Chronic myeloid leukaemia

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)

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

Chronic myeloid leukaemia

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

Chronic myeloid leukaemia

• Sex: 1.4:1 (m:f)• 40-60 yrs old• Aetiology?

– Unknown

– Atom bomb exposure Japan

Chronic myeloid leukaemia

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

15% of leukaemas

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)

Chronic myeloid leukaemia

• Laboratory findings:– Leukocytosis >50 x 109/L-

500

– Spectrum of myeloid cells

– Neutrophils myelocytes exceed blasts and promyelocytes

– Increased basophils

– Anaemia

– Hypercellular marrow

– Ph chromosome

Chronic myeloid leukaemia

• Hypercellular– Myeloid cells

– All stages

– Shift to early forms

– Less than 20% blasts

Chronic myeloid leukaemia

• CAT scan– Very large spleen

Wt 3kgs

Splenomegaly…CML

Normal c200gms

Mrs AL

0 1 2 3 4 5 6 7 8 9 10

0

50

100

150

200

250

300

350Leukocytes

Platelets

0

400

800

1200

1600

2000

2400

Years

WB

CP

lateletsChronic myeloid leukaemia Blast transformation

Blast cell crisis

marrow

blood

Chronic myeloid leukaemia

Chronic myeloid leukaemia

• Other studies– Flow cytometry

• Myeloid markers

• Maturity markers

– Cytogenetics• Chromosome studies

• FISH

• RT-PCR

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

Philadelphia

Chronic myeloid leukaemia

The Philadelphia Chromosome Chronic myeloid leukaemia

Chronic myeloid leukaemia

• Chromosomal banding at a microscopic level confirming the translocation

• Miss-placed genetic information

• Marker for CML

Chronic myeloid leukaemia

• Chromosomal banding at a microscopic level confirming the translocation

• Miss-placed genetic information

• Molecular changes• Marker for CML

Chronic myeloid leukaemia

• Treatment:– Chronic phase– 5-6 yrs….more

• Older regimens

• New regimens

– Acute blast phase• Brief survival 12 months

Chronic myeloid leukaemia

• Death caused by:– Acute transformation– Haemorrhage– Infection

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)

Chronic myeloid leukaemia