Acute lymphocytic leukemia (ALL(

Leukemia is a malignant disease of hematopoietic tissue characterized by the
accumulation of abnormal white cells in the bone marrow leading to bone
marrow failure, a raised circulating white cell count (leukocytosis) and
infiltrate organs (e.g liver, spleen, lymph nodes, brain)
Etiology and Risk Factors
The etiology of leukemia is unknown.
A. Oncogene mutation
1. Chromosomal abnormality
2. Gene rearrangement
B. Host factors.
C. Environmental factors
- It can be divided into 2 groups depending on the clinical behaviour of the
- Acute Leukaemia:
 Progresses quickly (presents in days - weeks and patient dies in
weeks – months without therapy).
 Characterized by the proliferation of undifferentiated cells in the
bone marrow
- Chronic Leukaemia:
 Slower progression (presents in months – years and patient dies in
months – years without therapy).
 Uncontrolled expansion of mature cells
- These can be further classified depending on the particular malignant white
cell: myeloid (marrow cell destined to make red cells, granulocytes and
platelets) and lymphoid (destined to make B and T lymphocytes).
This gives four main diseases:
Acute myeloid leukaemia (AML)
Acute lymphoblastic leukaemia (ALL)
Chronic myeloid leukaemia (CML)
Chronic lymphatic leukaemia (CLL)
slower progression
Hemopoiesis and Lymphopoiesis
 Pluripotent Stem Cells
 Most primitive cells
 Mature blood cells and lymphocytes develop from
pluripotent cells
– The pluripotent stem cells differentiate into either
 myeloid stem cells or lymphoid stem cells
– The myloid stem cells produce progenitors
 Progenitors lead to the production of mature functional
Leukemia Development
– Uncontrolled and accelerated production of progenitors which results
in incomplete or defective cell maturation
– Acute leukemia- rapid proliferation of primitive, undifferentiated stem
– Chronic leukemia- differentiated defective mature cells
Leukemia Symptoms
Symptoms result from interference with normal processes
The leukemic cells accumulate in the bone marrow
Hampers the production of normal blood cells
Results in decreased counts
Anemia, thrombocytopenia, neutropenia
Acute lymphocytic leukemia (ALL(
 ALL is typical childhood leukemia that most often occurs between the
ages of 2 and 5.
 Malignant lymphocytes replace the blood-forming bone marrow and
infiltrate the lymph nodes, spleen, liver and other organs.
 Most children do not survive very long without therapy. However,
many patients go into remission after undergoing different forms of
cytostatic therapy. Patients with childhood ALL have great potential to
be cured.
Clinical picture:
 The disease begins suddenly and rapidly increases in severity.
 The symptoms result from infiltration of the bone marrow leading to
neutropenia, anemia and thombocytopenia. Weakness, pallor, fevers
and bleeding occur.
 Additional symptoms include irritability, loss of weight and appetite, as
well as aching of the joints. Headaches and vomiting can be signs of
involvement of the central nervous system.
 Enlargement of the spleen, liver and lymph nodes is usually present.
 WBC vary, in about 50% of cases, leukocytosis with distinct
neutropenia exists.
 Anemia, thrombocytopenia.
 The blasts are usually small and have high nuclear-cytoplasmatic ratio,
faint chromatin, and indistinct nucleoli.
 Normochromic, normocytic anemia is seen.
 Immunophenotyping: morphological evaluation, special stains, electron
microscopy, and surface markers
Bone marrow: A bone marrow biopsy is done to make a definitive
 The bone marrow is normally hypercellular with an infiltration by
leukemic blast cells of over 30%.
 The lymphoblasts stain negatively for peroxidase and Sudan-black but
are terminal deoxynucleotidyl transferase positive.
 30% of pts have low serum levels of immunoglobulins (proteins that
can act as antibodies)
 Like the acute myelocytic leukemias the acute lymphocytic leukemias
are classified based on their morphology by FAB (F=French,
A=American, B=British). There are 3 types:
L1: Most frequent form found in children. The morphology of the blasts is
uniform and large.
L2: Most frequent form found in adults. The morphology of the blasts can
L3: Rarest form, also call the Burkitt type.
