THE BATTLE TO BEAT LEUKEMIA
When it strikes children they always die. Our doctors don’t know of the blood” or how to cure it, but they killers before and we can do it again”
WHEN little Barbara first complained that she felt tired all the time her mother was not too worried. After all, what five-yearold doesn’t get tired once in a while after running around from morning till night? She made a mental note to see that the child got to bed earlier at night
Barbara got to bed earlier, but she stayed tired. Even a few minutes’ play with her dolls seemed to exhaust her and she seemed to be growing paler, thinner, more listless every day. Her temperature climbed to a hundred degrees and stayed there, and she complained of vague pains in her joints. Fearing rheumatic fever the mother hurried the child off to the doctor.
But it wasn’t rheumatic fever. The pediatrician examined Barbara from head to toe and what he saw he didn’t like. The child’s glands were enlarged and routine haemoglobin and blood-smear tests revealed a disturbing blood picture. Five-year-old Barbara, whose symptoms usually indicate nothing more serious than a pair of diseased tonsils, was one more child victim of the dreaded killer, leukemia, or “cancer of the blood.” She had no hope of recovery. In three months she was dead.
A deep, dark and terrifying secret that has baffled the medical profession since the time of Hippocrates, leukemia is known in every part of the world. It affects humans, animals, and fowl. It apparently chooses its human victims at random, regardless of race, economic background, diet, climate, family history or temperament. Whether it strikes in its fastest-killing acute form, or in its slower-progressing chronic form, it is always fatal. The best of medical care, the latest hormones, the most powerful drugs—nothing can cure leukemia. A child’s life expectancy, with acute leukemia, is two or three months. If hospitalized and treated with the most up-to-date drugs, he may live six months, with luck maybe a year. But no more.
Leukemia accounts for only three and a half percent of all malignant deaths in Canada. In 1949, six hundred and ten Canadians died from it.
The death rate has shown little fluctuation over the years. European statistics are not available, but a Danish publication estimates that only one person in fifty thousand dies annually from leukemia in that part of the continent. American figures are approximately the same as Canadian.
But, medically, leukemia remains a bewildering question mark to those who seek its cause and cure.
What makes the good white cells of the body —those same “soldiers of the blood” meant to fight infection—suddenly multiply in wild disorder until they clog the bloodstream, crowding out and destroying their companion cells, the nourishing red corpuscles? Doctors wish they knew. A normally healthy person has from four thousand to ten thousand of these white cells, or leucocytes (hence the name leukemia) in every cubic millimetre of his blood. What strange alchemy increases that number, sometimes in a matter of weeks, to a possible half million, and spells sure death? And the primitive “blast cells” of leukemia, those imperfect parents of the white cells that ordinarily make up only four percent of a healthy person’s blood—what accounts for their rapid increase to twenty-five percent, sometimes right up to one hundred percent of the white blood count?
Twice as Many Men Get I»
Is leukemia a true malignant disease, like cancer? Nobody can be sure. Its cells are similarly primitive, its manner of growth is the same as that of a malignant tumor, eventually invading and destroying every organ of the body. Yet, unlike other malignant diseases, leukemia seems to strike the body in every place at once.
Is leukemia then the result of some infection? Again no one knows. When a person gets pneumonia or glandular fever or whooping cough, his white-cell count rises steeply and his whole blood picture suggests leukemia. Yet leukemic mothers give birth to normal healthy babies: in fact, no
leukemic infant has yet been found whose mother or father was Continued on page 48
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leukemic at the time of its birth.
Why does the disease affect men twice as ofter^as -won.^n? Wny aoes it attack infants and children in its most virulent acute form? How does it choose its victims? And, when modern miracle drugs like ACTH and cortisone stamp out every sign of leukemia from a diseased body, how and why do the traitorous white cells march back into the bloodstream to claim their victim at last?
If doctors don’t know, it isn’t because they aren’t looking for the answers. Although leukemia has only been recognized as a distinct entity for the past century, since then dozens of European, British and American physicians have baffled their brains in preliminary research. They have studied leukemia in fowl, mice, guinea pigs, dogs, rabbits, monkeys, bats, cats and pigs, and found the disease was not necessarily the same in each. They have tried to transmit it from one animal to another and failed (except in the case of certain susceptible mice). They have tried to transmit it from animals to human beings, and failed again. They have even removed abnormal leukemic blood from one human being and injected it into the bloodstream of another, healthy human. In two and a half hours every last trace of the leukemia cells had disappeared from the healthy man’s bloodstream. They have injected healthy blood into the bloodstream of leukemics. It was soon filled with an army of errant white cells. They have wondered if the disease was due to fractures, bacteria, viruses, or parasites. They have reported unproved “cures” by quinine, iron, phosphorus, arsenic, blood transfusion, fever therapy, and feeding with the bone marrow of calves.
They are still seeking a clue.
