LEUKAEMIA

DR. ASAAVA
INTRODUCTION
• Group of disorders characterized by accumulation of malignant white
cells in BM and peripheral blood
• Cause of s/s: ACCUMULATION
• Crowd out and displace BM haematopoietic cells with resultant BM
failure: anaemia, neutropenia, thrombocytopaenia
• Malignant cells infiltrate organs: liver, spleen, LN, meninges, brain,
gums, skin, testes
CLASSIFICATION
• Four types
• Rapidity of s/s onset
• Cell type
• Acute myeloid leukaemia
• Acute lymphoblastic leukaemia
• Chronic myeloid leukaemia
• Chronic lymphocytic leukaemia
ACUTE LEUKAEMIAS
• Rapid onset
• Aggressive
• Accumulation of early BM haematopoietic progenitors (blast cells) in
BM, skin, testis,
• Rapid bone marrow failure
• Diagnosis: >30% blasts in bone marrow
ACUTE LYMPHOBLASTIC LEUKAEMIA
• Accumulation of lymphoblasts in bone marrow
• Most common malignancy of childhood
• Classification:
• Morphology FAB
• Immunologic markers
• Cytochemistry
• Ig and TCR genes
• Chromosomes
ACUTE LYMPHOBLASTIC LEUKAEMIA:
FAB CLASSIFICATION
• L1: small, uniform blasts, with scant cytoplasm
• L2: intermediate sized blasts with prominent nucleoli
• L3: large, prominent nucleoli, large cells, moderate amount of
cytoplasm, vacuoles
• Additional classification
• Immunologic markers: B cells-pre B ALL, B ALL (CD19, 22, TDT, 10); T
CELL: CD3, CD7
• Cytochemistry: PAS, acid phosphatase
ACUTE LYMPHBLASTIC LEUKAEMIA:
EPIDEMIOLOGY
• Commonest form of leukaemia in children 3-7 yrs; 2nd increase in
40yrs olds
• Pre B ALL: M:F 1:1
• T cell ALL M>F
• Good prognosis: low TWBC, F>M, child>adult, <1week to clear blast
after treatment, normal cytogenetics, <4weeks to remission, absent
CNS disease, negative MRD at 1-3 months after treatment
ACUTE LYMPHOBLASTIC LEUKAEMIA:
clinical features
• Due to BM failure (leukaemic cells-blasts, accumulate in BM and
crowd out, displace normal haematopoietic cells-anaemia,
neutropaenia, thrombocytopaenia)
• Organ infiltration: CNS meningeal syndrome, hepatomegaly,
splenomegaly, LN, bone pain,
ALL: LABORATORY DIAGNOSIS
• CBC (anaemia, normal, decreased or elevated TWBC,
thrombocytopaenia)
• PBF: Blasts
• BM: HYPERCELLULAR;> 30% BLASTS
ACUTE MYELOID LEUKAEMIA
• All age groups
• Most common leukaemia in adults; in childhood 10-15%
• Primary AML occurs de novo; secondary AML occurs after
chemotherapy; MDS; each has distinct genetic markers and different
prognosis
• Influence on prognosis: cytogenetic abnormality; initial response to
treatment
• CF: anaemia, thrombocytopaenia, in AML M3 thrombocytopaenia and
DIC; tumour cells infiltrate tissue and organs-gum hypertrophy, skin,
CNS disease in M4 and M5 variants
ACUTE MYELOID LEUKAEMIA
• FAB morphologic classification with differentiation
• Cytochemistry: PAS, MPO, Sudan black, non-specific esterase
• Immunophenotype: TdT –ve, CD13 +ve, CD33+ve
• Chromosomal abnormalities: confer favourable and unfavourable
prognosis; Favourable(t(17;17), t(8;21), inv(16) and unfavourable(del
chromosome 5 or 7, Flt-3 mutation,
• Lab investigations
• Fbc, pbf, bma cytogenetics
CHRONIC LEUKAEMIA
• Slower progression; difficult to treat
• Classification: myeloid/lymphoid
CHRONIC MYELOID LEUKAEMIA
• Further classification by Philadelphia chromosome and predominant
cells
• Five sub-types:
• CML Ph+ve
• CML Ph-ve
• Juvenile CML
• Chronic myelomonocytic leukaemia
• Eosinophilic leukaemia
CHRONIC MYELOID LEUKAEMIA
• Philadelphia chromosome positive or negative (atypical)
• Clonal disorder of pluripotent stem cells
• 15% of leukaemias
• Any age
• T(9;22) translocation between chromosomes 9 and 22; part of Abelson
protro-oncogene ABL on chromosome 9 is translocated/moved to
chromosome 22 and part of chromosome 22 is moved to chromosome 9; the
abnormal chromosome 22 is the Philadelphia chromosome that now codes
for abnormal fusion protein that has excess tyrosine kinase activity that
results in excess cell division
• Philadelphia chromosome also found in some ALL
CHRONIC MYELOID LEUKAEMIA
• Clinical features is due to increase in total myeloid mass
• M:F 1.4:1;
• 40-60 yr olds; can occur in children and neonates and very old
• No predisposing factors; increased rate in radiation
• Weight loss:hypermetabolism
• Splenomegaly
• Anaemia
• Bleeding due to abnormal platelet function
• Hyperuricaemia: gout, renal impairement
CHRONIC MYELOID LEUKAEMIA:
LABORATORY FEATURES
• Leucocytosis: >50x109/L at time >500x109/L
• Basophilia
• Platelets: normal, increased, low
• Increased serum Vitamin B12
• NAP score: low
• PBF: complete spectrum of myeloid cells
• BMA: Hypercellular-increased granulopoiesis
• Cytogenetics: Philadelphia chromosome