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Chapter 67 Chronic Myeloid Leukemia 1057

B C

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A D E F
Fig. 67.2 CHRONIC MYELOID LEUKEMIA, PERIPHERAL BLOOD TUBE, AND IMAGES OF
BLOOD SMEAR AND BONE MARROW BIOPSY AND ASPIRATE IN CHRONIC PHASE. (A) The
spun tube of peripheral blood (ethylenediaminetetraacetic acid collected) is from a patient with chronic-phase
chronic myeloid leukemia who presented with a white blood cell count of about 600 K/µL. Note the markedly
expanded “buffy coat” layer (asterisk) due to the severe leukocytosis. (B) Peripheral smear showing marked
leukocytosis due to a granulocytic proliferation of all stages with particularly increased myelocytes and absolute
basophilia. (C) Bone core biopsy illustrating markedly hypercellular marrow due to granulocytic proliferation
and increased small hypolobated megakaryocytes. (D) Bone marrow aspirate showing the same granulocytic
proliferation and small, “dwarf” megakaryocytes. Mild fibrosis as seen on reticulin stain (E), and pseudo-
Gaucher cells (F).

alternative kinase deregulation. Other studies suggest that the Laboratory Manifestations
granulocyte/macrophage progenitor (GMP) pool is expanded in
patients with blast-phase CML, and that these cells have increased Laboratory findings at presentation generally include leukocytosis,
levels of BCR-ABL expression and increased WNT signaling activity thrombocytosis, and anemia (Fig. 67.2). The total leukocyte count is
9
that may lead to increased self-renewal capacity, transforming GMP always elevated at the time of diagnosis and is usually over 25 × 10 /L.
cells into leukemic stem cells. 1,2 The WBC count rises progressively if patients are left untreated.
Striking cyclic variations in WBC counts have been described in rare
patients. Differential counts reveal granulocytes at all stages of dif-
CLINICAL FEATURES ferentiation in peripheral blood cells. Circulating granulocytes are
usually normal in appearance. The blast percentage is between 0.5%
History and 10%. Neutrophil alkaline phosphatase activity is low or absent
in more than 90% of patients. However, activity can increase in
Most CML patients (>90%) present in CP. CML is often diagnosed response to infection, inflammation, and reduction of counts by
incidentally during routine examination or examination for another treatment. Functional abnormalities of neutrophils are mild and are
illness. Symptoms usually include fatigue, weight loss, bone pain, not associated with predisposition to infection. Although the propor-
sweating, and abdominal discomfort and early satiety related to tion of eosinophils is usually not increased, the absolute eosinophil
splenomegaly. Symptoms are generally gradual in onset over weeks count is usually increased. The absolute basophil count is almost
to months. Uncommon presenting symptoms include those related always increased in CML. The proportion of basophils is usually less
to leukostasis, acute abdominal pain related to splenic infraction, than 15% in CP patients, although rarely this may be higher. In
priapism, and hypermetabolism, hyperuricemia, and gouty arthritis. contrast to mastocytosis, hyperhistaminemia is uncommon. The
absolute lymphocyte count is increased as a result of an increase in
T but not B cells.
Physical Examination The platelet count is elevated in 50% of patients at the time of
diagnosis. The platelet count may increase during the course of CP.
Physical examination may detect pallor and splenomegaly. In the Platelet dysfunction may occur, but disorders of thrombosis and
past, the incidence of splenomegaly was often greater than 90% at hemorrhage are rare. Thrombocytopenia is rare at diagnosis and
diagnosis, but this has been decreasing in frequency since the disease usually is a sign of progression toward AP. A deficiency in the second
is being diagnosed earlier. wave of aggregation to epinephrine is the most common abnormality