Acute Lymphocytic Leukemia
Disease Details
Family Health Simplified
- Description
- Acute lymphocytic leukemia (ALL) is a type of cancer that originates in the bone marrow and results in the overproduction of immature lymphocytes, a type of white blood cell.
- Type
- Acute lymphocytic leukemia (ALL) is a type of cancer that affects the blood and bone marrow. It is most common in children but can also occur in adults. ALL is typically not inherited in a simple Mendelian manner; rather, it usually results from genetic mutations that occur spontaneously. However, certain genetic conditions, like Down syndrome, can increase the risk of developing ALL. Overall, the genetic transmission of ALL is not straightforwardly inherited from parent to child but rather involves a combination of genetic and environmental factors.
- Signs And Symptoms
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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.The signs and symptoms of acute lymphoblastic leukemia are variable and include:
Generalized weakness and feeling tired
Anemia
Dizziness
Headache, vomiting, lethargy, neck stiffness, or cranial nerve palsies (CNS involvement)
Frequent or unexplained fever and infection
Weight loss and/or loss of appetite
Excessive and unexplained bruising
Bone pain, joint pain (caused by the spread of "blast" cells to the surface of the bone or into the joint from the marrow cavity)
Breathlessness
Enlarged lymph nodes, liver, and/or spleen
Pitting edema (swelling) in the lower limbs and/or abdomen
Petechiae, which are tiny red spots or lines in the skin due to low platelet levels
Testicular enlargement
Mediastinal mass - Prognosis
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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)Cytogenetics, the study of characteristic large changes in the chromosomes of cancer cells, is an important predictor of outcome. Some cytogenetic subtypes have a worse prognosis than others. These include:
Person with t(9,22) positive-ALL (30% of adult ALL cases) and other Bcr-abl-rearranged leukemias are more likely to have a poor prognosis, but survival rates may rise with treatment consisting of chemotherapy and Bcr-abl tyrosine kinase inhibitors.
A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.Hyperdiploidy (>50 chromosomes) and t(12;21) are good prognostic factors and also makeup 50% of pediatric ALL cases.Unclassified ALL is considered to have an intermediate prognosis risk, somewhere in-between the good and poor risk categories. - Onset
- Acute lymphocytic leukemia (ALL) can have a rapid onset, with symptoms developing quickly over a few days to weeks. It is characterized by the overproduction of immature white blood cells called lymphoblasts. The exact onset age can vary, but ALL is most common in children, particularly between the ages of 2 and 5 years, though it can also occur in adults.
- Prevalence
- Acute lymphocytic leukemia (ALL) is relatively rare, with an incidence rate of about 1.7 per 100,000 people annually in the United States. It is more common in children, especially those aged 3 to 5 years, but can occur at any age. For adults, the incidence is lower compared to children.
- Epidemiology
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Acute lymphoblastic leukemia affected about 876,000 people and resulted in 111,000 deaths globally in 2015. It occurs in both children and adults with highest rates seen between the ages three and seven years. Around 75% of cases occur before the age of 6 with a secondary rise after the age of 40. It is estimated to affect 1 in 1500 children.Accounting for the broad age profiles of those affected, ALL newly occurs in about 1.7 per 100,000 people per year. Acute lymphoblastic leukemia represents approximately 20% of adults and 80% of childhood leukemias, making it the most common childhood cancer. Although 80 to 90% of children will have a long term complete response with treatment,: 1527 it remains the leading cause of cancer-related deaths among children. 85% of cases are of B-cell lineage and have an equal number of cases in both males and females. The remaining 15% of T-cell lineage have a male predominance.
Globally, ALL typically occurs more often in Caucasians, Hispanics, and Latin Americans than in Africans.: 1617 In the US, ALL is more common in children from Caucasian (36 cases/million) and Hispanic (41 cases/million) descent when compared to those from African (15 cases/million) descent. - Intractability
- Acute lymphocytic leukemia (ALL) is not inherently intractable. Treatment outcomes vary depending on factors such as patient age, overall health, and genetic characteristics of the leukemia. Advances in chemotherapy, targeted therapy, and stem cell transplantation have significantly improved prognosis, particularly in children. However, refractory or relapsed ALL can be more difficult to treat and may require more aggressive or novel therapies.
- Disease Severity
- Acute lymphocytic leukemia (ALL) is a severe disease that typically requires prompt and aggressive treatment. It can rapidly progress and worsen if not treated effectively. The severity can vary depending on factors such as patient age, white blood cell count at diagnosis, genetic features of the leukemia cells, and overall patient health.
- Healthcare Professionals
- Disease Ontology ID - DOID:9952
- Pathophysiology
- Acute lymphocytic leukemia (ALL) is a malignancy of the bone marrow and blood characterized by the overproduction of immature lymphocytes, known as lymphoblasts. The pathophysiology involves genetic mutations or chromosomal abnormalities that disrupt normal cell growth and differentiation. These mutations can lead to uncontrolled proliferation of lymphoblasts, which fail to mature into functional lymphocytes. The accumulation of these immature cells in the bone marrow suppresses the production of normal blood cells, leading to anemia, thrombocytopenia, and neutropenia. As a result, patients with ALL often present with symptoms such as fatigue, frequent infections, and bleeding tendencies.
