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Leukemia ( Acute Lymphatic Leukemia

)

Acute lymphocytic leukemia

Highlights

Acute Lymphocytic Leukemia (ALL)

There are four major types of leukemia. ALL is the most common type of leukemia diagnosed in children, and the least common type diagnosed in adults. About 5,200 people are diagnosed with ALL each year. Children account for two-thirds of these cases. In general, children with ALL have a better prognosis than adults. Most children with ALL can be cured of this cancer.

Symptoms and Diagnosis

Symptoms of ALL include fatigue, pale skin, recurrent infections, bone pain, bruising, and small red spots under the skin. Doctors use various tests, including blood counts and bone marrow biopsies, to diagnose ALL.

Treatment

ALL is treated with chemotherapy and, sometimes, radiation. Children receive different types of chemotherapy regimens than adults. Patients with advanced cancer that has not responded to these treatments may need a stem cell transplant.

these blasts remain immature and multiply continuously. especially during cold and flu season Eat only well-cooked foods (no raw fruits or vegetables) Boil tap water before drinking it Do not keep fresh flowers or plants in your house as they may carry mold Make sure you are up to date with vaccinations. Patients must take serious precautions to avoid exposure to germs. platelets. blasts constitute 5% or less of healthy bone marrow. As the number of normal cells decline. They spill out of the marrow into the bloodstream and lymph system and can travel to the brain and spinal cord (the central nervous system). Children may need to be reimmunized Introduction The word leukemia literally means "white blood" and is used to describe a variety of cancers that begin in the blood-forming cells of the bone marrow. however. Eventually these malignant blast cells fill up the bone marrow and prevent production of healthy red cells. White blood cells (leukocytes) evolve from immature cells referred to as blasts. Ways to prevent infection include: Practice good hygiene including regular handwashing and dental care (brushing. which. eventually constituting between 30 . if . flossing) Avoid crowds. dangerous symptoms develop.Infection Prevention Both chemotherapy and transplantation increase the risk for infection.100% of the bone marrow. which generally progresses as follows: Normally. Malignancy of these blast cells is the source of leukemias. and mature white cells (leukocytes). In leukemia.

become lethal. the spongy material filling the body's bones. The majority of childhood leukemias are of the ALL type. Acute leukemias are in turn subdivided into two classifications according to whether the malignant blasts are lymphocytes or myeloid: Acute lymphocytic leukemia (ALL). which is not covered in this report Acute Lymphocytic Leukemia Acute lymphocytic leukemia (ALL) is also known as acute lymphoid leukemia or acute lymphoblastic leukemia. Blood Cell Lines and the Lymph System Blood Cell Lines In adults. About 85% of ALL cases are of the B-cell lymphocyte lineage (often referred to as "early" or "pre" B-cell lineage). blood cells are produced by the bone marrow. which is the subject of this report Acute myeloid leukemia (AML). T cell ALL is diagnosed in 15% of children and adults with ALL.untreated. The bone marrow produces two blood cell groups. myeloid and lymphoid. Malignancies in this disease can arise either in T-cell or B-cell lymphocytes. Leukemias are divided into two major types: Acute (which progresses quickly with many immature white cells) Chronic (which progresses more slowly and has more mature white cells) Some blasts are called lymphoblasts (which become mature cells called lymphocytes) and others are called myeloblasts (which mature to myeloid cells). .

including macrophages (which act as scavengers for bacteria and other foreign particles). factors that can target and attack specific foreign substances (antigens). after which it atrophies (shrinks). certain lymphocytes are responsible for producing antibodies. which are the body's primary infection fighters. The lymphoid cell line includes the lymphocytes. and neutrophils (the main defenders against bacterial infections) Lymphoid Cell Line. Among other vital functions. Lymphatic vessels begin as tiny tubes and lead to larger lymphatic ducts and branches. eosinophils (which trigger allergies and also react to parasites).Myeloid Cell Line. Lymphocytes develop in the thymus gland or bone marrow and are therefore categorized as either B cells (bone marrow-derived cells) or T cells (thymus gland-derived cells). The myeloid cell line includes the following: Immature cells called erythrocytes that later develop into red blood cells Blood clotting cells (platelets) Some white blood cells. They drain into two ducts in the neck. T cells also start out in the bone marrow but differentiate and mature in the thymus gland. . Lymphocytes and the Lymph System Understanding how acute lymphocytic leukemia (ALL) arises requires knowledge of lymphocytic development and function: B cells develop and mature in their final form (known as differentiation) in the bone marrow. This small gland is active mostly in the fetal stage through the first 10 years of life. located beneath the breastbone. where the fluid re-enters the bloodstream.