Canada is a comparative newcomer to the field of medical research, but in this country today trained medical and scientific minds are examining every facet of leukemia. At the Hospital for Sick Children in Toronto two hundred cases of leukemia in children have been studied in the past twenty years (average age of children suffering from the disease, four years eleven months). There, a medical team under the joint direction of Dr. C. E. Snelling, senior attending physician, and Dr. W. L. Donohue, chief pathologist, is currently treating young patients with ACTH, cortisone, and the amazing threesome known as “the folic acid antagonists” — aminopterin, amethopterin and adenopterin. Admitting that a cure is nowhere in sight they nevertheless admit some extremely interesting “remissions”—that is, periods of weeks and even months when all signs of the disease have vanished. At Toronto General Hospital, Professor J. K. R. Wightman of the University of Toronto heads a two-man team studying and treating adult patients with chronic leukemia and allied disorders and restoring many of them to good health and gainful employment for months and even years. These research projects are subsidized by the Ontario Cancer and Treatment Foundation.
As for fundamental research—laboratory research as opposed to clinical —the National Cancer Institute is spending four hundred thousand dollars this year on thirteen fellowships and numerous grants-in-aid for cancer research, including leukemia. Under the institute’s financial encouragement doctors and biochemists are studying
mice and men, drugs and radiation, marrow cells, enzymes and hormones in the laboratories of McGill, Montreal, Toronto, Western Ontario and Manitoba universities.
Largest of the institute’s grants (thirty thousand dollars) goes to a research group at Montreal General Hospital k^-.ded by Dr. J. H. Quastel, one of the world’s leading enzyme chemists.
Here is a layman’s picture of leukemia:
Two kinds of corpuscles, or cells, exist in blood: the red cells, whose
function it is to nourish the body by carrying oxygen and removing carbon dioxide; and the white cells, whose job is to fight infection. Both are manufactured in the bone marrow, especially in the flat bones of chest, hip and spine. There the cells grow and divide and mature, at last evolving into mature, granular cells and spilling out into the bloodstream. Red cells are seven hundred times more numerous than white. They survive in the circulation anywhere from two weeks to three months, but usually about a month. White cells contain nucleo-protein and other substances, including a variety of enzymes, but stay alive in the circulation only about five days. It is their job, when infection strikes, to pour out of the marrow in large numbers and vanquish the invading forces of disease. This accomplished the excess white cells disappear again, leaving the bloodstream with its normal white-cell count.
The leukemia blood picture is fatally different.
A doctor preparing to examine a blood-smear sample from a leukemia victim knows he’ll find one of three main possible abnormalities. First, the patient may be leukemic—his blood has too many of both white and parent “blast” cells. Or he may be subleukemic—Le has the normal number of white cells but far too many “blast” cells. Finally he may be aleukemic —his blood has too few of either type of cell.
They Tried Phosphate Cocktails
These three categories can be subdivided further still because white cells themselves are broken down into three types, each of which can be involved in a different form of leukemia. Whatever type of leukemia is involved the leading question is whether the disease is acute or chronic—whether the patient will live a few months or a few years.
In the case of a child the question is already answered; in children up to fourteen leukemia is almost always acute. Chronic leukemia strikes adults between twenty-five and sixty-five (depending on the type of white cell involved) and life expectancy in many cases can be extended to five, ten, even fifteen comfortable years if the disease is treated with suitable X-ray treatments and modern drugs.
Even this is a vast change in prospect for the leukemia victim compared with fifty years ago, when no form of treatment had any effect. Treatment is at once the hope and the despair with leukemia. Over the past two hundred years there have been intermittent medical reports and newspaper stories of experiments being conducted, new drugs and hormor.es being tried out, radiation being called into use, and many a hoped-for cure proving useless.
In Barrie, Ont., a doctor tried iron arsenate with some success on one patient, but it did not have the slightest effect on others. At the University of California School of Medicine patients were fed “cocktails” of radioContinued on page 50
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Continued from page 48 active sodium phosphate. The disease seemed arrested, hut not for long. Ten years later the California researchers admitted their experiments had failed. In Toronto six adults and four children treated with phosphorus lived for several months beyond their time but none were cured.
In Memphis a doctor suggested the disease be fought with chicken pox and ’flu germs so the leukemia “virus” would feed upon them and not upon
the patfeit:---Canadian''doctors were
sceptical. From Banting Institute
Professor W. L. Robinson said it had never been proved that either cancer or leukemia was due to a virus.
But researchers were making some headway. They discovered:
Urelhan, a twenty-milligram dose of which will give some chronicleukemia patients of one type a healthy interlude in the cpursë'-'ôf their disease.
Nitrogen ffiusiard, the poison gas aí World War I, effective in cases of chronic lymphatic leukemia.
X-ray treatment and radium, still
the best means of easing certain types of chronic leukemia.
The remarkable “folic acid antagonists” now being used extensively in the United States to treat acute leukemia in children.
