A. Bone marrow suppression is one of the most common problems experienced by patients with cancer.
B. Bone marrow suppression is defined as a reduction in the production and maturation of all blood cell lines of the bone marrow resulting in leukopenia, anemia, and thrombocytopenia of the peripheral blood.
1. Hematopoiesis begins in the yolk sac of the embryo by the third month, but by the end of the seventh month, the bone marrow throughout the body is the primary site of hematopoiesis.
2. By adulthood, hematopoiesis is normally confined to the proximal ends of long bones, and flat bones such as the sternum, vertebrae, ribs, ileum, and skull where the red bone marrow resides.
3. In certain disease states, the marrow can reexpand back into the long bones as well as the spleen and liver, known as extramedullary hematopoiesis.
4. Adults have 1.7 L of bone marrow comprised primarily of reticular tissues and hemopoietic progenitor cells.
5. The reticular tissue and hemocytoblasts form a framework of sinusoids that feed into the marrow drainage system and venous system of the body.
6. The reticular tissue provides support and nutrition for developing blood cells and secretes several colony-stimulating factors.
7. The hemocytoblast, or colony-forming unit, is the pluripotent stem cell.
a. Pluripotent stem cells express a surface protein or antigen, CD34, and have receptors for stem cell growth factors, which promotes their proliferation.
b. Once “committed,” the hemocytoblast becomes a progenitor cell for a specific hematopoietic cell line.
c. These cell lines are erythroid (red cells); granulocytic, monocytic, and lymphoid (white cells); and megakaryocytic (platelets).
d. Commitment, or differentiation and maturation, occurs due to the acquisition or loss of specific growth factor receptors and the action of cytokines.
8. Marrow function is tightly regulated to provide appropriate numbers and types of blood cells needed to meet the body’s physiologic requirements.
a. Glycoprotein hormones, or growth factors, regulate the proliferation, differentiation, maturation, and activation of progenitor and mature blood cells, and prevent apoptosis of them.
b. Each growth factor has a specific receptor and their presence on the cell surface varies with cell lineage and stage of differentiation.
c. Some hematopoietic growth factors include interleukins 1, 3, 5, and 6, granulocyte-macrophage colony-stimulating factor (GMCSF), granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF), thrombopoietin, and erythropoietin.
9. Normally, mature blood cells, except for platelets, enter the bloodstream by migrating through the epithelial lining of the sinusoidal walls. Platelets are released directly from megakaryocytes, which form part of the sinusoidal wall.
II. Etiology:
More than 50% of cancer patients will experience bone marrow suppression during the course of their disease (Shelton, 2003). Like any rapidly dividing cell, the bone marrow is prone to injury. Bone marrow suppression can be related to the cancer itself, cancer treatment, comorbidities, other treatment modalities, or a combination of these factors.
A. Cancer-Induced Bone Marrow Suppression
1. Hematologic malignancies such as leukemias and multiple myeloma involve a defect of a specific blood cell type. Often, this results in overproduction of this cell type, usually with immature, poorly functioning cells; this overproduction results in overcrowding of the marrow compartment with suppression of other cell lines.
2. Lymphomas, which often present as extramedullary disease, can infiltrate the bone marrow leading to decreased function of the cell lines, particularly the lymphocytes.
3. Certain solid tumor malignancies infiltrate the bone marrow in the course of metastasis, most commonly breast and lung cancer.
B. Chemotherapy-Induced Bone Marrow Suppression
1. The organ most consistently and frequently affected by cancer chemotherapeutic agents is the bone marrow, and secondarily the peripheral blood cells.
2. The effect on stem cell lines is predictable based on the agent used.
3. The degree of bone marrow suppression desired or tolerated is a guide for what agent or combination of agents to use, as well as the dosage, the route of administration, and the frequency of administration.
4. A few chemotherapeutic agents affect the pluripotent stem cells, thereby affecting all cell lines; an example is the class of nitrosoureas. These agents tend to be noncycle active and result in the longest period of myelosuppression.
5. Most agents are cell-cycle active, phase nonspecific, such as anthracyclines and alkylators, resulting in a moderate degree of suppression; whereas others are phase specific, such as antimetabolites and vinca alkaloids. Such agents have the shortest degree of suppression.
6. The only chemotherapeutic agents that are completely nontoxic to bone marrow are steroidal hormones (Table 22-1).
7. The rate of proliferation of the three major cell lines, erythrocytes, platelets, and leukocytes, helps determine the severity of depression of that specific cell type.
