The natural history of Chronic Myeloid Leukemia is the chronic phase, accelerated phase, and the blast phase.
Chronic Phase: This is generally stable, chronic disease and patients can be asymptomatic. Often they are picked up on routine blood count showing leukocytosis. There is a 6% 5 year risk of progressing to blast phase when they are treated with Imatinib.
Accelerated Phase: This is when blasts are detected but they haven’t reached a high level of > 20%.
Blast Phase: This is conversion of CML to acute leukemia with > 20% blasts on peripheral smear or bone marrow. About 70% present with AML blast crisis and roughly 30% with ALL blast crisis. Treatment depends on whether flow cytometry/analysis shows AML or ALL.
Imatinib (Gleevec) is a first generation tyrosine kinase inhibitor. It is used for patients with chronic CML to help prevent progression to blast phase. Side effects include pulmonary edema, peripheral edema, muscle cramps, QTC prolongation, arrhythmias, among others.
Leukostasis which is defined as hyperleukocytosis (>50K WBC) with symptoms including CNS, respiratory, and cardiac. There are various thresholds for initiating leukapharesis depending on the type of leukemia, presence of symptoms, and level of WBC elevation. In general, AML is more likely than ALL to cause leukostasis. The acute leukemia’s are more likely to cause leukostasis than the chronic leukemias.
Leukopharesis can have serious side effects so only used when absolutely necessary.
Hydroxyurea blocks DNA synthesis and can be use in myeloproliferative disorders and CML. Of note also used in sickle cell disease as it increased Fetal Hemoglobin levels.
Clinical Pearl: ALL is more likely than AML to present with tumor lysis syndrome.