The Standard Miracle in Lymphomas:
Another
year has gone by, and in a few short weeks, we celebrate National Cancer
Survivor's Day. When this day arrives I am always taken back and remember those
who never had a chance to celebrate this day.
Having
practiced medicine for more than three decades, as physician I was deeply
involved with the care of little children. As a hospitalist, I saw lymphoma cancer my fair share of childhood diseases. I can gladly say I was allowed to
save many lives with help from others on the medical teams I worked with, and
of course the cutting edge technologies afforded those of us who are privileged
to practice medicine in the United States. It is interesting, the things in
life which will push a man toward an education and prepare him for the great
profession of medicine. One of those things was an event in my childhood in the
early 1960s.
When
I was a boy, I had many friends in school and outside of school alike. Growing
up on a ranch in Nebraska, it was not unusual to have many friends who lived in
other towns come to visit. One of my friends outside of school lived in a
nearby town, but came over often. David and I were both eight years old. I
remember fondly of playing "army" with David in the yard, and board
games with him when he would come to visit. I liked him. He was friendly and
got along with my sister and little brother too. We were both Cub Scouts but in
different troops. You would always hear about how much David loved Scouting.
Soon
though, the visits became fewer and fewer. David seemed to look frail and
discolored to me as time went by. The color thing really bothered me. I asked
Mom, "What's wrong with David?" Mom said, "He's sick, honey. He
has cancer of the blood. It's called leukemia". As you can imagine, this
was a little difficult for an eight year old to take in, but as time went by, I
learned more and more.
David's
parents were good friends of my parents, so we saw each other as families
often. After he became ill, we saw less and less of them. Very rarely did I get
to see my friend. David had an ever advancing condition of weight loss,
bruising, sore joints, infections, was easily brought to tears, and I thought
his hair looked funny. How does an eight year old process this inevitable plunge?
As children, David, his sister, my brother, my sister and I, we were not
emotionally mature enough to process this whole thing.
At
home we would get the occasional phone call that he was back in the hospital.
My parents were great. When we would get these calls, Mom and Dad would sit
with us and try their best to explain this thing called leukemia. Understand,
this was 1961, and leukemia was known as an unrelenting killer of children.
There were no cures. Not even a good treatment. The medical community was
desperate for a foothold.
One
night we received a phone call from David's father. David had passed away at
the young age of eight. I remember, it was really the first time I heard those
words, "passed away". It was also the first funeral I went to for a
friend. Friends are not supposed to die when you are kids. It caused me to take
pause, and realize that we are mortal. I know, I was just a child. I had seen
two grandfathers buried, but I was very quiet and overcome by this intense
event. All of these grownups I knew as strong would breakdown and start to cry.
I never the less watched in a surreal world of sadness, my parents' good
friends bury my buddy, David.... And that image which is still so clear.... My
friend, asleep in his Cub Scout uniform.
All
the while I was there, I remember thinking David might come running out from
behind that marble stone, but he never did. Why had this happened? I seemed to
feel a pull even then, "The Calling", so many of us drawn to
"medicine" and trained as healers will occasionally and quietly talk
about.
Time
went by, but I often thought of David and how unfair it had been for him and
his family. The early 1960s saw almost all children die who had leukemia. The
five-year survival rates of children then were only one in ten. All families
could do, was wait and watch while their babies died in agony. He never had a
chance, I often reflected. A sweet kid, taken from his family at such a young
age. He never got the chance to do anything after he became sick. Never got to be
an Eagle Scout, play baseball, is cool at school, or fall in love. How scared
he must have been.
Time
marched on and while in high school, I would hear of small advances in the
fight against cancer and leukemia. Then, in the early 1970s, when I was in college
studying chemistry, we began hearing about a new drug, a drug with great
promise in the fight against leukemia. It killed leukemia cancer cells by
attacking their ability to process folic acid for DNA synthesis. Called
Methotrexate, I remember thinking.... Damn! it's a little late, but in less
than ten years they came up with a weapon.
I
had grown up with kids who had polio, but now, it was gone. Diphtheria was
gone. Small pox was all but vanquished. Psychiatric hospitals were giving way
to more advanced narcoleptic drugs, allowing former patients to re-enter
society and become productive citizens. They had just invented the CAT scanner.
They had started to use lasers in ophthalmology. And, I thought, even William Debarked
is transplanting hearts with Denton Cooley down in Texas of all places! Things
were really happening, and I wanted to be on the inside not the outside. It was
an epiphany. Already a man of science, I realized then, that I was going to
become a physician.
