Aplastic Anemia Patient & Family Handbook

A Handbook for Families

Aplastic Anemia

HEMATOLOGY SERIES

A HANDBOOK FOR FAMILIES

Aplastic Anemia

HEMATOLOGY SERIES

APLASTIC ANEMIA A HANDBOOK FOR FAMILIES

Authors Lynnette Anderson, MS RN CPNP Mollie Haddigan Mulberry, MS RN CPNP CPON ® Susan Burke, MA RN CPNP CPHON ®

Content Reviewer 2015–2016 Steering Council

Parent Reviewer Peter Rodriguez

ABOUT THIS COVER This cover is specially designed for your child to color and personalize. When your child finishes deco- rating the cover, return it to the clinic or doctor’s office where you received the handbook. Your child’s healthcare provider will then send it to APHON for posting on the APHON website. This handbook is published by the Association of Pediatric Hematology/Oncology Nurses (APHON) for educational purposes only. The material has been developed by sources believed to be reliable. The ma- terial is not intended to represent the only acceptable or safe treatment of aplastic anemia. Under certain circumstances or conditions, additional or different treatment may be required. As new research and clinical experience expand the sources of information available concerning the treat- ment of aplastic anemia, adjustments in treatment and drug therapy may be required. APHON makes no warranty, guarantee, or other representation, express or implied, concerning the valid- ity or sufficiency of the treatments or related information contained in this handbook. APHON grants the purchaser of this handbook unrestricted permission to photocopy or print the handbook for educational use by the purchaser or the purchaser’s institution. Purchaser may not alter content or receive monetary gain from distributing photocopies of this product.

n WHAT IS APLASTIC ANEMIA? Aplastic anemia is a bone marrow failure syndrome. The bone marrow “shuts off” and stops producing white blood cells (WBCs), red blood cells (RBCs), and platelets. As a result, children with aplastic anemia are at risk for life-threatening infections, anemia, and bleeding. Children with aplastic anemia can become very sick and may require prolonged hospitalization, blood and platelet transfusions, intravenous (IV) antibiotics, and other medical tests and treatments. n WHAT IS BONE MARROW? Bone marrow is spongy material located within the bones. It is like the “garden” for the body where the blood-forming cells (WBCs, RBCs, and platelets) grow. These cells are formed from a very young stem cell, which is like a seed. As the seed grows, it blossoms into fully functional and mature WBCs, RBCs, and platelets.

n WHAT DO THE CELLS OF THE BONE MARROW DO?

White Blood Cells WBCs help the body fight infection. They are part of the immune system. Different types of WBCs have different functions. Lymphocytes produce antibodies that allow the body to remember an infection. This memory helps the body to fight and control future exposure to these infections and to respond to immu- nizations. If these cells do not work properly, very serious and life-threatening infections can develop. Neutrophils, which are part of the WBCs, specifically fight bacterial and fungal infections. The absolute neutrophil count (ANC) is a calculated percentage of the WBCs that are neutrophils. This number tells you how well your child’s body is able to fight bacterial infection.

ANC is calculated using the following formula: ANC = total WBCs x (segs/polys + bands)

Multiply total WBCs by the total of segs/polys + bands. (Segs or polys are mature WBCs that fight infec- tion. Bands are immature segs or polys that cannot fight infections as well but do help. The segs/polys and bands are both neutrophils. Different labs may use different terminology to identify neutrophils. Your child’s nurse can show you how to calculate the ANC.) Example: WBC is 5. This means 5,000. Your child has 20% segs (0.20) and 5% bands (0.05). Calculate the ANC as follows: ANC = 5,000 x (.20 + .05) ANC = 5,000 x (.25) ANC = 1,250 A child with a low ANC (less than 1,000) is considered neutropenic or not able to fight infection. A child with an ANC less than 500 is considered severely neutropenic.

Red Blood Cells RBCs carry oxygen to all parts of the body. Oxygen is food and nourishment for all the organs, including the heart, lungs, stomach, intestines, and brain, and keeps them working well. Hemoglobin is the protein in the RBCs that attaches to oxygen. Anemia occurs when the blood does not have enough healthy RBCs or hemoglobin. When hemoglobin levels are very low, cells in the body do not get enough oxygen. Platelets Platelets are sticky and help the body control bleeding by clumping together. An example of this is when a cut stops bleeding. As the bleeding slows, the blood cells stick together and form into a clot. If the blood has a low number of platelets, bleeding may be quick and spontaneous (without injury). When platelet levels are very low, a child could bleed into his or her head or another vital part of the body, which can be life threatening. n HOW DID MY CHILD GET APLASTIC ANEMIA? Most cases of aplastic anemia are idiopathic, which means the cause is unknown. We do know that aplas- tic anemia is not caused by anything a parent or child did or did not do. Aplastic anemia has been linked to exposure to radiation and some chemicals, such as benzene. Some inherited diseases, such as Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, and Diamond-Blackfan anemia, have been associated with the development of aplastic anemia. Infections such as Epstein Barr virus, hepatitis, and parvovirus (fifth disease) also have been associated with causing aplastic anemia. n WHAT ARE THE SIGNS AND SYMPTOMS OF APLASTIC ANEMIA? Signs and symptoms of aplastic anemia occur as a result of bone marrow failure. If your child’s WBC count is low, he or she is at risk for developing fever and infection. It is important to monitor your child closely for fever and to contact your healthcare team immediately if a fever develops. If your child’s RBC count is low, he or she may become pale, suffer from fatigue (decreased energy), and experience shortness of breath or headaches. If your child’s hemoglobin level becomes extremely low, he or she may receive a packed RBC transfusion. If your child’s platelet count is low, he or she is at risk for bleeding and can have spontaneous nosebleeds, bleeding gums, excessive bruising, bruising in unusual areas such as the back or chest, and petechiae (pinpoint purple dots on the skin that are small hemorrhages). If your child’s platelet count is very low and he or she is experiencing bleeding, a platelet transfusion may be given.

