Acute lymphoblastic leukemia
Encyclopedia
Acute lymphoblastic leukemia (ALL) is a form of leukemia
, or cancer of the white blood cells
characterized by excess lymphoblast
s.
Malignant
, immature white blood cells continuously multiply and are overproduced in the bone marrow
. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (infiltrating) to other organs. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.
Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of chronic lymphocytic leukemia
which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic. This refers to the cells that are involved, which if they were normal would be referred to as lymphocytes but are seen in this disease in a relatively immature (also termed 'blast') state.
ALL begins with a medical history, physical examination
, complete blood count, and blood smears. Because the symptoms are so general, many other diseases with similar symptoms must be excluded. Typically, the higher the white blood cell count, the worse the prognosis. Blast cells are seen on blood smear in majority of cases (blast cells are precursors (stem cells) to all immune cell lines). A bone marrow biopsy
is conclusive proof of ALL. A lumbar puncture
(also known as a spinal tap) will tell if the spinal column and brain
has been invaded.
Pathological
examination, cytogenetics
(particularly the presence of Philadelphia chromosome
) and immunophenotyping
, establish whether the Myeloblastic (neutrophils, eosinophils or basophils) or Lymphoblastic (B lymphocytes or T lymphocytes) cells are the problem. RNA testing can establish how aggressive the disease is; different mutations have been associated with shorter or longer survival. Immunohistochemical
testing may reveal TdT
or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells while CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML
.
Medical imaging
(such as ultrasound
or CT scanning) can find invasion of other organs
commonly the lung
, liver, spleen, lymph nodes, brain, kidneys and reproductive organs.
Initial symptoms are not specific to ALL, but worsen to the point that medical help is sought. They result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature leukocytes (white blood cells). Therefore, people with ALL experience symptoms from malfunctioning of their erythrocytes (red blood cells), leukocytes, and platelets. Laboratory tests which might show abnormalities include blood count tests, renal function tests, electrolyte tests and liver enzyme tests.
The signs and symptoms of ALL are variable but follow from bone marrow replacement and/or organ infiltration.
ALL is associated with exposure to radiation
and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl
nuclear reactor and atom bombs in Hiroshima
and Nagasaki. In animals, exposure to benzene
and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Some evidence suggests that secondary leukemia can develop in individuals who are treated for other cancers with radiation and chemotherapy as a result of that treatment.
12:21 is the most common translocation and portends a good prognosis. 4:11 is the most common in children under 12 months and portends a poor prognosis.
s on new chemotherapeutic agents and improvements in stem cell transplantation (SCT) technology.
Five-year survival rates evaluate older, not current, treatments. New drugs, and matching treatment to the genetic characteristics of the blast cells, may improve those rates. The prognosis for ALL differs between individuals depending on a variety of factors:
Cytogenetics
, the study of characteristic large changes in the chromosomes of cancer cell
s, is an important predictor of outcome.
Some cytogenetic subtypes have a worse prognosis than others. These include:
Correlation of prognosis with bone marrow cytogenetic finding in acute lymphoblastic leukemia
Unclassified ALL is considered to have an intermediate prognosis.
, which was used for all acute leukemias (including acute myelogenous leukemia, AML).
Each subtype is then further classified by determining the surface markers of the abnormal lymphocytes, called immunophenotyping. There are 2 main immunologic types: pre-B cell and pre-T cell. The mature B-cell ALL (L3) is now classified as Burkitt's lymphoma
/leukemia. Subtyping helps determine the prognosis and most appropriate treatment in treating ALL.
1- Acute lymphoblastic leukemia/lymphoma Synonyms:Former Fab L1/L2
2- Burkitt's leukemia/lymphoma Synonyms:Former FAB L3
3- Biphenotypic acute leukemia
Immunophenotypic categories of acute lymphoblastic leukemia (ALL)
|->
Types
FAB Class
Tdt
T cell associate antigen
B cell associate antigen
c Ig
| Precursor B
| L1,L2
| +
| -
| +
| -/+
| -
|-
| Precursor T
| L1,L2
| +
| +
| -
| -
| -
|-
| B-cell
| L3
| -
| -
| +
| -
| +
|}
Treatment for acute leukemia can include chemotherapy
, steroid
s, radiation therapy
, intensive combined treatments (including bone marrow
or stem cell
transplants), and growth factors.
is the initial treatment of choice. Most ALL patients will receive a combination of different treatments. There are no surgical options, due to the body-wide distribution of the malignant cells. In general, cytotoxic chemotherapy for ALL combines multiple antileukemic drugs in various combinations. Chemotherapy for ALL consists of three phases: remission induction, intensification, and maintenance therapy.
