View source for Acute lymphoblastic leukemia

{{DiseaseDisorder infobox |
  Name        = Acute lymphoblastic leukemia |
  ICD10       = C91.0 |
  ICD9        = {{ICD9|204.0}} |
  ICDO        = 9821/3 |
}}
'''Acute lymphoblastic leukemia''' ('''ALL'''), also known as '''acute lymphocytic leukemia''', is a [[cancer]] of the [[white blood cell]]s, characterised by the overproduction and continuous multiplication of [[malignant]] and immature white blood cells (referred to as [[lymphoblast]]s) in the [[bone marrow]]. It is a [[hematological malignancy]]. It is fatal if left untreated as ALL spreads into the bloodstream and other vital organs quickly (hence "acute"). It mainly affects young children and adults over 50.

==Symptoms== 
Initial symptoms of ALL are quite aspecific, but worsen to the point that medical help is sought. The signs and symptoms of ALL are variable but follow from bone marrow replacement and / or organ infiltration. 
* Generalised weakness and [[Fatigue (physical)|fatigue]]
* [[Anemia]]
* Frequent or unexplained [[fever]] and [[infection]]s
* Weight loss and/or loss of appetite
* Excessive [[bruising]] or [[hemorrhage|bleeding]] from wounds, [[nosebleed]]s, [[petechiae]] (red pinpoints on the skin)
* [[Bone pain]], [[joint pain]]s (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]]

The signs and [[symptoms]] of ALL result from the lack of normal and healthy blood cells because they are crowded out by malignant and immature white blood cells.  Therefore, people with ALL experience symptoms from their red blood cells, white blood cells, and platelets not functioning properly.  Laboratory tests which might show abnormalities include [[blood count]]s, [[renal function]]s, [[electrolyte]]s and [[liver enzyme]]s.

==Diagnosis==
[[Diagnosis|Diagnosing]] -----leukemia usually begins with a medical history and [[physical examination]]. If there is a suspicion of leukemia, the patient will then proceed to undergo a number of tests to establish the presence of leukemia and its type. Patients with this constellation of symptoms will generally have had [[blood test]]s, such as a [[full blood count]].

These tests may include [[Full blood count|complete blood count]] (''blasts'' on the [[blood film]] generally lead to the suspicion of ALL being raised). Nevertheless, 10% have a normal blood film, and clinical suspicion alone may be the only reason to perform a [[bone marrow biopsy]], which is the next step in the diagnostic process.

Bone marrow is examined for blasts, cell counts and other signs of disease. [[Histopathology|Pathological]] examination, [[cytogenetics]] (e.g. presence of the [[Philadelphia chromosome]]) and [[immunophenotyping]] establish whether the "blast" cells began from the [[B lymphocyte]]s or [[T lymphocyte]]s.

If ALL has been established as a diagnosis, a [[lumbar puncture]] is generally required to determine whether the malignant cells have invaded the [[central nervous system]] (CNS).

Lab tests (mentioned above) and clinical information may also be used to determine whether other [[medical imaging]] (such as [[medical ultrasonography|ultrasound]] or [[CT scan]]ning) may be required to find invasion of other [[Organ (anatomy)|organs]] such as the [[lung]]s or liver.

==Pathophysiology==
The [[etiology]] of ALL remains uncertain although some doctors believe that ALL develops from a combination of [[Genetics|genetic]] and environmental factors.  However, there is no definite way of determining the cause of leukemia.

Scientific research has shown that all malignancies are due to subtle or less subtle changes in [[Deoxyribonucleic Acid|DNA]] that lead to unimpaired cell division and breakdown of inhibitory processes. In leukemias, including ALL, [[chromosomal translocation]]s occur regularly. It is thought that most translocations occur before birth during fetal development. These translocations may trigger [[oncogene]]s to "turn on", causing unregulated [[mitosis]] where cells divide too quickly and abnormally, resulting in leukemia. There is little indication that propensity for ALL is passed on from parents to children.

There have been indications that excessive exposure to high dose [[ionizing radiation|radiation]] (such as that of [[nuclear reactor]]s, notably [[Chernobyl]], and the [[atomic bomb]]s in Nagasaki and [[Hiroshima|Hiroshima, Japan]] 1945) increases the risk of developing acute leukemia. There has also been inconclusive evidence suggesting that exposure to chemicals such as [[benzene]] can cause an increased risk for developing acute leukemia.

==Classification==
Subtyping of the various forms of ALL is done according to the FAB (French-American-British) classification, which is used for all acute leukemias (including [[acute myelogenous leukemia]], AML). As ALL is not a solid tumour, the [[TNM|TxNxMx]] notation used in those cancers is of little use.