n HOW IS APLASTIC ANEMIA DIAGNOSED? When a child develops signs of aplastic anemia, one of the first steps to making the diagnosis is a blood test. Blood tests are done by inserting a needle into the child’s arm or hand to draw blood that can be sent to a laboratory for analysis. Drawing blood can be difficult for the child and parent, but it is necessary to obtain an accurate diagnosis. A test called the complete blood count (CBC) measures the number of WBCs, RBCs, and platelets that are circulating in the blood. In a child with aplastic anemia, all of these numbers are low. A reticulocyte count, which assesses the number of healthy young RBCs the body is making, may be low as well.

Your healthcare team also will order a chem- istry panel to check your child’s electrolyte balance and to evaluate how well the kidneys and liver are working. The blood sample also may be be tested for recent viral infections. These tests will help your healthcare team look for other causes of decreased blood counts and help confirm the diagnosis of aplastic anemia. The diagnosis of aplastic anemia is confirmed by a bone marrow aspirate and biopsy. These tests help your healthcare team to understand the reason for your child’s marrow failure

and to rule out other reasons for low blood counts. During a bone marrow aspirate, a needle is inserted through the bone, generally into the iliac crest (hip bone), and a sample of the bone marrow from the spongy space in the bone is removed. The bone marrow is then examined under a microscope by a specially trained doctor (pathologist or hematologist) to see if WBCs, RBCs, and platelets are being pro- duced normally. The pathologist also looks for any abnormal cells, such as immature blood forming cells (blasts), which can indicate leukemia, and dysmorphic (abnormal-looking) cells, which can indicate a dif- ferent disease. The bone marrow also is assessed for protein expression of malignant (cancer) cells, which can indicate leukemia, and chromosomal abnormalities, which can diagnose other diseases. In children with aplastic anemia, protein expression and chromosome tests are normal. A bone marrow biopsy is necessary to diagnose aplastic anemia. During the bone marrow biopsy, a nee- dle is inserted into the hip bone and a small “core,” or a cylinder-shaped piece of the bone, is obtained. The pathologist looks at this core and determines how cellular the marrow is. In children with aplastic anemia, the bone marrow is hypocellular, which means very few of the blood-forming cells are seen under the microscope. The degree of cellularity is graded as a percentage. That percentage helps determine the severity of the aplastic anemia. The bone marrow aspirate and biopsy are performed at the same time. Children usually are given seda- tion or general anesthesia during the procedure to prevent discomfort. Upon awakening from sedation, your child may complain of bone pain at the bone marrow site; however, this pain is usually mild and resolves within 1–2 days. If your child is uncomfortable, a mild pain medication may be given.

n HOW IS APLASTIC ANEMIA CLASSIFIED OR STAGED? The International Aplastic Anemia Study Group has identified specific criteria for the blood and bone marrow values. This criteria is used in the staging of aplastic anemia. The values in the blood are • ANC less than 500 (normal is greater than 1,000) • platelet count less than 20,000 (normal is 150,000–400,000) • reticulocyte count less than 1%. The values in the bone marrow are • bone marrow biopsy with less than 25% of normal cellularity • bone marrow biopsy less than 50% of normal cellularity with the blood-forming cells representing less than 30% of all cells. Severe aplastic anemia (SAA) is defined by meeting at least two of the three criteria for blood and either of the marrow criteria. Very severe aplastic anemia (VSAA) includes the above diagnosis of severe aplastic anemia, but with an ANC less than 200.

n HOW IS APLASTIC ANEMIA TREATED?

HLA Typing Your child’s physician may order human leukocyte antigen (HLA) typing to determine if a bone marrow transplant is a recommended treatment option. HLA typing can be done through a blood sample or a swab on the inside of the cheek. This often is done on the child diagnosed with aplastic anemia, any siblings, and parents. This testing can determine if there is a family member who may be a possible donor for bone marrow transplant or if a search for an unrelated person is needed. HLA are proteins or markers found on the surface of most cells in the body. The immune system uses these markers to recognize which cells belong in your body and which do not. A child generally inherits

half of his or her HLA markers from their mother and half from their father. Siblings who have the same parents have a 25% chance of having the same proteins. When two people share the same HLA pro- teins, this is called a “match.” A biologic parent is generally only half matched, or haploidentical, to their child. For a parent to be matched with his or her child, both parents must by chance have some HLA genes in common with each other. There is only a one in 200 chance that a parent and child will be HLA matched. A close match between a donor’s and a patient’s HLA markers is essential for a successful transplant outcome. Immune Suppression Aplastic anemia is thought to be an autoimmune disorder in which the body’s own immune system attacks the blood-forming cells. Medica- tions that suppress the immune system are used to try to stop this process from continuing. For children who do not have an available matched related bone marrow donor, immunosuppressive therapy is