As the chemotherapy regimens
can be intensive and protracted (often about 2 years in case of the GMALL UKALL, HyperCVAD or CALGB protocols; for ALL about 3 years, 2 months for males on COG protocols; 2 years, 2 months for females- longer for males as testicles are a potential reservoir), many patients have an intravenous catheter inserted into a large vein (termed a central venous catheter
or a Hickman line
), or a Portacath, a cone-shaped port with a silicone nose that is surgically planted under the skin, usually near the collar bone, and the most effective product available, due to low infection risks and the long-term viability of a portacath.
(or radiotherapy) is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant
(total body irradiation). Radiation in the form of whole brain radiation is also used for central nervous system prophylaxis, to prevent recurrence of leukemia in the brain. Whole brain prophylaxis radiation used to be a common method in treatment of children’s ALL. Recent studies showed that CNS chemotherapy provided results as favorable but with less developmental side effects. As a result, the use of whole brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS prophylaxis, instead using intrathecal chemotherapy.
, Fanconi anemia
, Bloom syndrome
, Ataxia telangiectasia
, X-linked agammaglobulinemia
and Severe combined immunodeficiency
.
It is possible, although extremely rare, for leukemia to spread from mother to the child. This is called vertical transmission
.
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
, or cancer of the white blood cells
Hematological malignancy
Hematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
characterized by excess lymphoblast
Lymphoblast
Lymphoblasts are immature cells which typically differentiate to form mature lymphocytes. Normally lymphoblasts are found in the bone marrow, but in acute lymphoblastic leukemia , lymphoblasts proliferate uncontrollably and are found in large numbers in the peripheral blood.The size is between 10...
s.
Malignant
Malignant
Malignancy is the tendency of a medical condition, especially tumors, to become progressively worse and to potentially result in death. Malignancy in cancers is characterized by anaplasia, invasiveness, and metastasis...
, immature white blood cells continuously multiply and are overproduced in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
. ALL causes damage and death by crowding out normal cells in the bone marrow, and by spreading (infiltrating) to other organs. ALL is most common in childhood with a peak incidence at 2–5 years of age, and another peak in old age. The overall cure rate in children is about 80%, and about 45%-60% of adults have long-term disease-free survival.
Acute refers to the relatively short time course of the disease (being fatal in as little as a few weeks if left untreated) to differentiate it from the very different disease of chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
which has a potential time course of many years. It is interchangeably referred to as Lymphocytic or Lymphoblastic. This refers to the cells that are involved, which if they were normal would be referred to as lymphocytes but are seen in this disease in a relatively immature (also termed 'blast') state.
Diagnosis
DiagnosingMedical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
ALL begins with a medical history, physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
, complete blood count, and blood smears. Because the symptoms are so general, many other diseases with similar symptoms must be excluded. Typically, the higher the white blood cell count, the worse the prognosis. Blast cells are seen on blood smear in majority of cases (blast cells are precursors (stem cells) to all immune cell lines). A bone marrow biopsy
Bone marrow biopsy
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, lymphoma, anemia, and pancytopenia...
is conclusive proof of ALL. A lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
(also known as a spinal tap) will tell if the spinal column and brain
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
has been invaded.
Pathological
Histopathology
Histopathology refers to the microscopic examination of tissue in order to study the manifestations of disease...
examination, cytogenetics
Cytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...
(particularly the presence of Philadelphia chromosome
Philadelphia chromosome
Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
) and immunophenotyping
Immunophenotyping
Immunophenotyping is a technique used to study the protein expressed by cells. This technique is commonly used in basic science research and laboratory diagnostic purpose. This can be done on tissue section , cell suspension, etc. An example is the detection of tumor marker, such as in the...
