Chronic myeloid leukaemia (CML)

1. Chronic myeloid leukaemia (CML) • CML is characterized by an uncontrolled clonal proliferation of myeloid cells. It accounts for 15% of leukaemias. It is a myeloproliferative disorder having features in common with these diseases eg splenomegaly. It occurs most often between 40-60yrs, with a slight male predominance, and is rare in childhood

2. Philadelphia chromosome • (Ph) Present in >80% of those with CML. It is a hybrid chromosome comprising reciprocal translocation between the long arm of chromosome 9 and the long arm of chromosome 22 t(9;22) . • Those without Ph have a worse prognosis.

3. Symptoms • Mostly chronic and insidious: • weight decreases, tiredness, fever, sweats. • There may be features of gout (due to purine breakdown), • bleeding (platelet dysfunction), and abdominal discomfort (splenic enlargement). ~30% are detected by chance. Signs • Splenomegaly (>75%) often massive. • Hepatomegaly, anaemia, bruising

4. Investigation • WBC increases(often upto 500,000/mm cu) with whole spectrum of myeloid cells ie increase in myelocytes, neutrophils, basophils, eosinophils. • Hb decrease or normal, platelets variable. Urate increase, B12 increase. Neutrophil alk phos score decrease. • Bone marrow is hypercellular. • Ph found on cytogenetic analysis of blood or bone marrow.

5. Treatment of CML • Chemotherapy • Imatinib, has revolutionized CML therapy. It is more effective than the previous gold standard of – interferon, cytarabine in chronic phase patients, in terms of preventing disease progression. • The drug may also be effective in accelerated phase and blast crises. • Imatinib gives high haematological response rates (>90) • SE: usually mild: nausea, cramps, oedema, skin rash, headache, arthralgia. May cause myelosuppression

6. Hydroxyurea may still be used in patients intolerant of imatinib • Busulfan is very rarely used now. • The use of interferon in CML has declined dramatically with the introduction of imatinib, but -interferon may still have a role in combination therapy. • Treatment of myeloblastic transformation with chemotherapy rarely achieves lasting remission and allogeneic transplantation offers the only hope of long-term survival

7. Stem cell transplantation • Allogeneic transplantation from a HLA matched sibling or unrelated donor is the only curative treatment but carries significant morbidity and mortality.

8. Chronic lymphocytic leukaemia (CLL) • This is a monoclonal proliferation of non-functional mature B lymphocytes (T cell CLL occurs rarely). CLL constitutes 25% of all leukaemias. • Male:female=2:1. It is a disease of the elderly, median age at diagnosis is ~65 years.

9. Staging correlates with survival:

10. Symptoms • (none in 25%) Infection, anaemia, bleeding. • If severe: • weight decreases, sweats, anorexia. Signs • Enlarged, rubbery, non-tender nodes. • Splenomegaly, hepatomegaly.

11. Investigation Increase lymphocytes may be marked 95 % of WBC. Later: autoimmune haemolysis , Marrow infiltration: decrease Hb, decrease neutrophils, decrease platelets. • Complications • 1 Autoimmune haemolysis. • 2 Increase Infection due to hypogammaglobulinaemia (=decrease IgG), bacterial, viral especially herpes zoster. • 3 Marrow failure

12. Death is often due to infection (commonly pneumococcus, haemophilus, meningococcus, Candida or aspergillosis), or transformation to aggressive lymphoma .

13. Treatment • If asymptomatic, the patient can be monitored. • Chlorambucil is used to decrease lymphocyte count, improve marrow function, and reduce node size. Dose: eg 0.1- 0.2mg/kg daily PO. • Steroids are used in autoimmune haemolysis. Radiotherapy: • For relief of lymphadenopathy or splenomegaly. Supportive care: • Transfusions, IV human immunoglobulin if recurrent infections. • Bone marrow transplant is currently experimental.

14. Prognosis • Current treatments are mainly non-curative at present. Prognosis is often good: depends on stage and molecular/immunological factors.

15. Difference between CML and CLL