It occurs in about 20 . and environmental factors. about 3. the lymphocytes are either filtered out or are added to the contents of the node. ALL is the most common type of cancer diagnosed in children.5% of children with ALL. Here.Along the way. called translocations. and white blood cells. Genetic Translocations Up to 65% of leukemias contain genetic rearrangements. It occurs in about 20% of patients with ALL. which is referred to as TELAML1 fusion. in which some of the genetic material (genes) on a chromosome may be shuffled or swapped between a pair of chromosomes. which are oval structures composed of lymph vessels. Researchers believe that this translocation may occur during fetal development in some patients. The most common genetic translocation in ALL is the Philadelphia (Ph) chromosome where DNA is swapped between chromosomes 9 and 22 [t(9:22)]. the fluid passes through lymph nodes.600 American children and adolescents are diagnosed with ALL. Each year. but researchers believe that ALL develops from a combination of genetic. Another common translocation in ALL is t(12. Causes The causes of the disease are not known. biologic. Risk Factors Age ALL in Children. ALL accounts for about 75% of cases of childhood leukemia. Both leukemia and lymphomas (Hodgkins disease and non-Hodgkins lymphomas) are cancers of lymphocytes. The difference is that leukemia starts in the bone marrow while lymphomas originate in lymph nodes and then spread to the bone marrow or other organs. .30% of adults and 3 .21). connective tissue.

small appliances. ALL is the least common type of leukemia among adults. Symptoms . Other rare genetic disorders associated with increased risk include Klinefelter syndrome. video screen emissions. Lower levels of radiation (living near power lines. ALL in Adults. Shwachman syndrome. Bloom syndrome. but is most likely to occur when children are 2 . and congenital X-linked agammaglobulinemia. About 1 in 3 cases of ALL occur in adults. children with Down syndrome have a 20times greater risk of developing ALL than the general population. cell phones) are unlikely to pose any cancer risk. Prenatal exposure to x-rays may also increase risk in children. neurofibromatosis. Radiation and Chemical Exposure Previous cancer treatment with high doses of radiation or chemotherapy can increase the risk for developing ALL. But certain inherited genetic disorders may increase risk. Fanconi anemia. IgA deficiency. For example.ALL can strike children of all ages.4 years of age. Race and Ethnicity Caucasian and Hispanic children have a higher risk for ALL than AfricanAmerican children. It is slightly more common in boys than in girls. ataxia-telangiectasia. Hereditary Disorders ALL does not appear to run in families.

. They may be present one day. red spots on the skin (petechiae) Vision changes (rare) Diagnosis ALL is diagnosed based on various tests. and absent the next. a condition called thrombocytopenia.The symptoms of ALL may be difficult to recognize. Symptoms include: Fatigue Paleness -. There are not enough healthy platelets to prevent bleeding.patients may have poor coloring from anemia caused by insufficient red blood cells Recurrent minor infections Fever without known cause Bone pain Abdominal swelling Bruising -. The depleted oxygen-bearing red blood cells can't provide enough oxygen to organs.may result from only slight injury Poor healing of minor cuts Uncontrolled bleeding -.bleeding events increase as the bone marrow fails to produce enough platelets to make a normal blood clot. Symptoms develop when: There are not enough healthy mature white blood cells (leukocytes) to mount a defense against infection. particularly in children. but in some cases symptoms may develop slowly. ALL usually begins abruptly and intensely. Small.