, establish whether the Myeloblastic (neutrophils, eosinophils or basophils) or Lymphoblastic (B lymphocytes or T lymphocytes) cells are the problem. RNA testing can establish how aggressive the disease is; different mutations have been associated with shorter or longer survival. Immunohistochemical
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
testing may reveal TdT
Terminal Deoxynucleotidyl Transferase
Terminal deoxynucleotidyl transferase , also known as DNA nucleotidylexotransferase or terminal transferase, is a specialized DNA polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphoma cells...
or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells while CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML
Chronic myelogenous leukemia
Chronic myelogenous leukemia , also known as chronic granulocytic leukemia , is a cancer of the white blood cells. It is a form of leukemia characterized by the increased and unregulated growth of predominantly myeloid cells in the bone marrow and the accumulation of these cells in the blood...
.
Medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
(such as ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
or CT scanning) can find invasion of other organs
Organ (anatomy)
In biology, an organ is a collection of tissues joined in structural unit to serve a common function. Usually there is a main tissue and sporadic tissues . The main tissue is the one that is unique for the specific organ. For example, main tissue in the heart is the myocardium, while sporadic are...
commonly the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...
, liver, spleen, lymph nodes, brain, kidneys and reproductive organs.
Symptoms
Initial symptoms are not specific to ALL, but worsen to the point that medical help is sought. They result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature leukocytes (white blood cells). Therefore, people with ALL experience symptoms from malfunctioning of their erythrocytes (red blood cells), leukocytes, and platelets. Laboratory tests which might show abnormalities include blood count tests, renal function tests, electrolyte tests and liver enzyme tests.
The signs and symptoms of ALL are variable but follow from bone marrow replacement and/or organ infiltration.
- Generalized weakness and fatigue
- Anemia
- Frequent or unexplained feverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
and infectionInfectionAn infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease... - 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
- Petechia, which are tiny red spots or lines in the skin due to low plateletPlateletPlatelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
levels
Pathophysiology
In general, cancer is caused by damage to DNA that leads to uncontrolled cellular growth and spread throughout the body, either by increasing chemical signals that cause growth, or interrupting chemical signals that control growth. Damage can be caused through the formation of fusion genes, as well as the dysregulation of a proto-oncogene via juxtaposition of it to the promoter of another gene, e.g. the T-cell receptor gene. This damage may be caused by environmental factors such as chemicals, drugs or radiation.ALL is associated with exposure to radiation
Ionizing radiation
Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons...
and chemicals in animals and humans. The association of radiation and leukemia in humans has been clearly established in studies of victims of the Chernobyl
Chernobyl
Chernobyl or Chornobyl is an abandoned city in northern Ukraine, in Kiev Oblast, near the border with Belarus. The city had been the administrative centre of the Chernobyl Raion since 1932....
nuclear reactor and atom bombs in Hiroshima
Hiroshima
is the capital of Hiroshima Prefecture, and the largest city in the Chūgoku region of western Honshu, the largest island of Japan. It became best known as the first city in history to be destroyed by a nuclear weapon when the United States Army Air Forces dropped an atomic bomb on it at 8:15 A.M...
and Nagasaki. In animals, exposure to benzene
Benzene
Benzene is an organic chemical compound. It is composed of 6 carbon atoms in a ring, with 1 hydrogen atom attached to each carbon atom, with the molecular formula C6H6....
and other chemicals can cause leukemia. Epidemiological studies have associated leukemia with workplace exposure to chemicals, but these studies are not as conclusive. Some evidence suggests that secondary leukemia can develop in individuals who are treated for other cancers with radiation and chemotherapy as a result of that treatment.
