Chronic myeloid leukaemia

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Chronic myeloid leukaemia
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Chronic myeloid leukaemia

• THE STORY OF CHRONIC MYELOID LEUKAEMIA
• It is moreover, the same conclusion which
  Bennett came to in the much-discussed matter of
  priority between us when he observed a case of
  indubitable leukaemia, some months before I saw
  my first case'. With these words, spoken at a
  lecture in Berlin in 1858, Robert Virchow
  generously acknowledged that John Hughes
  Bennett's description of chronic myeloid
  leukaemia in Edinburgh in 1845 preceded his by a
  short period and called a truce to the unseemly
  controversy which had marred its discovery.

Rudolf Virchow (1821-1902)
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Chronic myeloid leukaemia

• The patient , a 49yr old teacher, saw her family
  physician because of fatigue for about six
  months.
• Physical exam. Showed little except for pallour,
  normal temperature
• Blood tests were ordered to investigate possible
  anaemia

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Chronic myeloid leukaemia

• Laboratory results indicated a high white count
  consistent with Chronic Myeloid Leukaemia

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Chronic myeloid leukaemia

• Sex 1.41 (mf)
• 40-60 yrs old
• Aetiology?
• Unknown
• Atom bomb exposure Japan

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Chronic myeloid leukaemia

• About 4,400 new cases of chronic myelogenous
  leukemia (CML) are diagnosed each year in the
  United States.

15 of leukaemas
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Chronic myeloid leukaemia

• Clinical features
• Wt loss, lassitude anorexia night sweats
• Splenomegaly
• Anaemia pallor dyspnea tachycardia
• Bruising epistaxis menorrhagia
• Gout renal impairment
• Incidental finding (CBC)

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Chronic myeloid leukaemia

• Laboratory findings
• Leukocytosis gt50 x 109/L-?500
• Spectrum of myeloid cells
• Neutrophils myelocytes exceed blasts and
  promyelocytes
• Increased basophils
• Anaemia
• Hypercellular marrow
• Ph chromosome

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Chronic myeloid leukaemia

• Hypercellular
• Myeloid cells
• All stages
• Shift to early forms
• Less than 20 blasts

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Chronic myeloid leukaemia

• CAT scan
• Very large spleen

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Wt 3kgs
Normal c200gms
SplenomegalyCML
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Blast transformation
Chronic myeloid leukaemia
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Chronic myeloid leukaemia
blood
Blast cell crisis
marrow
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Chronic myeloid leukaemia

• Other studies
• Flow cytometry
• Myeloid markers
• Maturity markers
• Cytogenetics
• Chromosome studies
• FISH
• RT-PCR

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Chronic myeloid leukaemia

• In 1960, two physicians studying chromosomes in
  cancer cells noticed that a chromosome in CML
  patients was shorter in length than that of the
  same chromosome in normal cells. They named this
  shortened chromosome the Philadelphia chromosome,
  because the observation was made at the
  University of Pennsylvania School of Medicine in
  that city.

Janet Rowley
Peter Nowell
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Philadelphia
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Chronic myeloid leukaemia
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The Philadelphia Chromosome
Chronic myeloid leukaemia
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Chronic myeloid leukaemia

• Chromosomal banding at a microscopic level
  confirming the translocation
• Miss-placed genetic information
• Marker for CML

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Chronic myeloid leukaemia

• Chromosomal banding at a microscopic level
  confirming the translocation
• Miss-placed genetic information
• Molecular changes
• Marker for CML

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Chronic myeloid leukaemia

• Treatment
• Chronic phase
• 5-6 yrs.more
• Older regimens
• New regimens
• Acute blast phase
• Brief survival 12 months

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Chronic myeloid leukaemia

• Death caused by
• Acute transformation
• Haemorrhage
• Infection

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Chronic myeloid leukaemia

• References
• Clinical features at diagnosis in 430 patients
  with CML seen at a referral centre over a 16yr
  period. Savage et al Br J Haem 1997 96, 111-116.
• Chronological sequence in Appearance of Clinical
  and Laboratory findings Characteristic of CML.
  Kamada N, Uchino H, Blood 1978 51, 843-850.
• The Story of CML. Geary C.G. Br J Haem 2000 110,
  2-11. (historical review)

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Chronic myeloid leukaemia
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