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CHRONIC MYELOID LEUKEMIA (CML) By: Dr Waqar Asst. Professor Maarefa Medical College NORMAL WBC FORMATION CML DEFINITION • It is a cancer of WBCs in which there is excess production of granulocytes (neutros.,basophils & eosinophils) & their precursors( myeloid cells). The cells are mature looking but functionally abnormal. REMEMBER ! AML is also a malignancy of myeloid cells but: • It runs an acute course ( rapid) • The leukemic cells are immature looking “blasts” SOME GENERAL POINTS • It has an insidious and gradual onset. • Occurs in middle to old age • The cells contain an abnormal chromosome called “Philadelphia chromosome” • In most cases, it is curable • The drug IMATINIB has revolutionized the treatment & prognosis EPIDEMIOLOGY • Age group : Middle to old age. Rare in children • Gender: Slightly more in males • Accounts for 8% of all leukemias in U.K. PHASES OF CML CML is classified into 3 phases , based on clinical features and lab findings: Chronic phase Accelarated phase Blast crisis CHRONIC PHASE * This is the initial phase & lasts for 3-4 yrs, if no treatment is given * Tumour grows slowly & gradually * Patients often asymptomatic & discovered on routine CBC ( v. high WBC) * May be fatigue, wt. loss, night sweats, huge spleen causing abdominal heaviness. * Fever, night sweats * If treatment is not given, this progresses into the next phase. ACCELERATED PHASE * The cancer grows faster during this phase & WBC count rises fast * There are specific W.H.O. criteria for diagnosis of accelerated phase ( increased no. of basophils & blast cells, spleen size etc) * Patients may present with features of anemia, bleeding or infections BLAST CRISIS * Final phase in the course of CML * Cancer progresses very rapidly and quick death occurs (behaves like acute leukemia) * Excess blast cells in the marrow and blood * Patients present with fever anemia, bleeding, & infections (more severe now.) If treatment is given during the chronic phase, it may stop the tumor progression into the next phases S/S Depend on the phase of the disease at the time of diagnosis : • Asymptomatic • Fatigue, weakness, wt. loss, pain or heaviness in the left hypochondrium ( splenomegaly) • Features of anemia, bleeding & infections • Fever, night sweats • Massive splenomegaly, hepatomegaly DIAGNOSIS 1) Blood: * Very high WBC count 30, 000 and more) * High neutros., basophils & eosinophils ( myeloid cells) * Anemia, low platelets ( may be normal also) 2) Bone Marrow : * Hypercellular, with very high number of myeloid cells BLOOD FILM BLOOD FILM BONE MARROW • Note the excess myeloid series cells Diagnosis (contd) 3) Cytogenetics ( gene analysis of the cells) * Leukemic cells have the Philadelphia chromosome (Ph chromosome) TREATMENT 1) Chronic phase : * Tyrosine kinase inhibitors (eg Imatinib) * Introduced in the 2000s. Very good survival rates with this drug (response in more than 95% cases) 2) Accelerated & blast phase: * Imatinib not very effective * These phases treated like acute leukemia( more aggressive treatment with other chemo drugs) PROGNOSIS *Greatly improved after “tyrosine kinase inhibitors” * 5 yr survival is around 89% How to remember leukemia drugs 1) AML: Cytarabine, Daunorubicin ( C.D.) 2) ALL: Very Dark And Dirty Clothes (Vincristine, Dexa., Asparaginase, Daunorubicin, Cytarabine) 3) CLL: Chocolate Cake From Riyadh ( Chlorambucil, Cyclophosphamide, Fluda-rabine 4) CML : Imatinib Quick Points 1) 2) 3) 4) Most common leukemia in children: ALL Auer Rods: AML Philadelphia Chromosome: CML Massive splenomegaly: CML THANK YOU & ENJOY YOUR DAY