TABLE 22-1 Myelosuppressive Chemotherapy Agents
Drug or Class
Type of Action
Degree of Myelosuppression
Nadir (days)
Duration of Myelosuppression (days)
Alkylating agents
Cell-cycle nonspecific
Moderate
10-21
18-40
Antimetabolites:
Cell-cycle specific
Anthracyclines
Severe
6-13
21-24
Antifolates
Severe
7-14
14-21
Antipyrimidines
Severe
7-14
21-24
Antipurines
Moderate
7-14
14-21
Antitumor antibiotics
Cell-cycle nonspecific
Moderate
Camptothecins
Cell-cycle specific
Moderate
4-7
6-12
Epipodophyllotoxins
Cell-cycle specific
Moderate
5-15
22-28
Nitrosureas
Cell-cycle nonspecific
Severe
26-60
35-85
Miscellaneous:
Busulfan
Cell-cycle nonspecific
Severe
11-30
24-54
Carboplatin
Cell-cycle nonspecific
Severe
16
21-25
Dacarbazine
Cell-cycle nonspecific
Severe
21-28
28-35
Hydroxyurea
Cell-cycle specific
Moderate
7
14-21
Mitomycin
Cell-cycle nonspecific
Moderate
28-42
42-56
Mithramycin
Cell-cycle nonspecific
Mild
5-10
10-18
Nitrogen mustard
Cell-cycle nonspecific
Severe
7-14
28
Procarbazine
Cell-cycle nonspecific
Moderate
25-36
35-50
Plant alkaloids
Cell-cycle specific
Mild to moderate
4-9
7-21
Taxanes
Cell-cycle specific
Moderate
8-12
15-21
Adapted from Perry, M. C. (Ed.). (2001). The chemotherapy source book (3rd ed., p. 562). Philadelphia: Lippincott Williams & Wilkins.
8. Typically, erythrocytes have a half-life of 120 days, platelets have a half-life of 5 to 7 days, and granulocytes have a half-life of 6 to 8 hours.
a. Generally, leukopenia is the earliest indicator of bone marrow suppression but the quickest to recover.
b. Platelets have the longest nadir.
c. Red cells, with their long half-life, rarely present a serious problem unless a bleeding problem also exists.
9. In the past decade, use of hematopoietic growth factors (colony stimulating factors) has resulted in an earlier recovery of bone marrow cell lines. Their basic mechanism of action is to enhance stem cell differentiation and maturation (Shelton, Ashenbrenner & Shane, 2002).
C. Radiation-Induced Bone Marrow Suppression
1. Occurs after radiation therapy when:
a. The treatment field involves marrow-producing tissue.
b. Patients have received doses greater than 1,500 rads.
D. Miscellaneous reasons for bone marrow suppression, such as other disease states and treatment modalities, will be covered in the following sections on leukopenia, anemia, and thrombocytopenia.
III. Patient management varies depending on the cell line predominantly affected.
Leukopenia
I. Definition:
Leukopenia is defined as a reduced number of circulating leukocytes (white blood cells [WBC]).
A. The two major types of WBC are granulocytes and agranulocytes. Granulocytes include neutrophils, eosinophils, and basophils. Agranulocytes include lymphocytes and monocytes. (See Table 22-2 for specific functions of white cells.)
TABLE 22-2 Types and Functions of Leukocytes and Complications That Present When Their Numbers Are Reduced
Type of Cell
Function
Complication When Reduced or Absent
GRANULOCYTES
Neutrophils
Phagocytosis
Bacterial infections
Eosinophils
Allergic reactions, defense against parasites
Inadequate inflammatory responses, parasitic infections, dermatologic or pulmonary infections
Basophils
Allergic reactions, inflammatory reactions
Inadequate inflammatory responses
AGRANULOCYTES
Lymphocytes
Immunity (T cells and B cells)
Viral or opportunistic infections, cancer
Monocytes
Phagocytosis
Fungal infections
B. Neutropenia is defined as a decrease in the number of neutrophils in the blood.
1. Neutropenia most often occurs in diseases involving bone marrow production, as a result of excess destruction by autoimmune mechanisms or certain marrow toxic treatments, or increased consumption during chronic illness. (See Box 22-1 for specific etiologies.)
a. A diminished number of neutrophils alters the body’s defenses against bacterial invaders.
b. There is some disagreement as to what constitutes neutropenia. Some argue that the condition occurs when the absolute neutrophil count (ANC) is less than 2,500 cells/mm3. Others define it as an ANC less than 1,000 cells/mm3. In patients with normal WBC counts, the higher, more conservative number is used to trigger infection precautions (Shelton, 2003).
C. Lymphocytopenia is defined as a reduction in the number of lymphocytes in the blood.
1. The suppression of T-lymphocyte function results in reduced ability to recognize foreign tissue, malignant cells, and viruses.