Cytogenetics
Cytogenetic translocations associated with specific molecular genetic abnormalities in ALL| Cytogenetic translocation | Molecular genetic abnormality | % |
|---|---|---|
| cryptic t(12;21) | TEL ETV6 ETV6 is an oncogene.-Interactions:ETV6 has been shown to interact with Grb2, FLI1 and HTATIP.-See also:* TEL-JAK2Mouse Mutant Alleles for Etv6 Marker Symbol for Mouse Gene. This symbol is assigned to the genomic locus by the... -AML1 RUNX1 Runt-related transcription factor 1 also known as acute myeloid leukemia 1 protein or core-binding factor subunit alpha-2 is a protein that in humans is encoded by the RUNX1 gene.... fusion |
25.4% |
| t(1;19)(q23;p13) | E2A-PBX Pre-B-cell leukemia homeobox Pre-B-cell leukemia homeobox refers to a family of transcription factors.Types include:* PBX1* PBX2* PBX3... (PBX1 PBX1 Pre-B-cell leukemia transcription factor 1 is a protein that in humans is encoded by the PBX1 gene.-Interactions:PBX1 has been shown to interact with HOXB1, MEIS1 and HOXB7.-Further reading:... ) fusion |
4.8% |
| t(9;22)(q34;q11) | BCR-ABL fusion(P185) | 1.6% |
| t(4;11)(q21;q23) | MLL MLL (gene) Histone-lysine N-methyltransferase HRX is an enzyme that in humans is encoded by the MLL gene.MLL is a histone methyltransferase deemed a positive global regulator of gene transcription... -AF4 fusion |
1.6% |
| t(8;14)(q24;q32) | IGH-MYC Myc Myc is a regulator gene that codes for a transcription factor. In the human genome, Myc is located on chromosome 8 and is believed to regulate expression of 15% of all genes through binding on Enhancer Box sequences and recruiting histone acetyltransferases... fusion |
|
| t(11;14)(p13;q11) | TCR TCR TCR can mean:*Time Code Reading, a method of accounting for video or film footage and frames in media editing*T cell receptor*Tobacco Control Research*Toronto Civic Railways... -RBTN2 fusion |
12:21 is the most common translocation and portends a good prognosis. 4:11 is the most common in children under 12 months and portends a poor prognosis.
Prognosis
The survival rate has improved from zero four decades ago, to 20-75 percent currently, largely due to clinical trialClinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s on new chemotherapeutic agents and improvements in stem cell transplantation (SCT) technology.
Five-year survival rates evaluate older, not current, treatments. New drugs, and matching treatment to the genetic characteristics of the blast cells, may improve those rates. The prognosis for ALL differs between individuals depending on a variety of factors:
- Sex: females tend to fare better than males.
- Ethnicity: Caucasians are more likely to develop acute leukemia than African-AmericansAfrican AmericanAfrican Americans are citizens or residents of the United States who have at least partial ancestry from any of the native populations of Sub-Saharan Africa and are the direct descendants of enslaved Africans within the boundaries of the present United States...
, AsiansAsian AmericanAsian Americans are Americans of Asian descent. The U.S. Census Bureau definition of Asians as "Asian” refers to a person having origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent, including, for example, Cambodia, China, India, Indonesia, Japan,...
or Hispanics. However, they also tend to have a better prognosis than non-Caucasians. - Age at diagnosis: children between 1–10 years of age are most likely to develop ALL and to be cured of it. Cases in older patients are more likely to result from chromosomal abnormalities (e.g. the Philadelphia chromosome) that make treatment more difficult and prognoses poorer.
- White blood cell count at diagnosis of less than 50,000/µl
- Cancer spread into the Central nervous systemCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(brainBrainThe brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
or spinal cordSpinal cordThe spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
) has worse outcomes. - Morphological, immunological, and genetic subtypes
- Patient's response to initial treatment
- Genetic disorderGenetic disorderA genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s such as Down's SyndromeDown syndromeDown syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
Cytogenetics
Cytogenetics
Cytogenetics is a branch of genetics that is concerned with the study of the structure and function of the cell, especially the chromosomes. It includes routine analysis of G-Banded chromosomes, other cytogenetic banding techniques, as well as molecular cytogenetics such as fluorescent in situ...
, the study of characteristic large changes in the chromosomes of cancer cell
Cancer cell
Cancer cells are cells that grow and divide at an unregulated, quickened pace. Although cancer cells can be quite common in a person they are only malignant when the other cells fail to recognize and/or destroy them. In the past a common belief was that cancer cells failed to be recognized and...
s, is an important predictor of outcome.
Some cytogenetic subtypes have a worse prognosis than others. These include:
- A translocation between chromosomeChromosomeA chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s 9 and 22, known as the Philadelphia chromosomePhiladelphia chromosomePhiladelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
, occurs in about 20% of adult and 5% in pediatric cases of ALL. - A translocation between chromosomes 4 and 11 occurs in about 4% of cases and is most common in infants under 12 months.
- Not all translocations of chromosomes carry a poorer prognosis. Some translocations are relatively favorable. For example, Hyperdiploidy (>50 chromosomes) is a good prognostic factor.
