9 leukaemias

Prof. Dhammika M. Dissanayake

Consultant haematologist

The leukaemias

Abnormal proliferation of haemopoietic cells

Causes progressively increasing infiltration of bone marrow or lymphatic tissues.

Aetiology Leukaemic cell population can have one or more

different pathways of differentiation. Critical step is is the alteration of the structure of of

DNA in the nucleus. In humans chromosomal abnormalities are very

common in leukaemias. Associated aetiological factors are

RadiationChemicalsVirusesGenetic factors

4

Aetiology – Genetic Abnormalities

Downs’s Fancony’s anaemia

– Chemical agents & Chemotherapeutic agents Hydroxyurea Chorambucil

– Infections HTLV1 : east asian countries EBV: Burkits lymphoma / ALL HIV

– Radiation – Immunological deficiencies

Genetic abnormalitiesCertain genetic abnormalities predisposes to

leukaemias– Fancony’s anaemia – Down’s syndrome

Many leukaemias are associated with cytogenetic abnormalities & some of these are even used in – Diagnosis & classification

Philadelphia chromosome: t(9:22) Promyelocytic leukaemia t (15: 17)

– Assess prognosis

Infections associated with leukaemia/lymphoma

Virus – HTLV: – EBV– HHV-8– HIV-1

Bacterial– Helicobacter pylori

Protozoal– malaria

Classification of leukaemiaAcute Chronic

Agressive clinical course

Dominant cell is an immature blast cell

Classified to lymphoblastic and myeloblasti c

Chronic clinical course

Dominant cell is more mature

Classified to lymphatic and myeloid

Acute leukaemia

Clinical features

Suppression of normal bone marrow elements – Anaemia – Thrombocytopenia : petichae, purpura, bleeding gums– Granulocytopenia : fever, infections, sore throat

Organomegaly– Lymphadenopathy: often in ALL– Hepatosplenomegaly: Often in AML– Gum hypertrophy/skin infiltrates

Acute Lymphoblastic leukaemiasT cell/ B cell

FAB classification

L1: small round blast

L2: pleomorphic large blasts

L3: very large blasts with vacoalated

cytoplasm

Acute Myeloid Leukaemia FAB classification

M1-no differentiation

M2-minimal differentiation

M3-promyelocytic

M4-myelomonocytic

M5-monocytic

M6-erythroid

M7-megakaryocytic

AML

Clinical features Occur at any age Onset Abrupt Clinical features are often due to:

1. Bone marrow infiltration due to blast cell proliferation causing

Anaemia: Pallor, tiredness

Thrombocytopenia: gum bleeding, purpura

Neutropenia: Infections, fever, pharyngitis

2.Organomegaly: ALL-lymphadenopathy

AML-hepato/splenomegaly

Gum hypertrophy-M4

3.Bone pain/joint pain

Laboratory investigations

Full blood count:

WBC: increased

DC: neutropenia

blast cells

Platelet count: low

Red cell count: low

Hb:low Blood picture

Bone marrow biopsy

Hypercellular fragments

Erythropoiesis: Granulopoiesis: Megakaryocytes: Blast cells more

than 30%

Differential diagnosis: clinically Other causes of ulceration of mouth Infectious mononucleosis:

sore throatlymphadenopathysplenomegaly

Joint and bone pain:Acute osteomyelitisRheumatic fever

Fever and malaise

Similar blood pictures

Leukaemoid blood picturePancytopeniaMyelodysplastic syndromes

Treatment

General considerationsSpecific therapeutic agentsTherapy in individual patientsSymptomatic and supportive therapyBone marrow transplantation

Specific therapeutic agents in ALL

Remission InductionConsolidationProphylactic treatmentMaintainance therapyAMLRemission inductionMaintainance therapy

Chronic leukaemias

CLL CML

Chronic lymphocytic leukaemia

Clonal proliferation of mature lymphocytesDisease of old age (over the age of 40yrs)Males affected twice the femalesOnset insidiousVery often the incidental finding.Without treatment 10 yrsOften patients die of some other reason

Clinical features

Enlargement of superficial lymph nodesAnaemia: AIHAConstitutional symptomsSplenomegalyRespiratory and other infectionsLesions of the skin

Laboratory investigations WBC/DC: absolute

lymphocyte count over 10x109/l

Blood picture

Smudge cells

Small lymphocytosis Bone marrow biopsy Prognosis depend on the

stage of the disease

Chronic myeloid leukaemia

Due to proliferation of more mature myeloid cells (myelocyte is the most prominent cell.

Associated with Philadelphia chromosome (9/22 translocation).

Triphasic disease: Chronic phaseAccelerated phaseBlastic phase

Clinical features

A disease of middle life, rare under the age of 20yrs.

Onset insidiousPresenting symptoms:

AnaemiaConstitutional symptoms: weight loss,

night sweatsSplenomegaly

Laboratory investigations

NeutrophilsStab form

myelocyte

promyelocyte

Blasts

Eosinophils

Basophils

Laboratory investigation

WBC/DC:

Very high Bone marrow:

Useful in staging

Treatment Chronic phase:

Chemotherapy: BusulphanAlpha interferon:Imanitib

Accelerated and blastic phase : more intensive

treatment Leucapharesis Bone marrow transplantation

Bone marrow transplantation

Autologous transplantationAllogenic bone marrow transplantationStem cell harvesting methods

1. Bone marrow stem cells

2. Peripheral blood stem cell harvesting

MCQs

Which ONE of these inherited conditions is associated with an increased risk of

haematological malignancy?

A Cystic fibrosisB Thalassaemia major C Down's syndromeD Spinocerebellar degeneration E Hereditary spherocytosis

C

Which one of the following infection is not associated with

acute lymphoblastic leukaemia ? HIV-1EBV Human Herpes virus -8HTLVCytomegalo virus

Which of the following is /are true /false of Philadelphia

chromosome

Translocation is between chromosome 8 & 22

Seen in chronic lymphocytic leukaemia Seen in chronic myeloid leukaemia BCR and ABL genes juxtapositioned Present only in myeloblasts cells