This year an estimated 5,730 people of all ages will be diagnosed with ALL. ALL is much more common in children than adults, with about two-thirds of new cases occurring in boys and girls under age 18. Children with ALL have a higher chance of being cured compared to adults.
The cause of ALL is not known. It occurs more often in children and adults over the age of 50. People who have been exposed to high doses of radiation, such as survivors of atomic bomb blasts, have a higher incidence of ALL, as do people with certain genetic disorders. These include Down syndrome and a number of less well known conditions. Research indicates that some young children with ALL may have actually had the disease before they were born, even though it can take years for the disease to develop. More research is underway to understand how this occurs.
People with ALL can have a variety of symptoms. These include
All of these symptoms can be caused by conditions other than cancer but if they occur, especially in young children, they should be checked by a doctor. ALL can begin very suddenly and cause a person to become sick very quickly.
If a doctor suspects that someone has ALL, the first step is to do a complete physical examination and medical history. For ALL, the primary diagnostic test is a blood test to examine the levels of different kinds of blood cells. People with ALL have high levels of abnormal, immature lymphoblasts and low levels of other blood cells, including red blood cells and platelets.
Patients with diagnosed or suspected ALL will also have a series of other blood and laboratory tests. Many centers now recommend saving some cells for future research. This is something that you should discuss with your doctor.
If the blood tests indicates leukemia, the next step is usually a bone marrow biopsy. The pathologist then examines the cells to determine the type of leukemia. ALL tends to spread to the brain and central nervous system so doctors also do a procedure called a lumbar puncture or spinal tap to withdraw fluid and look for cancer cells.
Men and boys with ALL should also be tested to see if the leukemia is affecting their testicles. ALL patients are very susceptible to infections, so the diagnostic process includes a careful examination to find and treat any infections that might be present. Since many ALL patients will become possible candidates for stem cell transplants, it is important to do HLA typing at the time of the initial diagnosis. This helps identify potential donors, especially for patients who do not have a sibling donor.
Lymphoblastic lymphoma and ALL are classified as the same disease, with the difference being the location of the disease. In ALL, the disease affects the blood and bone marrow, while in lymphoma, it affects the lymph nodes or other organs in the body. Lymphoblastic lymphoma and ALL are treated in a very similar way.
ALL is one kind of leukemia, but there are subtypes of this disease as well. The pathologist distinguishes ALL from other kinds of leukemia and identifies the subtype by the distinctive markers found on the surface of the cells. This process is called immunophenotyping and is important to determining the prognosis. People with leukemia also have specific changes in their chromosomes or genetic mutations. The pathologist analyses these changes for each patient.
Specific recurrent genetic abnormalities. When doctors analyze leukemic cells, they look for very specific changes that occur in the cell's chromosomes and are present in a large number of cells. These are called specific recurrent genetic abnormalities. There are at least six different subtypes of ALL that have been identified using this method. The presence or absence of these abnormalities allows doctors to assign patients to a risk category depending on the prognosis. For example, ALL patients who have the Philadelphia chromosome (PH+) offer a poorer prognosis than those who do not. Identifying the subtype based on recurrent genetic abnormalities is critical to deciding on the best treatment option.
Most patients may also undergo imaging procedures such as x-rays, CT scans, MRIs or PET scans to determine whether the leukemia/lymphoma involves other organs.
Classification is the system that is used to describe leukemias. Knowing the precise kind and subtype helps plan treatment and predict the prognosis. There are different kind of lymphoblasts, B cells, T cells and NK cells. About 85% of ALL patients have leukemia that affects their B cells. Most of the other 15% have T cell leukemia. Leukemia affecting the NK cells is very rare. Doctor also look for specific gene mutations that are found in some leukemias.
Once all the diagnostic tests are completed, the doctors will use all of the available information to determine a risk level. The most important factors in determining this level are the cytogenetics--the specific gene abnormalities that are found--but other factors are important as well. Age is a key factor as the treatment for children and young adults is often different than that for older patients.
Young adults, classified as people between the ages of 15-39, are considered as a separate population when planning ALL treatment. Doctors currently use the genetic profile to decide whether these patients should be treated with protocols developed for pediatric patients. A critical factor is whether the patient is positive for the Philadelphia chromosome, PH positive ALL.
The Philadelphia chromosome occurs when parts of chromosome 9 are exchanged, or translocated, with parts of chromosome 22. The shorter of the two chromosomes is called the Philadelphia chromosome and contains a specific gene mutation called BCR-ABL. BCR-ABL results in the over production of a protein called tyrosine kinase which leads to the production of too many white blood cells. These cells are also immature and abnormal as well. PH status is an important prognostic indicator for people with ALL.
