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1286 Part X: Malignant Myeloid Diseases Chapter 83: Classification and Clinical Manifestations of the Clonal Myeloid Disorders 1287

and renal failure ensues. Hyponatremia can occur in AML, and in of glucose, especially in polycythemic patients. True hypoglycemia has
some cases results from inappropriate antidiuretic hormone secretion. been observed rarely in patients with leukemia. Arterial blood oxygen
Hyponatremia also can result from an osmotic diuresis of urea, creatin- content also can be lowered spuriously as a result of in vitro utilization
ine, urate, and other substances released from blast cells and wasting by large numbers of leukocytes, while the anticoagulated blood awaits
muscles. Hypernatremia is rare but may be seen in cases with central measurement.
diabetes insipidus. Hypokalemia is commonly seen in AML 89–91 and is
thought to be caused by injury to the kidney by increased plasma and
urine lysozyme and subsequent kaliuresis. Hypokalemia is related to SPECIFIC ORGAN INVOLVEMENT
excessive urinary potassium loss, but the correlation with lysozymuria
is imperfect. Other mechanisms probably are responsible in most cases, Clonal myeloid diseases lead to disturbances principally in marrow,
including osmotic diuresis and tubular dysfunction. Kaliuretic antibiot- blood, and spleen. Although clusters of cells may be found in all organs,
ics, often administered to patients with AML, may accentuate the hypo- major infiltrates and organ dysfunction are unusual. In AML and the
kalemia. Hyperkalemia is very unusual, but may be seen with tumor acute blastic phase of CML, clinically significant infiltration of the lar-
lysis syndrome. Hypercalcemia occurs in occasional patients with AML. ynx, central nervous system, heart, lungs, bone, joints, gastrointestinal
Several causes have been proposed, including bone resorption as a result tract, genitourinary tract, skin, or virtually any other organ can occur.
of leukemic infiltration. This explanation is in keeping with the nor-
mal serum inorganic phosphate in most patients. Occasional patients Splenomegaly
with hypercalcemia, and hypophosphatemia can have ectopic parathy- In AML, palpable splenomegaly is present in approximately one-third
roid hormone secretion by leukemic blast cells. Hypophosphatemia of cases, but usually is slight in extent. In the chronic myeloproliferative
also can occur because of rapid utilization of plasma inorganic phos- diseases, palpable splenomegaly is present in a high proportion of cases
phate in some cases of myelogenous leukemia with a high blood blast (polycythemia vera ~80 percent, CML ~90 percent, primary myelofibro-
cell count and a high fraction of proliferative cells. Hyperphosphate- sis ~100 percent). In essential thrombocythemia, splenic enlargement
mia is uncommon, except as a reflection of the tumor lysis syndrome. is present in approximately 30 percent of patients. A predisposition
Approximately 10 percent of persons with AML show varying degrees to silent splenic vascular thrombi, infarction, and subsequent splenic
of tumor lysis syndrome in the week after onset of therapy, reflected in atrophy, analogous to that occurring in sickle cell anemia, is postulated
at least doubling of baseline creatinine, and increases in serum phos- as the cause of the lower frequency of splenic enlargement in essen-
phate (>1.6 mmol/L [>5 mg/dL]), uric acid (>416 mmol/L [>7mg/dL]), tial thrombocythemia. Early satiety, left-upper-quadrant discomfort,
or potassium (>5 mmol/L [>5 mEq/L]). Hypomagnesemia is common splenic infarctions with painful perisplenitis, diaphragmatic pleuritis,
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as a result of low intake coupled with gastrointestinal loss and a shift of and referred shoulder pain may occur in patients with splenomegaly,
magnesium to the intracellular compartment. especially in the acute phase of CML and in primary myelofibrosis. In
Acid–base disturbances occur in approximately 25 percent of primary myelofibrosis, the spleen can become enormous, occupying the
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patients, the majority having respiratory or metabolic alkalosis. The left hemiabdomen. Blood flow through the splenic vein can be so great
latter may be secondary to volume depletion, upper gastrointestinal as to lead to portal hypertension and gastroesophageal varices. Usually,
fluid loss, and hypokalemia. Lactic acidosis also has been observed reduced hepatic venous compliance also is present (Chap. 86). Bleed-
in association with AML, although the mechanism is obscure. True ing and, occasionally, encephalopathy can result from portal–systemic
hypoxia can result from the hyperleukocytic syndrome as a conse- venous shunts.
quence of pulmonary vascular leukostasis (see also “Factitious Labora-
tory Results” below). Marrow Necrosis
Increased serum concentrations of lipoprotein (a) and decreased Extensive marrow necrosis, an uncommon event, can occur in any
concentrations of both low-density and high-density lipoproteins clonal myeloid disease, especially AML, and less often, primary mye-
93
have been observed in a high proportion of patients with AML. The lofibrosis, CML, essential thrombocythemia, and polycythemia vera.
increased level of lipoprotein (a), which returns to normal after success- Bone pain and fever are the most common initial findings. Anemia
ful treatment, correlates with the presence of leukemic blast cells. Serum and thrombocytopenia are very common, as are nucleated red cells
94
prolactin also is increased in some patients with AML. Leukemic blast and myelocytes in the blood (leukoerythroblastic reaction). 96,97 Marrow
cells may be an ectopic source of this hormone. 94 aspiration does not result in a useful sample but biopsy early in the pro-
Colony-stimulating factor-1 is elevated in a variety of lymphoid cess usually shows hypocellularity with loss of marrow cell structural
and hemopoietic malignancies, including AML and CML. The malig- definition (blurred staining of residual cells), evidence of cell necro-
95
nant cells have been proposed as the source of excess cytokine. sis, gelatinous transformation of marrow, and, often, an amorphous
eosinophilic material throughout. The mechanism is thought to be
microvascular dysfunction. Restitution of marrow and repopulation of
FACTITIOUS LABORATORY RESULTS hematopoietic tissue often may follow. The prognosis is a function of the
Elevations of serum potassium levels have resulted from the release underlying disease.
of potassium from platelets or, less often, leukocytes in patients with
myeloproliferative diseases and extreme elevations in those blood cell
concentrations. If blood is collected in a tube that contains an antico- REFERENCES
agulant and the plasma is removed after high-speed centrifugation, the
potassium concentration is normal. Glucose can be falsely decreased, 1. Dick JE, Lapidot T: Biology of normal and acute myeloid leukemia stem cells. Int J
Hematol 82:389, 2005.
especially because autoanalyzer techniques call for omission of glyco- 2. Eppert K, Takenaka K, Lechman ER, et al: Stem cell gene expression programs influ-
lytic inhibitors such as sodium fluoride in collection tubes. Blood with ence clinical outcome in human leukemia. Nat Med 17:1086, 2011.
high leukocyte counts, if it stands prior to separation of the plasma, may 3. Pei S, Jordan CT: How close are we to targeting the leukemia stem cell? Best Pract Res
Clin Haematol 25:415, 2012.
have a significant amount of glucose metabolism by leukocytes. Fac- 4. Rozman CGM, Feliu E, Rubio D, et al: Life expectancy of patients with chronic nonleu-
titious hypoglycemia also can occur as a result of red cell utilization kemic myeloproliferative disorders. Cancer 67:2658, 1991.

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