Leukemia

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Neoplastic diseases of white blood cells are divided into four main groups:
Malignant lymphomas are diseases of tissue-based and nodal lymphocytes.
Leukaemias and myeloproliferative disorders are malignant neoplasms derived from cells of the bone
marrow. Neoplastic cells may circulate in the blood, secondarily colonizing other tissues.
Plasma cell tumours are neoplasms derived from terminally differentiated B-cells derived from bone
marrow.
Histiocytoses are neoplasms derived from histiocytic cells, particularly Langerhans' cells.

LEUKAEMIA

Leukaemias are the most common neoplastic disease of white cells
The most common neoplastic disease of white cells is leukaemia, the incidence of which is 9 per 100,000.
The disease may be acute or chronic.
The general characteristics of leukaemias include: neoplastic proliferation of marrow cells, forming one or more cell lines; circulation of neoplastic cells in peripheral blood in most but not all cases; and suppression of other marrow elements, leading to symptoms due to lack of normal red cells, white cells and platelets.

Acute leukaemias are characterized by proliferation of immature cells known as blast cells.
Typically there is rapid progression of disease which, without treatment, is fatal in a short period of time.

Chronic leukaemias are characterized by proliferation of more mature cells. Typically there
is slow progression of disease, but this type may also transform into a more aggressive pattern.
Common to all leukaemias is expansion of the bone marrow and infiltration by neoplastic white cells.

In leukaemia, neoplastic cells replace normal red (haemopoietic) and yellow (inactive) bone marrow.
Vertebrae, ribs and long bones show diffuse replacement of marrow space by pale , cellular, neoplastic cells.

Histologically, the normal marrow is replaced by abnormal,monotonous, leukaemic cells.
Acute leukaemias are divided into those derived from lymphoid cells, acute lymphoblastic leukaemia (ALL),
and those derived from myeloid, monocytic, erythroid, and megakaryocytic cells, which are grouped as the
acute non-lymphoblastic leukaemias (ANLL).

In acute leukaemia, replacement of the bone marrow by blast cells causes anaemia due to loss of red cells,
susceptibility to infection due to loss of normal white cells, and susceptibility to bleeding due
to loss of platelets.
Patients develop fever, malaise, bleeding (petechial haemorrhages), and mouth ulcers due
to infections. The peripheral blood shows an increased white cell count (including blast cells)
in about 50% of cases; importantly, in many cases the white cell count may be normal or reduced.
The diagnosis of acute leukaemia is based on examination of bone marrow aspirate.
Acute leukaemias frequently show infiltration of many organs, especially
the brain and gonads. Splenomegaly and lymphadenopathy are not usually prominent,
except in some cases of acute lymphoblastic leukaemia.
Marrow in acute leukaemia is extensively replaced by neoplastic cells, which efface
normal marrow. There is hypercellularity, large numbers of blast cells characterized
by large nuclei and mitoses, and reduced amounts of normal haemopoietic elements.
Acute lymphoblastic leukaemia (ALL) most commonly affects children, only rarely occurring
in young adults. The prognosis is related to the type of leukaemia as defined by the FAB classification.
ALL is classified by morphology into groups L1-L3. Using immunochemistry, the nature
of the cells can be further defined, and this is related to prognosis. Patients with
L3 morphology, a high white count, and mature B-cell type have worst prognosis.

Acute non-lymphoblastic leukaemia (ANLL) is most commonly seen in adults and encompasses
several different types of disease as categorized by the FAB classification.
M1-M3 are myeloblastic in type.
They are separated according to the degree of differentiation, which is assessed by
cytochemical detection of myelocyte markers.
M5 is composed of monoblasts, and M4 is an overlap between myeloblastic and monoblastic types.
Although M6 is termed 'erythroblastic leukaemia' both myeloblastic and erythroblastic cells are seen.


Chronic leukaemias are mainly seen in adults over the age of 40 years, but can develop in childhood.
Accounting for about 30% of all cases of leukaemia, {\B chronic lymphocytic leukaemia
(CLL) is mainly seen in patients over the age of 50 years. It is characterized by
neoplastic proliferation of small mature lymphocytes.
The vast majority of cases of CLL cases are of the B-cell type, with only
about 5% of cases of T-cell type. The bone marrow is infiltrated by abnormal clusters of lymphocytes,
initially sparing normal haemopoietic elements, but later effacing the marrow. The peripheral blood
contains large numbers of circulating abnormal lymphoid cells. Lymphadenopathy is common and is
often a presenting feature of disease; affected nodes show the same histological picture as that
of small-cell diffuse lymphocytic lymphoma.

Splenomegaly is also commonly seen.
Autoimmune haemolytic anaemia and thrombocytopenia are present in about 10% of cases, and
a paraproteinaemia is found in about 5% of cases.
Hairy-cell leukaemia is a form of B-cell leukaemia in which cells have many fine surface
projections. Typically, there is diffuse marrow involvement and the spleen is very large with
hypersplenism and pancytopenia, but lymphadenopathy is uncommon. Increase in circulating white cells
is not marked. As several of the clinical problems are derived from hypersplenism, splenectomy may
alleviate many of the symptoms. Many cases also respond to interferon treatment.
The bone marrow is replaced by small mature lymphoid cells. In early stages of disease
this replacement is focal, allowing normal platelet and red-cell production.

Chronic myeloid (granulocytic) leukaemia (CGL) is also considered as one of the
myeloproliferative disorders. It is most common in adults between 30 and 40 years,
accounting for about 20% of all cases of leukaemia.

Affected patients develop hepatosplenomegaly, with massive enlargement of the spleen due to
infiltration by leukaemic cells. The peripheral blood shows a leukocytosis with an excess of neutrophils,
myelocytes and metamyelocytes. There is usually a moderate anaemia, but thrombocytopenia
is not marked. Basophils may be increased in number.
The bone marrow shows increased cellularity, with marrow replaced by neutrophil precursors.
The natural history of the disease is for transformation into an acute leukaemia:
75% transform into acute myeloblastic leukaemia, and 25% into acute lymphoblastic leukaemia.
The onset of transformation is usually associated with the development of increasing numbers of
blast cells in the marrow, together with increasing anaemia and thrombocytopenia, but in some patients
is abrupt. Most patients die within 6 months of blast transformation.
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