2. Lymphocytopenia is seen most commonly in acquired immunodeficiency syndrome (AIDS).
a. The CD4 molecules destroyed by the human immunodeficiency virus (HIV) are reflected in the helper lymphocyte count (also called T4 count, or absolute lymphocyte count).
BOX 22-1 Etiologies of Neutropenia
Malnutrition
Protein deficiency
Calorie deficiency
Vitamin B deficiency
Health States
Chronic fever
Chronic illness
Diabetes mellitus
Elderly
Medications
Alkylating agents (antineoplastic and immunosuppressive; eg, cyclophosphamide)
b. AIDS is classified by the CD4 count and the presence of other defining clinical syndromes.
3. Other etiologies of lymphocytopenia:
a. Therapeutically induced to suppress rejection of a transplanted organ before, during, and after transplantation (see Chapter 5)
b. Certain medications, such as corticosteroids
c. Acquired phenomenon from other physical disorders, suchas intravenous (IV) drug use
d. Genetic abnormalities, such as congenital T-lymphocyte suppression
e. Hodgkin’s disease, which has been linked to familial tendencies, history of viral infection, or unknown congenital causes
f. Acquired specific immune system dysfunctions, such as viralinduced lymphoproliferative disorders. These syndromes may also cause T-cell non-Hodgkin’s lymphoma.
II. Patient Management
A. Assessment: The following are signs and symptoms of leukopenia:
1. Fever is the cardinal symptom of infection.
2. Other inflammatory symptoms (eg, swelling, erythema, pus formation) may not occur due to the lack of WBC.
3. Fatigue with or without infectious complications.
4. Organ-specific signs and symptoms of infection (Table 22-3) are the prevalent clinical presentations for leukopenia. Virtually all who are leukopenic for 21 days become infected, often being colonized by normal body flora.
B. Diagnostic Parameters: Serum tests are the only tests that can be used to detect leukopenia.
1. Total WBC count and differential determine whether there is an adequate number of WBCs to combat infection and mount inflammatory responses to injury. A low WBC count signals the probability of reduced neutrophil efficacy.
a. Normally, the total WBC count is 5,000 to 10,000 cells/mm3.
b. About 35 % to 75% of these cells are neutrophils.
2. The ANC is indicative of the number of neutrophils available to combat infection
a. It is calculated by using the WBC differential with the following formula:
Total number of WBC × % neutrophils = ANC
Example:
5,000 × 0.20 = 1,000
3. CD4 count reflects the absolute number of CD4 molecule-containing cells, which are primarily helper T lymphocyte cells, but also include monocytes (Shelton, 2001).
a. CD4 counts lower than 500/mm3 are considered significant.
b. CD4 counts are used to diagnose, plan treatment, and evaluate therapeutic response to treatment for AIDS.
C. Treatment: Leukopenia is best treated by reversing the underlying cause, if known, and by the administration of growth factors, cytokines, immune globulin, or granulocyte transfusions (Boxes 22-2, 22-3, and 22-4).
D. Nursing Diagnoses
TABLE 22-3 Organ-Specific Signs and Symptoms of Infection
Signs and symptoms presented here are unique features of each process and do not include the common constitutional signs and symptoms seen with all infections (eg, fever, chills, malaise, leukocytosis, positive tissue culture for microorganisms, increased erythrocyte sedimentation rate, adenopathy).
Shelton, B. K. (1996b). Immunologic disorders. In J. Hebra & M. M. Kuhn (Eds.). Manual of critical care nursing (pp. 221-225). Boston, MA: Little, Brown.
Single daily (filgrastim) IV or SQ dose of 5-10 μg/kg every day for up to 2 weeks based on postchemotherapy nadir. Administer slowly SQ, over 1 minute. Administer over 30 minutes IV.
Should not be used 24 hours before to 24 hours after the administration of antineoplastic chemotherapy.
Therapy should be continued within this 2-week time frame until the WBC count reaches 10,000 cells/mm3.
Pegfilgrastim is administered as a single 6 mg IV or SQ injection once per cycle or no more frequently than every 21 days. It is administered 24 hours after the last chemotherapy dose, although same-day administration is currently under investigation. Its prolonged half-life is the consequence of pegylation of the filgrastim molecule.
Nursing Implications
Hypersensitivity reactions may occur. Administer slowly, observing for signs/symptoms of respiratory distress.
Check insurance coverage guidelines for each patient; reimbursement criteria differ among providers.
Monitor WBC and differential.
Prepare patient for possible side effects: fever, bone pain, pain and redness at injection site.
