HIV Was the Last Hope For Girl With Leukemia, Did it Work?
Jeff Swensen for The New York Times
Emma Whitehead, with her mother, Kari. Last spring, Emma was near
death from acute lymphoblastic leukemia but is now in remission after an
experimental
treatment at the
Children’s Hospital
of Philadelphia
death from acute lymphoblastic leukemia but is now in remission after an
experimental
treatment at the
Children’s Hospital
of Philadelphia
By DENISE GRADY
It is hard to believe, but last spring Emma,
then 6, was near death from leukemia.
She had relapsed twice after
chemotherapy, and
doctors had run out of options.
Desperate to save her, her parents sought an experimental treatment
at the Children’s Hospital of Philadelphia, one that had never before
been tried in a child, or in anyone with the type of leukemia
Emma had. The experiment, in April, used a disabled form of the virus
that causes AIDS to reprogram Emma’s immune system genetically
to kill cancer cells.
at the Children’s Hospital of Philadelphia, one that had never before
been tried in a child, or in anyone with the type of leukemia
Emma had. The experiment, in April, used a disabled form of the virus
that causes AIDS to reprogram Emma’s immune system genetically
to kill cancer cells.
The treatment very nearly killed her. But she emerged from it
cancer-free, and about seven months later is still in complete
remission. She is the first child and one of the first humans
ever in whom new techniques have achieved a long-sought goal
— giving a patient’s own immune system the lasting ability to
fight cancer.
cancer-free, and about seven months later is still in complete
remission. She is the first child and one of the first humans
ever in whom new techniques have achieved a long-sought goal
— giving a patient’s own immune system the lasting ability to
fight cancer.
Emma had been ill with acute lymphoblastic leukemia since 2010,
when she was 5, said her parents, Kari and Tom. She is their
only child.
when she was 5, said her parents, Kari and Tom. She is their
only child.
She is among just a dozen patients with advanced leukemia to have
received theexperimental treatment, which was developed at
the University of Pennsylvania. Similar approaches are also
being tried at other centers, including the National Cancer
Institute and Memorial Sloan-Kettering Cancer Center
in New York.
received theexperimental treatment, which was developed at
the University of Pennsylvania. Similar approaches are also
being tried at other centers, including the National Cancer
Institute and Memorial Sloan-Kettering Cancer Center
in New York.
“Our goal is to have a cure, but we can’t say that word,” said
Dr. Carl June, who leads the research team at the University of
Pennsylvania. He hopes the new treatment will eventually replace
bone-marrow transplantation, an even more arduous, risky and
expensive procedure that is now the last hope when other
treatments fail in leukemia and related diseases.
Dr. Carl June, who leads the research team at the University of
Pennsylvania. He hopes the new treatment will eventually replace
bone-marrow transplantation, an even more arduous, risky and
expensive procedure that is now the last hope when other
treatments fail in leukemia and related diseases.
Three adults with chronic leukemia treated at the University of
Pennsylvania have also had complete remissions, with no signs
of disease; two of them have been well for more than two years,
said Dr. David Porter. Four adults improved but did not have
full remissions, and one was treated too recently to evaluate.
A child improved and then relapsed. In two adults, the
treatment did not work at all. The Pennsylvania researchers
were presenting their results on Sunday and Monday in Atlanta
at a meeting of the American Society of Hematology.
Pennsylvania have also had complete remissions, with no signs
of disease; two of them have been well for more than two years,
said Dr. David Porter. Four adults improved but did not have
full remissions, and one was treated too recently to evaluate.
A child improved and then relapsed. In two adults, the
treatment did not work at all. The Pennsylvania researchers
were presenting their results on Sunday and Monday in Atlanta
at a meeting of the American Society of Hematology.
Despite the mixed results, cancer experts not involved with the
research say it has tremendous promise, because even in this
early phase of testing it has worked in seemingly hopeless cases.
