IN THIS CHAPTER YOU’LL DISCOVER
JOANNE FILINA HADN’T FELT right in years, but her doctor had been brushing off her concerns. “Because I work in the medical field, he implied I was a hypochondriac,” says Filina, who is an ultrasound technician. Finally, he referred her to a doctor who specializes in diseases of the blood and the diagnosis came back showing Joanne had an advanced form of leukemia.
“I remember my doctor saying words like ‘no cure,’ and ‘this cancer doesn’t respond to treatment.’” After local doctors told her she had only 18 months to live, she decided she had better be seen at a major cancer center. “There, they hit me hard with chemotherapy,” she says. Now, nearly two years later, her leukemia is in remission.
All of our blood cells begin as stem cells, generated mainly in our bone marrow. As different genetically coded pathways lead each cell to maturity, some become white blood cells (meant to fight infection), some red blood cells (which carry oxygen), and others become platelets (responsible for clotting).
In the case of leukemia, our bone marrow produces abnormal white blood cells. These don’t tend to die off like normal cells, and eventually crowd out healthy blood cells, preventing them from performing their essential life functions. Leukemia cells don’t have the ability to fight infection like normal white cells, thus they compromise the entire body’s immune system, collecting in the lymph nodes, spleen, and liver.
Though medical science is unsure of the exact trigger that causes the onset of the different types of leukemia, one thing is certain: environmental and genetic factors (chemical exposure or genetic abnormalities) seem to be the culprit. The word leukemia comes from the Greek leukós and haîma, which literally means “white blood.”
An estimated 45,000 new cases of adult leukemia cancer are diagnosed each year; almost 90 percent of cases occur in those over the age of 20, with the majority of sufferers aged 60 or older.
Men are about one-third more likely to develop leukemia than are women, and they are also more likely to die from it. Caucasians are more apt to get leukemia, with those of Jewish ancestry particularly susceptible to the disease.
People may develop leukemia even with no risk factors for the disease, but there are several factors that increase the probability. Some genetic syndromes can increase risk, such as Down syndrome, T-lymphotropic virus (HTLV-1), and HIV. Those who have undergone certain medical treatments are also at risk for developing leukemia because of repeated doses of radiation, especially certain cancer survivors who’ve received specific types of chemotherapy. As well, those who’ve suffered high-dose radiation exposure for any reason face a higher risk for the disease. Long-term or high-dose chemical exposure to benzene and other products containing this substance are also known to cause leukemia.
It is estimated that there are about 300,000 leukemia survivors in the United States. Treating leukemia is made especially complicated by the fact that there are many different forms of the disease, so deriving a prognosis from its various stages is markedly problematic. Generally, though, the outlook is fairly optimistic for leukemia patients because treatment has made remarkable progress over the past 50 years. In the early 1960s, the overall five-year survival rate was four percent. Today it stands at 64 percent.
Leukemia is classified according to the type of white blood cell that is multiplying:
If the abnormal white blood cells are primarily granulocytes or monocytes, the leukemia is categorized as myelogenous, or myeloid leukemia. If the abnormal blood cells arise from bone marrow lymphocytes, the cancer is called lymphocytic leukemia.
There are four types of leukemia, which are divided into two broader categories: acute leukemia and chronic leukemia. The difference between the two is that the abnormal cells in acute leukemia appear more as stem cells, or blast cells, while in chronic leukemia, the abnormal cells appear to be closer in likeness to a normal white blood cell.
Acute leukemia is a disease in which the bone marrow cells cannot mature properly so immature cells reproduce and build up in the bloodstream. Symptoms appear to come on suddenly, so patients feel ill right away. Types of acute leukemia include acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL). Acute leukemia means that the form of the disease is very dangerous and could be fatal within a few months if untreated; it must be treated immediately and intensively, eliminating all traces of the abnormal cells so the patient can be brought into remission.
AML is the most common form of adult leukemia. Most of those diagnosed are older (the average age of diagnosis is 65), and more men are affected than women. Generally, treatment can keep approximately 60 to 70 percent of people in remission, with an overall cure rate of 40 to 50 percent.
In a healthy individual, the bone marrow’s myeloblast cells (or simply blast cells) mature into granulocytes, one of three major types of white blood cells, along with monocytes and lymphocytes. The main function of the granulocyte is to destroy bacteria. In the case of AML, blasts overproduce and do not grow into fully matured granulocytes; instead, these blasts become too numerous in the blood and bone marrow, crowding out healthy red and white blood cells, and platelets. As the blast cells build up, they hamper the body’s ability to fight infection and prevent bleeding. Therefore, AML can become life-threatening if not treated quickly.
