| Carolyn Vachani, RN, MSN, AOCN
Updated by: Lara Bonner Millar, MD
|The Abramson Cancer Center of the University of Pennsylvania|
This article is a more specific discussion of ALL. Please be sure to read Leukemia: The Basics first, so you have a basic understanding of leukemia.
What is ALL?
ALL is a blood cancer that affects the white blood cells. There are two main types of white blood cells, lymphocytes (affected by ALL) and myelocytes (affected by AML). Lymphocytes are further broken down into B and T cell lymphocytes. ALL is a spectrum of disease comprised of several different subtypes, named for the cell type that is affected (B or T) and how abnormal the cell appears under a microscope. A person with ALL develops abnormal numbers of white blood cells rather quickly, usually over weeks, giving the disease the name "acute".
The white blood cell (WBC) count may be higher or lower than normal, but the WBCs that are being produced are immature and do not function well. Because WBCs are an important part of fighting infections, patients often have multiple infections that don't respond to treatment before they are diagnosed. Some people will have low red blood cell or platelet counts because the overpopulation of WBCs crowds out these cells.
There will be an estimated 6000 new cases of ALL diagnosed in 2009 in the United States, and two thirds of these cases will be in children. ALL accounts for 1-2% of all adult cancer cases (and 20% of adult leukemia cases), but makes up 25% of all childhood cancers (all types). ALL can occur at any age, but is most common in children, ages 2 to 4, and adults over age 50. This article will address ALL in adults.
What causes ALL?
In most cases, the cause of ALL is unknown. There are some factors that are known to increase a person's risk of developing ALL, including previous treatment with chemotherapy or radiation therapy, exposure to large amounts of radiation (such as an atomic bomb), or the presence of a genetic disorder (i.e. Down's syndrome, Klinefelter's syndrome). Research has identified viruses, such as Epstein-Barr, HTLV1, and HIV, as potential causes in some cases.
How do people with ALL present?
In ALL, white blood cells do not fully mature and therefore cannot function properly. These immature cells, called "blasts", also suppress normal blood cells from forming, further compounding the problem. Symptoms are related to the abnormal numbers and function of blood cells and/or infiltration of other organs, and can include weight loss, fever, infection, easy bleeding or bruising, shortness of breath, or weakness. These symptoms can also be signs of common illnesses, like a cold or flu, and it is not uncommon for a person to be seen several times by a healthcare provider before receiving a diagnosis of ALL. Most infections are just infections and not leukemia, so treating a suspected infection is appropriate and this short delay in diagnosis is not likely to affect the course of the disease. What is important is that a person returns to their physician for further investigation if the symptoms they have are not responding to the prescribed treatment (often antibiotics).
ALL is most often discovered when a person has an infection that does not improve with treatment or has unexplained bleeding or bruising. When a blood count is checked, abnormal counts or blasts are seen on the results. Once this occurs, further testing is required to clarify a diagnosis of leukemia and determine the type of ALL.
What happens once someone is suspected of having ALL?
Once ALL is suspected, further blood tests, including a blood smear may be drawn and a bone marrow biopsy and aspiration performed to better classify the ALL. On a blood smear, blast cells are usually seen. Bone marrow biopsy confirms the diagnosis. A lumbar puncture (spinal tap) is also done to evaluate if there are blast cells in the spinal fluid.
ALL is classified using the World Health Organization system, which replaced the FAB (French American British) system in 2001. This classification guides the treatment of the disease. The classification system uses the following groups:
How is ALL treated?
Chemotherapy for ALL is one of the most complex treatment plans used in any type of cancer. It is broken down into phases, starting with the induction phase, followed by the consolidation (or intensification) and maintenance phases. Surgery is not used because ALL is a disease of the blood, which circulates throughout the whole body; this means an effective treatment must address disease throughout the body.
Induction therapy consists of a combination of several medications, most often a steroid (dexamethasone or prednisone), vincristine, an anthracycline (daunorubicin, epirubicin or idarubicin) and asparaginase. In some subtypes, other medications may be used, such as cytarabine, cytoxan, methotrexate and rituximab. Many patients will be treated as part of a clinical trial to allow researchers to better identify the best regimens.
Consolidation therapy uses some similar medications, but is more variable in its schedule and depends upon the particular subtype of ALL. Consolidation is given over a period of 4 to 8 months. If a patient was a candidate for stem cell transplant, then the transplant would likely be done in lieu of consolidation and maintenance therapy.
Maintenance therapy consists of 6-MP, methotrexate, vincristine, and prednisone, given over a period of 2 to 3 years. Studies found no benefit to increasing this time, but did find outcomes to be worse if the maintenance period was shorter. Maintenance therapy is not given for Burkitt's lymphoma leukemia, as this subtype has a high cure rate with induction and consolidation therapy alone.
