Snapshot A 67-year-old woman presents for her annual check-up. She feels great and denies any symptoms. Her physical exam is completely normal. Her routine blood tests come back with marked leukocytosis with increased neutrophils. Leukocyte alkaline phosphatase is low. Her physician is suspicious for a heme malignancy. Introduction Also known as chronic myelogenous leukemia Clonal hematopoietic stem cell disorder Pathogenesis Philadelphia chromosome translocation t(9;22) BCR-ABL fusion gene hyperactive tyrosine kinase Epidemiology typically in older patients median disease onset 67 years of age slightly male > female 15% of all adult leukemias Clinical course chronic phase (most present in this phase) some patients may be completely asymptomatic incident finding on CBC accelerated phase blast phase may transform into AML or ALL (“blast crisis”) Risk factors radiation from nuclear radiation radiation from radiography (radiologists may be at risk) radiation from cellular phone NOT a risk factor Presentation Chronic phase fatigue night sweats malaise weight loss fever splenomegaly LUQ discomfort early satiety pruritus after hot bath/showers Accelerated or blast phase bony pain lymphadenopathy variable skin findings extramedullary mass rapidly enlarging spleen Evaluation Complete blood count with differential ↑ WBC ↑ neutrophils ↑ basophils immature granulocytes (metamyelocytes, myelocytes, and promyelocytes) ↓ leukocyte alkaline phosphatase low activity in mature granulocytes Bone marrow aspirate and biopsy ↑ cellularity immature granulocytes blasts present in accelerated or blast phase Cytogenetic analysis or FISH showing Philadelphia chromosome (most accurate) bone marrow cells or peripheral blood Differential Diagnosis Chronic myelomonocytic leukemia Chronic eosinophilic leukemia Primary myelofibrosis Acute myeloid leukemic Leukemoid reaction ↑ WBC ↑ leukocyte alkaline phosphatase Treatment Medical management tyrosine kinase inhibitors are first-line imatinib (Gleevec) nilotinib dasatinib, especially for accelerated phase or blast phase Surgical management hematopoietic stem cell transplant never first-line the only curative therapy Prognosis, Prevention, and Complications Prognosis worse prognosis with older age at diagnosis increased overall survival with tyrosine kinase inhibitor therapy Complications transformation to acute leukemia (blast crisis) infection bleeding gout bone pain splenic infarcts due to splenomegaly