Description:
Acute lymphoblastic leukaemia is a type of blood cancer that affects white blood cells. Cancer starts in the bone marrow, the spongy tissue inside the bones where blood cells are produced
It is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or months if left untreated.
The underlying mechanism involves multiple genetic mutations that results in rapid cell division. The excessive immature lymphocytes in the bone marrow interfere with the production of new red blood cells, white blood cells, and platelets. Diagnosis is typically based on blood tests and bone marrow examination.
ALL affected about 876,000 people globally in 2015 and resulted in about 111,000 deaths. It occurs most commonly in children, particularly those between the ages of two and five. In the United States it is the most common cause of cancer and death from cancer among children. ALL is notable for being the first disseminated cancer to be cured. Survival for children increased from under 10% in the 1960s to 90% in 2015. Survival rates remain lower for babies (50%) and adults (35%).
Symptoms:
Initial symptoms can be nonspecific, particularly in children. Over 50% of children with leukemia had one or more of five features: a liver one can feel (64%), a spleen one can feel (61%), pale complexion (54%), fever (53%), and bruising (52%). Additionally, recurrent infections, feeling tired, arm or leg pain, and enlarged lymph nodes can be prominent features. The B symptoms, such as fever, night sweats, and weight loss, are often present as well.
Central nervous system (CNS) symptoms such as cranial neuropathies due to meningeal infiltration are identified in less than 10% of adults and less than 5% of children, particularly mature B-cell ALL (Burkitt leukemia) at presentation.
Signs and symptoms of acute lymphocytic leukemia may include:
*Bleeding from the gums
*Bone pain
*Fever
*Frequent infections
*Frequent or severe nosebleeds
*Lumps caused by swollen lymph nodes in and around the neck, armpits, abdomen or groin
*Pale skin
*Shortness of breath
*Weakness, fatigue or a general decrease in energy
Causes:
In most cases, the cause is unknown. Genetic risk factors may include Down syndrome, Li–Fraumeni syndrome, or neurofibromatosis type 1. Environmental risk factors may include significant radiation exposure or prior chemotherapy. Evidence regarding electromagnetic fields or pesticides is unclear. Some hypothesize that an abnormal immune response to a common infection may be a trigger.
The cancerous cell in ALL is the lymphoblast. Normal lymphoblasts develop into mature, infection-fighting B-cells or T-cells, also called lymphocytes. Signals in the body control the number of lymphocytes so neither too few nor too many are made. In ALL, both the normal development of some lymphocytes and the control over the number of lymphoid cells become defective.
ALL emerges when a single lymphoblast gains many mutations to genes that affect blood cell development and proliferation. In childhood ALL, this process begins at conception with the inheritance of some of these genes. These genes, in turn, increase the risk that more mutations will occur in developing lymphoid cells. Certain genetic syndromes, like Down Syndrome, have the same effect. Environmental risk factors are also needed to help create enough genetic mutations to cause disease. Evidence for the role of the environment is seen in childhood ALL among twins, where only 10–15% of both genetically identical twins get ALL. Since they have the same genes, different environmental exposures explain why one twin gets ALL and the other does not.
Infant ALL is a rare variant that occurs in babies less than one year old. KMT2A (formerly MLL) gene rearrangements are most common and occur in the embryo or fetus before birth. These rearrangements result in increased expression of blood cell development genes by promoting gene transcription and through epigenetic changes. In contrast to childhood ALL, environmental factors are not thought to play a significant role. Aside from the KMT2A rearrangement, only one extra mutation is typically found. Environmental exposures are not needed to help create more mutations.
Risk factors:
Factors that may increase the risk of acute lymphocytic leukemia include:
1.Previous cancer treatment. Children and adults who’ve had certain types of chemotherapy and radiation therapy for other kinds of cancer may have an increased risk of developing acute lymphocytic leukemia.
- Toomuch exposure to radiation. People exposed to very high levels of radiation, such as survivors of a nuclear reactor accident, have an increased risk of developing acute lymphocytic leukemia.
3.Genetic disorders. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of acute lymphocytic leukemia.
Diagnosis:
The doctor may ask for the following tests:
*Blood tests. Blood tests may reveal too many or too few white blood cells, not enough red blood cells, and not enough platelets. A blood test may also show the presence of blast cells — immature cells normally found in the bone marrow.
*Bone marrow test. During bone marrow aspiration and biopsy, a needle is used to remove a sample of bone marrow from the hipbone or breastbone. The sample is sent to a lab for testing to look for leukemia cells.
Doctors in the lab will classify blood cells into specific types based on their size, shape, and other genetic or molecular features. They also look for certain changes in the cancer cells and determine whether the leukemia cells began from B lymphocytes or T lymphocytes. This information helps your doctor develop a treatment plan.
*Imaging tests. Imaging tests such as an X-ray, a computerized tomography (CT) scan or an ultrasound scan may help determine whether cancer has spread to the brain and spinal cord or other parts of the body.
