Fever and Neutropenia Treatment Guidelines for Patients with Cancer – Version II/March 2006

Introduction

With this report, patients have access to information about how fever and neutropenia (new-trow-PEEN-ee-ah;  decrease in infection-fighting white blood cells) are treated at the nation’s leading cancer centers. Originally devised for cancer specialists by the National Comprehensive Cancer Network (NCCN), these treatment guidelines have now been translated for the general public by the American Cancer Society (ACS).

Since 1995, doctors have looked to the NCCN for advice on treating cancer. The NCCN Clinical Practice Guidelines were developed by a diverse panel of experts from 19 of the nations’ leading cancer centers.

For more than 90 years, the public has relied on the American Cancer Society for information about cancer. The Society’s books and brochures provide comprehensive, current, and understandable information to hundreds of thousands of patients, their families and friends. This collaboration between the NCCN and ACS provides an authoritative and understandable source of cancer treatment information for the general public.

These patient guidelines will help you better understand fever and how it is treated when a person has neutropenia. It also gives some background about the risk for and treatment of infection during cancer treatment, and suggestions to help reduce this risk. We urge you to discuss this information with your doctor or nurse and ask questions such as these:

• Will the cancer treatment that I am receiving cause neutropenia?
• How severe is the neutropenia likely to be, and how long is it expected to last?
• Will you be taking any special measures to prevent infections while I have neutropenia?
• What can I do to lower my risk of infection during that time?
• Does the presence of a fever while I have neutropenia mean that I have an infection?
• How will you decide how to treat my infection?
• What can be done if the treatment does not relieve my infection?
• What are the likely side effects of the proposed treatments?

Understanding Fever

Average body temperature is 98.6° Fahrenheit (F.), or 37° Centigrade (C.), but it varies with the time of day and from person to person. It can range between 96.4 and 99.1° F. and still be considered normal. A fever is a body temperature that is higher than normal. The NCCN guidelines define fever as a single temperature reading above 100.9° F (38.3° C), or a temperature higher than 100.4° F (38° C) that lasts for more than an hour.

Fever is often caused by an infection, but it can have other causes. For example, drug reactions, tumor growth, inflammation, and transfusion of blood products can cause fever. Sometimes the cause cannot be found. When you have an infection, the fever is a result of the body’s efforts to kill the germs that have entered your body.

Comparing Centigrade and Fahrenheit Temperatures

Infections

An infection occurs when germs such as bacteria, viruses, protozoa, and fungi enter your body, grow (make more germs), and cause you to be sick. Having cancer and receiving certain types of cancer treatment can increase your chance, or risk, of having an infection. This risk of infection depends on the type of cancer you have and the kind of treatment you receive. For example, surgery does not weaken a person’s resistance to infection nearly as much as having a stem cell transplant. And some chemotherapy drugs are less likely than others to affect a person’s resistance to infection. Although infections in cancer patients can be serious, there are treatments to help the infection go away.

How Your Body Protects Itself

Your body has a normal defense system that includes the skin, the lining of the nose, mouth, gastrointestinal tract (GI tract), and certain blood cells which are part of the immune system. All of these systems work to protect your body from foreign invaders such as germs that cause infections and other things that can make you sick.

Skin and Mucous Membranes

The skin is the body's largest organ. It is the first line of defense in protecting the body. When there is a break in the skin, germs can more easily enter the body and cause an infection. Another protection is the moist pink lining layer (called mucous membrane) of the eyelids, mouth, throat, nose, digestive system, urethra, and vagina. Mucous membranes also help protect us from germs in the air, in the environment, and in our food and drink.

The Immune System and Blood Cells

If germs get through the skin and mucous membranes, the job of protecting the body shifts to the immune system and some of its specialized blood cells. The immune system is a complex organization of cells and organs that work together to help destroy germs that cause infections.

When blood is made, cells in the bone marrow, called stem cells, grow into mature blood cells and are released into the blood stream to carry out their work. There are 3 kinds of blood cells:

• White blood cells or WBCs (leukocytes), of which there are several types
• Red blood cells or RBCs (erythrocytes)
• Platelets (thrombocytes)

Red blood cells carry oxygen to all cells in the body. Cells need oxygen to produce energy for all of the body's functions.

Platelets stop bleeding by clotting the blood. The clots plug up holes in blood vessels that occur from injuries or cuts, such as scrapes or bruises.

