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1446 Part X: Malignant Myeloid Diseases Chapter 89: Chronic Myelogenous Leukemia and Related Disorders 1447

A B

C D
Figure 89–7. Blood and marrow cells characteristic of chronic myelogenous leukemia. A. Blood film. Elevated leukocyte count. Elevated platelet
count (aggregates). Characteristic array of immature (myelocytes, metamyelocytes, band forms) and mature neutrophils. B. Blood film. Elevated leu-
kocyte count. Characteristic array of immature (myelocytes, metamyelocytes, band forms) and mature neutrophils. Two basophils in the field. Abso-
lute basophilia is a constant finding in CML. C. Blood film. Elevated leukocyte count. Characteristic array of immature (promyelocytes, myelocytes,
metamyelocytes, band forms) and mature neutrophils. Basophil in the field. Two myeloblasts in upper center. Note multiple nucleoli (abnormal) and
agranular cytoplasm. D. Marrow section. Hypercellular. Replacement of fatty tissue (normally approximately 60 percent of marrow volume in adults
of this patient’s age) with hematopoietic cells. Intense granulopoiesis and evident megakaryocytopoiesis. Decreased erythropoiesis. (Reproduced with
permission Lichtman’s Atlas of Hematology, www.accessmedicine.com.)

The total absolute lymphocyte count is increased (mean: approx- Myelogenous Leukemia” below) and may also occur in with massive
imately 15 × 10 /L) in patients with CML at the time of diagnosis as splenomegaly.
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a result of the balanced increase in T-helper and T-suppressor cells. Functional abnormalities of neutrophils (adhesion, emigration,
285
B lymphocytes are not increased. T lymphocytes also are increased phagocytosis) are mild; are compensated for by high neutrophil concen-
288
in the spleen. NK cell activity is defective in CML patients as a result trations; and do not predispose patients in chronic phase to infections
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of decreased maturation of these cells in vivo 287,288 and a decrease in by either usual or opportunistic organisms. 292–294 Platelet dysfunction
the absolute number of circulating NK cells in patients with CML. can occur but is not associated with spontaneous or exaggerated bleed-
The latter change can perhaps be related to increased apoptosis. The ing. A decrease in the second wave of epinephrine-induced platelet
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CD56 bright subset of NK cells is particularly decreased. These cells aggregation is the most common abnormality and is associated with a
are reduced more as CML progresses, and they respond less to stim- deficiency of adenine nucleotides in the storage pool. 295,296
uli that recruit clonogenic NK cells compared to NK cells from normal
subjects. 290 Marrow
The platelet count is elevated in approximately 50 percent of Morphology The marrow is markedly hypercellular, and hematopoi-
patients at the time of diagnosis and is normal in most of the rest. The etic tissue takes up 75 to 90 percent of the marrow volume, with fat
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median value in patients at diagnosis is approximately 400 × 10 cells/L. markedly reduced (see Fig. 89–7). 297,298 Granulopoiesis is dominant,
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The platelet count may increase during the course of the chronic phase. with a granulocytic-to-erythroid ratio between 10:1 and 30:1, rather
Platelet counts greater than 1000 × 10 /L are not unusual, and platelet than the normal 2:1 to 4:1. Erythropoiesis usually is decreased, and
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counts as high as 5000 to 7000 × 10 /L have occurred. Thrombohem- megakaryocytes are normal or increased in number. Eosinophils and
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orrhagic complications of thrombocytosis are infrequent. Occasionally, basophils may be increased, usually in proportion to their increase in
the platelet count may be below normal at the time of diagnosis, but the blood. Mitotic figures are increased in number. Mast cells are often
this finding usually signals an impending progression to the accelerated seen, and uncommonly a juxtamembrane domain mutant of KIT coin-
phase of the disease (see “Accelerated Phase and Blast Crisis of Chronic cides with BCR-ABL1 in CML. Rare reports of marrow mastocytosis
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