As
time went by, more of these ant metabolite drugs became available and we
started to see a real dent in childhood mortality from leukemia. Soon after, in
the late 1970s, when I was a biochemist and starting my medical career, a drug
from a flower called, "The Rosy Periwinkle", which only grows in the
rainforests of Madagascar (go figure), gave us a new drug called Vincristine. A
drug that could only be brewed in Mother Nature’s kitchen, this was a
monumental discovery. Never before had we been able to reach for a drug that
could stop mitosis in cancer cells directly by shutting down their ability to
pass through telophase. That's right, Vincristine and its sister, Vinblastine;
destroy microtubule formation, so cells can't make spindles, resulting in the
inability to replicate.
Then,
when I was a resident in medicine, we discovered a way to perform bone marrow
transplants, exchanging cancerous white cells for fresh, normal white cell
precursors. You guessed it. We were now seeing cures and not just remissions.
Lives were now being saved in this war.
My
friend David had what we call, "Acute Leukemia". There are many types
of leukemia, but there are two well-known leukemia’s that prey on children.
They are Acute Lymphoblastic Leukemia, ALL, the one David had, which generally
seeks out kids two to ten years of age, and Acute Myelogenous Leukemia, AML,
which generally hunts down our babies under 1 year of age.
The
acute leukemia’s are proliferating bone marrow tumors of cancerous precursor
white cells still in the immature blast cell phase. The cells do not work like
healthy white cells to combat infection. They multiply wildly, creating havoc
in the body, literally consuming the patient to death, a condition we call
"cachexia". Patients have intense bone pain, anemia, infections, swollen
lymph nodes, enlarged spleens and livers, and, for some, meningitis, strokes,
heart attacks, and renal failure. Without treatment, they are dead in a few
weeks to a few months.
We
still do not have a full grasp on their cause. Most are caused by ontogenesis,
which are mutated cancer inducing genetic codes for programming carcinogenesis
and disrupting programmed cell death we call "apoptosis". What causes
this, is the head scratcher. Many of us feel it is radiation exposure, or
certain viruses. Perhaps environmental toxins or even cosmic radioactive
bursts. And of course, man-made toxins are obvious suspects.
By
the early 1990s we were seeing cure rates in both ALL and AML of fifty percent
and remission rates in the eighty percent range. What a leap. In just 3 decades
we saw a paradigm shift in the treatment and outcomes of our children with
leukemia, moreover, a shift in therapies which utilizes a team approach to
protect our children from the acute depression and other collateral illness
which accompany these frightening diseases.
Newer
drugs like Daunorubicin have accelerated these therapies to even better
outcomes. Although this drug is very effective, it is extremely cardio toxic
and not generally used in children. However, it should be noted that we are now
seeing ninety five percent remission rates and sixty percent cure rates in our
children with ALL, and AML, a true shift in mortality that could only be
dreamed about just thirty five years ago.
The
drug Methotrexate is still at the heart of leukemia therapy, and is used in
combination with other drugs. Unfortunately, there has been a recent shortage
of this drug due to decreased production, and the drug makers asking for more
money and charging outrageous prices. This is an unethical practice, and
shameful in my opinion. It has been treated much in the press of late.
Hopefully attitudes will shift and our lobbying campaigns to continue
cost-effective production will be fruitful.
But
now, what treatments are on the horizon for leukemia? There is a new drug. This
drug arrived on the cancer chemotherapy shelves about a decade ago, but shows
outstanding promise even outside of cancer therapy. Used mainly for Chronic
Myelogenous Leukemia, CML, leukemia which is seen mostly in older adults, it is
highly effective. Rendering ontogenetic codes for cancer cell induction dead in
their tracks, it is a target directed drug aimed at a specific chromosome
translocation defect which exists in more than 90% of CML patients, called the
Philadelphia Chromosome. The drug, Imagine, was built from a rational drug
design based on biochemical research already in place regarding the specific
allele the Philadelphia Chromosome codes for, and shuts down the production of
a protein called tyrosine kinas which induces cancerous breakdown of normally
functioning white cells.
Imagine
has been used as therapy for other leukemia’s including refractory Acute
Lymphoblastic Leukemia and Myeloproliferative Disorders (chronic bone marrow
cancers generally seen in the elderly) with outstanding success. But what are
also very interesting are its experimental applications which are currently
being investigated.