the standard recommended treatment. Anti-thymocyte globulin (ATG) combined with cyclosporine is the most common first-line therapy. ATG is made from horse or rabbit serum. It is produced by injecting the animals with human lymphocytes (a type of WBC that participates in the body’s immune response), which produces antibodies (a protein made by the immune system) against these lymphocytes that are then harvested. The ATG is then infused into the child and suppresses (lowers) his or her immune system. While receiving ATG, your child will receive antipyretics (fever reducing medication, such as Tylenol), antihistamines (such as Benadryl), and steroids. It is common for children to have fevers and chills during the infusion, and the medications are used to reduce these side effects. ATG is given very slowly through an IV, usually during a 4-day period. Because there is a risk for an adverse reaction to this treatment, children are hospitalized while receiving ATG. Serum sickness is another side effect that usually occurs 1–2 weeks after ATG is given. Symptoms include fever, rash, joint pain, and muscle aches. Serum sickness is treated with steroids and can last from several days to a couple of weeks. The other medication that is used in combination with ATG is cyclosporine. Cyclosporine is a medication that can be given orally (by mouth) or intravenously (into the blood via an IV). This medication is give twice daily and helps to suppress the immune system. It will be started at the beginning of treatment and will continue for 6 months or longer after your child has been discharged from the hospital. Your child’s healthcare team will monitor medication levels of this drug to make sure your child receives a therapeutic dose. This medication can have side effects including kidney damage, high blood pressure, low magne- sium levels in the blood, seizures, and excess hair growth. It is important to discuss any side effects your child may be experiencing with your healthcare team. In November 2018, the U.S. Federal Drug Administration (FDA) approved the medication Eltrombopag (Promacta®) for first-line treatment of severe aplastic anemia in children aged 2 years and older. Eltrom- bopag is an oral medication that is given once a day in combination with standard immunosuppressive therapy. Because data on the use of Eltrombopag in children with aplastic anemia is limited, this medica- tion is usually only offered to children as part of a clinical trial. After discharge from the hospital, children will be seen frequently in the outpatient clinic and their blood counts will be monitored for response to treatment and the need for transfusion. While on immune system suppression, children are at risk for serious infection and need to be monitored closely. They may require supportive care medications to prevent infection or treat organ toxicity. Response to immunosuppressive therapy may be slow and can take 3–6 months. About 75% of children will have improvement or complete recovery of their blood counts. About one-third of children who respond to immunosuppressive therapy will have a recurrence (relapse) of their aplastic anemia. Bone marrow transplant with a matched unrelated donor is the recommended treatment for children who do not respond to their initial course of immune suppression or for those who have a recurrence of aplastic anemia. A second course of immune suppression may be considered for children who do not have an appropriate unrelated donor. Other immunosuppressive drugs also have been tried in place of

cyclosporine, including tacrolimus (Prograf), daclizumab (Zenepax), and mycopheolate (Cellcept). High- dose cyclophosphamide (Cytoxan) also may be considered.

Hematopoietic Stem Cell Transplant

MATCHED SIBLING DONOR For children with an HLA matched family member, generally a matched sibling donor, the recommended treatment is a bone marrow transplant, also called a hematopoietic stem cell transplant (HSCT). Children can proceed to transplant without receiving any other treatment for their aplastic anemia. Children are admitted to the hospital for an HSCT. At the hospital, they have a central line placed (see page 7) to receive medications, IV fluids, and blood products that they will need during their HSCT. Two medications are used to destroy the malfunctioning immune system: ATG and cyclophosphamide (Cytoxan), a chemotherapy agent. After these medications have been given, new, healthy bone marrow that has been harvested (collected) from a sibling is infused into the patient. After approximately 10–20 days, the new marrow starts to grow and repopulates the bone marrow. As a result, blood counts begin to return to normal. Children usually are hospitalized for 20–50 days after an HSCT. During this time, they are monitored closely for complications as they await the growth of the new marrow. When they are transitioned to the outpatient clinic, they are seen frequently and monitored closely for engraftment (growing of the new blood cells) and complications of HSCT, including graft-versus-host disease, infections, and organ toxicity. Matched-sibling HSCT is a very effective treatment for aplastic anemia; however, very serious complica- tions can occur. The greatest risk for complications occurs during the first 2 years after HSCT; therefore, close monitoring is required during this time frame. ALTERNATIVE DONOR TRANSPLANT Children who do not have a matched sibling and do not respond to immune suppression or have recur- rence of their aplastic anemia are often referred for an alternative HSCT. Potential bone marrow donors can be an unrelated person that is identified from the National Marrow Donor Program (NMDP) or a partially matched family member, such as a parent. A member of the bone marrow transplant team will further discuss with you details of identifying a donor if this is needed for your child. This process is similar

to a matched-sibling HSCT but may require dif- ferent medications and possibly radiation for the new bone marrow to grow. Complications of HSCT Children who undergo HSCT are at risk for complications. However, the risks of transplant- related complications are higher with alternative donor transplants. Complications include the following: • Nonengraftment occurs when the new bone marrow does not grow. • Rejection occurs when the child’s own immune system reacts with the donor’s new immune system and the donor’s cells do not grow.

