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Leukocytosis = increased WBC countNeutropenia = reduced neutrophills

Leukemia

- Hematological malignancy- Many forms

- All cause excess production of abnormal WBC- 4 groups of leukemia

1. acute myeloid leukemia (AML)2. acute lymphoblastic leukemia (ALL)

3. Chronic myeloid leukemia (CML)4. Chronic lymphoblastic leukemia (CLL)

Epidemiology- 5% of all cancers

- CLL most common

- CLL occurs in 90% of patients > 50-60 years(men > women)

- CML: occurs in middle aged (40-50) and can occur

in young people.- Acute leukemia is rare (AML more common than

ALL)

- AML risk rises with age- ALL occurs mostly in childhood (3-5 years) and

is most common childhood cancer

Aetiology

Radiation

Exposure to chemicals and cytotoxics:- risk for patients treated with cytotoxics for other

cancers (especially alkylating agents likecylcophosphamide)

- radiotherapy- Paints, insecticides, benzenes

Viruses: No link but there is in animals

Genetic factors (Downs syndrome)

Hematological disorders

- Increase risk of AML by myeloprofilerativedisorders, aplastic anaemia etc.

Pathophysiology

- Acute leukemia: accumulation of immature bloodcells (functionally useless) in bone marrow and

peripheral blood.

- Chronic leukemia: accumulation of mature bloodcells in bone marrow and tissue (variable function)

- Normal haemopoesis process is altered

- Cell transformation to malignancy occurs in asingle cell

- This occurs in pluripotent stem cell level but mayoccur in commited stem cell level (limited

differentiation)- Accumulation of cells leads to bone marrow failure

Pluripotent stem cell

Committed myeloid com. cells lymphoid com. cells

stem cells

myeoblasts lymphoblasts

Peripheral

blood granulocytes lymphocytes

Acute leukemia- normal bone marrow replaced by malignant immature

blast cells

- these blast cells can be from myeloid series (AML) orlymphoid (ALL)

- bone marrow elements are replaced with blasts and thisleads to appearance of blast cells in peripheral

circulation and showing pancytopenia- especially in ALL: blasts can go to lymph nodes and

infiltrate tissues

ALL

- cell lines affected are those of lymphoid cells which

differentiate into T and B cells.- Predominance of pre-lymphocyte cells =

microlymphoblasts- especially in ALL: blasts can go to lymph nodes and

infiltrate tissues- most common malignancy of children, rarely affects

>15yrs

Classification of ALL- Classified immunologicaly based on presence of B or T

cells- Common ALL: possess the common ALL antigen (c-

ALL)- T cell and B cell types (T/ B-ALL)

- Null (non-B, T and c-ALL)- C-ALL has best prognosis and B-ALL has worst

prognosis

AML

- affects myeloid cell lines

- depends on where in differentiation cells are- mostly there are myeloblasts affecting the production of

granulocytes cells- it is mostly a disease of adults

Classification of AML

- depends on degree of maturation and predominantdifferentiation

- M0 = AML with no differentiation- M1-2 = granulocytic differentiation

- M4 = mixed granulo and monocytic differentiation- M5 = monocytic

- M6 = erythroid- M7 = megakaryocytic

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Chronic leukemia Lymphocytic (CLL):- many mature long-lived lymphocytes which

accumulate in peripheral blood and causeleucocytosis

- Most show B-cell maturation but some show T-cell- Lymphocytes go to lymphnodes and spread to liver,

spleen which become enlarged

- Bone marrow is then infiltrated

- Cells appear normal but are unable to differentiateinto plasma cells or secrete immunoglobulins

Myelocytic (CML)

- Predominance of granulocytic cells in blood , bone

marrow, spleen and other organs- Chronic granulocytic leukemia (CGL) is most

common

- Others include chronic Philadelphia negative CGL,neutrophillic and eosinophillic leukemia

Clinical Symptoms

Acute leukemia

- related to bone marrow failure

- fever, pallor, hemorrhage, anorexia, fatigue, bonepain, joint pain, abdominal pain,

lymphoadenopathy, weight loss- infection and bleeding (evident by bruising,

purpura, bleeding mucus membranes andmenorrhagia)

- effects of infiltrating organs- skin and respiratory infections

- presents with a short history- involvement of other organs is more common in

ALL (lymph nodes)

- CNS involvement cause headache, vomit andirritable behavior

- CNS involvement is rare but need prophylaxis as it

can develop- Hypermetabolism, hyperuricameia and bone pain

Chronic leukemia

- non-specific- malaise

- weight loss

- night sweat- anaemia like fatigue- SOB

- Pallor - MAIN physical sign is enlargement of spleen

(abdominal pain)- Hepatomegaly and spleenomegaly

- Unlike acute stage: rare Haemorrhage andinfections

- Patients may be Asymptomatic and disease usuallydiagnosed from blood tests

COURSE of Chronic leukemia

- Initial chronic phase (1st

phase):- last from several months 20 years

- Is phase where most people with CL are diagnosed- Symptoms are generalized and non-specific

- There is leukocytosis and 10% in peripheral blood- Lasts < 6 weeks

- Blast crisis:- resembles acute leukemia

- blasts > 30% in blood and marrow

- leukocyte levels double- doesnt respond to treatment and survival is short (3

months)

- Survival is 2-20 years

- Increased susceptibility to infection

(immunocompromised) and autoimmune disease likehaemolytic anaemia and vasculitis

- CLL is less responsive to therapy

Investigations

- examination of peripheral blood and bone marrow- In all cases serum uric acid/ urate increased

AML ALL CML

(CGL)

CLL

WBC Increasedmostly,

Increased

mostly,

Increased

100x 10^9-250x10 9/L

Increased

Differential

WBC

Myelo-blasts Lympho-

blasts

Granulocytes

(esino,meylo, basoand

neuttrophills)

Lymphocytes

10 x 10^9/L

RBC Anaemia(severe)

Anaemia(severe)

Anaemia Anaemia

Platelets reduced reduced Reduced/increased orN

Reduced

Bone

marrowaspiration

blasts blasts hypercellular Lymphocytes

Cytogenicanalysis

Abnormalities

detected

Abnormalities

detected

Presence of

Ph1

Lymph-adenopathy

occasional Common Infrequent common

Spleenenlarged

common common Usual Usual