Treatment Techniques
 Used alone or in combination– Radiation Therapy (RT)- various techniques
– Chemotherapy– Bone Marrow Transplant-no longer experimental for certain
diagnosis and is the of choice for ALL, AML, and CML
Acute myelocytic leukemia (AML):
 AML most often occurs in adults, most frequency over age 50.
 Without therapy most patients only survive for a few months.
 By implementing different myelosuppressive chemotherapies, high
rates of remission can be achieved.
Staging and Classification:
o FAB system is used for morphological evaluation
o Maturation states are categorized from M0 (undifferentiated) to
M7 (megakaryocyte)
Clinical picture:
 The symptoms are characterized by failure of hematopoiesis. Pallor,
fatigue and weakness are due to anemia. Bruises and petechiae are due
to thrombocytopenia. Neutropenia leads to infections and fever.
Enlargement of the liver, spleen and lymph nodes occurs in about half
of the patients.
 Normochromic, normocytic anemia always exists.
 Thrombocytopenia, the platelets are usually moderately decreased.
The leukocyte count can vary between <1x109/L and >100x109/L.
 The presence of blasts in peripheral blood is diagnostic.
 Azurophilic granules indicate the presence of a myelocytic leukemia.
 Presence of Auer rods (structures found in myeloblasts, myelocytes,
and monoblasts)
 Chromosomal abnormalities-30-50% of AML pt
Bone marrow:
– Bone marrow aspiration biopsy for a definitive diagnosis
– The bone marrow is typically hypercellular. If 30% blast cells are
present, acute leukemia is confirmed
– Special staining with peroxidase is used to determine whether blasts
are myeloid in origin or lymphoid.
– Immunophenotyping as in ALL establishes diagnosis in 90% of cases
Treatment techniques
o a combination of chemo, radiation therapy, and bone marrow
Chronic lymphocytic leukemia (CLL)
– CLL constitutes 25% of all leukemias.
– CLL almost exclusively occurs in older age patients and rarely occurs
before age 40.
– The diagnosis is often found by chance with routine blood counts, in
asymptomatic patients.
– CLL progresses slowly and therapy is only given once symptoms
Clinical presentation
– Minor findings on blood tests
– Lymphocyte counts > 10,000/ mm
– Often asymptomatic
– Night sweats, fatigue, fever, weight loss
– Lymphadenopathy may be present, spleen almost always
– Uncomfortable neck masses are common at later stages
– Classified as B-cell or T-cell
– Anemia and thrombocytopenia are signs of increasing bone
marrow infiltration.
– 50% of patients have chromosome abnormalities
– A persistent increase of small, mature, B-lymphocytes greater
than 150 x 109/L. accompanies CLL.
– Crushed lymphocytes, or smudge cells, seen in the blood film
are typical for CLL.
Bone marrow:
– In the bone marrow an infiltration of small lymphocytes of over 40%
exists. Normal hematopoiesis is more or less replaced.
Chronic myelocytic leukemia
– CML most often occurs in older adults (median age around 50).
– In over 90% of the cases a chromosomal translocation (9;22) is found.
This cytogenetic abnormality is also known as the Philadelphia
Clinical picture:
– Symptoms of CML are fatigue, night sweats, loss of weight and
abdominal discomfort due to splenomegaly. Occasionally, bruises also
o Three distinct stages, chronic (stable), accelerated phase, and
acute phase (blast crisis)
– The diagnosis is difficult, insidious, found by accident
– CML often has very high leukocyte counts with values up to 300
x109/ L.
– In peripheral blood, all stages of granulopoiesis are represented.
– Eosinophils and basophils are also typically increased.
– Thrombocytosis is frequent.
– Anemia usually first develops with very high leukocyte counts.
– The leukocyte alkaline phosphatase (LAP) score in peripheral blood is
very low or absent.
– Most important–presence of Philadelphia chromosome
Bone marrow
– The bone marrow is hypercellular with a clear dominance of
– The number of megakaryocytes is also increased.
– The same is true for basophils and eosinophils.
– Sea-blue histiocytes can occur in CML, but they are also observed in
other diseases.
Treatment Techniques
– Radiation
– Chemotherapy