AML is also known as acute myelogenous leukemia, acute myelocytic leukemia, or acute nonlymphocytic leukemia.
ALL is a situation in which the bone marrow manufactures too many lymphoblasts — lymphoid stem cells that evolve into blasts, but never fully mature into lymphocytes. As with AML, these immature cells crowd the marrow and blood, causing the disease to progress quickly and require prompt treatment. Lymphoblasts (abnormal lymph cells) may also collect in the lymphatic system and cause swelling of the lymph nodes. Some cells may invade other organs, including the brain, liver, spleen, or testicles in men. But unlike other types of cancer, the fact that ALL is found in other parts of the body does not mean that the cancer is in an advanced stage — acute leukemia is usually found throughout the body when it is diagnosed.
Caucasian males are most at risk for ALL, especially those over 70, those having undergone chemotherapy or radiation in the past, or individuals with Down syndrome or other genetic disorders.
Chronic leukemia cells do not look as abnormal as those of acute leukemia; they can mature partially, but not completely. But even though the cells look fairly normal, they do not fight infection as well as normal white blood cells. The cells also live longer or don’t die at all as healthy cells do, so they can crowd out normal cells. Chronic leukemia can develop slowly — sometimes over the course of years — and people may remain asymptomatic for a very long time. The two types of chronic leukemia are chronic lymphocytic leukemia (CML) and chronic myeloid leukemia (CLL).
CLL is a type of leukemia in which the lymphocytes (white blood cells) begin to grow and change abnormally, preventing the production of oxygen-carrying red blood cells, healthy white blood cells, and platelets. Most often, the disease is diagnosed when too many lymphocytes are found in the blood; however, the same disease can occur when the abnormal lymphocytes are mostly in the lymph nodes but not in the blood. This is called small lymphocytic lymphoma, but it is very similar to CLL.
Chronic lymphocytic leukemia is the second most common type of adult leukemia, and is marked by slow progression. Caucasian males, middle-aged or older, bear the highest risk factor, as well as those with a family history of CLL or cancer of the lymph system. Also at higher risk are Russian or Eastern European Jews.
CML is a slowly progressing form of blood cancer that usually occurs beginning in middle age. Normally, the bone marrow produces stem cells (immature cells) that mature over time. These cells can become either a myeloid cell or a lymphoid cell. In CML, too many myeloid cells become abnormal. These abnormal cells are called “granulocytes.”
CML is easy to diagnose because it has a genetic marker, called the “Philadelphia chromosome,” named after the city in which it was discovered. This genetic marker occurs by chance, though, and is not passed down from generation to generation.
The classification of leukemia according to type is extremely complex, so a precise diagnosis must be done correctly right from the start in order for the patient to have the best chance for survival. There are also various types of more rare leukemias, such as monocytic leukemia, hairy-cell leukemia, promyelocytic leukemia, erythroleukemia, and others. “Most blood cancers like leukemia are uncommon, and if you go to a community hospital, they are most likely to treat only the most common cancers, so you need to make sure your doctor is either a hematologist (a doctor who specializes in blood diseases) or an oncologist with experience in treating adult leukemia,” advises Patrick J. Stiff, MD, hematologist and director of Loyola’s Cardinal Bernardin Cancer Center.
“Making an accurate diagnosis and getting the best possible therapy for leukemia is extremely important. There are a lot of nuances in therapy and so it’s difficult for a general oncologist, who treats only common cancers like breast or colon cancer, to keep up. It’s where you get your first therapy that could determine whether you’re cured or not,” he adds.
Leukemia and other blood cancers differ from solid-tumor cancers because the cancerous cells are scattered throughout the body via the bloodstream. Because of the progression of leukemia, most cases are classified according to phases. How the leukemia is treated will depend on the disease’s phase.
AML is divided into eight different subtypes according to the characteristics of the cells and other factors. Treatment and prognosis depends on the subtype of the disease. The vast majority of AML patients require prompt treatment due to the aggressive nature of the disease.
ALL is treated according to one’s age, condition at diagnosis, and specific results of cellular testing. The term recent is used to describe an individual who has been newly diagnosed, while relapsed refers to those no longer in remission, or whose condition is recurrent. The objective of ALL treatment is a cure, and it is divided into four stages. Heavy chemotherapy is used during the first two phases, while the third and fourth phases involve maintenance chemotherapies. The entire course of treatment takes between two to three years to complete.
The three phases of CML are chronic, accelerated, and blast (or blastic).