Single daily IV or SQ dose of 250 μg/m2 per protocol. Administer over 2 hours IV.
Should not be used 24 hours before to 24 hours after the administration of antineoplastic chemotherapy.
Nursing Implications
Local skin reaction is common; rotate sites daily.
Prepare patient for side effects of fever, bone pain, myalgias, facial flushing, and redness at injection site.
Mild capillary leak syndrome is rare side effect.
The following electrolyte imbalances may occur: increased glucose, BUN, cholesterol, bilirubin, creatinine, ALT, and alkaline phosphatase; and decreased albumin and calcium.
Therapy should be continued until WBC count reaches 20,000 cells/mm3.
Single dose of 50-150 units/kg every week SQ or a single dose of 40,000 units SQ every week.
IV doses must be 40% to 50% higher than SQ doses.
Darbepoetin has a prolonged half-life due to the addition of sailic acids to the molecule and is administered as an IV or SQ injection of 1-4.5 mcg/kg every 1 to 3 weeks. A common alternative dosing regimen is 200 mcg IV or SQ every 2 weeks
Nursing Implications
Do not shake vial.
Prepare patient for side effects of fever, headache, and fatigue.
Therapy should be continued until HCT reaches 34% to 36%.
Thrombotic events and hypertension may be indications for discontinuation of this agent.
BOX 22-3 Intravenous Administration of Immune Globulin Infusions
Single IV dose of 100-200 mg/kg and retest IgG levels (level should be >300 mg/dL after infusion therapy.
Dilute in large volume of fluid (approximately 1 L) and administer over at least 2 hours.
Nursing Implications
Hypersensitivity may occur. Administer slowly, observing frequent vital signs (every 15 minutes) and signs/symptoms of respiratory distress for the first 30-60 minutes of infusion.
High-volume infusion may precipitate congestive heart failure in susceptible patients. Monitor to detect signs and symptoms early.
Administer through central venous access only; produces severe phlebitis.
Dose may be repeated monthly if levels decrease or clinical improvement is not evident.
1. Potential for infection
a.Problem: Patients with reduced numbers or activity of WBCs are at risk for the development of life-threatening infections. The type of infecting organism will depend on which WBC activities are altered and other host risk factors. The signs and symptoms of infection in the immunocompromised host are subdued because there is insufficient WBC activity to produce the usual inflammatory symptoms.
b.Interventions
(1) Assess for signs and symptoms of infection (see Table 22-3) or sepsis/septic shock (Box 22-5).
(a) Monitor temperature every 2 to 4 hours (inpatient). Rectal temperatures are not advised due to the possibility of breaking the mucosal integrity.
(b) Observe all dressings daily for signs and symptoms of infection.
(c) Inspect all orifices (oral cavity, rectal area, urethra) every shift for evidence of localized infection.
(d) Inspect all excrement every shift for cloudiness, altered color, or odors that may signify infection.
(e) Assess for any localized pain; inspect painful area for erythema, swelling, exudate, or rebound tenderness of abdomen that may signal pocketed infection.
(f) Auscultate breath sounds at least every shift and report new adventitious sounds or diminished breath sounds that may herald pulmonary infection.
(g) Monitor WBC elevations for evidence of infections and response to interventions. If the WBC count is low, assess WBC total count and ANC daily.
(2) Control environmental risks of infection.
BOX 22-4 Intravenous Administration of Granulocytes
Administration Guidelines
Granulocytes must be gamma irradiated before administration.
Administer premedications 15-30 minutes before transfusion of WBC, diphenhydramine 25-50 mg, and acetaminophen 650 mg. Some patients require Solucortef 100 mg.
Obtain baseline vital signs, oxygen saturation, and breath sounds. Notify physician of abnormalities. Ongoing vital signs and breath sounds assessment are performed frequently during the infusion.
Administer via standard blood tubing, primed with normal saline only, without additional filters. Product must be transfused by gravity. Some infusion pumps are thought to damage the cells.
Transfusion must begin within 30 minutes of arrival on unit and infused at a rate of 1 × 1010.
Cells per 30 minutes, not to exceed 500 mL/h.
Gently agitate bottom of bag every 15 minutes to ensure mixing of cells in solution and to prevent settling of WBC in bottom of bag, resulting in bolus effect.
Nursing Implications
Reactions are common, ranging from rash and hives to anaphylaxis and severe respiratory distress.
WBCs should migrate to the site of infection, and the patient may demonstrate rapid onset of symptoms reflecting this WBC infiltration (eg, dyspnea and crackles in the presence of pneumonia).
Have emergency equipment, oxygen delivery system, and suction available.
