1. Chronic myeloid leukaemia

2. 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)

3. 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

4. Chronic myeloid leukaemia Laboratory results indicated a high white count consistent with Chronic Myeloid Leukaemia……

5. Chronic myeloid leukaemia Sex: 1.4:1 (m:f) 40-60 yrs old Aetiology? –Unknown –Atom bomb exposure Japan

6. Chronic myeloid leukaemia About 4,400 new cases of chronic myelogenous leukemia (CML) are diagnosed each year in the United States. 15% of leukaemas

7. 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)

8. Chronic myeloid leukaemia Laboratory findings: –Leukocytosis >50 x 10 9 /L-  500 –Spectrum of myeloid cells –Neutrophils myelocytes exceed blasts and promyelocytes –Increased basophils –Anaemia –Hypercellular marrow –Ph chromosome

9. Chronic myeloid leukaemia Hypercellular –Myeloid cells –All stages –Shift to early forms –Less than 20% blasts

10. Chronic myeloid leukaemia CAT scan –Very large spleen

11. Wt 3kgs Splenomegaly…CML Normal c200gms

12. Chronic myeloid leukaemia Blast transformation

13. Blast cell crisis marrow blood Chronic myeloid leukaemia

14. Other studies –Flow cytometry Myeloid markers Maturity markers –Cytogenetics Chromosome studies FISH RT-PCR

15. 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

16. Philadelphia

17. Chronic myeloid leukaemia

18. The Philadelphia Chromosome Chronic myeloid leukaemia

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

20. Chronic myeloid leukaemia Chromosomal banding at a microscopic level confirming the translocation Miss-placed genetic information Molecular changes Marker for CML

21. Chronic myeloid leukaemia Treatment: –Chronic phase –5-6 yrs….more Older regimens New regimens –Acute blast phase Brief survival 12 months

22. Chronic myeloid leukaemia Death caused by: –Acute transformation –Haemorrhage –Infection

23. 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)

24. Chronic myeloid leukaemia