ALL is not staged in the same way that many other cancers are because it is not a solid tumor. Leukemia cells are found throughout the body. Instead, ALL is described in the following ways:
Untreated: This is the newly diagnosed patient who has abnormal numbers of blood cells, lymphoblasts in the bone marrow and often has symptoms of leukemia.
In remission: Patients who have been treated for leukemia and have responded. These patients have normal blood cells counts, less than 5% lymphoblasts and no symptoms.
Recurrent/Refractory: The leukemia has either failed to respond to treatment or has come back. Patients with recurrent or refractory leukemia can receive other drugs or be considered as candidates for stem cell transplants or for clinical trials that test new approaches to treating their leukemia.
Treatment for ALL depends on a number of factors, including the person's age, type of leukemia, risk category and overall health. The treatment approach to ALL is one of the most complex and intense in all of cancer therapy. It requires expertise in many medical fields and disciplines, and the ability to provide extensive supportive care, and should only be done in cancer centers that have experience in treating this disease. There are many chemotherapy drugs and combinations used to treat ALL. The drugs used for each patient along with the doses and the duration of treatment depend on a complicated matrix that takes all the factors into account. Many patients are also candidates for clinical trials studying new approaches to treating ALL.
The first goal of treatment is to get the patient into a complete remission, meaning that all the signs and symptoms of the disease disappear. Doctors use combinations of anti-cancer drugs to induce remissions. For patients who have a high risk of having leukemia in their brain and central nervous system, radiation therapy is often given to as well. Patients who have specific genetic mutations also respond very well to therapies targeted to those mutations.
This is aggressive therapy, designed to deliver a knockout blow to the cancer. It usually requires three to four weeks of hospitalization and can have many side effects. The response rates for ALL patients to induction therapy are very high. More than 95% of all children and 75-80% of adults with ALL have a complete remission.
The prognosis for PH positive ALL is not as good as for patients who do not have this genetic mutation, and the treatment differs as well. In recent years, researchers have discovered a number of targeted therapies--drugs aimed directly at blocking the production of the abnormal protein, tyrosine kinase. These drugs are often combined with standard chemotherapy and with stem cell transplants in patients who are eligible for this procedure. This approach has resulted in improved survival rates for both young adults and adult patients with ALL.
Despite the very high response rates to induction therapy, doctors know that leukemia will almost always come back. Consolidation therapy uses different drugs to eliminate any remaining leukemia cells and reduce the risk of recurrence.
This treatment involves lower doses of drugs given over a two to three year period to keep the ALL from returning or relapsing.
Stem cell transplant is a medical procedure that replaces a person's diseased bone marrow with healthy stem cells. For ALL, these cells generally come from a donor, often a close relative, whose blood matches the patient's. Stem cell transplants are recommended for patients whose leukemia is refractory, meaning that it does not respond to treatment, or recurs, meaning that it comes back. In order to transplant the healthy cells, doctors have to first destroy the patient's diseased bone marrow using very high doses of chemotherapy. This has many side effects, both short and long term, and can be life threatening.
The treatment of people whose leukemia returns after treatment is challenging. Doctors currently have a number of second line treatments available but many patients do not respond to these treatments or the responses only last for a short period of time. Patients with relapsed ALL should discuss participating in a clinical trial.
ALL is a complex disease, and it requires complicated, intense treatment. Patients are often very sick and face a number of issues from both their disease and the treatments they receive. These include infections, weight loss, nausea and vomiting, other gastrointestinal problems among others. In addition, having leukemia and undergoing treatment is a very stressful, scary thing to face. Patients and their families need emotional support to get through this process. Not only is supportive care important to help the patient during treatment, but it is critical to being able to deliver the best therapy. If patients are too sick or are suffering from too many problems, they are unable to get the treatment they need. ALL patients should all be treated in cancer centers that can provide supportive care and symptom management for every issue that these patients encounter.
ALL, especially in children responds very well to therapy. Survival rates are increasing, especially with the introduction of new targeted therapies for high risk patients and improved supportive care. One of the major research goals for ALL is to reduce both the short and long term side effects that patients experience while continuing to improve the outcomes--but the treatment can be tough. Patients and families should be treated in centers that have both the expertise to provide state of the art therapy and address the many physical and emotional issues that can accompany leukemia treatment.
The treatment of ALL, especially in children, is one of the first and most enduring success stories in cancer research. In the last few decades, ALL has gone from a disease that was always fatal to one which can often be cured. We know a lot more now about the different types of ALL and the best ways to treat them. Despite the good results, ALL remains a complicated disease and the treatment can have both short and long term side effects. Adults with ALL don't always do as well as kids. We still have a ways to go in understanding how and why this disease occurs and developing improved ways to treat it.