The major function of the white blood cells is to defend the body against infections. Unlike RBCs and platelets, WBCs are part of the immune system. There are different types of WBCs, each playing a vital role in the body’s defense. One type, the neutrophil, protects against most types of infections and appears in greatest number in the blood. Neutrophils are sometimes called “segs” or “polys” and young neutrophils are called “bands.”

The other main cells of the immune system are the B lymphocyte (sometimes called B cells), T lymphocyte (called the T cells), and the monocyte. These immune system cells are all made in the bone marrow. They travel in the blood stream until they find germs, or other foreign invaders, to attack. The monocyte can actually swallow and digest germs. The B cell makes special proteins (called antibodies) that find, attach to, and kill specific germs and mark other germs to be destroyed. The T cell produces substances called cytokines that can tell other cells what to do. The T cell can also directly attack germs.

Lowered counts of all types of white blood cells are common during cancer treatment. However, neutrophils are singled out as important markers of immune function because they have such a big role in fighting infections common to cancer patients.

When Your Body's Immune System Doesn't Work Well

Some people with cancer have an increased risk for infection because of the changes in their body’s defense systems. Cancer and treatments for cancer can affect these systems in different ways. Two common effects of cancer and cancer treatment are a weakened immune system and a decreased production of blood cells by the bone marrow. All types of blood cells can be affected. The white blood cells—including the neutrophils—and the platelets are typically affected faster than the red blood cells. When numbers of neutrophils and lymphocytes are decreased, the body cannot protect itself against harmful germs and you are more likely to get an infection. And any infection you get at these times can be more serious than one that occurred if your immune system were normal.

The medical term for a low overall WBC count is leukopenia. Your WBC count is part of the complete blood count (CBC) that is done when a small amount of your blood is taken for a blood test. In the CBC test, a technician counts the numbers of red blood cells and white blood cells in a small quantity of blood (a microliter, or one millionth of a liter, written as µL). Blood normally has between 4,000 and 10,000 WBCs/µL, although this range may vary somewhat depending on your lab. (The normal range for your laboratory is usually listed on your lab report opposite your reported value.)

During cancer treatment, the doctor will also ask for a differential, sometimes called a “diff.” This test sorts the WBCs into different types, then counts each type and reports the percentage of each. So, for example, if you have 10,000 WBCs and 50% are neutrophils, your neutrophil count can be calculated to be 5,000. This is called the absolute neutrophil count, or ANC. (See box “How to Calculate Your Neutrophil Count” on the next page.) This number is very important to know when you have a fever during cancer treatment.

The normal range for the absolute neutrophil count (ANC) is somewhere between 2,500 and 6,000/µL. Neutropenia is the medical name for a decrease in the number of neutrophils in your blood. As the number of neutrophils gets lower, the chance of infection gets higher. If you have a neutrophil count below 500, your risk of infection is increased, and if it drops below 100, you are likely to get an infection—especially if your count stays low for more than a week. Very low neutrophil counts lasting more than a couple of weeks also mean that any infection you do get is likely to be more serious and difficult to treat. Because of this, fever that happens during a period of neutropenia is taken as a call to quick action. Your immune system is likely to need help in fighting infection during this time.

Level of Neutropenia

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CAUSES OF FEVER AND NEUTROPENIA

The mutual goal of the National Comprehensive Cancer Network® (NCCN®) and the American Cancer Society (ACS) partnership is to provide patients and the general public with state-of-the-art cancer treatment information in understandable language. This information, based on the NCCN's Clinical Practice Guidelines, is intended to assist you in the dialogue with your physician. These guidelines do not replace the expertise and clinical judgment of your physician. Each patient's situation must be evaluated individually. It is important to discuss the guidelines and all information regarding treatment options with your physician. To ensure that you have the most up-to-date version of the guidelines, consult the web sites of the ACS (www.cancer.org) or NCCN (www.nccn.org). You may also call the NCCN at 1-888-909-NCCN or the ACS at 1-800-ACS-2345 for the most recent information.

NCCN Clinical Practice Guidelines were developed by a diverse panel of experts. The guidelines are a statement of consensus of its authors regarding the scientific evidence and their views of currently accepted approaches to treatment. The NCCN guidelines are updated as new significant data become available. The Patient Information version will be updated accordingly and will be available on-line through the NCCN and the ACS web sites. To ensure you have the most recent version, you may contact the ACS or the NCCN.

© 2006 by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reproduced in any form for commercial purposes or downloaded and stored in any information-retrieval system without the express written permission of the NCCN and the ACS. Single copies of each page may be printed out for personal, noncommercial use only.