3 Pathophysiology

The etiology of Acute Lymphocytic Leukaemia remains uncertain although some doctors believe that ALL develops from a combination of genetic and environmental factors. However, there is no definite way of determining the cause of leukaemia.

Scientific research has shown that all malignancies are due to subtle or less subtle changes in DNA that lead to unimpaired cell division and breakdown of inhibitory processes. In leukaemias, including ALL, chromosomal translocations occur regularly. It is thought that most translocations occur before birth during foetal development. These translocations may trigger oncogenes to "turn on", causing unregulated mitosis where cells divide too quickly and abnormally, resulting in leukaemia. 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 radiation (such as that of nuclear reactors and the atomic bombs in Hiroshima, Japan 1945) increases the risk of developing acute leukaemia. There has also been inconclusive evidence suggesting that electromagnetic fields or chemicals such as benzene have an increased risk of developing acute leukaemia.

4 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 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 vacuoles (bubble-like features)

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
• 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 chromosomes 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.

5 Treatment

The earlier acute lymphocytic leukaemia 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 leukaemia can include chemotherapy, steroids, radiation therapy, intensive combined treatments (including bone marrow or stem cell transplants), and growth factors.

5.1 Chemotherapy

Chemotherapy will usually be the treatment of choice but 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, many patients have an intravenous catheter inserted into a large vein (termed a central line or a Hickman line ).

5.2 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).

6 Epidemiology

ALL accounts for approximately 80 per cent of all childhood leukaemia 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.

7 Prognosis

Advancements in medical 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 trials and improvements in bone marrow transplantation (BMT) and stem cell transplanation (SCT) technology.

However the prognosis for ALL differs between individuals depending on a wide variety of factors:

• Sex: females tend to fair better than males.
• Ethnicity: Caucasians are more likely to develop acute leukaemia than African-Americans, Asians and 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.
• Lymphoblast cell count at diagnosis
• Whether the cancer has spread to the brain or spinal cord
• Morphological, immunological, and genetic subtypes
• Response of patient to initial treatment
• Genetic disorders such as Down's Syndrome

8 External links

• The Leukemia & Lymphoma Society - provides information about leukaemia and related diseases, updates on current clinical trials, and discussion forums.
• Cancer Research UK - trains and supports scientists for cancer research, offers regional news about current research, and provides ways that individuals can become involved.
• Children's Cancer Web - a directory of children's cancer-related resources.
• Childrens Leukaemia and Cancer Research Foundation (INC) (Australia) - provides funding for children's leukaemia, especially to the Princess Margaret Hospital for Children [1].

Health science - Medicine - Hematology

Hematological malignancy and White blood cells

Lymphoma ( Hodgkin's disease, NHL) - Leukemia ( ALL, AML, CLL, CML) - Multiple myeloma - MDS - Myelofibrosis - Myeloproliferative disease ( Thrombocytosis, Polycythemia) - Neutropenia

Red blood cells

Anemia - Hemochromatosis - Sickle-cell anemia - Thalassemia - other hemoglobinopathies

Coagulation and Platelets

Thrombosis - Deep venous thrombosis - Pulmonary embolism - Hemophilia - ITP - TTP

Hematology Oncology

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