Marrow looks . Click the icon to see an illustrated series detailing a complete blood cell count test. parents may want to ask the doctor if sedation is appropriate for their child. red blood cells. These are very common and safe procedures. A small amount of marrow is withdrawn. and blood clotting status and to check for levels of certain minerals and proteins. Bone Marrow Biopsy If blood test results are abnormal or the doctor suspects leukemia despite normal cell counts.Physical Examination The doctor will examine a patient for signs of enlarged lymph nodes or enlarged liver or spleen. A local anesthetic is given. However. There may be brief pressure or pain. which checks for numbers of white cells. usually the rear hipbone. because this test can produce considerable anxiety. particularly in children. kidney. Blood Tests A complete blood cell count (CBC). is the first step in diagnosing ALL. Patients with ALL generally have a higher than normal white blood count and lower than normal red blood cell and platelet counts. Blood tests are also performed to evaluate liver. The doctor will also look for any signs of bruising or bleeding. a bone marrow aspiration and biopsy are the next steps. and platelets. A needle is inserted into the bone.

The patient will feel some pressure. particularly for children. Tests Performed after Diagnosis Once a diagnosis of leukemia has been made. further tests are performed on the bone marrow cells: . A larger needle is then inserted into the same place and pushed down to the bone. The health professional will rotate the needle to obtain a specimen for the biopsy.100% of the marrow. Click the icon to see an image of bone marrow removal. leukemia cells are not found in the cerebrospinal fluid. so parents should plan reading or other quiet activities that will divert the child during that time. Click the icon to see an image of a spinal tap. Parents should also be certain that the professional performing this test is experienced. abnormal blasts constitute between 30 . Normal bone marrow contains 5% or less of blast cells (the immature cells that ordinarily develop into healthy blood cells). All the results are completed within a couple of days. In most cases of childhood ALL. The sample is then taken to the lab to be analyzed. In leukemia. which uses a needle inserted into the spinal canal. The patient feels some pressure and usually must lie flat for about an hour afterward to prevent severe headache. a spinal tap (lumbar puncture) may be performed. This can be difficult. A sample of cerebrospinal fluid with leukemia cells is a sign that the disease has spread to the central nervous system. Spinal Tap If bone marrow examination confirms ALL.like blood.

FISH is used to identify specific changes within chromosomes. flow cytometry. Immunophenotyping shows if ALL cells are T cells or B cells based on the antigen located on the surface of the cell. B-Cell ALL Subtype Classfication: Early Pre-B Common ALL Pre-B ALL Mature B-cell ALL (Also called Burkitt leukemia) T-Cell ALL Subtype Classifcation: .Cytochemistry. L2. Cell Classification The results of cytogenetic. Genetic variations may help determine response to treatment. and other tests can help provide information on types and subtypes of ALL cells. and immunophenotyping tests are used to to identify and classify specific types of leukemia. Cytogenetics and fluorescent in situ hybridization (FISH) are used for genetic analysis. and L3 subtypes. An older classification system called the French-American-British (FAB) classification grouped ALL into L1. For example. antigens are substances not normally present in the body. cytochemistry distinguishes lymphocytic leukemia cells from myeloid leukemia cells. A newer classification system classifies ALL B cells or T cells based on their stage of maturity. The particular subtype of cell can aid in determining prognosis and treatment. An antigen is a substance that can provoke an immune response. immunophenotyping. flow cytometry. Cytogenetic testing can detect translocations (such as Philadelphia chromosome) and other genetic abnormalities. immunocytochemistry. Typically.

Pre-T ALL Mature T-cell ALL Prognosis Acute lymphocytic leukemia is responsible for about 1. Evidence of minimal residual disease (presence of leukemia cells in the bone marrow) may also affect prognosis.. Other factors. Outlook in Children with ALL. although new treatments are helping many of these patients achieve remission. ALL subtype. People who have Philadelphia chromosomepositive ALL tend to have a poorer prognosis. The subtype of T cell or B cell affects prognosis.000 tend to do better than people with higher WBC counts. certain factors can help determine prognosis: Age. .400 deaths a year in the U. According to the American Cancer Society. However. ALL is one of the most curable cancers and survival rates are now at an all-time high. may also indicate a poorer prognosis. More than 95% of children with ALL attain remission. Patients who achieve complete remission (disappearance of signs and symptoms of cancer) within 4 . For example. Response to chemotherapy. Patients who do not achieve remission at any time have a poor prognosis.5 weeks of starting treatment tend to have a better prognosis than those who take longer.) Chromosome translocations. such as central nervous system involvement or recurrence. and it can progress quickly if untreated. Initial white blood cell (WBC) count. patients with T-cell ALL tend to have a better prognosis than those with mature B-cell ALL (Burkitt leukemia. Younger patients (especially those younger than age 50) have a better prognosis than older patients. People diagnosed with a WBC count below 50.S.

