Info

Chronic Phase

Acceleratsed Phase

Blast Phase

Peripheral blood

Leukocytosis with the presence of neutrophils in all stages of maturation Blasts >2% Increased basophils Increased eosinophils Thrombocytosis Mild anemia NRBs

Increase in promyelocytes Blasts increased Basophils >20% Increase in circulation NRBs Erythrocytes Persistent thrombocytopenia Anemia

Blasts >20%

Increase in promyelocytes Increase in basophils and eosinophils Thrombocytopenia

Bone marrow

Hyperplasia myeloid Blasts <5% M:E ratio 10:1 Increased immature forms of basophils Reduced erythrocytes Increased megakaryocytes

Dysplasia Blasts >5% <20 Left shift of mature neutrophils Increased basophils Megakaryocytic proliferation in sheets and clusters Fibrosis

Blasts >20% Large clusters of blasts Increased fibrosis Marked dysplasia of all three cell lines

Diagnosis

CML must be distinguished from other myeloproliferative disorders. The presence of the Ph chromosome or BCR-ABL fusion gene and a low or absent leukocyte alkaline phosphate (LAP) score is diagnostic for this disorder. The LAP score is a cytochemical stain and is used to differentiate CML from a leukemoid reaction. Leukocyte alkaline phosphatase enzyme is located in the granules of the neutrophil and bands. LAP activity increases with the maturity of the neutrophil. One hundred mature neutrophils and bands are stained, counted, and scored for stain intensity and granulation. In a leuke-moid reaction, the LAP score is high, and in CML, it is low. A leukemoid reaction is caused by a severe infection or inflammation. This reaction can resemble a leukemic process. Table 12.5 summarizes the differentiation of a neutrophilic leukemoid reaction and CML.

Treatment

The goal of treatment for CML is to achieve hematolog-ical remission, which consists of a normal CBC, no organomegaly, and a negative Ph chromosome or negative BCR-ABL fusion gene. The chronic phase can be controlled with hydroxyurea, interferon-alfa, or busul-fan therapy.10 This type of therapy is called myelosup-pressive therapy, with the goal of controlling the hyperproliferation of the myeloid elements. The drug tries to decrease the WBC count by interfering with cell division. Neither cytotoxic drug can prevent the blast crisis. Another treatment is called leukapheresis. This therapy uses a cell separator to lower the WBC count rapidly (red cells are reinfused), and a cytotoxin drug is used to keep the patient in a longer remission.5,7

A new approach to treatment is to directly inhibit the abnormal molecular molecule, using a tyrosine kinase inhibitor. This inhibitor reacts to the BCL-ABL tyrosine kinase associated with the Ph chromosome. The drug is called imatinib mesylate (Gleevec), and it inhibits proliferation, slows down cell growth, and induces cell death.11-13 An additional treatment for CML is an allogeneic bone marrow or stem cell transplantation. However, bone marrow transplant has a high mortality rate.14 Allogeneic bone marrow transplant is currently the only curative therapy.1 There are many clinical trials now being studied for better prognosis.

Prognosis

The chronic phase CML is highly responsive to treatment. The median survival is 4 to 6 years, with a range of 1 year to longer than 10 years. Survival after development of an accelerated phase is usually less than 1 year, and after blast crisis survival, is only a few months.15 Poor prognosis in patients with CML is associated with several prognostic factors. These factors include

• Amount of blasts in the peripheral blood and bone marrow

• Size of the spleen at diagnosis

• Marrow fibrosis

• Patient's general health

Table 12.5 O Differentiating a Neutrophilic Leukemoid Reaction and CML

Criterion CML Leukemoid Reaction

Neutrophil

Eosinophil

Basophil

Platelet

Anemia

LAP score

Philadelphia chromosome Toxic granulation Döhle bodies

The whole spectrum of cells mature to the blast Increased Increased

Increased with abnormal forms

Usually present

Decreased

Present

Absent Absent

A shift to the left, more bands, metas, blast very rare Normal Normal Normal Not typical Increased Absent

Increased Increased

192 Part III • White Cell Disorders

For patients lacking the Ph chromosome, median survival is about 1 year.16

The Prevention and Treatment of Headaches

The Prevention and Treatment of Headaches

Are Constant Headaches Making Your Life Stressful? Discover Proven Methods For Eliminating Even The Most Powerful Of Headaches, It’s Easier Than You Think… Stop Chronic Migraine Pain and Tension Headaches From Destroying Your Life… Proven steps anyone can take to overcome even the worst chronic head pain…

Get My Free Audio Book


Post a comment