Chronic myeloid leukaemia, BCR-ABL1-positive Definition Chronic myeloid leukaemia (CML), BCR- ABLI-positve, isa myeloprolterave neoplasm (MPN) in which granulocytes are the major prolifetaive component. It arises in a haematopoietic stem cell and is characterized by the chromosomal translocation {(9:22\(q34.1;011.2), which results in the formation of the Philadel- pphia (Ph) chromosome, containing the ‘BCR-ABL! fusion gene |282,2620,2905, 3433). In CML, BCR-ABL! is found in all myeloid lineages and in some lymphoid and endothelial cells (12101496). The natural history of untreated CML is bipha- sic oF triphasic: an inital indolent chronic phase (CP) is followed by an accelerated phase (AP), a biast ohase (BP), or both ‘The diagnosis requires detection of the Ph chromosome and/or BCR-ABL! inthe ap= propriate cnical and laboratory settings. ICD-0 code 9875/3 ‘Synonyms Chronic myelogenous leukaemia, SCA- ‘ABLi-positive; chronic granulocytic leu kaemia, SCR-ABLI-postive (9863/3); chronic myelogenous leukaemia, Phila- delphia _chromosome-positive | (Phe) chronic myelogenous leukaemia, 19:22) (q34:a11); chronic granulocytic leukae- mia, Philadelphia chromosome-postive (Phe); chronic granulocytic leukeeria, 19:22\934q11); chronic granulocytic leukaemia, BCRIABLY; chronic myeloid leukaemia (9863/3) Epidemiology Worldwide, CML has an annualincidence of 1-2 cases per 100000 popuiation, with a slight male predominance. The annual incidence increases with age, from <0.1 cases per 100.000 children to 22.5 cases per 100 000 elderly individu als (1662,1749]. Significant ethnic or geo- ‘rephical variations in incidence have Not been reported, but an eerlier patient age at onset has been reported in areas where socioeconomic status is lower (2626), Due to the success of tyrosine kinase inhibitor (TKI) therapy in reducing mortality rates (down to only 2-3% per year), the prevalence of CML is expected to increase considerably (1725) Etiology ‘The predisposing factors for CML are largely unknown, Acute radiation expo- ‘sure has been implicated, largely due to the reported increased incidence of CML ‘among atomic bomb survivors {387,816} Unlike other MPN, there is slight, f any, Inherited predisposition (2209,3306), Localization In CP, the leukaemia cells are minimally invasive and mostly confined to the blood, bone marrow, spleen, and liver. In BP, the blasts can infiltrate any extra medullary site, with 2 predilection for spleen, liver, lymph nodes, skin, and soft tissue (822,1810,2776) Vardiman JW. Melo JV. Baccarani M. Radich JP Kvasnicka HM. Clinical features Most patients with CML are diagnosed in GP, which usually has én insicious onset. Nearly 50% of newly diagnosed cases are asymptomatic and discovered when a white blood cell (WBC) count per- formed as part of @ routine medical ex: amination is found to be abnormal (822, 41803}. Common findings at presentation Include ‘atigue, malaise, weight loss, night sweats, and anemia, and about 50% of patients have palpable epleno- megaly (822,1662,1809,3534). Atypical presentations include marked thrombo- cytosis without leukooytosis that rim ics essential thrombocythaemia or other types of MPN (512,618,3782). About 5% of cases are ciagnosed in AP or BP without a recognized CP (1662,3534}. Without effective therapy, most cases of CL progress from GP to BP (arecty or via AP) within 3-5 years aftr diagnosis (822.1602). These transformed stages ate characterized cinicaly by decin- ing performance status, constitutional signs such as fever and weight loss, and symptoms related to severe anae- mia, thrombocytopenia, increased WEC count, splenic enlargement, and in BP, a dismal outcome (1601,1808). With tar- goted TKI therapy and careful disease monitoring, the incidence of AP and BP has decreased, and the 10-year overall survival rate for CML is 80-20% (207, 573,1602,1904) a a0 ate Fig.201 Spieameyalyin chronic myeloid utsemia, SCR-ABLT-postive. AThe goss appearance of he spon sland ifemly dea re. sthoug areas ofan "5 sppear a igha-colurea repens. 8 The ed csrauton oe nial usualy compresses and citrate he whe pulp. © The eutseic cals are preset the Splenic ord an snes. In this cas th cele sites towards mature foms; care must be ake 1 8868 tha atu oh celsinslaactomy specmen,Deceuse ening sees, arbour inthe ae of Therapy, may be assocad wih ease progression, 30 _Myeloproliferative neoplasms