The goal of therapy is to induce a remission, usually defined as less than 5% blast cells found in the bone marrow.
Central Nervous System (CNS) Prophylaxis
While less than 10% of patients have CNS involvement of leukemia at the time of diagnosis, 50-75% of patients will develop this by 1 year if not given preventive therapy. In the past, radiation to the whole brain was used as central nervous system prophylaxis, to prevent recurrence of leukemia in the brain, and this is still sometimes done for childhood ALL. Currently, this has been abandoned in adults as the most effective therapy to prevent CNS disease is intrathecal chemotherapy. This involves giving chemotherapy directly into the spinal canal. This can be achieved by a lumbar puncture (spinal tap), or through a catheter called an Omaya reservoir that is surgically implanted in the head. This catheter allows for multiple, repeat intrathecal infusions without needing multiple lumbar punctures. The number of intrathecal infusions given is dependent on the subtype of ALL and the risk of CNS disease associated with that subtype.
The use of stem cell transplant for ALL is not completely clear. It is most often used early in therapy for patients with high-risk subtypes of ALL in first remission. Clinical trials are evaluating the optimal time for transplant (first or second remission, before maintenance therapy, etc.) and trying to determine which patients are best served with this modality.
Philadelphia Chromosome Positive ALL
The Philadelphia Chromosome is a genetic abnormality that was first identified in chronic myelogenous leukemia (CML), but is also seen in over 20% of adult ALL cases. (Read more about the Philadelphia Chromosome ) Philadelphia Chromosome positive ALL (Ph+ ALL) has long carried the poorest prognosis of all ALL types, but the discovery of a class of medications that target this genetic abnormality has brought new hope to these patients. The first and most widely studied drug in this class is imatinib. Studies found that imatinib alone did not improve outcomes (in most patients), but that in combination with chemotherapy, results were promising. The best combination and schedule for these medications has not yet been determined. Of note, in elderly patients, studies found imatinib alone to be superior to chemotherapy.
Unlike in CML treatment, imatinib is not a potential cure for Ph+ ALL or effective long-term treatment, but it can induce a temporary remission, and in patients who receive an autologous stem cell transplant, the addition of imatinib improves overall survival.
Complications & Concerns of Leukemia and Treatment
People with leukemia are at risk of infection (due to few and poorly functioning white blood cells) and bleeding (due to low numbers of platelets) even before any therapy is started. Because these abnormalities are a result of the leukemia, it is necessary to treat the leukemia in order to correct the abnormal blood counts. Leukemia treatment causes the blood cell counts and function to temporarily get worse. During this time, patients will receive blood and platelet transfusions, antibiotics and take precautions to prevent infection and bleeding.
Hand washing is the single best way to prevent infection and should be performed frequently by patients, visitors, caregivers and healthcare personnel. Even the best hand washers get infections, so we implement a few other restrictions to help in the cause. People with leukemia cannot receive or consume fresh fruit, vegetables or flowers while in the hospital. (See the gift guide for ideas on what to send a patient with these restrictions) You may think this sounds odd, but these items can harbor bacteria and may put the patient at higher risk of infection. We ask people who are sick (or who have sick family members at home) not visit the patient in person and if they absolutely must, they need to wear a mask and wash their hands well.
In most cases, some type of infection or fever is inevitable. When this happens, the patient will typically have several tests done to look for a source of the infection, including blood, urine and stool cultures and a chest x-ray. Antibiotics will be started or adjusted if they are already being given. Many times the source of the infection is never identified and general antibiotics that treat a variety of things will be used. The patient will receive these antibiotics until their white blood count reaches a level that will allow them to fight the infection on their own.
Over the course of their treatment, patients will require either blood (for low hemoglobin levels) or platelet (for low platelet counts) transfusions. People with low hemoglobin counts (also called anemia) can experience fatigue, shortness of breath or appear pale. A low platelet count (also called thrombocytopenia) can lead to bleeding. This can be as small as gums bleeding when brushing the teeth or a nosebleed to dangerous bleeding, such as a stroke. Patients should use caution to avoid bumping themselves with normal activities; they may not shave with a razor (electric razor is okay, with caution) and should avoid any activities that increase the risk of bleeding or bruising. Patients should always inform their healthcare team if they have symptoms of anemia or thrombocytopenia.
A diagnosis of leukemia is very scary, but understanding what is happening and what to expect can help alleviate some anxiety. Learning about the treatments, potential side effects and how the healthcare team will manage them can help patients and their caregivers, friends and family.
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