Acute Lymphoblastic Leukemia Causes, Symptoms, Diagnosis, Treatment, Prevention In Adults, Children

Acute Lymphoblastic Leukemia Causes, Symptoms, Diagnosis, Treatment, Prevention In Adults, Children


What Is Acute Lymphoblastic Leukemia?


Acute Lymphoblastic Leukemia is a type of leukemia that starts from white blood cells in the bone marrow, the soft inner part of bones. It develops from cells called lymphocytes, a type of white blood cell central to the immune system, or from lymphoblasts, an immature type of lymphocyte.

Leukemia cells do not function normally. In this case, they cannot fight infections. This means that the person is more likely to become infected with viruses or bacteria. The cancerous cells also overgrow the bone marrow. This forces other normal components, like platelets out. Platelets are needed to help the blood clot. As a result, people with leukemia may bleed more easily.

Acute lymphoblastic leukemia invades the blood and can spread throughout the body to other organs, such as the liver, spleen, and lymph nodes. But it does not normally produce tumors as do many types of cancer. It is an acute type of leukemia, which means it can progress quickly. Without treatment, it can be fatal within a few months.

The survival rate of acute lymphoblastic leukemia has improved dramatically in recent history up to anywhere from 20-75%, mainly due to advances in medicine and improvements in stem cell transplantation technology. Some characteristics may improve the prognosis, including gender, ethnicity and age.

What causes acute lymphoblastic leukaemia?


A leukaemia is thought to start first from one abnormal cell. What seems to happen is that certain vital genes which control how cells divide, multiply and die are damaged or altered. This makes the cell abnormal. If the abnormal cell survives it may multiply out of control and develop into a leukaemia.

In most cases of acute lymphoblastic leukemia, the reason why an immature lymphocyte becomes abnormal is not known. There are certain risk factors which increase the chance that leukaemia will develop, but these only account for a small number of cases. Risk factors known for acute lymphoblastic leukemia are high-dose radiation (for example, previous radiotherapy for another condition) and exposure to the chemical benzene.

Some genetic conditions can increase the risk of having acute lymphoblastic leukemia in the future. The most common is Down's syndrome. Genetic means that the condition is passed on through families through special codes inside cells called genes.

Acute lymphoblastic leukemia is not an inherited condition and does not run in families.

Risk Factors for Acute Lymphoblastic Leukemia


For most people, the cause of acute lymphoblastic leukemia is unknown. For this reason, there is no known way to prevent it. However, there are a few known risk factors for this type of leukemia. This means these factors may increase your chances of getting acute lymphoblastic leukemia. But it is not yet known whether these risk factors are actual causes of the disease:

  • Exposure to high levels of radiation to treat other types of cancer
  • Exposure to certain chemicals such as benzene, a solvent used in oil refineries and other industries and present in cigarette smoke, certain cleaning products, detergents, and paint strippers
  • Infection with human T-cell lymphoma/leukemia virus-1 (HTLV-1) in rarer cases outside the U.S. or Epstein-Barr virus (EBV), a related leukemia more commonly seen in Africa.
  • Having an inherited genetic syndrome such as Down syndrome
  • Being white
  • Being male

Symptoms of Acute Lymphoblastic Leukemia


Symptoms of Acute Lymphoblastic Leukemia in Adults


Acute lymphoblastic leukemia in adults can cause any or all of the following symptoms:
  • fevers, chills, sweats
  • weakness, fatigue, shortness of breath
  • frequent infections
  • depressed appetite, weight loss
  • enlarged lymph nodes
  • easy bleeding or bruising
  • rash of small, flat red spots (petechiae)
  • bone and joint pain
Symptoms of central nervous system involvement include:
  • headache
  • nausea and vomiting
  • confusion
  • seizures

Symptoms of Acute Lymphoblastic Leukemia in Children


Symptoms in children are similar, but young children may be unable to communicate them. They include:
  • fevers
  • frequent infections
  • fatigue, irritability, decreased activity levels
  • easy bruising or bleeding
  • bone or joint pain
  • a limp
  • swollen belly
  • enlarged lymph nodes
T-cell acute lymphoblastic leukemia can invade the thymus gland in the upper chest, which can cause compression of the windpipe, cough or shortness of breath, and superior vena cava syndrome (compression of a large vein that causes swelling of the head, neck, and arms).
Central nervous system involvement in children produces:
  • headache
  • nausea and vomiting
  • blurred vision
  • decline in school performance
  • seizures
Spread to the testicles can cause painless swelling in them.