- Genome-wide copy number changes can be assessed by conventional cytogenetics or virtual karyotypingVirtual KaryotypeVirtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
. SNP array virtual karyotyping can detect copy number changes and LOH status, while arrayCGH can detect only copy number changes. Copy neutral LOH (acquired uniparental disomy) has been reported at key loci in ALL, such as CDKN2A gene, which have prognostic significance. SNP array virtual karyotypingVirtual KaryotypeVirtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
can readily detect copy neutral LOH. Array CGH, FISH, and conventional cytogenetics cannot detect copy neutral LOH.
| Cytogenetic change | Risk category |
|---|---|
| Philadelphia chromosome Philadelphia chromosome Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t... |
Poor prognosis |
| t(4;11)(q21;q23) | Poor prognosis |
| t(8;14)(q24.1;q32) | Poor prognosis |
| Complex karyotype Karyotype A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28... (more than four abnormalities) |
Poor prognosis |
| Low hypodiploidy or near triploidy | Poor prognosis |
| High hyperdiploidy (specifically, trisomy 4, 10, 17) | Good prognosis |
| del(9p) | Good prognosis |
Correlation of prognosis with bone marrow cytogenetic finding in acute lymphoblastic leukemia
| Prognosis | Cytogenetic findings |
|---|---|
| Favorable | Hyperdiploidy > 50 ; t (12;21) |
| Intermediate | Hyperdiploidy 47 -50; Normal(diploidy); del (6q); Rearrangements of 8q24 |
| Unfavorable | Hypodiploidy-near haploidy; Near tetraploidy; del (17p); t (9;22); t (11q23) |
Unclassified ALL is considered to have an intermediate prognosis.
Classification
As ALL is not a solid tumour, the TNM notation as used in solid cancers is of little use.The FAB classification
Subtyping of the various forms of ALL used to be done according to the French-American-British (FAB) classificationFrench-American-British classification
The French-American-British classification systems refers to a series of classifications of hematologic diseases.It was first produced in 1976.Types include:* FAB classification of acute lymphoblastic leukemias...
, which was used for all acute leukemias (including acute myelogenous leukemia, AML).
- ALL-L1: small uniform cells
- ALL-L2: large varied cells
- ALL-L3: large varied cells with vacuoleVacuoleA vacuole is a membrane-bound organelle which is present in all plant and fungal cells and some protist, animal and bacterial cells. Vacuoles are essentially enclosed compartments which are filled with water containing inorganic and organic molecules including enzymes in solution, though in certain...
s (bubble-like features)
Each subtype is then further classified by determining the surface markers of the abnormal lymphocytes, called immunophenotyping. There are 2 main immunologic types: pre-B cell and pre-T cell. The mature B-cell ALL (L3) is now classified as Burkitt's lymphoma
Burkitt's lymphoma
Burkitt's lymphoma is a cancer of the lymphatic system...
/leukemia. Subtyping helps determine the prognosis and most appropriate treatment in treating ALL.
WHO proposed classification of acute lymphoblastic leukemia
The recent WHO International panel on ALL recommends that the FAB classification be abandoned, since the morphological classification has no clinical or prognostic relevance. It instead advocates the use of the immunophenotypic classification mentioned below.1- Acute lymphoblastic leukemia/lymphoma Synonyms:Former Fab L1/L2
- i. Precursor B acute lymphoblastic leukemia/lymphomaPrecursor B acute lymphoblastic leukemia/lymphomaPrecursor B-cell lymphoblastic leukemia is a form of lymphoid leukemia, sometimes additionally classified as a lymphoma, as designated leukemia/lymphoma.It consists of the following subtypes:* t-BCR/ ABL* t-MLL rearrangement...
. Cytogenetic subtypes:- t(12;21)(p12,q22) TEL/AML-1
- t(1;19)(q23;p13) PBX/E2A
- t(9;22)(q34;q11) ABL/BCR
- T(V,11)(V;q23) V/MLL
- ii. Precursor T acute lymphoblastic leukemia/lymphomaPrecursor T acute lymphoblastic leukemia/lymphomaPrecursor T-cell lymphoblastic leukemia is a form of lymphoid leukemia, sometimes additionally classified as a lymphoma, as designated Precursor T-cell lymphoblastic lymphoma.It comprises 85% to 90% of lymphoblastic lymphoma....