“I think this is a major breakthrough,” said Dr. Ivan Borrello,
a cancer expert and associate professor of medicine at the
Johns Hopkins University School of Medicine.
research say it has tremendous promise, because even in this
early phase of testing it has worked in seemingly hopeless cases.
“I think this is a major breakthrough,” said Dr. Ivan Borrello,
a cancer expert and associate professor of medicine at the
Johns Hopkins University School of Medicine.
Dr. John Wagner, the director of pediatric blood and marrow
transplantation at the University of Minnesota, called the
Pennsylvania results “phenomenal” and said they were “what
we’ve all been working and hoping for but not seeing to this extent.”
transplantation at the University of Minnesota, called the
Pennsylvania results “phenomenal” and said they were “what
we’ve all been working and hoping for but not seeing to this extent.”
A major drug company, Novartis, is betting on the Pennsylvania
team and has committed $20 million to building a research center
on the university’s campus to bring the treatment to market.
team and has committed $20 million to building a research center
on the university’s campus to bring the treatment to market.
Hervé Hoppenot, the president of Novartis Oncology, called the
research “fantastic” and said it had the potential — if the early
results held up — to revolutionize the treatment of leukemia and
related blood cancers. Researchers say the same approach,
reprogramming the patient’s immune system, may also eventually
be used against tumors like breast andprostate cancer.
research “fantastic” and said it had the potential — if the early
results held up — to revolutionize the treatment of leukemia and
related blood cancers. Researchers say the same approach,
reprogramming the patient’s immune system, may also eventually
be used against tumors like breast andprostate cancer.
To perform the treatment, doctors remove millions of the patient’s
T-cells — a type of white blood cell — and insert new genes that
enable the T-cells to kill cancer cells. The technique employs a
disabled form of H.I.V. because it is very good at carrying genetic
material into T-cells. The new genes program the T-cells to attack
B-cells, a normal part of the immune system that turn malignant
in leukemia.
T-cells — a type of white blood cell — and insert new genes that
enable the T-cells to kill cancer cells. The technique employs a
disabled form of H.I.V. because it is very good at carrying genetic
material into T-cells. The new genes program the T-cells to attack
B-cells, a normal part of the immune system that turn malignant
in leukemia.
The altered T-cells — called chimeric antigen receptor cells —
are then dripped back into the patient’s veins, and if all goes well
they multiply and start destroying the cancer.
are then dripped back into the patient’s veins, and if all goes well
they multiply and start destroying the cancer.
The T-cells home in on a protein called CD-19 that is found on the
surface of most B-cells, whether they are healthy or malignant.
surface of most B-cells, whether they are healthy or malignant.
A sign that the treatment is working is that the patient becomes
terribly ill, with raging fevers and chills — a reaction that
oncologists call “shake and bake,” Dr. June said. Its medical name
is cytokine-release syndrome, or cytokine storm, referring to the
natural chemicals that pour out of cells in the immune system as
they are being activated, causing fevers and other symptoms.
The storm can also flood the lungs and cause perilous drops in
blood pressure — effects that nearly killed Emma.
terribly ill, with raging fevers and chills — a reaction that
oncologists call “shake and bake,” Dr. June said. Its medical name
is cytokine-release syndrome, or cytokine storm, referring to the
natural chemicals that pour out of cells in the immune system as
they are being activated, causing fevers and other symptoms.
The storm can also flood the lungs and cause perilous drops in
blood pressure — effects that nearly killed Emma.
Steroids sometimes ease the reaction, but they did not help Emma.
Her temperature hit 105. She wound up on a ventilator, unconscious
and swollen almost beyond recognition, surrounded by friends
and family who had come to say goodbye.
Her temperature hit 105. She wound up on a ventilator, unconscious
and swollen almost beyond recognition, surrounded by friends
and family who had come to say goodbye.
But at the 11th hour, a battery of blood tests gave the researchers
a clue as to what might help save Emma: her level of one of the
cytokines, interleukin-6 or IL-6, had shot up a thousandfold.
