Chronic Myloid Leukemic Patients Treated With Tyrosine Kinase Inhibitor

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder in which leukemic cells display the Philadelphia chromosome generated from a reciprocal t(9:22) (q34:q11) translocation.1 The chromosome 9 and chromosome 22 transposal of t (9:22) and (q34:q11) causes the cancer gene C-ABL at 9q34 to link with the BCR gene at 22q11, forming the BCR-ABL gene on chromosome 22.2 CML is presented by constitutional complaints (fatigue, weight loss, and fever), those related to splenomegaly (abdominal fullness, anorexia, abdominal pain, and early satiety) and bleeding tendency (easy bruising or bleeding) are most frequent symptoms. Splenomegaly (≥ 95%), sternal tenderness, hepatomegaly, purpura, and retinal hemorrhage are commonly reported signs at physical exam. To diagnose CML, doctors use a variety of tests to analyze the blood and marrow cells.

*Complete Blood Count (CBC). This test is used to measure the number and types of cells in the blood. People with CML often have:

- Decreased hemoglobin concentration

- Increased white blood cell count, often to very high levels

- Possible increase or decrease in the number of platelets depending on the severity

Blood cells are stained (dyed) and examined with a light microscope. These samples show:

- Specific pattern of white blood cells

- Small proportion of immature cells (leukemic blast cells and promyelocytes)

- Larger proportion of maturing and fully matured white blood cells (myelocytes and neutrophils).

These blast cells, promyelocytes and myelocytes are normally not present in the blood of healthy individuals

- Bone Marrow Aspiration and Biopsy.

- Cytogenetic Analysis.

- FISH (Fluorescence In Situ Hybridization).

- Polymerase Chain Reaction (PCR).

The disease is classically staged into chronic phase (CP, most patients at presentation), accelerated phase (AP) and blast phase (BP).3 Many definitions have been used for these stages, but all the data generated from the tyrosine kinase inhibitor (TKI) studies has used the historically standard definition where AP is defined by the presence of one or more of the following: ≥15% blasts in the peripheral blood or bone marrow, ≥20% basophils in the peripheral blood , platelets <100,000/μL unrelated to treatment or the development of cytogenetic evolution. Blast phase is defined by the presence of ≥30% blasts in the peripheral blood or bone marrow, the presence of clusters of blasts in marrow or the presence of extramedullary disease with immature cells (i.e., a myeloid sarcoma).4 Progression to BP occurs at a median of 3-5 years from diagnosis in untreated patients, with or without an intervening identifiable AP.5. After initiating therapy for CML, patients should be monitored for treatment response assessment. The process of monitoring response to therapy is important to determine if an adequate response is being achieved, or if patients should be transitioned to a higher dose or different therapy Since therapy is continued indefinitely and relapse occurs upon cessation of therapy in most patients, it is critical that the disease is closely monitored. Continued monitoring over time is needed, even in the setting of an optimal response, in order to detect and treat potential recurrence. Specific response criteria, including optimal, suboptimal, and failure have been established to guide appropriate increase or change of therapy