Rejection can sometimes be stopped by making changes to the immune-suppression medica- tions. • Graft-versus-host disease is a process during which the new bone marrow recognizes the child’s body as foreign and attacks certain organ systems, such as the skin, gut, and liver. Symptoms include rash, nausea, vomiting, diarrhea, decreased appetite, and increased liver function tests. • Infections develop as a result of the chemotherapy regimen and immune suppression. Children are at high risk of developing infections. Infections can be caused by bacteria, viruses (often as a result of reactivation of viruses that are already living in the body), fungi, or other organisms. • Toxicity or damage to organs: Multiple organs in the body can be affected. The organ and the extent of damage are dependent on the type of HSCT the child has received as well as the com- plications he or she has experienced. Additional written materials specifically addressing HSCT will be provided if a transplant is recommended for your child.

n SUPPORTIVE CARE

Venous Access Device A venous access device (VAD), sometimes called a central line, is an IV catheter that may be used for the duration of your child’s therapy. There are different types of VAD. Your child’s healthcare team will discuss the risks and benefits of the different types. The VAD is inserted surgically when your child is under sedation or general anesthesia. A VAD can be used to administer medication, blood products, IV fluids, or nutritional support when needed. It also may be used to draw blood for testing purposes. The VAD may remain in your child for the duration of treatment and will be removed during surgery when it is no longer needed. Blood Product Transfusion RBCs are the cells that carry oxygen to different parts of the body. When a child’s hemoglobin is low, his or her heart has to work harder to pump blood. Children with a low hemoglobin level often feel tired (es- pecially with activity), have headaches, and may feel nauseated. Your child may receive an RBC transfusion to increase hemoglobin in the body and to ease the work of the heart by carrying oxygen to all parts of the body. This also may help him or her feel better. Packed RBC transfusions consist of blood donated by healthy people. The blood is stored in a bag and infused into the child through his or her IV access, such as a VAD. Blood transfusion risks include allergic reactions such as itching, hives, or difficulty breathing. Your child will be monitored for a reaction very closely by the nurse. Platelets are the parts of the blood system that prevent and stop bleeding. Children who have a low platelet count are at increased risk of bleeding. They may have bruising, gum bleeding, or little red spots on their skin called petechiae. Platelets can be infused to temporarily increase the platelet count. The platelet transfusion process is similar to an RBC transfusion. The reaction risks are the same, and your child will be monitored closely during the platelet transfusion. Although transfusions of blood and platelets may be necessary to help prevent serious complications,

they should not be given if they are not needed. In the HSCT setting, getting more transfusions can increase the chance of your child rejecting the bone marrow. WBCs help fight infection. Although children with aplastic anemia often have very low WBC counts, WBC transfusions are rarely given because WBCs only live a few hours, and serious side effects may develop. In certain situations, usually if there is evidence of a life-threatening infection, WBC transfusions may be recommended. Growth Factors Growth factors are medications that are given to help increase the body’s own production of various blood cells. They are generally given as a subcutaneous (under the skin) injection or as an IV infusion. WBC growth factors are the most commonly used and include granulocyte colony stimulating factor (G- CSF) or filgastrim (Neupogen), pegfilgastrim (Neulasta), and granulocyte macrophage stimulating factor (GM-CSF). These medications help decrease the risk of infection by increasing the ANC and the body’s ability to fight bacterial infections. Common side effects can include pain or redness at the injection site, bone pain, headache, and nausea. There are growth factors that can stimulate RBC and platelet production. These are typically not used to treat children with aplastic anemia. Your child’s healthcare team will discuss these options with you, if indicated. Infection Children with aplastic anemia are at risk for infection. The lower the ANC, the greater the child’s risk of infection. Children with an ANC less than 500 are at a high risk for infection, and those with an ANC of less than 200 are at very high risk for infection. Children with aplastic anemia will have their ANC monitored closely. Those with a low ANC may require growth factors to increase their ANC. If your child develops a fever with a low ANC, he or she requires prompt medical evaluation no matter what time of the day or night. Medical evaluation includes labora- tory tests, such as blood tests, exams, and other tests to determine the source of the fever. If a bacterial infection is suspected, your child needs to be started on antibiotics and may need to be admitted to the hospital for close observation. Children with aplastic anemia also may require prophylactic or preventative medications to decrease their

risk of developing an infection. Medication to prevent a specific type of pneumonia, called pneumocystic jirovecii pneumonia (PCP), is often needed. Although sulfamethoxazole/trimethoprim (Bactrim) is the best medication to prevent PCP pneumonia, a side effect of the medication is lower blood cell counts; therefore, it is not recommended in children with aplastic anemia. The use of this medication should be discussed with your healthcare provider. Other medications that may be used are pentamidine (given via aerosol or injection) or Dapsone (given orally). Children also may require medication to prevent fungal infections. Flucon- azole (Diflucan) is a commonly used oral medication.

Iron Overload

Iron overload can occur in children who receive multiple RBC transfusions. Excess iron can build up in the liver, heart, and other organs of the body, causing the organ to not function as well as it should. Decreas- ing the number of transfusions a child receives is the best way to prevent iron overload from occurring. For children who develop iron overload, medications called chelators may be prescribed to decrease the amount of excess iron. These medications are either given through an IV, under the skin, or as an oral medication. For children who no longer require transfusions, phlebotomy (removal of RBCs similar to donating a unit of blood) may be recommended to remove excess iron. n WHO WILL CARE FOR MY CHILD? A team of professionals at a specialty clinic will be caring for your child. This team usually consists of specially trained physicians called hematologists. These are doctors who are trained to care for children with blood problems. Nurse practitioners, nurses, pharmacists, social workers, child life specialists, psychologists, and dieticians also may be members of your child’s healthcare team. You and your family are an important part of that team. You know your child better than anyone else. Be sure that you feel comfortable talking to your healthcare team members about symptoms you are noticing; questions you have regarding diagnosis, treatment, and medications; or any other concerns you may have.