How is acute lymphoblastic leukaemia diagnosed


Your doctor will ask about your symptoms and medical history. A physical exam will be done. The doctor may also check for swelling of the liver, spleen, or lymph nodes. You will likely be referred to an oncologist. This is a doctor who specializes in treating cancer.


Blood tests

Bone marrow aspiration

Bone marrow biopsy

Spinal tap

Routine microscopic exam—examination of a sample of blood, bone marrow, lymph node tissue, or cerebrospinal fluid

Cytogenetic analysis—a test to look for certain changes of the chromosomes (genetic material) of the lymphocytes; certain genetic abnormalities include:
  • Relocation of genetic material from one chromosome to another
  • Presence of a particular gene
  • Presence of a variant gene, which controls an enzyme that influences folate metabolism
Immunophenotyping—examination of the proteins on cell surfaces and the antibodies produced by the body; to distinguish lymphoblastic from myeloid leukemia and determine types of therapy

Tests to help the doctor see the structures in your body:
  • Chest x-ray
  • Computed tomography (CT) scan
  • Magnetic resonance imaging (MRI) scan
  • Gallium scan and Bone scan—injection of a radioactive chemical into the bloodstream to detect areas of cancer or infection
  • Ultrasound—a test that uses sound waves to examine masses and organs inside the body

Clinical Staging, Treatments, and Prognosis


Acute lymphoblastic leukemia does not have a formal staging system, but treatment is different in different phases of the disease. These phases are often divided into untreated acute lymphoblastic leukemia, acute lymphoblastic leukemia in remission, and recurrent acute lymphoblastic leukemia. Conventional treatment for acute lymphoblastic leukemia consists of chemotherapy for disease in the bone marrow and treatment aimed at preventing central nervous system disease.

Clinical Staging, Treatments, and Prognosis in Adults


The first phase of treatment is remission induction. The chemotherapeutic drugs typically include prednisone, vincristine, cytarabine, cyclophosphamide and asparaginase. Most are given intravenously and a few are given orally. Depending on the disease, these drugs can achieve a complete remission in 60% to 90% of adults. The relapse rate is higher in adults than in children. A 50% 3-year survival has been noted in some research series, and very aggressive treatment with multiple drugs has produced up to a 70% survival rate.

Adverse effects of these drugs include:
  • bone marrow suppression
  • anemia, pallor, fatigue, shortness of breath, and angina in older patients
  • bleeding, bruising
  • increased risk of infection
  • hair loss (alopecia)
  • mouth sores
  • nausea and vomiting
  • menopausal symptoms
  • lower sperm counts
  • tumor lysis syndrome, in which the dead cancer cells can harm healthy organs
Treatment that is directed at preventing central nervous system spread is called prophylactic. Because of the blood brain barrier, a physical and chemical barrier that prevents toxins from reaching the brain and spinal cord, chemotherapeutic drugs do not easily reach the central nervous system. Thus, chemotherapeutic drugs are administered directly into spinal fluid, which circulates around the brain and spinal cord. This is called intrathecal chemotherapy. The drugs are given by spinal tap or through an Ommaya reservoir, which is surgically inserted under the scalp. This reservoir empties into the spinal fluid around the brain.

Some patients receive prophylactic radiation therapy to the brain, in addition to or instead of intrathecal chemotherapy.

Clinical Staging, Treatments, and Prognosis in Children


The treatment of acute lymphoblastic leukemia in children represents one of the great success stories of modern oncology. In contrast to adults, most children with cancer enter into research protocols, strict treatment regimens with careful follow-up that are built on the most successful aspects of earlier treatments. Childhood acute lymphoblastic leukemia now has an 80% long-term survival rate, due in large part to the extensive and widely disseminated research on the disease. Within the United States, research on acute lymphoblastic leukemia was conducted for many years under the auspices of either the Children's Cancer Group or the Pediatric Oncology Group. In 1998, recognizing the benefits of cooperation and collaboration, these two groups joined forces with the National Wilms' Tumor Study Group and the Intergroup Rhabdomyosarcoma Study Group to form the Children's Oncology Group.

Remission induction chemotherapy for children includes vincristine, a steroid, and asparaginase. Children at higher risk of relapse are often given daunomycin as well. The adverse effects of these drugs include bone marrow suppression, risk of infection, nausea, vomiting, hair loss, and mouth sores. Although these drugs can reduce sperm counts, most survivors of childhood acute lymphoblastic leukemia grow up to have normal fertility. The drugs can be administered intravenously or as oral preparations. Oral prednisone has a particularly unpleasant taste that is hard to disguise and parents must be vigilant to ensure that their children are taking their proper doses.