Certain children are at higher risk for a poor outcome than others: Infants and children age 10 years and older tend to have a poorer outcome than young children (ages 1 . and 35 . Some studies indicate a better prognosis for girls than boys. This may be partly due to boys risks for testicular cancer. but this may be due to poorer access to treatment. Still.000 blasts per microliter on peripheral smear after 7 days Outlook in Adults with ALL.9 years). usually given . even if they are carrying the same ALL genes. Treatment Treatment Phases There are typically four treatment stages for the average-risk patient with ALL: Induction therapy in order to achieve a first remission Central nervous system prophylaxis (preventive treatment). Younger adults with ALL have better long-term survival rates than older adults with the disease.40% survive beyond 2 years with aggressive treatments. Other positive predictors include: Less than 5% of cells being blasts after 7 . Adults tend to have a more severe condition than children. Responding well to early treatment is a good sign regardless of the risk category. Survival rates for African-American and Hispanic children are lower than Caucasian and Asian children. 60 .80% of adults with ALL can expect to achieve full remission with standard treatments.14 days of treatment Less than 1.

and various white blood cells. platelets. Blood is made of red blood cells. particularly after a first remission. which are becoming more common in these patients. Radiation to the brain and spinal cord is also administered in some cases. Doctors are increasingly concerned about fungal infections. Neutropenia. particularly after transplant procedures. . A bone marrow transplant is often recommended for relapsed ALL or in cases that cannot be induced into remission (refractory disease). especially if patients also have low levels of the white blood cells called neutrophils (a condition called neutropenia). Half of all patients with ALL develop fever in the early stages. intensive therapy to prevent relapse after remission has been achieved Maintenance treatment. although it has produced excellent longterm survival rates in appropriate patients. is a significant risk factor for serious infection. The timing of bone marrow transplantation can be controversial. lower intensity therapy given for several years to prevent relapse after remission Specific Treatments Used in ALL The following are specific treatments used for ALL: Chemotherapy is the primary treatment for each stage. Supportive Treatment Drugs Used to Prevent Infections During Treatment. common in ALL. New drugs known as biological therapies are also being used. It is also sometimes considered after remission is achieved for certain high-risk ALL types.along with induction therapy Consolidation.

the first treatment phase. After the first cycle of induction.) Treatment to Achieve Remission The aim of induction therapy. Intravenous Fluids. Hospitalization is usually necessary at some point to help prevent infection and to administer blood products. However. which can cause abnormal levels of sodium. Another bone marrow test is sometimes done about a week later to confirm . The general guidelines for induction therapy are as follows: Patients are given intensive chemotherapy that uses powerful multi-drug regimens. filgrastim) is often given to patients who receive chemotherapy in order to stimulate the growth of infection-fighting white blood cells. and aluminum hydroxide or calcium carbonate. Red blood cell or platelet transfusions may be needed. some of these therapies are administered orally. Transfusions. calcium. allopurinol. bone marrow tests are done to determine if the patient is in remission. potassium.) For both children and adults. much of this therapy can be given on an outpatient basis. Patients may also need to receive intravenous fluids and be treated for fluid imbalances.Antibiotics and Antifungal Medications. This helps prevent neutropenia. Granulocyte Colony-Stimulating Factor. patients may need preventive antibiotics. and uric acid. is to reduce the number of leukemia cells to undetectable levels. others intravenously. The use and timing of antibiotics and antifungal medications depend on the particular organisms and severity of the infection. In some cases of neutropenia. Granulocyte colony-stimulating factor (lenograstim. Such treatments might include sodium bicarbonate. (Patients who may need allogeneic transplantations should not receive transfusions from potential donors. (Infants require special regimens not discussed here.

