ALL is the most common type of cancer in children occurring between the ages of 2 and 5 years and adults over the age of 65. It is the most successfully treated childhood leukemia. In ALL, the DNA in the diseased cells is damaged and the cells cannot mature beyond the early stage in their life cycle. These immature (blast) cells reproduce very rapidly and take over the bone marrow so it cannot produce healthy blood cells and platelets. These low counts of disease fighting white cells can lead to infection, and bruising or bleeding from the low levels of platelets. Immediate treatment is required because of the rapid progression and accumulation of the malignant cells, which then spill over into the bloodstream and spread to other organs of the body.
In 2012 an estimated 6,050 people of all ages (3,450 men and boys and 2,600 women and girls) in the United States will be diagnosed with ALL. About one-third of these will be adults. An estimated 1,440 deaths (820 men and boys and 620 women and girls) will occur this year; about three-fourths of these deaths will be among adults.
The five-year survival rate (percentage of people who survive at least five years after the cancer is detected, excluding those who die from other diseases) of people with ALL is 67%. Survival depends on several factors, including biologic features of the disease and the age of the person. These estimates are based on data from thousands of people with this type of cancer in the US each year, but the risk for a particular person may be different.
Exposure to high levels of radiation, or certain chemicals at work, like benzene or having some types of chemotherapy to treat another cancer, can put you at higher risk for developing leukemia. But, unfortunately, most people who have these risk factors don’t develop leukemia and most people who develop leukemia have no known risk factors. Most types of leukemia are associated with certain gene mutations (changes in the DNA of the diseased cells), but it is not clear what causes those changes.
The symptoms can generally appear suddenly and can be similar to a virus or the flu. These symptoms can be from a wide range of conditions and illnesses, but if they continue then you should consult a physician.
Symptoms can include:
In order to diagnose leukemia your doctor will ask you questions about your past health and symptoms. Your doctor will do a physical exam, will look for swollen lymph nodes and check to see if your liver or spleen is larger than normal. Blood tests will be ordered to check to see if your white blood cells are high and your other blood cells levels are low. If you have abnormal blood tests then your doctor may do a bone marrow biopsy. This test will look at the inside of your bone. Imaging such as a CT scan or ultrasound can find out if other organs such as the lung, liver, spleen, lymph nodes, brain and kidneys have been affected as well.
If you have acute lymphocytic leukemia then you will need quick treatment to stop the rapid growth of the leukemia cells. Treatment focuses on control of the bone marrow and the whole body disease. The treatment must prevent leukemic cells from spreading to other sites, especially the central nervous system (CNS). Treatment may make the leukemia go into remission. Standard treatment usually involves chemotherapy and radiation therapy. The survival rates vary by age, but are close to 85% in children and 50% in all adults.
Clinical trials may be an option for some people. Clinical trials are research projects that test new medicines and treatments. Many people with leukemia take part in clinical trials. Many children with ALL take part in clinical trials.
Treatment is divided into several phases:
Induction chemotherapy brings the bone marrow into remission. The goal is to rid the blood and bone marrow of all visible leukemic blast cells. For adults the standard induction usually includes either a 4 drug regimen of vincristine, prednisone, anthracycline, or L-asparaginase or a 5 drug regimen of vincristine, prednisone, anthracycline, cyclophosphamide and L-asparaginase given over 4-6 weeks. Using this complete remissions can be obtained in 65-85% of patients. If there are still some blast cells then a second round of the same chemotherapy is given. Other drugs can be added or substituted for those patients who are higher-risk, refractory (do not respond) or are relapsed. The initial therapy may take place in a hospital because of the severity of the disease or the severity of the side effects. Patients may stay up to 6 weeks. This would depend on who a patient may have as a caregiver at home.
For children with low-risk ALL, standard therapy usually consists of three drugs: prednisone, L-asparaginase and vincristine for the first month of treatment. Children with ALL are generally admitted to the hospital as soon as they are diagnosed. This can be a very traumatic time for a child since they will be away from home for an extended period of time. It is important to provide age appropriate information about their illness and treatment and allow them to feel comfortable in talking to their treatment team.
Consolidation therapy is used to remove any remaining leukemia cells. There may be some leukemia cells left that you can’t see in either the blood or bone marrow after remission. This is additional intensive treatment that is postremission. Consolidation is usually given in cycles for 4-6 months. There are many different ways to do consolidation but it is usually a high dose, multi-drug therapy with antimetabolite drugs like vincristine, cyclophosphamide, cytarabine, daunorubicin, etoposide, thioguanine or merceptopurine given in different combinations. High risk patients may get higher drug doses. There are individual factors such as age, ability to tolerate treatment and the availability of a stem cell donor and other things that will influence the treatment provided at all stages.
CNS prophylaxis (preventive therapy) is used to stop the cancer from spreading to the brain and nervous system in high risk patients. Often ALL cells can collect in the lining of the spinal cord and brain, called the meninges. If it is not treated before this occurs the leukemic cells can remain there causing a relapse. The treatment may include radiation of the head and/or drugs delivered directly into the spine (intrathecal). For CNS protection, intrathecal methotrexate or cytarabine is usually used combined with or without cranio-spinal irradiation (the use of radiation therapy to the head and spine). Central nervous system relapse is treated with intrathecal hydrocortisone, methotrexate, and cytarabine.
Maintenance therapy with chemotherapeutic drugs will be used to prevent the disease from recurring once remission has been achieved. Maintenance therapy usually involves lower dose drugs and may continue for up to three years. For this purpose, daily oral mercaptopurine or once weekly oral methotrexate, once monthly 5-day course of intravenous vincristine and oral corticosteroids are usually used. The length of maintenance therapy is 2-3 years.
As the chemotherapy can be intensive and often last for 2-3 years, many patients have an intravenous catheter inserted into a large vein (termed a central venous catheter or a Hickman line), or a portacath, a cone-shaped port with a silicone nose that is surgically planted under the skin, usually near the collar bone. Portacaths are most often used and have a low infection risk and a long-term viability.
After treatment, a patient who is in remission and has completed therapy will continue to be followed regularly by their oncologist. This could include following their general health, blood counts and bone marrow if it is needed. These assessments may become less frequent but will continue indefinitely. The reason is because there are specific late effects from the chemotherapy and other treatments given. Some children and young adults treated for ALL may be at increased risk for heart damage, other cancers and neurologic or cognitive problems. Therefore patients should be seen by a primary care doctor once a year in addition to their oncologist.
Radiation therapy (or radiotherapy) is used on painful bony areas, in areas where there is a large mass in a local area or as part of the preparations for a bone marrow transplant (total body irradiation). Radiation in the form of whole-brain radiation is also used for central nervous system prophylaxis, to prevent recurrence of leukemia in the brain. Whole-brain prophylaxis radiation used to be a common method in treatment of children’s ALL. Recent studies showed that CNS chemotherapy provided results as favorable but with less developmental side-effects. As a result, the use of whole-brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS preventive therapy, instead using intrathecal (into the spinal canal) chemotherapy.
Allogeneic (using donor cells) or autologous (using a patient’s own cells) bone marrow transplantation may also be appropriate for high risk or relapsed patients.