n WHAT RESOURCES EXIST FOR CHILDREN DIAGNOSED WITH APLASTIC ANEMIA AND THEIR FAMILIES? Aplastic Anemia and MDS International Foundation www.aamds.org Blood & Marrow Transplant Information Network www.bmtinfonet.org

n HOW CAN I WORK WITH THE HEALTHCARE TEAM? The care of your child requires a team approach. You are a key player on your child’s healthcare team. You know your child better than anyone else and your input is important. Always communicate openly with the other members of your child’s healthcare team. Ask questions when there is anything you are not sure about. It may help to write down your questions as you think of them. This will help you remember all of your questions when you are talking to the healthcare team. Many families find it helpful to create a folder or binder in which they can store all of the information they have received about their child’s diagnosis including copies of laboratory results. This also can be a good place to write down any questions that arise between appointments. Important questions you may want to ask include

• How severe is my child’s aplastic anemia, and what does that mean? • What treatment choices are available? • What treatment do you recommend and why?

• What are the risks or side effects during the treatment? • What are the risks and side effects after the treatment?

• What are my child’s chances for survival? • What are the chances for recurrence?

n ARE MY FEELINGS NORMAL? Hearing that your child has a serious illness is often shocking and overwhelming. Parents often feel numb and have a hard time believing the diagnosis. It is important to know that this is normal and expected. Most families have difficulty processing all of the information the healthcare team is providing to them. However, with time, information will be absorbed. Many families feel somehow responsible for their child’s disease. Feelings of guilt because they could not protect their child from illness or about the amount of time it took to diagnose the child also are com- mon. This disease is not caused by anything that you did or did not do. The cause of aplastic anemia is usually not known. Feelings of sadness, anger, and helplessness about your child’s diagnosis also are common. These feel- ings are normal. Each member of the family may express these emotions in different ways and at different times. Talking honestly with one another about these feelings, emotions, and reactions will help everyone in the family. Keep in mind that there is no right or wrong way to feel. Everyone needs the chance to express their feelings when they are ready and in their own way. Talking to friends, family, and members of the healthcare team can be difficult at times, but expressing your feelings can help you cope. Your child will benefit from family and friends showing their care through communication and support.

n HOW CAN I HELP MY CHILD? Children often think that something they did caused their illness; reinforce that this is not the case. Make sure your child understands that your feelings of anger and sadness are directed at the disease and not at him or her. This will help to keep your relationship honest and to maintain closeness. Your child will

need to share his or her feelings with someone whom he or she trusts. Sometimes, children choose to share their feelings with someone other than a parent because they are afraid they

might upset the parent. Don’t be afraid to ask your child about his or her feelings—it may be what your child is waiting for. Also, don’t be afraid to share information with your child about what is happening and why it is happening. The things children imagine on their own often are more frightening than what is actually happening. In spite of your child’s disease, keep in mind

that he or she is still a child. All children need love, attention, the opportunity to learn and try new skills, and limits. As your child goes through treatment, keep in mind that he or she still has all the needs of a growing child. Do not avoid talking to your child about therapy; use direct terms and explanations your child will understand. Children tolerate treatment better if they understand it and are allowed to help make decisions about their care when appropriate. As a parent, it may be difficult to watch your child go through a serious illness and treatment. Your child may sometimes seem sicker than before the therapy. Your feelings about what your child is going through during treatment must be balanced with the knowledge that treatment provides the chance of curing

the disease and having your child live a full and meaningful life. Ac- cepting the changes in your child that the aplastic anemia and the treatment may cause often is difficult, but keep in mind that many of these changes are often temporary. Always remember that, despite outward changes, your child is still the same person on the inside.

n IS MY CHILD’S DIET IMPORTANT DURING THERAPY?

Your child’s diet is very important during therapy. Research has shown that well-nourished children toler- ate therapy better. Offer foods that are high in calories, protein, and carbohydrates. Small frequent meals often are better tolerated than three larger meals. When possible, avoid junk foods and foods that are high in salt in favor of more nutritious foods. Your child’s hydration status is also an important part of his or her well being. It is important to offer your child fluids to drink frequently throughout the day, or he or she may become dehydrated. Signs of dehy- dration include decreased urine output, dizziness, and a dry mouth. Multivitamins, herbs, and medicines should be avoided unless approved by your child’s healthcare team. These medications may interact with your child’s therapy. A dietician is a part of your child’s healthcare team. He or she is trained in the caloric and nutritional needs of children. The dietician can provide you with information regarding your child’s dietary needs and

ideas about how you can meet these needs during treatment. Your child’s healthcare team will monitor your child’s nutri- tional status, height, and weight during and after treatment to try to prevent problems. When there is a concern about nutri- tional problems, your child’s healthcare team will intervene.

n CAN MY CHILD ATTEND SCHOOL DURING THERAPY?

