LEUKEMIA

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Staging

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Staging

Most cancer patients are assigned a clinical "stage" after undergoing a diagnostic work-up. American physicians often use the four-stage TNM system - a classification system developed and recently revised by the American Joint Committee on Cancer (AJCC) and the Union Internationale Contre le Cancer (UICC; International Union Against Cancer). According to this system, staging is based on the size of the tumor and how far it has spread from its original location in the body.

Because leukemia starts in the bone marrow and often has spread to other organs by the time it is detected, there is no need for traditional staging. Instead, physicians rely upon cytologic (cellular) classification systems to identify the type and subtype of leukemia. Cell classification systems, in turn, help to predict the prognosis, or outcome, of specific forms of leukemia and the likely response to treatment.

The most popular classification method for acute leukemia is the French-American-British (FAB) system. According to FAB classification, acute leukemia is divided into eight subtypes of acute myelogenous leukemia (AML) and three subtypes of acute lymphocytic leukemia (ALL) (see Types of Leukemia). FAB originally was based upon the microscopic appearance of leukemia cells; however, in recent years, researchers have discovered that cellular characteristics such as genetic make-up and numbers of specific cell types help to classify leukemia and predict its outcome.

Chronic lymphocytic leukemia (CLL) is classified by one of two cytologic staging systems, which known as Rai Classification and Binet Staging, respectively.

Rai Classification
Rai Classificationseparates chronic lymphocytic leukemia into low-, intermediate-, and high-risk categories, which correspond with stages 0, I & II, and III & IV, respectively:

  • Rai Stage 0 patients are low risk and have lymphocytosis, a high lymphocyte count defined as more than 15,000 lymphocytes per cubic millimeter (> 15,000 /mm3).
  • Rai Stage I patients are intermediate risk and have lymphocytosis plus enlarged lymph nodes (lymphadenopathy).
  • Rai Stage II patients are also intermediate risk but have lymphocytosis plus an enlarged liver (hepatomegaly) or enlarged spleen (splenomegaly), with or without lymphadenopathy.
  • Rai Stage III patients are high-risk and have lymphocytosis plus anemia, a low red blood cell count (hemoglobin < 11 g/dL), with or without lymphadenopathy, hepatomegaly, or splenomegaly.
  • Rai Stage IV patients are also high-risk but have lymphocytosis plus thrombocytopenia, a low number of blood platelets (< 100 ´ 103 /µL).
Binet Staging
Binet Staging classifies CLL according to the number of lymphoid tissues that are involved (i.e., the spleen and the lymph nodes of the neck, groin, and underarms), as well as the presence of low red blood cell count (anemia) or low number of blood platelets (thrombocytopenia):
  • Binet Stage A patients have fewer than three areas of enlarged lymphoid tissue. Enlarged lymph nodes of the neck, underarms, and groin, as well as the spleen, are each considered "one group," whether unilateral (one-sided) or bilateral (on both sides).
  • Binet Stage B patients have more than three areas of enlarged lymphoid tissue
  • Binet Stage C patients have anemia plus thrombocytopenia (platelets <100 ´ 103 /µL).
One major advantage of the Binet system is its ability to highlight the splenic form of CLL, which may have a better prognosis than when classified by the Rai system.

Table 3: Clinical Features in Rai & Binet Staging

STAGE LYMPHO-
CYTOSIS
LYMPHA-
DENOPATHY
HEPATOMEGALY or SPLENOMEGALY HEMO-
GLOBIN (g/dL)
PLATE-
LETS
(x 103/µL)
RAI
0 YES NO NO greater than 11 greater than 100
I YES YES NO greater than 11 << div> greater than 100
II YES YES/NO YES greater than 11 greater than 100
III YES YES/NO YES/NO < div> less than 11 greater than 100
IV YES < div> YES/NO YES/NO ANY less than 100
BINET
A YES YES / NO(less than 3 nodal groups positive) YES / NO greater than 10 greater than 100
B YES YES / NO(<3 nodal groups positive) YES / NO less than 10 greater than 100
C YES YES / NO YES / NO less than 10 less than 100

Lymphocytosis = high numbers of lymphocytes
Lymphadenopathy = lymphatic disease
Hepatomegaly = enlarged liver
Splenomegaly = enlarged spleen

There are a few more types and subtypes of chronic leukemia, the most notable of which are hairy cell leukemia, prolymphocytic leukemia, T-cell chronic lymphocytic leukemia, and chronic myelomonocytic leukemia.

Hairy cell leukemia (HCL), like CLL, is a slow-growing lymphocytic cancer. It is distinguished by its appearance under the microscope, because the lymphocytes have many fine, "hairy" projections from their surfaces. HCL is typically a disease of middle-aged males. Most individuals report nonspecific symptoms that are partially caused by anemia. Yet HCL differs from CLL with respect management.

Both prolymphocytic leukemia (PLL) and T-cell chronic lymphocytic leukemia (T-CLL; also known as large granular lymphocyte leukemia, or LGL) are unusual forms of CLL. They are very rare, and account for only about 1% of all CLL cases. PLL, like CLL, is mostly seen in men. More than half of the cells in PLL are prolymphocytes, which are larger than CLL cells and have less condensed genetic material. T-CLL results from the reproduction of cells that resemble normal large granular lymphocytes. PLL and T-CLL are more aggressive in nature than other forms of CLL, and they are less likely to respond to treatment.

There is some dispute about the categorization of chronic myelomonocytic leukemia (CMML). Some groups consider CMML to be a "pre-leukemia," or "myelodysplastic syndrome," rather than a malignant disorder. It is a disease that is found in older individuals. Patients may be asymptomatic (without symptoms) and be diagnosed accidentally, or they may have symptoms of tiredness, bruising and/or abdominal discomfort from an enlarged spleen. CMML may be inactive, or it may progress slowly over months and years. CMML eventually transforms into an acute, usually fatal form of leukemia.

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