2- Burkitt's leukemia/lymphoma Synonyms:Former FAB L3
3- Biphenotypic acute leukemia
Variant Features of ALL
- 1- Acute lymphoblastic leukemia with cytoplasmic granules
- 2- Aplastic presentation of ALL
- 3- Acute lymphoblastic leukemia with eosinophilia
- 4- Relapse of lymphoblastic leukemia
- 5- Secondary ALL
Immunophenotyping in the diagnosis and classification of ALL
The use of a TdT assay and a panel of monoclonal antibodies (MoAbs) to T cell and B cell associated antigens will identify almost all cases of ALL.Immunophenotypic categories of acute lymphoblastic leukemia (ALL)
| Precursor B
| L1,L2
| +
| -
| +
| -/+
| -
|-
| Precursor T
| L1,L2
| +
| +
| -
| -
| -
|-
| B-cell
| L3
| -
| -
| +
| -
| +
|}
Treatment
The earlier acute lymphocytic leukemia is detected, the more effective the treatment. The aim is to induce a lasting remission, defined as the absence of detectable cancer cells in the body (usually less than 5% blast cells on the bone marrow).Treatment for acute leukemia can include chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
, steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
s, radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
, intensive combined treatments (including bone marrow
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
or stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
transplants), and growth factors.
Chemotherapy
ChemotherapyChemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
is the initial treatment of choice. Most ALL patients will receive a combination of different treatments. There are no surgical options, due to the body-wide distribution of the malignant cells. In general, cytotoxic chemotherapy for ALL combines multiple antileukemic drugs in various combinations. Chemotherapy for ALL consists of three phases: remission induction, intensification, and maintenance therapy.
| Phase | Description | Agents |
|---|---|---|
| Remission induction | The aim of remission induction is to rapidly kill most tumor cells and get the patient into remission. This is defined as the presence of less than 5% leukemic blasts in the bone marrow, normal blood cells and absence of tumor cells from blood, and absence of other signs and symptoms of the disease. Central nervous system Central nervous system The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish... (CNS) prophylaxis should begin during this phase of treatment and continue during the consolidation/intensification period. The rationale is based on the presence of CNS involvement in 10%-40% of adult patients at diagnosis. |
Combination of Prednisolone Prednisolone Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as... or dexamethasone Dexamethasone Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant... , vincristine Vincristine Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to... , asparaginase Asparaginase Asparaginase is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. Asparaginases are naturally occurring enzymes expressed and produced by microorganisms. Different types of asparaginases can be used for different industrial and pharmaceutical purposes. The most common use of... (better tolerance in pediatric patients), and daunorubicin Daunorubicin Daunorubicin or daunomycin is chemotherapeutic of the anthracycline family that is given as a treatment for some types of cancer. It is most commonly used to treat specific types of leukaemia... (used in Adult ALL) is used to induce remission. |
| Consolidation/Intensification | Intensification uses high doses of intravenous multidrug chemotherapy to further reduce tumor burden. Since all cells sometimes penetrate the CNS, most protocols include delivery of chemotherapy into the CNS fluid (termed intrathecal chemotherapy). Some centers deliver the drug through Ommaya reservoir Ommaya reservoir An Ommaya reservoir is an intraventricular catheter system that can be used for the aspiration of cerebrospinal fluid or for the delivery of drugs into the cerebrospinal fluid. It consists of a catheter in one lateral ventricle attached to a reservoir implanted under the scalp... (a device surgically placed under the scalp and used to deliver drugs to the CNS fluid and to extract CNS fluid for various tests). Other centers would perform multiple lumbar punctures as needed for testing and treatment delivery. |
Typical intensification protocols use vincristine, cyclophosphamide Cyclophosphamide Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group.... , cytarabine Cytarabine Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C... , daunorubicin, etoposide Etoposide Etoposide phosphate is an anti-cancer agent. It is known in the laboratory as a topoisomerase poison. Etoposide is often incorrectly referred to as a topoisomerase inhibitor in order to avoid using the term "poison" in a clinical setting... , thioguanine or mercaptopurine Mercaptopurine Mercaptopurine is an immunosuppressive drug.It is a thiopurine.-Uses:... given as blocks in different combinations. For CNS protection, intrathecal methotrexate or cytarabine is usually used combined with or without cranio-spinal irradiation (the use of radiation therapy to the head and spine). Central nervous system relapse is treated with intrathecal administration of hydrocortisone, methotrexate, and cytarabine. |
| Maintenance therapy | The aim of maintenance therapy is to kill any residual cell that was not killed by remission induction, and intensification regimens. Although such cells are few, they will cause relapse if not eradicated. | For this purpose, daily oral mercaptopurine Mercaptopurine Mercaptopurine is an immunosuppressive drug.It is a thiopurine.-Uses:... , once weekly oral methotrexate Methotrexate Methotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate... , once monthly 5-day course of intravenous vincristine Vincristine Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to... and oral corticosteroids are usually used. The length of maintenance therapy is 3 years for boys, 2 years for girls and adults. |
As the chemotherapy regimens
Chemotherapy regimens
A fundamental philosophy of combination cancer therapy is that different drugs work through different cytotoxic mechanisms. Because they have different dose-limiting adverse effects, they can be given together at full doses in chemotherapy regimens....