The FAB classification is: 
* ALL-L1: small uniform cells
* ALL-L2: large varied cells
* ALL-L3: large varied cells with [[vacuole]]s (bubble-like features)

Note: The recent WHO International panel on ALL recommends that this classification be abandoned, since the morphological classification has no clinical or prognostic relevance. It instead, advocates the use of the immunophenotypic classification mentioned below.

Each subtype is then further classified by determining the surface markers of the abnormal lymphocytes, called immunophenotyping. There are three main immunologic types: [[B-cell]], pre-B cell and [[T-cell]]. Subtyping helps determine the prognosis and most appropriate treatment in treating ALL.

Some cytogenetic subtypes have a worse prognosis than others. These include:
* A translocation between [[chromosome]]s 9 and 22, known as the [[Philadelphia chromosome]], 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 favourable.

==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]], [[steroid]]s, [[radiation therapy]], intensive combined treatments (including [[bone marrow transplant|bone marrow]] or stem cell transplants), and growth factors. 

===Chemotherapy===
Chemotherapy is the initial treatment of choice.  Most ALL patients end up receiving a combination of different treatments. There are no surgical options, due to the body-wide distribution of the malignant cells.

As the [[chemotherapy regimens]] can be intensive and protracted (often about 2 years in case of the GMALL or UKALL protocols; about 3 years for males on COG protocols), 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 pot 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 therapy is used on painful bony areas, in high disease burden, 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.

==Epidemiology==
ALL accounts for approximately 80 per cent of all childhood [[leukemia]] cases, 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 Syndrome, Fanconi's anemia, Bloom's syndrome, ataxia-telangiectasia, X-linked agammaglobulinemia and severe combined immunodeficiency.

==Prognosis==
Advancements in medical [[Medical technology|technology]] and [[research]] over the past four decades in the treatment of ALL has improved the overall prognosis significantly from a zero to 20-75 percent survival rate, largely due to the continuous development of [[clinical trial]]s and improvements in [[bone marrow transplant]]ation (BMT) and stem cell transplanation (SCT) technology.   

It is worth noting that advances of the last years, both through matching the best treatment to the genetic characteristics of the blast cells and through the availability of new drugs, are not fully reflected in statistics that usually refer to five-year survival rates.  Patients (and other readers of this article) should not be discouraged by general treatment success rates because individual results vary substantially depending on the large number of variables that affect treatment outcomes.  Even the Philadelphia Chromosome mentioned above can now be treated with several drugs, the most famous of which is Gleevec.   For patients, like in other cancers, the success rate is either 100% or zero, rendering overall statistical rates meaningless.  Patients can affect their outcome through their choice of experienced doctors and major medical centers. 
However the prognosis for ALL differs between individuals depending on a wide variety of factors:
* Sex: females tend to fare better than males.
* Ethnicity: [[Whites|Caucasians]] are more likely to develop acute leukemia than [[African American|African-Americans]], [[Asian American|Asians]] and [[Hispanic American|Hispanics]] and tend to have a better prognosis than non-Caucasians.
* Age at diagnosis: children between 1-10 years of age are most likely to be cured.
* White blood cell count at diagnosis of less than 50,000
* Whether the cancer has spread to the [[brain]] or [[spinal cord]]
* Morphological, immunological, and genetic subtypes
* Response of patient to initial treatment
* [[Genetic disorder]]s such as [[Down syndrome|Down's Syndrome]]

==External links==
* [http://www.leukemia-lymphoma.org The Leukemia & Lymphoma Society] - provides information about leukemia and related diseases, updates on current [[clinical trial]]s, and discussion forums.
* [http://www.cancerresearchuk.org Cancer Research UK] - trains and supports scientists for cancer research, offers regional news about current research, and provides ways that individuals can become involved.
* [http://spade39.ncl.ac.uk/ccw/ Children's Cancer Web] - a directory of children's cancer-related resources.
*[http://www.kids-cancer.org/wilms.htm The Centre for Cancer and Blood Disorders] at Sydney Children’s Hospital provides information on cancers in children and adolescents, including Acute lymphoblastic leukemia.
* [http://www.childcancerresearch.com.au/ Children's Leukemia and Cancer Research Foundation (INC)] (Australia) - provides funding for children's leukemia, especially to the Princess Margaret Hospital for Children [http://www.pmh.wa.gov.au/].
*[http://www.acor.org/ped-onc/diseases/ALL.html Ped-Onc Resource Center] - provides information on childhood ALL, 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.
* [http://leukemia.acor.org/ Association of Cancer Online Resource (ACOR) Leukemia Links] - provides links to information on leukemia, including ALL, primarily in adults.

{{Hematology}}

[[Category:Blood disorders]]
[[Category:Hematology]]
[[Category:Types of cancer]]

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