For rigors during transfusion, administer Demerol 10 mg. IVP every 5 minutes up to 50 mg.
Avoid infusion of amphotericin within 6 hours of WBC transfusion.
(a) Strict handwashing between patients and all procedures to reduce nosocomial infection.
(b) Follow universal precautions.
(c) Cohort neutropenic patients and do not assign with patients who are infected.
(d) Monitor visitors for any recent history of communicable disease and institute precautions as indicated.
(f) Do not permit live flowers or standing water (eg, in vases) in the patient’s room because these may harbor bacteria.
(3) Implement patient care routines to prevent infections and to enhance immune system functioning.
(a) Bathe patient and change linen daily; perform oral care three to four times daily and perineal care twice daily. Minimize use of lotions and deodorants, which enhance bacterial growth.
BOX 22-5 Phases of Sepsis
Hyperdynamic (Warm Shock)
Hypodynamic (Cold Shock)
SBP (systolic blood pressure) <90 mm Hg, or >40 mm below baseline, low diastolic pressure
Profound hypotension, relatively high diastolic pressure
High cardiac output
Low cardiac output
UO < 0.5 mL/kg/h
Anuria
Warm, flushed, dry skin
Cold, pale, clammy skin
Increased heart rate
Tachycardia, dysrhythmias
Bounding pulses
Weak, thready pulse
Fever
Decreased core body temperature
Decreased level of consciousness
Decreased LOC
Increased respiratory rate
Shortness of breath
Decreased respiratory depth
Decreased respiratory depth
Crackles
Crackles, wheezes
Increased WBC count
Increased or decreased WBC count
Hyperglycemia, amylase increased
Hypoglycemia, increased serum and lipase
Metabolic acidosis/respiratory alkalosis
Metabolic/respiratory acidosis
Thrombocytopenia increased
Decreased clotting factors, liver transaminases
Increased fibrine degradation products (FDPs)
Increased bilirubin, BUN
Increased creatinine
(b) Ensure that nutritional needs are being met.
(c) Protect the patient from consuming possibly contaminated foods by labeling all foods brought from home to be discarded in 1 to 2 days. Avoid commercial foods with meat, seafood, eggs, or mayonnaise. Clean fresh fruits and vegetables before giving them to the patient. Some institutions require a “cooked food diet,” in which only foods previously cooked are permitted—no fresh fruits or vegetables, nuts, or unprocessed herbs are permitted; patients drink only bottled water and processed beverages. This practice has not been validated by research (Shelton, 2003).
(d) Ensure that sleep needs are being met.
(e) Control glucose levels so unintentional hyperglycemia does not occur (hyperglycemia compromises phagocytic activities that fight infection).
(f) Use sterile technique for inserting and dressing IV catheters. Dressings should be changed at least every 24 hours if site is draining, less frequently if site is dry and dressing is occlusive.
(g) Cover all open wounds with a sterile dressing. Skin abrasions may be treated with antimicrobial ointment and dressings—or open air, provided that frequent cleansing is performed.
(h) Encourage incentive spirometry or deep breathing and coughing.
(i) Encourage ambulation if patient is physically able, or turn bedridden patients every 2 to 4 hours to prevent skin breakdown and atelectasis.
(j) If building construction is occurring, consider applying a mask on the patient during intrahospital transport. If hepa-filtration or other airflow protection is provided to patients while in the unit and building air systems are old, masks may be considered for transport of these patients as well.
(k) Avoid stopcocks in hospital IV systems; use closed injection-site systems.
(l) Change IV tubing every 96 hours if a closed system is maintained. More frequent changes are advocated if the line is open, or blood or total parenteral nutrition has been administered through the tubing.
(m) Consider closed endotracheal tube suction systems, provided there is an in-line flush port to clean the catheter after each use.
(n) Change oxygen set-ups that have standing water (eg, nasal cannula) every 24 hours.
(4) Institute rapid treatment measures for suspected infections.
(a) For first fever or new fever, perform routine culture and assessment activities as indicated or ordered before initiation of antimicrobial therapy. New fever is defined as one that exceeds 38.3°C initially or after 72 hours on an antibiotic regimen. A temperature of 38.0°C on two separate occasions at least 4 hours apart may also be considered a new fever (Shelton, 2003). Box 22-6 lists the routine culture and assessment functions that should be performed.
Only gold members can continue reading. Log In or Register to continue
BOX 22-1 Etiologies of Neutropenia
BOX 22-2 Cell Line Stimulating Factors
BOX 22-3 Intravenous Administration of Immune Globulin Infusions
BOX 22-4 Intravenous Administration of Granulocytes
BOX 22-5 Phases of Sepsis
