What is an Acute Lymphoblastic Leukemia?

May 16 23:03 2019 Print This Article

It is defined as a disorder in which there is a cancer of the myeloid line of blood cells. In this there is a rapid growth of the abnormal white blood cells which get accumulated in the bone marrow. It is also known as the ALL. It refers to acute lymphoblastic leukemia. They interfere with the production of normal blood cells. It causes the damage and death by crowding out the normal cells. It has the ability to spread to the other organs and is known as the metastasis. It is more common in the childhood with the peak incidence at 2 to 5 years of age.

One can see the other peak in the old age. The overall cure rate in the children is 85 percent and the overall cure rate in the adults is 50 percent. The term acute refers to the relatively short time and it is used to differentiate it from the other diseases. It includes the CLL Chronic Lymphocytic Leukemia which has a potential time course. It is also known as the lymphocytic or lymphoblastic. It refers to the cells which are involved. The normal cells are known as the lymphocytes. They occur in the immature state in this disorder. The lymphoblastic is the most preferred term.

What are the signs and symptoms of Acute lymphoblastic leukemia?

It includes the initial symptoms which are not specific for this disorder. They may get worse and require a medical help in this regard. They are followed from the bone marrow replacement with the organ infiltration. The signs and symptoms are variable. It includes the anemia, general weakness, fatigue, unexplained fever and bruising, infections, loss of weight and pain in the bones and joints. There is an enlarged lymph nodes, liver and spleen. It is followed by the breathlessness and a pitting edema present in the legs and abdomen.

One can also notice the presence of petechiae which are small red spots present in the skin as a result of low platelet count. The absence of normal and healthy cells may lead to the signs and symptoms of ALL. The malignant and immature cells are more in number as compared to the normal cells. The people with the ALL experience symptom due to the mal functioning of red blood cells, white blood cells and platelets. The laboratory cells show the abnormalities which include the blood cell counts, renal function tests and electrolyte tests which are followed by the liver enzyme tests.

What is the diagnosis of Acute lymphoblastic leukemia?

It includes the use of medical history, physical examination, blood count and smears. The symptoms are general and the diseases with these symptoms are excluded. The higher is the white blood cell count worse is the prognosis. The blood smears show blood cells which are seen in most of the patients. The proof of ALL is established by the bone marrow biopsy. A lumbar puncture is very useful to tell about the invasion in the brain and spinal column.

The pathological examination, cyto genetics and immune phenol typing helps to know whether the blast cells originated from the B or T lymphocytes. A DNA testing establishes the aggressiveness of the disease and the different mutations have been associated with the shorter or longer survival. There is a medical imaging like ultra sound or CT scan which can find invasion in the other organs.

What is the patho physiology of Acute lymphoblastic leukemia?

The cause of ALL is not known. It may occur due to the damage to DNA. It leads to the uncontrolled cellular growth and it spreads throughout the body. It acts by increasing the chemical signals that cause the growth or disturb the chemical signals which control the growth. The formation of fusion genes can cause the damage. It also occurs by the dys regulation of proto oncogene by the juxta position of the promoter of other gene. It includes the T cell receptor gene.

This can also occur by the environmental factors like chemicals, drugs or radiations. It is associated with the exposure to radiation and chemicals in animals and humans. The studies of the victims of Chernobyl nuclear reactor and atom bombs in the Hiroshima and Nagasaki have shown an association between the radiation and leukemia. In the case of animals the exposure to benzene can cause leukemia. There are epidemiological studies which have shown the association between the leukemia and work place exposure to chemicals. These studies are not dependable. In some individuals the secondary leukemia can develop who are treated with the radiation or chemo therapy.

What is the cyto genetics of Acute lymphoblastic leukemia?

It includes the translocations which are associated with the specific molecular genetics abnormalities in ALL. It includes mainly the fusion.

What is the prognosis of Acute lymphoblastic leukemia?

The prognosis has improved a lot during the last four decades. It was zero but it came to 50 percent. It was mainly due to the clinical trials and the improvement in bone marrow transplantations. It was also related to the stem cell transplantation. The 5 year survival rate was evaluated with the older treatments. The introduction of new drugs and the matching of treatment to the genetic characteristics of the blasts can also improve those rates. The prognosis is not static and is different for different individuals. It depends on the number of factors. The males have poor prognosis as compared to the females. The cancer which is spread into the brain or spinal cord has worse outcomes. The white blood cell counts at diagnosis of less than 50,000 per ul also have the same condition.

The children less than 10 years of age are more likely to develop ALL and can be cured. In the older patients the cases are more likely due to the chromosomal abnormalities. It makes the treatment difficult to cure and form a poor prognosis. The Caucasians are more likely to develop acute leukemia than the other species of humans involving Asian, African and Hispanic. It also depends on the patient initial response and on the genetic disorders like down syndrome. It depends on the morphological, immunological and genetic sub types. It helps to know about the changes in the chromosome of cancer cells and is an important predictor for the prognosis of ALL. A few cyto genetics sub types have a poor prognosis. It includes the translocation between chromosome 9 and 22 which is known as the Philadelphia chromosome.