. Dexamethasone may be more effective than prednisone. For children. daunorubicin.the first results. the standard drugs are: Vincristine (Oncovin). Some adult chemotherapy regimens also add on an asparaginase drug or cyclophosphamide (Cytoxan). For adults. the standard drugs are: Vincristine Prednisone Anthracycline drug. a vinca alkaloid drug Prednisone or dexamethasone. patients need only 3 injections over a 20-week period instead of the 21 injections required for L-asparaginase. Drugs Used for Induction Chemotherapy Both children and adults typically start with a 3-drug regimen. or epirubicin. Preventing Central Nervous System Disease (CNS Prophylaxis) The induction chemotherapy described above does not penetrate the bloodbrain barrier sufficiently to destroy leukemic cells in the brain. CNS prophylaxis is critical for preventing disease that has spread to the brain. These drugs are corticosteroids. Asparaginase. but it increases the risk for infections and other serious side effects. With pegaspargase. Imatinib (Gleevec) or dasatanib (Sprycel) may be added for patients with Philadelphia chromosome-positive ALL. Generally provided as pegaspargase (Oncaspar) in place of Lasparaginase (Elspar) for treating newly diagnosed ALL in children. such as such as doxorubicin. A bone marrow transplant is considered for patients who do not respond at all to induction treatment.

For children.70% of children who don't receive prophylactic preventive treatment. in which a drug is injected directly into the spinal fluid. It is generally used only in children who have evidence of the disease in the central nervous system at the time of diagnosis. cytarabine.spine. bone marrow. and cerebrospinal . Although only 3% of children with ALL have evidence of leukemia in the central nervous system (CNS) at the time of diagnosis. Although not always clear-cut. Cranial radiation is also associated with increased risks for stroke and secondary cancers. Intrathecal chemotherapy is given with methotrexate alone or a combination of methotrexate. may significantly reduce the risk for mental impairment. and testes (called sanctuary disease sites). and hydrocortisone. Later complications can include learning and neurologic problems. radiation to the spine. Some high-risk children also receive radiation to the skull (cranial irradiation). CNS prophylaxis uses intrathecal chemotherapy. however. remission is indicated by the following: All signs and symptoms of leukemia disappear. This combination can be very toxic and can cause later learning problems. There are no abnormal cells in the blood. leukemia will spread to this region in 50 . Adult CNS prophylaxis is performed in one of three ways: Cranial radiation plus intrathecal chemotherapy with methotrexate High-dose systemic infusion of methotrexate plus intrathecal methotrexate without cranial radiation Intrathecal methotrexate chemotherapy alone Evidence of Remission after Induction Treatment Survival in acute leukemia depends on complete remission. or both at the same time. Using lower-dose units of radiation. The brain is one of the first sites for relapsing leukemia.

Typical side effects include: Nausea and vomiting. The percentage of blast cells in the bone marrow is less than 5%. Patients who show low disease levels within 7 . Blood platelet count returns to normal. Induction can produce extremely rapid results.14 days have an excellent outlook. Drugs known as serotonin antagonists. . are more severe with higher doses. particularly if they have favorable genetic factors. and may need lessintensive treatments afterward. and the shorter the time to remission the better the outlook: A complete remission usually occurs within the first 4 weeks. Side Effects and Complications Side effects and complications of any chemotherapeutic regimen and radiation therapy are common. Administering drugs for shorter duration can sometimes reduce toxicities without affecting the drugs' cancerkilling effects. Serious side effects can also occur and may vary depending on the specific drugs used. Patients with high disease levels at 14 days or who require more than 4 weeks to achieve remission are at higher risk for relapse and most likely need more aggressive treatment. and increase over the course of treatment. such as ondansetron (Zofran) or granisteron (Kyril). Diarrhea Hair loss Weight loss Depression Serious Side Effects. Common Side Effects. can relieve these side effects.fluid.

filgrastim) to stimulate the growth of infection-fighting white blood cells.Infection from suppression of the immune system or from severe drops in white blood cells is a common and serious side effect. Patients should make all efforts to prevent infection. The patient at high risk for infection may need very potent antibiotics and antifungal medications as well as granulocyte colony-stimulating factors or G-CSF (lenograstim. Patients should make all efforts to minimize exposure to bacteria and viruses. .