This last discovery is an exciting medical story*. A-few years ago doctors fóuncT that the vitamin folic acid could, like liver, restore the normal blood picture in patients with pernicious anaemia. Next, workers at Mount Sinai Hospital in New York reported that folic acid seemed to retard the
Only a Matter of Time
growth of tumors in mice. Dr. Sidney Färber, of the Children’s Hospital in Boston, then tried folic acid on children suffering from acute leukemia and found that it speeded up the course of their disease. Obviously, then, what was needed was someth-'"" ’"Jt would act in aopposite manner to folic acid. And so there came into the picture the folic acid antagonists — aminopterin, amethopterin, and adenopterin—which can cause a partial (sometimes almost complete) return to normalcy in the blood of some youngsters with leukemia. Unfortunately they have certain poisonous side-effects, including nausea, and are fairly short-lived in their effect.
Finally, at long last, came ACTH and cortisone, both of which act on the blood in dramatic fashion and are the most promising news to date in fighting acute leukemia. A three-week course of ACTH, injected at four-hour intervals, will in certain cases rout every last excess white cell, including the dread “blasts,” from both the blood and the bone marrow of a child with advanced acute leukemia, returning him to his home and family for weeks, sometimes even months. (Unhappy side effects of the hormones include high blood pressure and dropsy.) These temporary returns to good health do not last, and seldom does a child respond so well to a second dose.
In 1950 and 1951 the Toronto Hospital for Sick Children treated thirtyseven patients with ACTH. The results were dramatic. Nineteen of these children were swept back into good health and sent home with their blood and bone marrow cleansed of all diseased white cells, their anaemia halted, their fatigue gone. Four children were slightly improved by the hormone; fourteen showed absolutely no change. Unhappily, in a matter of months the nineteen who had returned to good health had all suffered the usual leukemic relapse and returned to the hospital. Given a second ACTH treatment, nine or ten children responded with a second return to good health: these in due course suffered
a second relapse and were again hospitalized for a third dose of ACTH. This time only four or five showed any improvement. One child out of the original thirty-seven responded to the hormone the fourth time, but he too was dead within the year.
As this was written, a six-year-old girl called Maisie was enjoying a summer vacation with her family at Muskoka, Ont., although her acute leukemia had been diagnosed almost a year before. An energetic lad named Bobbie, ten years old, had just finished his school year and had passed with good marks although doctors had pronounced the hopeless verdict “acute leukemia” six months earlier. Both Maisie and Bobbie are out-patients and are expected to return to the hospital for a bone-and-blood test every month —for doctors know it is only a matter of time until the enemy cells come out of hiding and strike again. When that happens Maisie and Bobbie will go back to their beds in the Hospital for Sick Children for further treatment, first with ACTH, and if that fails, with one of the anti-folic group or possibly with nitrogen mustard in small doses.
The folic-acid trio, while seldom showing the dramatic results of ACTH or cortisone, nevertheless keep the disease under control and can be administered at home, either intravenously or by mouth. The hospital estimates that about thirty percent of the children treated with anti-folics get
at least one return to health in the course of their disease.
Oddly enough, an attack of measles or chicken pox, or some such infectious disease, may temporarily clear up leukemia. “It’s as if the bone marrow, under the stimulus of infection, de. Med to function in oa^orderly manner for a change,” one doctor says. Another guesses, “It’s as if the infection mustered more hormones from the body, which in turn fight the leukemia.” Nobody knows for sure. The one thing everybody knows is: No
child with acute leukemia lives very long.
Some Sufferers Can Still Work
Acute leukemia in adults is another thing—in fact there are some doctors who wonder secretly if perhaps acute leukemia in adults isn’t an entirely different disease process from acute leukemia in children, since the drugs and hormones which work so effectively in one case don’t always work in the other. ACTH, for example, has comparatively little effect on adults; the same is true of the anti-folic group. Symptoms of acute leukemia in adults are the same as in children: progressive anaemia, pains in the joints, pallor, fatigue. In chronic adult leukemia doctors can sometimes combine nitrogen mustard, radiation and one of the anti-folics so successfully that many a patient is kept in comfortable health for a year beyond his expected span. Rut one physician recently observed, “The trouble is that each patient is different from the others. There is a completely disorganized pattern of reaction to the various treatments.” One man with chronic leukemia may stubbornly resist all treatment; another may develop the disease suddenly in its advanced acute form; a third will show great improvement after treatment. Some farmers with chronic leukemia are working their farms today, laborers are doing heavy manual work with no ill effects, and pregnant women are bearing fine healthy infants.
A doctor at the Toronto General Hospital sums up the treatment situation this way: “The first step is to
make our chronic leukemia patients feel well. The next is to keep them feeling well longer. The third step is to extend that time and feeling of wellbeing longer still. It’s true there’s no cure for the disease in sight yet, but we’re laying our hands on an army of drugs to fight with. Look at mercury for syphilis, quinine for malaria, liver for pernicious anaemia, insulin for diabetes. Look at diseases like tuberculous meningitis, ‘galloping consumption,’ typhus, tetanus—all these were considered hopelessly fatal once, but not any more. Look at drugs like sulfa, streptomycin, penicillin, and the things they do.
“We haven’t any cure for leukemia yet, but we’re showing that the very process of the disease can be affected, altered, interfered with. That may not look like much to the layman, but medically it’s a great step forward. Some day there’ll be a cure.” jç