CML: Clinical diagnosis, differential diagnosis and scoring systems

Chronic myeloid leukemia (CML) is an indolent malignancy that commonly presents in a chronic phase of the disease. It is often diagnosed incidentally with hematological abnormalities being identified during routine laboratory tests. About half of the patients are clinically asymptomatic at the time of diagnosis. Symptomatic disease commonly manifests with fatigue, shortness of breath, weight loss, abdominal discomfort, easy bruisability and excessive bleeding. Headaches, confusion, lethargy and other neurological symptoms are less common and are usually associated with hyperleukocytosis. Rapid development of new symptoms such as generalized pain, organ enlargement and worsening lymphadenopathy may indicate CML progression to more advanced accelerated phase or blast crisis. Differential diagnosis of CML includes other myeloproliferative neoplasms, philadelphia (Ph) chromosome-positive acute leukemia, myelodysplastic/myeloprolyferative neoplasms, myeloid/lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1. Negative bcr/abl testing by FISH is a quick and practical tool to exclude most of the non-CML diagnoses. Unlike CML with blast crisis, Ph-positive acute lymphoblastic and acute myeloid leukemia lack Ph-chromosomal abnormality in all myeloid cells except blasts.