- Carrier Status
- Acute lymphocytic leukemia (ALL) is a type of cancer that affects the blood and bone marrow. It is characterized by the overproduction of immature white blood cells, known as lymphoblasts or leukemic blasts. There is no "carrier status" for ALL, as it is not an inherited condition in the traditional sense, like some genetic diseases. Instead, ALL arises from genetic mutations that occur in a person's cells during their lifetime.
- Mechanism
- Several characteristic genetic changes lead to the creation of a leukemic lymphoblast. These changes include chromosomal translocations, intrachromosomal rearrangements, changes in the number of chromosomes in leukemic cells, and additional mutations in individual genes. Chromosomal translocations involve moving a large region of DNA from one chromosome to another. This move can result in placing a gene from one chromosome that promotes cell division to a more actively transcribed area on another chromosome. The result is a cell that divides more often. An example of this includes the translocation of C-MYC, a gene that encodes a transcription factor that leads to increased cell division, next to the immunoglobulin heavy- or light-chain gene enhancers, leading to increased C-MYC expression and increased cell division. Other large changes in chromosomal structure can result in the placement of two genes directly next to each other. The result is the combination of two usually separate proteins into a new fusion protein. This protein can have a new function that promotes the development of cancer. Examples of this include the ETV6–RUNX1 fusion gene that combines two factors that promote blood cell development and the BCR-ABL1 fusion gene of the Philadelphia chromosome. BCR–ABL1 encodes an always-activated tyrosine kinase that causes frequent cell division. These mutations produce a cell that divides more often, even in the absence of growth factors.Other genetic changes in B-cell ALL include changes to the number of chromosomes within the leukemic cells. Gaining at least five additional chromosomes, called high hyperdiploidy, occurs more commonly. Less often, chromosomes are lost, called hypodiploidy, which is associated with a poorer prognosis. Additional common genetic changes in B-cell ALL involve non-inherited mutations to PAX5 and IKZF1. In T-cell ALL, LYL1, TAL1, TLX1, and TLX3 rearrangements can occur.Acute lymphoblastic leukemia results when enough of these genetic changes are present in a single lymphoblast. In childhood ALL, for example, one fusion gene translocation is often found along with six to eight other ALL-related genetic changes. The initial leukemic lymphoblast copies itself into an excessive number of new lymphoblasts, none of which can develop into functioning lymphocytes. These lymphoblasts build up in the bone marrow and may spread to other sites in the body, such as lymph nodes, the mediastinum, the spleen, the testicles, and the brain, leading to the common symptoms of the disease.
- Treatment
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The aim of treatment is to induce a lasting remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells in the bone marrow) or the absence of minimal residue disease.
Over the past several decades, there have been strides to increase the efficacy of treatment regimens, resulting in increased survival rates. Possible treatments for acute leukemia include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), targeted therapy, and/or growth factors. - Compassionate Use Treatment
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Compassionate use treatment for acute lymphocytic leukemia (ALL) often involves access to experimental therapies that are still under investigation when standard treatments are not efficacious or suitable. Some off-label or experimental treatments include:
1. **CAR T-cell Therapy (e.g., Tisagenlecleucel):** Genetic modification of a patient's T-cells to attack leukemia cells. Approved for certain pediatric and young adult patients but may be used experimentally in other cases.
2. **Blinatumomab (Blincyto):** A bispecific T-cell engager (BiTE) antibody that is FDA-approved for certain ALL cases but might be used off-label for other specific subtypes or patient groups.
3. **Inotuzumab Ozogamicin:** An antibody-drug conjugate targeting CD22 on B-cells, used for relapsed or refractory ALL often as part of experimental protocols.
4. **Venetoclax (Venclexta):** A BCL-2 inhibitor, typically used for chronic lymphocytic leukemia (CLL) but might be explored off-label for certain ALL cases.
5. **Other TKIs (Tyrosine Kinase Inhibitors):** Such as dasatinib or nilotinib for Ph+ (Philadelphia chromosome-positive) ALL, beyond the typically approved imatinib.
6. **Experimental monoclonal antibodies or small molecule inhibitors under clinical trials:** These target specific mutations or antigens associated with ALL cells.
Involvement in clinical trials can offer access to such treatments, often providing options when other therapies fail. - Lifestyle Recommendations
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For patients with acute lymphocytic leukemia (ALL), lifestyle recommendations often focus on supporting treatment and overall well-being:
1. **Nutrition**: Eat a balanced diet rich in fruits, vegetables, lean proteins, and whole grains. This can help maintain strength and energy. Consult a dietitian for specific dietary needs.
2. **Hydration**: Stay well-hydrated by drinking plenty of water daily. Proper hydration is essential, especially during chemotherapy.