In this initial phase, there are fewer than five percent blast cells, or promyelocytes (immature granulocytes), in the blood and bone marrow. There are only mild symptoms, and conventional treatment is effective.
There are more than five percent but fewer than 30 percent blast cells. The leukemic cells exhibit more chromosomal abnormalities, and so more abnormal cells are produced. Treatment is more intensive.
In this final phase, the disease transforms into an aggressive, acute leukemia (either AML or ALL). More than 30 percent of the cells in the blood and bone marrow samples are blast cells, and these cells often invade other tissues and organs. If untreated, this form of CML claims roughly 20 percent of all patients each year.
There are five stages of CLL. Each stage is classified according to a scale called the Rai system (the Binet system is widely used in Europe), and depends on the amount of lymphocytes in the blood and whether the lymph nodes, spleen, or liver is involved, as well as whether the patient is anemic. Also taken into consideration is whether the blood platelet count is normal or reduced. The Rai system ranges from Stage 0 to IV, with each stage increasing in severity.
The symptoms of leukemia vary according to type:
Early signs of AML can mimic the flu. Symptoms can also include the following:
Like AML, early ALL can also produce flu-like symptoms. Additional symptoms are also similar to those of AML.
In its early stages, there may be no symptoms, and the disease may be discovered accidentally. Symptoms of advanced CML include the following:
This chronic phase can last from several months to several years.
Usually, CLL does not cause any symptoms and is discovered during a routine blood test. Symptoms are similar to ALL and AML.
The spleen is an organ in the abdomen that is involved in the production and removal of blood cells. In leukemia, abnormal blood cells form so fast that the spleen can become enlarged.
A physical examination and blood tests are the first steps used in diagnosing leukemia. If the results of the blood test are not normal, the following tests may be used:
For this test, the doctor inserts a long needle into a bone (usually the pelvic bone or breastbone) and then draws out some fluid to analyze the blood cells and see if they are mature or abnormal. If something is wrong, the percentage of abnormal cells is used to classify the leukemia according to type.
If leukemia is diagnosed, there are several different methods that can be used to determine its exact type, such as staining the cells, attaching special antibodies to them, or analyzing the antigens (foreign bodies that prompt immune response) they have. These tests are called cytochemistry, flow cytometry, and immunohistochemistry, respectively.
Leukemia cells may undergo genetic changes, and recognizing them can help determine both the form of the disease and the most effective treatment. Tests involve studying the cells under the microscope to analyze the DNA and determine whether any abnormal changes have occurred. These tests go by different names, which include cytogenics, fluorescent in situ hybridization (FISH), and polymerase chain reaction (PCR).
This test involves using a hollow needle to remove fluid from the spine. It is performed to see if there are any leukemia cells in the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord.
CT (CAT) scans, PET scans, and ultrasound tests can be used to determine if leukemia cells have spread to lymph nodes or organs inside the abdomen, like the kidneys, liver and spleen, or to the bones.
The way leukemia is treated differs according to its stage, and whether the disease is acute or chronic. Generally, intensive chemotherapy is used for acute leukemia to cure it, put it into remission, manage the disease, and for use in case of relapse. Chronic leukemia sometimes only needs monitoring in its early stages, and chemotherapy once the condition becomes threatening. Treatments that leukemia patients undergo, especially intensive chemotherapy, and/or bone marrow transplantation, leave the body very vulnerable to infections and lung diseases, so supportive care and strict avoidance of infection are essential.
Chemotherapy is a mainstay in the treatment of leukemia. In fact, imatinib (Gleevec), a chemotherapy drug that dates back a half century, is credited with the turnaround in leukemia survival rates. Gleevec received FDA approval in 2001, made the cover of Time magazine the following year, and has been hailed for transforming leukemia from a potentially fatal disease to a chronic, manageable one. It is a first-line therapy for acute and chronic leukemia patients, and used at higher dosages for bone marrow transplants recipients.
In 2014, the FDA approved Blinocyto (blinatumomab), an immunological agent to treat a rare form of ALL known as “Philadelphia chromosome-negative precursor B-cell acute lymhoblastic leukemia,” or B-cell ALL.
This surgery is not usually needed, but is performed when the disease has caused the organ to enlarge and is pressing on other organs, or it is turning out too many abnormal white cells, depriving the body of red blood cells and/or or platelets. Most live very well without a spleen, but it does increase the risk of infections. In some cases, radiation is done to shrink the spleen.
A bone marrow transplant can be done in severe cases of adult leukemia and non-Hodgkin’s lymphoma. This procedure replaces damaged or destroyed marrow with healthy marrow stem cells.