Like adults, children also receive prophylaxis against central nervous system spread. They receive multiple doses of intrathecal chemotherapy, with the drugs delivered directly to the spinal fluid through a lumbar puncture or spinal tap. Cranial radiation as central nervous system prophylaxis for children is infrequently used. Though once standard, brain radiation produced a high incidence of cognitive and learning disabilities, especially among those younger than five years old. Cranial radiation is reserved for those children felt to be at high risk of central nervous system disease, including those older than ten at the time of diagnosis, those with initial white blood cell counts of more than 50,000 per microliter, and those with T-cell leukemia. Some high-risk children who enter remission rapidly with induction chemotherapy receive intrathecal chemotherapy alone, without radiation therapy.

Alternative and Complementary Therapies


Alternative and Complementary Therapies in Adults


Individuals with leukemia often employ alternative or complementary therapies. Some of these provide pain relief and improve psychological well being. No controlled studies have yet shown that alternative treatments offer cures for acute lymphoblastic leukemia, although some may hold promise of benefit.

Patients with acute lymphoblastic leukemia sometimes use acupuncture, which offers relief from generalized pain, nausea, and vomiting. Other methods that may help with the physical and often emotional side effects of treatment include hypnosis, guided imagery, and yoga.

Nutritional supplements and herbs are sometimes utilized by persons with leukemia. Coenzyme Q10 is an antioxidant, a substance that protects cells from toxic byproducts of metabolism. Early studies suggest, although it is not proven, that coenzyme Q10 can improve immune function and counteract some of the harmful effects of chemotherapy and radiation on healthy cells. Adverse effects of coenzyme Q10 include headache, rash, heartburn and diarrhea. Another supplement with potential benefit is polysaccharide K (PSK). A few studies have shown PSK to have some benefit in improving immunity.

Supplements that have not been proven to be of value or are potentially dangerous to those with leukemia include camphor, sometimes called 714-X. Green tea has received much press for its reported abilities to enhance the immune system and fight cancer, but studies have had conflicting results. Some show that green tea has preventive benefits and others show no effect. A few animal studies suggest that growth of tumors might be slowed by green tea, but this has not been shown in humans yet.

Hoxsey is another supplement touted as a cancer treatment, but no studies have confirmed any benefit. Some of its ingredients have serious adverse effects. Vitamin megadoses have long been advocated as beneficial in cancer, but no conclusive studies show benefit, and they have significant potential for adverse effects, such as diarrhea, kidney stones, iron overload, nerve damage and liver disease.

Laetrile, or amygdalin, was once touted as a cure for cancer and leukemia. No human or animal studies conducted in the decades since have shown any benefit other than relief of some pain. Laetrile can, however, cause cyanide poisoning.

Alternative and Complementary Therapies in Children


Complementary and alternative treatments are recommended less frequently for children. Real caution must be used in administering herbal remedies to children, whose metabolisms are very different from those of adults. For example, jin bu hua, a traditional Chinese medicine, can cause heart or breathing problems. Life root and comfrey can both cause fatal liver damage in children.

While many children are too young for formal guided imagery, they can be distracted from the fears and pain associated with some treatments by toys and videotapes. Reading favorite books during scary procedures can relieve some of their fears.

Acute Lymphoblastic Leukemia in Remission


Adults


Remission is achieved in many people within days of beginning treatment. Treatment does not end at that point, but rather enters into the next phases, called consolidation and maintenance. Several different approaches can be used in these. Some patients receive long term chemotherapy with drugs that might include Ara-C (cytarabine), cyclophosphamide, methotrexate, mercaptopurine, vincristine, prednisone, or doxorubicin. Other patients undergo high-dose chemotherapy or combination chemotherapy and radiation therapy to ablate or wipe out their own bone marrow, and then have bone marrow or stem cell transplants. Adverse effects of bone marrow transplant include significant risk of serious infection and graft-vs.-host disease (GVHD), in which the transplanted cells fail to "recognize" the host's cells as self and attack the host cells. Medications to decrease this risk include those that suppress the immune system and steroids.
Central nervous system prophylaxis, as either intrathecal chemotherapy or radiation therapy or both, typically continues through at least a portion of the postremission therapy.

Adults who receive intensive chemotherapy have a 40% likelihood of long-term survival.

Children


In children, remission induction therapy is followed by a phase termed consolidation or intensification, and then by a phase termed maintenance. During intensification, children receive intermediate or high-dose methotrexate, plus some of the same drugs that are used in induction, new drugs that do not crossreact with those used in induction, high-dose asparaginase, or some combination of these.