Your child’s ability to attend school during therapy will depend on the intensity of the treatment, your child’s response to treatment, and how susceptible to infection your child is based on the ANC. There may be extended periods when your child is unable to attend school because of hospitalizations or

treatments. However, it is important that even during these times your child keeps up with his or her schoolwork. Talk with your child’s healthcare team and school about arranging for homebound services, including a tutor, until he or she is able to return to school. Many children’s hospitals have school pro- grams that allow patients to attend school while hospitalized. These programs often help coordinate home tutors and obtain homework and schoolwork. Discuss your child’s ability to attend school with the healthcare team. Some children are able to attend school between hospitalizations or treatments and to use homebound services. The healthcare team can help coordinate the school services your child needs. When a child returns to school for the first time after starting treatment or at the end of therapy, many healthcare teams go to the school to educate teachers and students prior to a student’s return. Once your child does return to school, the healthcare team can continue to assist you with getting any special services your child may need.

n BIBLIOGRAPHY

Bacigalupo, A. (2017). How I treat acquired aplastic anemia. Blood, 129 (11), 1428–1436. Marsh, J. C., & Kulasekararaj, A. G. (2013). Management of the refractory aplastic anemia patient: what are the options?. ASH Education Program Book, 2013 (1), 87–94. Scheinberg, P. (2018). Activity of eltrombopag in severe aplastic anemia. Blood advances, 2 (21), 3054–3062. Scheinberg, P., & Young, N. S. (2012). How I treat acquired aplastic anemia. Blood, 120 (6), 1185–1196. Townsley, D. M., et al. (2017). Eltrombopag added to standard immunosuppression for aplastic anemia. New England Journal of Medicine, 376 (16), 1540–1550. Williams, D. A., et al. (2014). Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): An initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC). Pediatric Blood & Cancer, 61 (5), 869–874.

n IMPORTANT PHONE NUMBERS

n NOTES

8735 W. Higgins Road, Suite 300 Chicago, IL 60631 847.375.4724 • Fax 847.375.6478

info@aphon.org www.aphon.org

Manual para la Familia

Anemia Aplásica

SERIE HEMATOLOGÍA

Manual para la Familia

Anemia Aplásica

SERIE HEMATOLOGÍA

Anemia Aplásica MANUAL PARA LA FAMILIA

Autores Lynnette Anderson, MS RN CPNP Mollie Haddigan Mulberry, MS RN CPNP CPON® Susan Burke, MA RN CPNP CPHON®

Revisor de contenido 2015–2016 Steering Council

Revisor por parte de los padres Peter Rodriguez

ACERCA DE ESTA PORTADA Esta portada está especialmente diseñada para que tu hijo(a) la ilumine y personalice. Cuando tu hijo(a) termine de colorearla, devuélvela a la clínica o al consultorio médico donde te dieron el manual. El encargado de la atención médica de tu hijo(a) la enviará a APHON para que la publiquen en su sitio web. Este manual ha sido publicado por Association of Pediatric Hematology/Oncology Nurses (APHON) con fines educativos únicamente. El contenido ha sido desarrollado por fuentes confiables y no pretende ser el único tratamiento aceptable o seguro para la anemia aplásica. Bajo ciertas circunstancias o condicio- nes, es posible que se requiera un tratamiento adicional o diferente. A medida que nuevas investigaciones y experiencias clínicas amplíen las fuentes de información dis- ponibles sobre el tratamiento para la anemia aplásica, es posible que sea necesario hacer ajustes en el tratamiento y la terapia con fármacos. APHON no garantiza ni asegura, ni hace ninguna otra declaración, expresa o implícita, con respecto a la validez o suficiencia de los tratamientos o a la información relacionada contenida en este manual. APHON otorga al comprador de este manual un permiso ilimitado para fotocopiar o imprimir el manual para uso educativo del comprador o de la institución del comprador. El comprador no puede alterar el contenido ni recibir ninguna ganancia económica por la distribución de fotocopias de este producto.

n ¿QUÉ ES LA ANEMIA APLÁSICA? La anemia aplásica es un síndrome de insuficiencia de la médula ósea. La médula ósea “se cierra” y deja de producir glóbulos blancos (WBC), glóbulos rojos (RBC) y plaquetas. Como resultado, los niños con anemia aplásica corren el riesgo de contraer infecciones o padecer anemia y hemorragias potencialmente mortales. Los niños con anemia aplásica pueden enfermarse gravemente y requerir hospitalización prolongada, trans- fusiones de sangre y plaquetas, antibióticos intravenosos (IV) y otras pruebas y tratamientos médico s. n ¿QUÉ ES LA MÉDULA ÓSEA? La médula ósea es un material esponjoso que se encuentra dentro de los huesos. Es como un “jardín” en el cuerpo, donde crecen las células productoras de sangre: los glóbulos blancos (WBC), los glóbulos rojos (RBC) y las plaquetas. Estas células se forman a partir de una célula madre muy joven, que es como una semilla. A medida que la semilla crece, desarrolla glóbulos blancos, glóbulos rojos y plaquetas completamente funcionales y maduros .

n ¿QUÉ HACEN LAS CÉLULAS DE LA MÉDULA ÓSEA?