It occurs in 20 percent of the adults and 5 percent in the children. It also includes the translocation between chromosome 4 and 11 which occurs in 4 percent of the cases and is common in the infants less than 1 year of age. Some of the translocations have a good prognosis like in the case of hyper diploidy which refers to more than 50 chromosomes is a good prognostic sign. The wide number copy changes can be assessed by the conventional cyto genetics or virtual karyo typing. It helps to detect copy number changes by the LOH status. The CGH can detect only the copy number changes. A key locus is seen in the copy neutral LOH like the CDKN2A gene. The virtual karyo typing can also detect the copy neutral LOH. The array CGH, FISH and conventional cyto genetics cannot detect the copy neutral LOH. The un classified ALL has an intermediate prognosis.

What is the classification of Acute lymphoblastic leukemia?

The Acute lymphoblastic leukemia is not a solid tumor. The TNM notation is of little use. The most common is the FAB classification. It is known as the French American British classification. It is used for all the leukemia’s. The ALL L1 refers to small uniform cells. The ALL L2 refers to large varied cells. The ALL L3 refers to large varied cells along with the vacuoles. Each sub type is further classified depending on the surface markers of abnormal lymphocytes. This is known as the immune phenol typing. The immunologic types are of two types mainly the pre B and pre T cell. The mature B cell is classified as a Burkitts Lymphoma or leukemia.

The sub typing helps to know about the prognosis and treatment of the ALL. The WHO also classified so that the FAB classification can be left. As the morphological classification has no clinical significance. It advocates the use of immune phenol typing classification. The acute lymphoblastic leukemia or lymphoma includes the precursor B acute lymphoblastic leukemia with different cyto genetics sub types. It also includes the precursor T acute lymphoblastic leukemia. The Burkitt leukemia or lymphoma and bi phenotypic acute leukemia is also included under it. The variant features of the ALL are acute lymphoblastic leukemia with cytoplasmic granules, aplastic presentation of acute lymphoblastic leukemia, acute lymphoblastic leukemia with eosinophilia and a relapse of acute lymphoblastic leukemia. There is a secondary acute lymphoblastic leukemia. The use of assay and a panel of mono clonal antibodies to T cell and B cell associated an antigen which identifies the most cases of ALL.

What is the epidemiology of Acute lymphoblastic leukemia?

It includes the number of annual cases of the US is 4000. Out of which 3000 are children and it accounts for 80 percent of the cases of childhood leukemia. It is the most common type of childhood cancer with a peak incident rate seen in 2 to 5 years old. It decreases in the incidence with the increasing age and increases after the age of 50. It is more common in males as compared to the females. An increased incidence is seen in the people already suffering from Down syndrome, fanconi anemia, bloom syndrome, severe combined immune deficiency and x linked agamma globulinemia.

What is the treatment of Acute lymphoblastic leukemia?

There are many ways by which the treatment of this disorder can be done. It includes the use of chemo therapy, steroids, radiation therapy and the combination of treatments including the stem cell transplantation and bone marrow transplantation with growth factors. The earlier the condition is detected and better it is treated. It induces a lasting remission in which there is a absence of the detectable cancer cells in the body.

1. In the chemo therapy the patient receives a combination of different treatments. It is the initial treatment of the choice. As the malignant cells are distributed throughout the body it cannot be treated with the help of surgery. In this case the anti leukemic drugs are used in various combinations. It consists of three phases involving the remission induction, maintenance and intensification therapy. In the remission induction phase there is a remission induction which helps to kill the tumor cells and puts the patient in the remission. In this case the leukemic blasts are less than 5 percent in the bone marrow, normal blood cells and the absence of tumor cells. There is absence of other signs and symptoms.

The agents used in this phase are the combination of prednisolone with vincristine, asparginase and daunorubicin. It helps to induce remission. In the intensification therapy a high dose of intra venous multi drug chemo therapy which reduces further tumor burden. The cells of ALL can go in the central nervous system. Some centres deliver the drug by ommaya reservoir which is a device placed under the scalp and the drugs are delivered to the CNS. It also extracts the CNS fluid for the various tests. The other centers perform many lumbar punctures as required for the testing and treatment delivery. The agents used in this phase are the combination of vincristine, cyclo phosphamide, cytarabine and daunorubicin.

A mercapto purine is also given as a block in the different combinations. In order to protect the CNS an intra thecal combination of methotrexate with cranio spinal irradiation is given. A central nervous system relapse is treated with the intra thecal combination of methotrexate and hydrocortisone. In the maintenance therapy the residual cells are killed which were not killed by the other therapies. These cells are very few but can cause relapse if they are not treated. The agents used in this therapy are the oral mercapto purine with the weekly administration of methotrexate. It is given once a monthly and is a 5 day course of intra venous vincristine and cortico steroids. The length of this therapy is 3 years for boys and 2 years for girls and adults.

The chemo therapy regimens are intensive and protracted so in many patients the intravenous catheter is inserted into the large vein. It is known as the central venous catheter or Hickman line. It is also known as the protacath which is a cone shaped port with a silicone nose which is surgically placed under the skin near the collar bone. It is the most effective product due to its low infection risk and its long term viability.

2. The radiation therapy is used in the painful areas and in the high disease burden areas. It is used to prepare the bone marrow transplant area. It is the form of whole brain radiation therapy. It is used in the prophylaxis of central nervous system. It prevents the recurrence of leukemia. It is the most common method in the treatment of children ALL. There are few studies which have recommended that the CNS chemotherapy provides results which are favorable with fewer side effects. So, the use of whole brain radiation is limited.