can be intensive and protracted (often about 2 years in case of the GMALL UKALL, HyperCVAD or CALGB protocols; for ALL about 3 years, 2 months for males on COG protocols; 2 years, 2 months for females- longer for males as testicles are a potential reservoir), many patients have an intravenous catheter inserted into a large vein (termed a central venous catheter
Central venous catheter
In medicine, a central venous catheter is a catheter placed into a large vein in the neck , chest or groin...
or a Hickman line
Hickman line
A Hickman line is an intravenous catheter most often used for the administration of chemotherapy or other medications, as well as for the withdrawal of blood for analysis. Some types of Hickman lines are used mainly for the purpose of apheresis or dialysis...
), or a Portacath, a cone-shaped port with a silicone nose that is surgically planted under the skin, usually near the collar bone, and the most effective product available, due to low infection risks and the long-term viability of a portacath.
Radiation therapy
Radiation therapyRadiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
(or radiotherapy) is used on painful bony areas, in high disease burdens, or as part of the preparations for a bone marrow transplant
Bone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
(total body irradiation). Radiation in the form of whole brain radiation is also used for central nervous system prophylaxis, to prevent recurrence of leukemia in the brain. Whole brain prophylaxis radiation used to be a common method in treatment of children’s ALL. Recent studies showed that CNS chemotherapy provided results as favorable but with less developmental side effects. As a result, the use of whole brain radiation has been more limited. Most specialists in adult leukemia have abandoned the use of radiation therapy for CNS prophylaxis, instead using intrathecal chemotherapy.
Epidemiology
In the US, the incidence of ALL is roughly 6000 new cases per year (as of 2009), or approximately 1 in 50,000. ALL accounts for approximately 70 percent of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. It has a peak incident rate of 2–5 years old, decreasing in incidence with increasing age before increasing again at around 50 years old. ALL is slightly more common in males than females. There is an increased incidence in people with Down SyndromeDown syndrome
Down syndrome, or Down's syndrome, trisomy 21, is a chromosomal condition caused by the presence of all or part of an extra 21st chromosome. It is named after John Langdon Down, the British physician who described the syndrome in 1866. The condition was clinically described earlier in the 19th...
, Fanconi anemia
Fanconi anemia
Fanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...
, Bloom syndrome
Bloom syndrome
Bloom's syndrome , also known as Bloom–Torre–Machacek syndrome, is a rare autosomal recessive chromosomal disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes. The condition was discovered and first described by dermatologist Dr...
, Ataxia telangiectasia
Ataxia telangiectasia
Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease...
, X-linked agammaglobulinemia
X-linked agammaglobulinemia
X-linked agammaglobulinemia is a rare X-linked genetic disorder that was discovered in 1952 which affects the body's ability to fight infection. XLA is an X-linked disorder, and therefore is more common in males...
and Severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
.
In pregnancy
Leukemia is rarely associated with pregnancy, affecting only about 1 in 10,000 pregnant women. How it is handled depends primarily on the type of leukemia. Acute leukemias normally require prompt, aggressive treatment, despite significant risks of pregnancy loss and birth defects, especially if chemotherapy is given during the developmentally sensitive first trimester.It is possible, although extremely rare, for leukemia to spread from mother to the child. This is called vertical transmission
Vertical transmission
Vertical transmission, also known as mother-to-child transmission, is the transmission of an infection or other disease from mother to child immediately before and after birth during the perinatal period. A pathogen's transmissibility refers to its capacity for vertical transmission...