3. **Exercise**: Engage in light to moderate physical activity as tolerated. Exercise can help reduce fatigue, improve mood, and maintain physical function. Always consult your healthcare provider before starting any exercise program.
4. **Rest**: Ensure adequate rest and sleep. Fatigue is common, so balancing activity with rest is important.
5. **Infection Prevention**: Practice good hygiene, avoid large crowds, and stay away from individuals who are sick. This can help minimize the risk of infections, as the immune system can be weakened by both the disease and its treatment.
6. **Mental Health**: Seek support from mental health professionals, support groups, or counselors to help cope with the emotional challenges of ALL.
7. **Avoid Smoking and Alcohol**: Refrain from smoking and limit alcohol consumption, as these can interfere with treatments and overall health.
8. **Follow Medical Advice**: Adhere closely to your treatment plan and attend all medical appointments. Communicate openly with your healthcare team about any side effects or concerns.
These recommendations should be tailored to individual needs in consultation with healthcare providers. - Medication
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Acute lymphocytic leukemia (ALL) treatment typically involves a combination of medications including:
1. **Chemotherapy drugs**: These can include agents like methotrexate, vincristine, cyclophosphamide, and cytarabine.
2. **Corticosteroids**: Prednisone and dexamethasone are commonly used to reduce inflammation and manage symptoms.
3. **Immunotherapy/Biologic agents**: Examples are blinatumomab, a bispecific T-cell engager (BiTE), and inotuzumab ozogamicin.
4. **Targeted therapy**: Tyrosine kinase inhibitors (TKIs) such as imatinib or dasatinib may be used, especially in cases of Philadelphia chromosome-positive ALL.
5. **Central Nervous System (CNS) prophylaxis**: Intrathecal chemotherapy (e.g., methotrexate or cytarabine administered directly into the spinal fluid) is often used to prevent or treat CNS involvement.
Treatment plans are tailored based on individual factors such as age, specific genetic features of the leukemia, and response to initial therapy. - Repurposable Drugs
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Repurposable drugs for acute lymphocytic leukemia (ALL) include:
1. **Dasatinib** - Originally used for chronic myeloid leukemia, it targets the BCR-ABL tyrosine kinase and is effective in Philadelphia chromosome-positive ALL.
2. **Imatinib** - Another BCR-ABL tyrosine kinase inhibitor also utilized in Philadelphia chromosome-positive ALL.
3. **Ruxolitinib** - A JAK1/2 inhibitor used in myeloproliferative disorders, exploring efficacy in ALL with certain genetic alterations.
4. **Venetoclax** - A BCL-2 inhibitor initially approved for chronic lymphocytic leukemia, showing promise in combination therapies for ALL.
5. **Blinatumomab** - An anti-CD3/CD19 bispecific T-cell engager (BiTE) antibody, used for B-cell precursor ALL relapse.
Research and clinical trials are continuously exploring the efficacy and safety of these and other repurposed drugs for ALL treatment. - Metabolites
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Metabolites associated with acute lymphocytic leukemia (ALL) include various altered cellular metabolites due to the disease's impact on cellular metabolism. Key metabolites of interest in ALL research can include:
1. **Amino Acids**: Abnormal levels of amino acids like glutamine, glycine, and serine are often seen.
2. **Nucleotides**: Disrupted purine and pyrimidine metabolism, affecting levels of ATP, GTP, UTP, and CTP.
3. **Lipids**: Changes in lipid metabolism, including alterations in phospholipids and sphingolipids.
4. **Carbohydrates**: Dysregulated glucose and its metabolic intermediates, such as lactate and pyruvate.
5. **TCA Cycle Intermediates**: Altered levels of citrate, succinate, fumarate, and other tricarboxylic acid cycle components.
These altered metabolites can influence cell proliferation and survival, contributing to the pathophysiology of ALL.
Note: "nan" typically stands for "not a number," which is not relevant in this context. If you intended another term, please clarify. - Nutraceuticals
- There is currently no strong scientific evidence to support the use of nutraceuticals (food-derived products with additional health benefits) as a treatment for acute lymphocytic leukemia (ALL). Medical treatments typically involve chemotherapy, radiation therapy, and sometimes stem cell transplants. Any consideration of nutraceuticals should be discussed with a healthcare provider to ensure they do not interfere with conventional treatments.
- Peptides
- Acute lymphocytic leukemia (ALL) is a type of cancer of the blood and bone marrow that affects white blood cells. It is characterized by the overproduction of immature lymphoblasts. Peptides are short chains of amino acids that have potential therapeutic and diagnostic applications in treating ALL. Some peptides can act as antigens, helping to elicit an immune response against leukemia cells. Nanotechnology (nan) is increasingly being explored for its potential in ALL, including the use of nanoparticles for targeted drug delivery, improving the efficacy and reducing the toxicity of treatments. These approaches aim to enhance the precision and effectiveness of ALL therapies.