C h r o n i c M y e l o i d L e u k e m i a
General
• CML is a clonal disorder characterized hematologically by marked
neutrophilic leukocytosis and by basophilia.
• In all cases, CML is associated with the Philadelphia chromosome (t[9;22]).
Clinical Features
Age
• Usually occurs in 40s and 50s - but may occur at any age.
Symptoms
• Slow onset - may be asymptomatic for a long time.
• Later: fevers, fatigue, night sweats, abdominal fullness.
Signs
• Splenomegaly (massive).
• Hepatomegaly.
• Lymphadenopathy.
Phases of CML
• Chronic phase
• High but stable number of neutrophils and precursors.
• Stable hemoglobin and platelet count.
• Easily controlled by therapy.
• Usually lasts 3-4 years; is then followed by accelerated phase and/or
blast crisis.
• Accelerated phase
• Characterized by a change in the patient's previously stable state.
• Usually see increasing leukocytosis, decreasing hemoglobin and platelet
count.
• Usually fatal within several months.
• Blast crisis
• Characterized by marked increase in blasts (myeloblasts or
lymphoblasts).
• Short survival at this stage (a few weeks or months).
Morphology
Blood
• Neutrophilia with left shift and "bulges" at myelocyte and segmented
neutrophil stages
• A few myeloblasts (usually <3%)
• Basophilia
Bone marrow
• Hypercellular
• Numerous neutrophils, neutrophil precursors, and megakaryocytes
Laboratory Findings
• WBC markedly increased. Basophilia.
• Hgb slightly decreased
• Platelet count normal to increased.
• Leukocyte alkaline phosphatase decreased or absent.
Pathophysiology/Genetics
Philadelphia chromosome (Ph)
• Result of a translocation between chromosomes 9 and 22.
• The c-abl proto-oncogene on chromosome 9 moves next to the bcr gene on
chromosome 22. A new, fusion gene is created: the bcr-abl gene.
• The bcr-abl gene encodes a protein called p210, which increases tyrosine
kinase activity and disrupts the cell cycle.
• In cases of Ph -positive CML, Ph is found in all myeloid cells and in some
B lymphocytes!
• Almost all cases of CML are Ph-positive. A small percentage of acute
lymphoblastic leukemias are also Ph-positive.
Treatment
• Gleevec (imatinib) really prolongs survival (95% 5-year suvival rate, so far!),
but does not appear to cure patients (if you stop the drug, patients may
relapse).
• Allogeneic bone marrow transplant is the only hope for a cure.