.
See also
- Maarten van der WeijdenMaarten van der WeijdenMaarten van der Weijden is a Dutch long distance and marathon swimmer born in Alkmaar.Van der Weijden was known as a promising swimming talent in his youth, becoming Dutch national champion at the 1500 m freestyle , 400 m freestyle and 5 km open water...
, diagnosed with ALL in 2001, winner of the 10 km open water marathon race at the 2008 Summer Olympics2008 Summer OlympicsThe 2008 Summer Olympics, officially known as the Games of the XXIX Olympiad, was a major international multi-sport event that took place in Beijing, China, from August 8 to August 24, 2008. A total of 11,028 athletes from 204 National Olympic Committees competed in 28 sports and 302 events...
in BeijingBeijingBeijing , also known as Peking , is the capital of the People's Republic of China and one of the most populous cities in the world, with a population of 19,612,368 as of 2010. The city is the country's political, cultural, and educational center, and home to the headquarters for most of China's... - Andrew McMahonAndrew McMahonAndrew Ross McMahon is a singer/songwriter. He is the vocalist, pianist and primary songwriter for the bands Something Corporate and Jack's Mannequin; he also performs solo.-Early life:...
, diagnosed in 2005, singer of the bands Something CorporateSomething CorporateSomething Corporate is an American rock band from Orange County, California, formed in 1998. Their current line-up includes pianist and vocalist Andrew McMahon, guitarist Josh Partington, bassist Kevin Page and drummer Brian Ireland....
and Jack's MannequinJack's MannequinJack's Mannequin is an American rock band formed in 2004, originally hailing from Orange County, California. The band began as a side project of Andrew McMahon, the frontman for Something Corporate, and is composed of guitarist Bobby Anderson, bassist Mikey "The Kid" Wagner, and drummer Jay... - Edward "Edd" Gould, diagnosed in 2011, creator of EddsworldEddsworldEddsworld is an independent British comedic flash animation production company created by Edward Gould in 2004. Eddsworld was also part of CakeBomb , but has always stood out as its own franchise...
online cartoons - Virtual KaryotypeVirtual KaryotypeVirtual karyotype detects genomic copy number variations at a higher resolution level than conventional karyotyping or chromosome-based comparative genomic hybridization .-Background:...
External links
- Acute Lymphocytic Leukemia at American Cancer SocietyAmerican Cancer SocietyThe American Cancer Society is the "nationwide community-based voluntary health organization" dedicated, in their own words, "to eliminating cancer as a major health problem by preventing cancer, saving lives, and diminishing suffering from cancer, through research, education, advocacy, and...
- Information about ALL from the Leukemia & Lymphoma SocietyLeukemia & Lymphoma SocietyThe Leukemia & Lymphoma Society , founded in 1949, is the world's largest voluntary health organization dedicated to funding blood cancer research, education and patient services. LLS's mission is to cure leukemia, lymphoma, Hodgkin's disease and myeloma, and to improve the quality of life of...
- Clinically reviewed acute lymphoblastic leukemia information for patients, from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- UK leukaemia statistics from Cancer Research UKCancer Research UKCancer Research UK is a cancer research and awareness charity in the United Kingdom, formed on 4 February 2002 by the merger of The Cancer Research Campaign and the Imperial Cancer Research Fund. Its aim is to reduce the number of deaths from cancer. As the world's largest independent cancer...
- Directory of children's cancer-related resources from Children's Cancer Web
- Information about ALL from the Centre for Cancer and Blood Disorders at Sydney Children’s Hospital
- Information about ALL from European LeukemiaNet
- Information on childhood ALL from ACOR's Ped-Onc Resource Center, including disease details (MRD, phenotypes, molecular characterization), a layman's list of current and past clinical trials, a collection of articles on the possible causes of ALL, a bibliography of journal articles, and links to sources of support for parents of children with ALL.
- Association of Cancer Online Resource (ACOR) Leukemia Links - provides links to information on leukemia, including ALL, primarily in adults.