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

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.

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

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.

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

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

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

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.

Staging correlates with survival: Stage 0 Lymphocytosis alone. Median Survival >13yrs I Lymphocytosis + lymphadenopathy. 8yrs II Lymphocytosis + spleno- or hepatomegaly. 5yrs III Lymphocytosis + anaemia (Hb <11g/dL). 2yrs IV Lymphocytosis + platelets < 1yr

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

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

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

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.

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

Difference between CML and CLL Anemia Early presentation Late presentation Sternal tenderness Present Absent Lymphadenopathy May present in terminal stage Present from early stage Splenomegaly Huge Moderate Bleeding episodes May occur in terminal stage May occur from early stage WBC 100000 to 500000/mm cu., mainly myelocyte 10000 to 50000/mm cu. ,mainly lymphocytes