Chronic Myeloid
Leukemia
Clarence Adoo MD FACP
Phoenix, April 2013
CML
One day in the life of Mr. James B. Smith,
who has been diagnosed with CML
JB: fatigue, intolerance of large meals,
weight loss, low grade fevers, cough.
Presentation
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Fever, pallor, few scattered bruises
Splenomegaly
No lymphadenopathy
WBC 247,000 /ul (normal is 12 /ul)
Mild thrombocytopenia and anemia
Normal chemistry, coags.
Buffy coat.
Peripheral Film
Acute Myeloid
Acute
Lymphoblastic
Chronic Myeloid
Chronic
lymphocytic
Molecular genetic lesions in
leukemia
• Increased rate of growth
• Decreased rate of cell death
• Impaired maturation
AML
maturation
growth
ALL
growth
maturation
CML
growth
CLL
cell death
Nowell and Hungerford
The Ph Chromosome
Etiology: ionizing radiation,
DNA toxins
non hereditary.
Male: female 1.4 : 1
1-2 per 100K in US
Detection: cytogenetics
FISH
RT PCR
Pathology
• Peripheral blood “like marrow”
• Mature neutrophils predominate
• Bone marrow:
– elevated Myeloid:erythroid ratio
– Blast percentage
– Trilineage dysplasia
– Increased reticulin
Tyrosine kinases
• Highly conserved in nature
• Ubiquitous (90 in human genome)
• Almost one half are receptor proteins
Ligand
Tyrosine kinase inhibitors
• Imatinib, dasatinib, nilotinib, posatinib
• Sunitinib, vorafenib, erlotinib, ibrutinib,
lapatinib, gefitinib, lafatinib, sorafenib…
Lung cancer, breast cancer, colon cancer,
pancreatic cancer, kidney cancer,
melanoma, sarcoma, liver cancer.
Tyrosine kinase inhibitors
India’s Supreme Court has rejected a bid from
Swiss pharmaceutical company Novartis AG
to patent an updated version of its cancer drug Gleevec.
JBS: his outlook.
Natural history of CML:
Chronic Phase
Accelerated phase
Blast crisis
Median survival 1-2 years
Rx pre 1990
• Hydroxyurea or busulfan
– control counts
• Interferon alfa:
– Maintenance, delay transformation
• Younger, w suitable donor:
– Allogeneic stem cell transplant
– Remains the only curative therapy
JBS’ future outlook
• 95% likely to get hematologic response
• Cytogenetic response
– Minor, major or complete (percentage Ph’)
• Maintenance therapy
• Monitoring of minimal residual disease
• Risk of TKI resistance