The maintenance phase of treatment for children with acute lymphoblastic leukemia continues for 18 to 30 months. Daily oral 6-mercaptopurine and weekly oral or injected methotrexate are given on an outpatient basis, with frequent blood tests and examinations. Some protocols add pulses of vincristine and prednisone during the maintenance phase.

Recurrent Acute Lymphoblastic Leukemia


Adults


Adults who relapse after initial remission and maintenance therapy often undergo reinduction chemotherapy and are then referred for bone marrow or stem cell transplant. Some receive transplants of umbilical cord blood. Such transplants carry the risk of graft versus host disease, but also carry the possibility of graft versus leukemia, in which the transplanted cells attack the residual leukemic cells. Unlike graft versus host disease, graft versus leukemia is useful.

New treatments for relapsed acute lymphoblastic leukemia include immunotherapies or biological response modifiers. Some reduce adverse effects of treatment and others are used to fight the leukemia. Some of these include cytokines, substances that stimulate the production of blood cells after treatment has suppressed the bone marrow, and colonystimulating factors, which have the same effect. Other immunotherapies, such as monoclonal antibodies and interferon, have not yet been shown effective against acute lymphoblastic leukemia, but are still under study.

Children


The treatment and prognosis of children who relapse depends on the timing of that relapse. Relapse that occurs within six months is often treated with bone marrow transplantation. Early relapse carries the least favorable prognosis, with only 10% to 20% chance of long term survival. Relapse that occurs more than a year after initial treatment is finished can be treated with another full round of chemotherapy, and bone marrow transplant reserved for those children who relapse a second time. Those with such late relapses have a 30% to 40% chance of long term survival.

Recurrent disease may occur in a sanctuary site, or a part of the body difficult to penetrate with chemotherapeutic drugs. The central nervous system is the most common site of such recurrences. Children who have an isolated central nervous system relapse during the first 18 months of treatment have a 45% likelihood of long-term survival. Children with central nervous system relapse after the first 18 months of treatment have up to an 80% chance of long-term survival. Treatment for relapse in the central nervous system includes intrathecal chemotherapy, and for most children, the use of radiation therapy to the brain and spinal cord.

The testicles are the second most common site of relapse. Early testicular relapse (within the first 18 months of treatment) carries a 40% chance of long-term survival, and late testicular relapse carries an 85% chance of long-term survival. Another sanctuary site is the eye, but isolated relapse here is unusual.

Coping With Cancer Treatment


The treatment of acute lymphoblastic leukemia can be particularly draining, not only due to adverse effects but due to its prolonged time course. Although much of the treatment can be given on an outpatient basis, many protocols utilize lengthy intravenous infusions of chemotherapy and require hospitalization.

Coping With Cancer Treatment in Adults

To prevent nausea and vomiting, adults can take oral anti-nausea medication an hour or so before scheduled treatments, including intrathecal treatments. To avoid headache, they should remain flat for at least 30 to 60 minutes after intrathecal chemotherapy. Nurses can give instructions in mouth care if mouth sores occur and skin care if rashes occur after radiation treatment. Books, music, and television can provide distraction and reduce anxiety during chemotherapy infusions.

Patients scheduled for inpatient stays can bring their own pillows, pajamas and even food, with their doctor's approval. Temporary issuance of handicapped parking stickers are often helpful.

Coping With Cancer Treatment Children


The presence of parents during treatment is critical. While some hospitals exclude parents during treatments, others invite them to be present. Blood can be drawn and intravenous catheters placed while children sit in their parents' laps. If at all possible, a parent should spend the night during any hospitalizations.

Like adults, children can take anti-nausea drugs an hour or so before scheduled treatments. Children, and some adults, can apply topical anesthetic creams to sites of bone marrow aspirates or spinal taps. Favorite stuffed animals or blankets can be present for most procedures.

Play and fun are as important to children with cancer as to healthy children. Items such as board games, modeling clay, video games, dolls, and toy cars can be enjoyed even with intravenous lines in place. Play dates with friends should be encouraged, with proper screening to limit exposure to contagious illnesses.
School districts are required to accommodate the special needs of children. Children with acute lymphoblastic leukemia might require shorter school days or the provision of a tutor at home. Children who develop learning disabilities due to treatment might require the intervention of a special education team.

Prevention for Acute Lymphoblastic Leukemia


There are few preventive measures to take against acute lymphoblastic leukemia. Those who work with chemicals should be cautious, particularly around benzene. Pregnant women should avoid exposure to ionizing radiation to reduce the risk to their unborn children.