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Chronic myeloid leukemia
Diagnosis
Complete blood count (CBC)
- The most common feature of CML is an elevated WBC count,
usually > 25,000 and frequently > 100,000.
- The finding of unexplained, persistent leukocytosis (>
12,000) in the absence of infections or other causes of WBC
count elevation should prompt a work-up for CML.
The WBC differential usually shows granulocytes in all stages of
maturation, from blasts to mature, morphologically normal
granulocytes.
- Basophils are elevated, but only 10%-15% of patients have ≥
7% basophils in the peripheral blood.
- Eosinophils may also be mildly increased.
- The absolute lymphocyte count is elevated at the expense of
T lymphocytes.
- The platelet count is elevated in 30%-50% of patients and is
higher than 1,000 × 109/L in a small percentage of patients with
CML.
However, in some cases blood elements may be decreased:
- Thrombocytopenia is usually signals disease acceleration.
- Some patients have mild anemia at diagnosis.
- Neutrophil function is usually normal or only mildly
impaired, but natural killer (NK) cell activity is impaired.
- As in the other myeloproliferative diseases, platelet
function is frequently abnormal and nonspecific; it may have no
clinical significance. Clinically, thrombosis and hemorrhage are
not common despite elevated platelet counts and platelet
function abnormality.
Bone marrow examination
All stages of maturation of the WBC series are usually seen, but
the myelocyte predominates. Histopathologic examination of bone marrow aspirate demonstrates a
shift in the myeloid series to immature forms that increase in number
as patients progress to the blastic phase of the disease.
- The marrow
is hypercellular with cellularity of 75%-90% and maybe accompanied by increased numbers of eosinophils or basophils, and sometimes monocytosis is seen.
- Increased megakaryocytes are often found in the marrow, and sometimes fragments
of megakaryocytic nuclei are present in the blood, especially when the
platelet count is very high.
- The percentage of lymphocytes is reduced
in both the marrow and blood in comparison with normal subjects, and
the myeloid/erythroid ratio in the marrow is usually greatly elevated
(usually 10-30:1).
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Neutrophil alkaline phosphatase
The leukocyte alkaline phosphatase enzyme is either absent or markedly
reduced in the neutrophils of patients with chronic myelogenous
leukemia.
The Philadelphia chromosome
CML (Chronic Myeloid Leukemia) is a clonal disorder that is usually easily diagnosed because
the leukemic cells of more than 95% of patients have a distinctive
cytogenetic abnormality, the Philadelphia chromosome (Ph1).
The Philadelphia chromosome (Ph1) is usually more readily
apparent in marrow metaphases than in peripheral blood metaphases;
in some cases, it may be mashed and reverse transcriptase–polymerase
chain reaction (RT–PCR) or fluorescent in situ hybridization (FISH)
analyses on blood or marrow aspirates may be necessary to
demonstrate the 9;22 translocation.
-
Conventional cytogenetics has a sensitivity 1 in 20
cells.
-
FISH has a sensitivity 1 in 500 cells.
-
PCR has a sensitivity of 1 in 10,000 to 1,000,000.
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