Page 2524 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 155

HEMATOLOGIC MANIFESTATIONS OF MALIGNANCY

Page Widick, Andrew M. Brunner, and Fred Schiffman

Hematologic abnormalities are commonly seen among patients with during therapy this increased to almost 40% and was correlated with
malignancy. These derangements range from the incidental to the a worsening performance status. In the same study, radiation therapy
life-threatening, and may complicate management and require alone had less impact on the incidence of anemia, but the combina-
additional therapy. Hematologic abnormalities can be seen as the tion of chemotherapy and radiation led to a greater degree of anemia
initial manifestation of cancer, providing a crucial diagnostic clue. In than chemotherapy alone. Anemia caused by chemotherapy is related
addition, the hematologic aspects of cancer, as well as the therapies to the cumulative dose, combination of chemotherapeutics, and dose
that we use to treat these irregularities, can provide insight into the schedule. For example, in the treatment of lung cancer with cisplatin
biology of tumorigenesis. This chapter reviews some of the impact and paclitaxel, anemia worsens with an increasing total dose of cis-
that malignancy can have on erythrocytes, leukocytes, platelets, and platin, when cisplatin is added to paclitaxel, and if paclitaxel is given
hemostasis. over a 24-hour period rather than shorter courses.
Anemia in cancer patients can also occur in the setting of red cell
destruction, such as is seen in autoimmune hemolytic anemia, or in
ERYTHROCYTES the setting of microangiopathic hemolytic anemia (MAHA), which
is associated with concurrent thrombocytopenia. Although a true
Anemia incidence of MAHA among cancer patients is difficult to determine,
some studies suggest that 5% to 10% of mucin-producing dissemi-
The most common hematologic manifestation of cancer is anemia; nated adenocarcinomas are associated with a MAHA. It is important
anywhere from 30% to 90% of patients with cancer have documented to distinguish secondary thrombotic microangiopathies (TMAs), as
anemia before the initiation of any treatment. Anemia occurs across seen in patients with malignancy, from thrombotic thrombocytopenic
many different malignancies, including 40% of patients with early- purpura (TTP), given the marked differences in underlying patho-
stage colon cancer and 80% of patients with advanced colon cancer. physiology. TTP is the result of congenital or acquired absence or
The pathogenesis of cancer-related anemia is multifactorial, and can inhibition of the von Willebrand cleaving enzyme, a disintegrin and
arise from direct cancer tissue invasion with resultant blood loss, metalloproteinase with thrombospondin motifs-13 (ADAMTS13).
involvement of the bone marrow, hemolysis, a direct effect of che- Secondary TMAs may have a slight decrease in ADAMTS13 activity,
motherapy or radiation therapy, and chronic renal dysfunction associ- but do not have the severe deficiency of ADAMTS13 activity, with
ated with malignancy, among other causes. These causes can be a level of less than 10%, such as seen in TTP. Accordingly, patients
further divided among anemia resulting from blood loss, anemia with secondary TMAs typically have a poor response to therapeutic
caused by erythrocyte destruction, and anemia caused by a hypopro- plasma exchange. Cancer-associated TMAs may arise from direct
liferative marrow state. A number of cancer-specific mechanisms can endothelial damage rather than diminished ADAMTS13 activity.
be responsible for a hypoproliferative state, including nutritional Cancer patients may also develop a MAHA related to the use of a
deficiencies, decreased erythropoietin (EPO) production because of number of drugs used in the treatment of cancer, including cyclospo-
acute or chronic kidney injury, and injury to the bone marrow itself. rine, mitomycin, and gemcitabine, and antivascular endothelial
The most common nutritional abnormality in cancer-related anemia growth factor (anti-VEGF) agents.
is iron deficiency; up to 29% to 60% of all cancer patients may have
iron-deficiency anemia, which can be secondary to poor oral intake,
as well as from blood loss, commonly seen in gastrointestinal and Treatment of Cancer-Related Anemia
gynecologic malignancies. Compounding any deficiency in total
body iron stores are the effects on erythropoiesis and iron homeostasis Hemoglobin levels typically decrease early in the course of chemo-
as a result of cancer-associated inflammation and cytokine activation. therapy treatment; with greater than half of patients experience a
Many cancers are associated with a systemic inflammatory state, greater than 1 g/dL drop over the course of the first 9 weeks of
manifested by elevated levels of cytokines, which can directly inhibit therapy. The treatment of anemia related to malignancy depends
erythropoiesis and suppress the amount of iron available for erythro- upon correct identification of the underlying etiology. As noted previ-
poiesis. When serum EPO concentrations are measured among ously, iron-deficiency anemia is very common in patients with
cancer patients, these levels are inappropriately low in comparison to malignancy. Among those patients with cancer who have an absolute
patients without malignancy but who have the same degree of anemia iron deficiency (transferrin saturation <20%, ferritin <30 ng/mL),
caused by iron deficiency. Cancer patients also often demonstrate there is evidence that they may benefit from a short course of either
increased levels of hepcidin, a protein critical to iron homeostasis, oral or low-dose intravenous iron. In this setting, the addition of
which acts by decreasing the binding to and breaking down of the erythropoiesis stimulating agents (ESAs) is not necessary.
iron transporter ferroportin. This subsequently results in increased For many patients, transfusion of blood products is an effective
storage of iron in the form of ferritin, and at the same time decreases therapeutic intervention. Red cell transfusion provides rapid symp-
free iron that would be used in erythropoiesis. In contrast to iron tomatic relief and is also a source of iron; one unit of packed red
deficiency, B 12 deficiency is a less common cause of anemia in malig- blood cells (RBCs) contains roughly 200 mg of iron. Logistic limita-
nancy, seen in only 5% to 10% of patients. tions with RBC transfusion, and transfusion-related morbidities have
Many chemotherapeutics have hematologic sequelae; patients spurred the incorporation of ESAs as alternative agents for treating
undergoing treatment may experience varying degrees of anemia anemia in cancer patients. The use of ESAs during myelosuppressive
resulting from chemotherapy-induced bone marrow suppression. The treatment increases the hemoglobin level and decreases transfusion
European Cancer Anaemia Survey prospectively studied over 15,000 requirements by approximately 50%; however, ESA use is associated
patients with a variety of solid tumors undergoing treatment. Before with an increased rate of cardiovascular and thrombotic events, and
therapy, 10% of patients had hemoglobin levels below 10 g/dL, and may be associated with poorer overall survival and time to cancer

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