeping next to her on a cot. Doctors stopped by almost every day bearing needles — small needles for delivering shots, medium-sized needles for taking blood, and impossibly long, thick needles for drawing spinal fluid out of her back, which made her scream in pain.
“We nicknamed her the Cancer Slayer because she is such a fighter,” says her father. “Sometimes she would ask me, ‘Why don’t other kids have to do this?’ And I would say, ‘Because only you are strong enough. Only you can take it.’”
And she did take it. Little by little, she got better. By the spring of 2013, there was no more cancer detectable in her body, and doctors stopped the most powerful chemotherapy regimens. They would continue to give her relatively mild doses of chemotherapy for the next two years, just in case any traces of cancer still lingered, but Myrrah soon regained her strength and returned to school. That summer, her parents celebrated by taking her on vacation to Europe. Life was, for a few precious months, normal again.
Then, in January 2015, during a routine checkup, Sajid and Rubina learned that Myrrah’s cancer had returned. This time, the doctors said there was nothing more they could do. “I almost blacked out,” says Sajid. “I couldn’t see anything, and there was this loud buzzing in my head that drowned almost everything out. After a few seconds, I heard my voice saying: ‘No, this cannot be true.’”