Glóbulos blancos o leucocitos (WBC) Los glóbulos blancos forman parte del sistema inmunológico y ayudan al cuerpo a combatir las infec- ciones. Los diferentes tipos de WBC tienen diferentes funciones. Los linfocitos producen anticuerpos que le permiten al cuerpo recordar una infección. Esta memoria ayuda al cuerpo a combatir y controlar una exposición futura a estas infecciones y a responder a las vacunas. Si estas células no funcionan correcta- mente, se pueden desarrollar infecciones muy graves y potencialmente mortales. Los neutrófilos, que forman parte de los glóbulos blancos, combaten específicamente las infecciones bacterianas y fúngicas. El recuento absoluto de neutrófilos (ANC) es un porcentaje calculado de los glóbulos blancos (WBC) que son neutrófilos. Este número indica la capacidad que tiene el cuerpo de tu hijo(a) para combatir las infecciones bacterianas. El recuento absoluto de neutrófilos (ANC), se calcula utilizando la siguiente fórmula: ANC = total de WBC x (segs o polys + bandas) Se multiplica el total de WBC por el total de segs o polys + las bandas. (Los segs o polys son glóbulos blancos maduros que combaten las infecciones. Las bandas son segs o polys inmaduros que no pueden combatir las infecciones con igual eficiencia, pero ayudan. Tanto los segs o polys como las bandas son neutrófilos. Los distintos laboratorios pueden usar terminologías diferentes para identificar a los neutrófi- los. La enfermera de tu hijo(a) te puede enseñar cómo calcular el ANC. Ejemplo: El total de WBC es 5. Esto significa 5,000. Tu hijo(a) tiene 20% de segs (0.20) y 5% de bandas (0.05). El ANC se calcula de la siguiente manera: ANC = 5,000 x (.20 + .05) ANC = 5,000 x (.25) ANC = 1,250

Los niños con un ANC bajo (menos de 1,000) son considerados neutropénicos o no capaces de combatir una infección. Los niños con un ANC inferior a 500 son considerados neutropénicos graves.

Glóbulos rojos Los glóbulos rojos transportan oxígeno a todas las partes del cuerpo. El oxígeno alimenta y nutre todos los órganos, incluyendo al corazón, los pulmones, el estómago, los intestinos y el cerebro, permitiendo que funcionen bien. La hemoglobina es la proteína en los glóbulos rojos que se une al oxígeno. La ane- mia ocurre cuando la sangre no tiene suficientes glóbulos rojos sanos o hemoglobina. Cuando los niveles de hemoglobina son muy bajos, las células del cuerpo no obtienen suficiente oxígeno. Plaquetas Las plaquetas son adherentes y al agruparse ayudan al cuerpo a controlar el sangrado. Un ejemplo de esto es cuando una herida deja de sangrar. A medida que disminuye el sangrado, los glóbulos se unen y forman un coágulo. Si la sangre tiene un número bajo de plaquetas, el sangrado puede ser rápido y es- pontáneo (sin ser causado por alguna lesión). Cuando los niveles de plaquetas son muy bajos, se pueden producir sangrados en la cabeza u otras partes del cuerpo, lo que puede ser mortal. n ¿CÓMO CONTRAJO ANEMIA APLÁSICA MI HIJO(A)? La mayoría de los casos de anemia aplásica son idiopáticos, esto quiere decir que se desconoce la causa. Sabemos que la anemia aplásica no es causada por algo que los padres o los niños hicieron o dejaron de hacer. La anemia aplásica se ha relacionado con la exposición a la radiación y a algunos productos químicos, como el benceno. Algunas enfermedades hereditarias, como la anemia de Fanconi, la disqueratosis con- génita, el síndrome de Shwachman-Diamond y la anemia de Diamond-Blackfan, se han asociado con el desarrollo de la anemia aplásica. Las infecciones como el virus de Epstein Barr, la hepatitis y el parvovirus (quinta enfermedad) también se han asociado con las causas de la anemia aplásica. n ¿CUÁLES SON LOS SIGNOS Y SÍNTOMAS DE LA ANEMIA AP- LÁSICA? Los signos y síntomas de la anemia aplásica aparecen como resultado de la insuficiencia de la médula ósea. Si el recuento de glóbulos blancos de tu hijo(a) es bajo, está en riesgo de desarrollar fiebre e infec- ciones. Es importante controlar a tu hijo(a) de cerca para detectar si tiene fiebre, de ser así, ponte en contacto con el equipo de atención médica de inmediato. Si el recuento de glóbulos rojos de tu hijo(a) es bajo, es posible que se ponga pálido(a), sufra fatiga (disminución de la energía), experimente dificultad para respirar o sufra dolores de cabeza. Si el nivel de hemoglobina se vuelve extremadamente bajo, puede recibir una transfusión de glóbulos rojos. Si el recuento de plaquetas es bajo, está en riesgo de sufrir sangrados y puede tener hemorragias nasales espontáneas, encías sangrantes, hematomas excesivos, hematomas en áreas inusuales como la espalda o el pecho, y petequias (puntos color púrpura en la piel que son pequeñas hemorragias). Si el recuento de plaquetas es muy bajo y está experimentando sangrados, se le puede administrar una transfusión de plaquetas.

n ¿CÓMO SE DIAGNOSTICA LA ANEMIA APLÁSICA? Cuando un niño presenta signos de anemia aplásica, uno de los primeros pasos para hacer el diagnóstico es el análisis de sangre. Los análisis de sangre se realizan insertando una aguja en el brazo o la mano del niño para extraer la sangre que se enviará a un laboratorio para su análisis. La extracción de sangre puede resultar difícil para los niños y los padres, pero es necesaria para obtener un diagnóstico preciso. Una prueba llamada hemograma o recuento sanguíneo completo (CBC) mide la cantidad de glóbulos blancos (WBC), glóbulos rojos (RBC) y plaquetas que circulan en la sangre. En los niños con anemia aplásica, todos estos números son bajos. El recuento de reticulocitos, que mide la cantidad de glóbulos rojos jóvenes y saludables que el cuerpo está