Doctors had never seen such a spike before and thought it might
be what was making her so sick.
a clue as to what might help save Emma: her level of one of the
cytokines, interleukin-6 or IL-6, had shot up a thousandfold.
Doctors had never seen such a spike before and thought it might
be what was making her so sick.
Dr. June knew that a drug could lower IL-6 — his daughter takes
it for rheumatoid arthritis. It had never been used for a crisis like
Emma’s, but there was little to lose. Her oncologist,
Dr. Stephan A. Grupp, ordered the drug. The response, he said,
was “amazing.”
it for rheumatoid arthritis. It had never been used for a crisis like
Emma’s, but there was little to lose. Her oncologist,
Dr. Stephan A. Grupp, ordered the drug. The response, he said,
was “amazing.”
Within hours, Emma began to stabilize. She woke up a week later,
on May 2, the day she turned 7; the intensive-care staff sang
“Happy Birthday.”
on May 2, the day she turned 7; the intensive-care staff sang
“Happy Birthday.”
Since then, the research team has used the same drug, tocilizumab,
in several other patients.
in several other patients.
In patients with lasting remissions after the treatment, the altered
T-cells persist in the bloodstream, though in smaller numbers than
when they were fighting the disease. Some patients have had the
cells for years.
T-cells persist in the bloodstream, though in smaller numbers than
when they were fighting the disease. Some patients have had the
cells for years.
Dr. Michel Sadelain, who conducts similar studies at the Sloan-
Kettering Institute, said: “These T-cells are living drugs.
With a pill, you take it, it’s eliminated from your body and you
have to take it again.” But T-cells, he said, “could potentially be
given only once, maybe only once or twice or three times.”
Kettering Institute, said: “These T-cells are living drugs.
With a pill, you take it, it’s eliminated from your body and you
have to take it again.” But T-cells, he said, “could potentially be
given only once, maybe only once or twice or three times.”
The Pennsylvania researchers said they were surprised to find any
big drug company interested in their work, because a new batch
of T-cells must be created for each patient — a far cry from the
familiar commercial strategy of developing products like Viagra
orcholesterol medicines, in which millions of people take the
same drug.t would have a big, unmistakable impact on a small
number of patients. Such home-run drugs can be approved more
quickly and efficiently, he said, with smaller studies than are
needed for drugs with less obvious benefits Novartis drug Gleevec,
which won rapid approval in 2001 for use against certain types of
leukemia and gastrointestinal tumors. It can cost more than
$5,000 a month, depending on the dosage.
big drug company interested in their work, because a new batch
of T-cells must be created for each patient — a far cry from the
familiar commercial strategy of developing products like Viagra
orcholesterol medicines, in which millions of people take the
same drug.t would have a big, unmistakable impact on a small
number of patients. Such home-run drugs can be approved more
quickly and efficiently, he said, with smaller studies than are
needed for drugs with less obvious benefits Novartis drug Gleevec,
which won rapid approval in 2001 for use against certain types of
leukemia and gastrointestinal tumors. It can cost more than
$5,000 a month, depending on the dosage.
The research is still in its early stages, and many questions remain. The researchers are not entirely sure why the treatment works, or why it sometimes fails. One patient had a remission after being treated only twice, and even then the reaction was so delayed that it took the researchers by surprise. For the patients who had no response whatsoever, the team suspects a flawed batch of T-cells. The child who had a temporary remission apparently relapsed because not all of her leukemic cells had the marker that was targeted by the altered T-cells.
It is not clear whether a patient’s body needs the altered T-cells forever. The cells do have a drawback: they destroy healthy B-cells as well as cancerous ones, leaving patients vulnerable to certain types of infections, so Emma and the other patients need regular treatments with immune globulins to prevent illness.
So far, her parents say, Emma seems to have taken it all in stride. She went back to school this year with her second-grade classmates, and though her grades are high and she reads about 50 books a month, she insists impishly that her favorite subjects are lunch and recess.
“It’s time for her to be a kid again and get her childhood back,” Mr. Whitehead said
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