*Spinal fluid test. A lumbar puncture test, also called a spinal tap, may be used to collect a sample of spinal fluid — the fluid that surrounds the brain and spinal cord. The sample is tested to see whether cancer cells have spread to the spinal fluid.
Treatment:
In general, treatment for acute lymphocytic leukemia falls into separate phases:
Induction therapy. The purpose of the first phase of treatment is to kill most of the leukemia cells in the blood and bone marrow and to restore normal blood cell production.
Consolidation therapy. Also called post-remission therapy, this phase of treatment is aimed at destroying any remaining leukemia in the body.
Maintenance therapy. The third phase of treatment prevents leukemia cells from regrowing. The treatments used in this stage are usually given at much lower doses over a long period of time, often years.
Preventive treatment to the spinal cord. During each phase of therapy, people with acute lymphocytic leukemia may receive additional treatment to kill leukemia cells located in the central nervous system. In this type of treatment, chemotherapy drugs are often injected directly into the fluid that covers the spinal cord.
Depending on your situation, the phases of treatment for acute lymphocytic leukemia can span two to three years.
Treatments may include:
*Chemotherapy. Chemotherapy, which uses drugs to kill cancer cells, is typically used as an induction therapy for children and adults with acute lymphocytic leukemia. Chemotherapy drugs can also be used in the consolidation and maintenance phases.
*Targeted therapy. Targeted drug treatments focus on specific abnormalities present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die. Your leukemia cells will be tested to see if targeted therapy may be helpful for you. Targeted therapy can be used alone or in combination with chemotherapy for induction therapy, consolidation therapy or maintenance therapy.
*Radiation therapy. Radiation therapy uses high-powered beams, such as X-rays or protons, to kill cancer cells. If the cancer cells have spread to the central nervous system, your doctor may recommend radiation therapy.
*Bone marrow transplant. A bone marrow transplant, also known as a stem cell transplant, may be used as consolidation therapy or for treating relapse if it occurs. This procedure allows someone with leukemia to reestablish healthy bone marrow by replacing leukemic bone marrow with leukemia-free marrow from a healthy person.
A bone marrow transplant begins with high doses of chemotherapy or radiation to destroy any leukemia-producing bone marrow. The marrow is then replaced by bone marrow from a compatible donor (allogeneic transplant).
*Engineering immune cells to fight leukemia. A specialized treatment called chimeric antigen receptor (CAR)-T cell therapy takes your body’s germ-fighting T cells, engineers them to fight cancer and infuses them back into your body.
CAR-T cell therapy might be an option for children and young adults. It might be used for consolidation therapy or for treating relapse.
Clinical trials. Clinical trials are experiments to test new cancer treatments and new ways of using existing treatments. While clinical trials give you or your child a chance to try the latest cancer treatment, the benefits and risks of the treatment may be uncertain. Discuss the benefits and risks of clinical trials with your doctor.
Treatment for older adults:
Older adults, such as those older than 65, tend to experience more complications from treatments. And older adults generally have a worse prognosis than children who are treated for acute lymphocytic leukemia.
Some people may choose to forgo treatment for the cancer, instead focusing on treatments that improve their symptoms and help them make the most of the time they have remaining.
Prognosis:
Prior to the development of chemotherapy regimens and hematopoietic stem cell transplant, children were surviving a median length of 3 months, largely due to either infection or bleeding. Since the advent of chemotherapy, the prognosis for childhood leukemia has improved greatly and children with ALL are estimated to have a 95% probability of achieving a successful remission after 4 weeks of initiating treatment. People in pediatric care with ALL in developed countries have a greater than 80% five-year survival rate. It is estimated that 60–80% of adults undergoing induction chemotherapy achieve complete remission after 4 weeks, and those over the age of 70 have a cure rate of 5%
However, there are differing prognoses for ALL among individuals depending on a variety of factors:
*Gender: Females tend to fare better than males.
*Ethnicity: Caucasians are more likely to develop acute leukemia than African-Americans, Asians, or Hispanics. However, they also tend to have a better prognosis than non-Caucasians.
*Age at diagnosis: children 1–10 years of age are most likely to develop ALL and to be cured of it. Cases in older people are more likely to result from chromosomal abnormalities (e.g., the Philadelphia chromosome) that make treatment more difficult and prognoses poorer. Older people are also likely to have co-morbid medical conditions that make it even more difficult to tolerate ALL treatment.
*White blood cell count at diagnosis of greater than 30,000 (B-ALL) or 100,000 (T-ALL) is associated with worse outcomes
*Cancer spreading into the Central nervous system (brain or spinal cord) has worse outcomes.
*Morphological, immunological, and genetic subtypes
Person’s response to initial treatment and longer length of time required (greater than 4 weeks) to reach complete remission
*Early relapse of ALL
*Minimal residual disease
*Genetic disorders, such as Down syndrome, and other chromosomal abnormalities (aneuploidy and translocations)
Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.
Resources:
https://en.wikipedia.org/wiki/Acute_lymphoblastic_leukemia
https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077
