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1444 Part X: Malignant Myeloid Diseases Chapter 89: Chronic Myelogenous Leukemia and Related Disorders 1445

CML. Telomerase activity is increased in the accelerated phase. When 100
244
therapy permits restoration of Ph chromosome–negative cells in the 90
blood, these cells have telomere length comparable to that in matched 80
healthy controls. 245 70

CLINICAL FEATURES Cumulative % of patients 60 White cell count
50
40
SIGNS AND SYMPTOMS 30 Platelet count
In the 70 percent of patients who are symptomatic at diagnosis, the 20
most frequent complaints include easy fatigability, loss of sense of well- 10
being, decreased tolerance to exertion, anorexia, abdominal discomfort, 0
early satiety (related to splenic enlargement), weight loss, and excessive 0 100 200 300 400 500 600 700 8001000 5000
9
sweating. 246–248 The symptoms are vague, nonspecific, and gradual in Cell count (x 10 /L)
onset (weeks to months). A physical examination may detect pallor Figure 89–6. Total white cell count and platelet count of 90 patients
and splenomegaly. The latter was present in approximately 90 percent with CML at the time of diagnosis. The cumulative percent of patients
of patients at diagnosis, but with medical care being sought earlier, the is on the ordinate, and the cell count is on the abscissa. Fifty percent of
9
presence of splenomegaly at the time of diagnosis is decreasing in fre- patients had a white cell count greater than 100 × 10 /L and a platelet
9
quency. Sternal tenderness, especially the lower portion, is common; count greater than approximately 300 × 10 /L at the time of diagnosis.
247
occasionally, patients notice it themselves.
Uncommon presenting symptoms include those of dramatic may have dramatic cyclic variations in white cell counts as much as an
hypermetabolism (night sweats, heat intolerance, weight loss) simulat- order of magnitude with cycle intervals of approximately 60 days. 267,268
ing thyrotoxicosis; acute gouty arthritis, presumably related in part to Granulocytes at all stages of development are present in the blood and
hyperuricemia; priapism, tinnitus, or stupor from the leukostasis asso- are generally normal in appearance (Fig. 89–7). In this series, the mean
ciated with greatly exaggerated blood leukocyte count elevations 249–251 ; blast cell prevalence was approximately 3 percent but can range from 0
left upper quadrant and left shoulder pain as a consequence of splenic to 10 percent; progranulocyte prevalence was approximately 4 percent;
infarction and perisplenitis; vasopressin-responsive diabetes insip- myelocytes, metamyelocytes, and bands accounted for approximately
idus 252,253 ; and acne urticata associated with hyperhistaminemia. 40 percent; and segmented neutrophils accounted for approximately
254
Acute febrile neutrophilic dermatosis (Sweet syndrome), a perivascular 35 percent of total leukocytes (Table 89–1). Often, there is a “myelocyte
infiltrate of neutrophils in the dermis, can occur. In the latter situation, bulge” in which the differential count shows an exaggerated proportion
fever accompanied by painful maculonodular violaceous lesions on the of myelocytes compared to the proportion observed in normal persons.
trunk, arms, legs, and face are characteristic. 255,256 Spontaneous rupture Hypersegmented neutrophils are commonly present.
of the spleen is a rare event. 257,258 Digital necrosis has been reported as a Neutrophil alkaline phosphatase activity is low or absent in more
rare paraneoplastic event. 259,260 than 90 percent of patients with CML. 269–271 The mRNA for alkaline
In an increasing proportion of patients, the disease is discovered, phosphatase is undetectable in neutrophils of patients with CML. The
272
coincidentally, when blood cell counts are measured at a periodic med- activity increases toward or to normal in the presence of intense inflam-
ical examination.
mation or infection and when the total leukocytic count is decreased to
or near normal with treatment. 271,273 CML neutrophils regain alkaline
CHILDHOOD PRESENTATION phosphatase activity after infusion into leukopenic recipients, suggest-
Hyperleukocytosis and symptoms or signs therefrom are a more ing the effect of regulators or factors extrinsic to the neutrophils. With
common feature in patients who present with CML before the age of the availability of specific markers, BCR-ABL1 in CML and JAK2 muta-
20 years. The white cell counts at diagnosis are on average more than tions in polycythemia, leukocyte alkaline phosphatase is no longer used
twice that in adults, the fraction of blood blasts, promyelocytes, and for diagnostic purposes.
myelocytes is significantly higher, and clinical manifestations of hyper- The proportion of eosinophils usually is not increased, but the
leukocytosis are far more frequent in children than adults. 250 absolute eosinophil count nearly always is increased. Rarely, eosinophils
are so prominent that they dominate the granulocytic cells and lead to
LABORATORY FINDINGS the designation Ph chromosome–positive eosinophilic CML. An absolute
increase in the basophil concentration is present in almost all patients,
Blood and this finding can be useful in preliminary consideration of the dif-
The presumptive diagnosis of CML can be made from the results of the ferential diagnosis. 26,278 Basophilic progenitor cells are increased in the
blood cell counts and examination of the blood film. 26,246,247 The blood blood. The proportion of basophils usually is not greater than 10 to
279
hemoglobin concentration is decreased in most patients at the time of 15 percent during the chronic phase but may, in rare patients, represent
diagnosis. Red cells usually are only slightly altered, with an increase in 30 to 80 percent of the total leukocyte count during chronic phase and
variation from small to large size and only occasional misshapen (ellip- lead to the designation of Ph chromosome–positive basophilic CML.
280
tical or irregular) erythrocytes. Small numbers of nucleated red cells are Flow cytometry using anti-CD203c provides very accurate assessment
commonly present. The reticulocyte count is normal or slightly elevated, of the basophil frequency. Basophils may be hypogranulated or have an
but clinically significant hemolysis is rare. 246,261,262 Rare cases of mild ery- immature phenotype and may be left uncounted in an optical differen-
throcytosis 263,264 or erythroid aplasia 265,266 have been documented. tial white cell count. Anti-CD203c recognizes these cells as basophils.
281
The total leukocyte count is always elevated at the time of diagnosis Granules of basophils in patients with CML, unlike normal basophils,
and is nearly always greater than 25 × 10 /L; at least half the patients have contain mast cell α-tryptase. 281,282 Granulocytes containing both eos-
9
total white counts greater than 100 × 10 /L (Fig. 89–6). 26,246,247 The total inophilic and basophilic granules (mixed granulation) are commonly
9
leukocyte count rises progressively in untreated patients. Rare patients present. 283

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