Imagine
has been touted as a treatment for pulmonary hypertension, a rapidly fatal form
of high blood pressure in the lungs. It has been shown to reduce outcropping we
call smooth muscle hypertrophy and hyperplasia of the pulmonary vascular tree.
In systemic sclerosis, the drug has been tested for potential use in slowing
down pulmonary fibrosis. In addition, current laboratory investigations show
promise in stopping the progression of atherosclerotic vascular disease in
mice. Yes, a treatment for coronary artery disease and heart attacks.
At
Emory University in Atlanta, there are promising studies suggesting that Imagine
could be used as an antiviral against smallpox. Why is this important? Although
this disease has been wiped off the face of the earth with the remarkable
efforts of the World Health Organization, and no case has been identified in
almost thirty years, we continue to believe a weapon zed form of small pox
launched from a rogue nation is possible.
Studies
also suggest that a modified version of Imagine can bind to the protein which
increases the production and accumulation of amyloidal plaques in Alzheimer's
disease, rendering it inert. Yes, a treatment for Alzheimer's induced dementia.
But
with all of this in our doctor bags, there is still a dark and ominous specter.
Although great strides have been made, and I was privileged to meet and take
care of children with leukemia, and even watch them overcome the illness and
move on with their lives, one patient stands out.
I
was working the Emergency Department one night in 1995. It had been relatively
quiet that evening, when at approximately two in the morning a man walked in
carrying his teenage son. We acted quickly and helped him get his son to a
gurney in an open bay.
The
staff and I immediately recognized the man's son as Eric, a well-known high
school football star. The father said he found his son crawling on the floor
trying to get to the kitchen to get a drink of water. Eric looked awful. There
was that damn color again. Eric was delirious with fever, weak, and poor to
respond. We went to work on him immediately. His dad said that he was fine just
a month ago, but had developed a sore throat at about that time, and was seeing
one of our local doctors who just kept giving him antibiotics. We managed to
get young Eric stabilized. Just as we were settling him in and making his
father comfortable, I received a call from the laboratory. The lab tech asked
me to come down to the lab. I ran to the laboratory. When I got there the tech
was shaking her head as if to say, "This is really bad". I looked at
the blood count machine's screen. "My God", I said to the tech.
"His white count is seventy thousand". I looked in the microscope,
"blast cells". I knew right away we were looking at an acute type of
leukemia, but couldn't recognize it.
When
I dashed back to the Emergency Department, Eric was coming around a little. I
spoke with him and reassured him. But the look on my face when I turned to his dad
could not be masked. He knew I didn't have good news. We talked at length,
then, I called in Eric's regular doctor. They talked while the team and I
continued to work on Eric. I called in the helicopter, spoke with the
hematology fellows at the university, returned to Eric and his dad, made sure
they knew what we were doing and flew them both to University Hospital. All
eyes turned to the Hematology Oncology Service with hope that they could help
young Eric.
One
week later, while seeing patients in my office, the Hematology service at the
university telephoned me to say that Eric had "passed away". You sit
by yourself and reach for introspection when these things sting you as a
healer. I wondered. How does a robust young athlete get sick with leukemia,
fail in health so quickly, and die in one month? As it turned out, Eric
contracted a type of AML, called Promyelocytic Leukemia, one of the most deadly
forms of AML, one which preys on teenaged children, and takes them away from us
with stealth and quickness. So you see, our job is not done. I am reminded as
to why we call it a "practice".
Our
knowledge of the genome, stem cell technology, ontogenetic, and nanotechnology
races onward. Our ability for rational drug design is extraordinary, and the
technical savvy to produce these great magic potions has been nothing short of
miraculous. In just four decades, we have all but squashed the disease that
took my friend, David. But as you can see with Eric, we are not finished. I
still think of David fifty years later, and how his death stirred in a young
boy, the spark of becoming a physician. If I was educated only to save but one
human being, it was all worth it.
We
already have at our fingertips two technologies that must be placed into
motion. Stem cell research has already given us the ability to crush this
killer, and should never be interrupted. And, the science to manipulate the ontogenesis
so responsible for the fuel that drives these diseases is already available. My
hope is that with our new technologies, in the near future, we will not need
any drugs for leukemia. We will simply turn off the genetic machinery of bone
marrow cancer and not allow leukemia even to exist, and therefore, never
threaten our children again.
The Standard Miracle In Lymphomas