produciendo, también puede ser bajo. El equipo de atención médica también ordenará un perfil químico para verificar el equilibrio electrolítico de tu hijo(a) y qué tan bien están funcionando sus riñones e hígado. Se puede realizar también una muestra de sangre para detectar infecciones virales recientes. Estas pruebas ayudarán al equipo de atención médica a buscar otras causas del recuento sanguíneo bajo y a confirmar el diagnóstico de anemia aplásica. El diagnóstico de anemia aplásica se confirma

mediante un aspirado de médula ósea y una biopsia. Estas pruebas ayudan al equipo de atención médi- ca a comprender la causa de la insuficiencia de médula ósea de tu hijo(a) y a descartar otros motivos para los recuentos sanguíneos bajos. Durante un aspirado de médula ósea, se inserta una aguja a través del hueso, generalmente en la cresta ilíaca (hueso de la cadera), y se extrae una muestra de la médula ósea del espacio esponjoso del hueso. Después, un médico especializado (patólogo o hematólogo) examina la médula ósea bajo un microscopio para ver si los glóbulos blancos (WBC), los glóbulos rojos (RBC) y las plaquetas se están produciendo normalmente. El patólogo también busca células anormales, como células inmaduras productoras de sangre (blastos), que pueden indicar leucemia, y células dismórficas (de aspecto anormal), que pueden indicar una enfermedad diferente. La médula ósea también se examina para determinar la expresión proteica de las células malignas (cancerosas), lo que puede indicar leucemia y anomalías cromosómicas, que son signos de otras enfermedades. En niños con anemia aplásica, la expresión de proteínas y las pruebas cromosómicas son normales. Es necesaria una biopsia de médula ósea para diagnosticar la anemia aplásica. Durante la biopsia de médula ósea, se inserta una aguja en el hueso de la cadera y se obtiene un pequeño “núcleo”, o una pieza del hueso en forma de cilindro. El patólogo observa este núcleo y determina qué tan celular es la médula, o sea qué tantas células productoras de sangre tiene. En niños con anemia aplásica, la médula ósea es hipocelular, lo que significa que se ven muy pocas células productoras de sangre bajo el microscopio. El grado de celularidad se establece en porcentaje. Ese porcentaje ayuda a determinar la gravedad de la anemia aplásica. El aspirado de médula ósea y la biopsia se realizan al mismo tiempo. Los niños generalmente son sedados o reciben anestesia general durante el procedimiento para evitar molestias. Al despertar de la sedación o de la anestesia, tu hijo(a) puede quejarse de dolor de hueso en el sitio de la médula ósea; sin embargo, este dolor suele ser leve y desaparece en 1 o 2 días. Si tu hijo(a) se siente incómodo(a), se le puede dar un medicamento leve para el dolor.

n ¿CÓMO SE CLASIFICA O ESTADIFICA LA ANEMIA APLÁSICA? El International Aplastic Anemia Study Group (Grupo Internacional de Estudios de la Anemia Aplásica) ha establecido criterios específicos de valores de sangre y médula ósea. Estos criterios se utilizan para la estadificación de la anemia aplásica. Los valores en la sangre son: • recuento absoluto de neutrófilos (ANC) menor a 500 (lo normal es mayor a 1,000) • recuento de plaquetas inferior a 20,000 (lo normal es 150,000-400,000) • recuento de reticulocitos inferior al 1%. Los valores en la médula ósea son: • biopsia de médula ósea con menos de 25% de celularidad normal • biopsia de médula ósea con menos de 50% de celularidad normal y con las células productoras de sangre representando menos del 30% de todas las células. Se definirá como anemia aplásica severa (AAS) si se cumplen al menos dos de los tres criterios de los valores en sangre y cualquiera de los criterios de los valores en médula. La anemia aplásica muy grave (VSAA) incluye el diagnóstico anterior de anemia aplásica severa, pero con un ANC menor de 200.

n ¿CÓMO SE TRATA LA ANEMIA APLÁSICA?

Tipificación de antígenos leucocitarios humanos (HLA) El médico de tu hijo(a) puede ordenar un examen de tipificación de antígenos leucocitarios humanos (HLA) para determinar si un trasplante de médula ósea es una opción de tratamiento recomendada. La tipificación de HLA se puede realizar a través de una muestra de sangre o frotando un hisopo en el interior de la mejilla. Esto a menudo se hace con los hermanos y padres de los niños diagnosticados con anemia aplásica. Esta prueba puede determinar si hay un miembro de la familia que puede ser un posible donante para un trasplante de médula ósea o si es necesario buscar una persona ajena a la familia.

Los HLA son proteínas o marcadores que se encuentran en la superfi- cie de la mayoría de las células del cuerpo. El sistema inmunitario usa estos marcadores para reconocer qué células pertenecen al cuerpo y cuáles no. Los niños generalmente heredan la mitad de sus marcado- res HLA de su madre y la otra mitad de su padre. Los hermanos que tienen los mismos padres tienen un 25% de posibilidades de tener las mismas proteínas. Cuando dos personas comparten las mismas proteínas HLA, se dice que son “compatibles”. Un padre o una madre biológico(a) generalmente sólo tiene la mitad de compatibilidad o sea, es haploidéntico con su hijo(a). Para que un padre sea compat- ible con su hijo(a), debe tener algunos genes HLA en común con la madre, y viceversa. Sólo existe una probabilidad entre 200 de que un padre o una madre sea 100% compatible con su hijo(a). Para que el re- sultado del trasplante sea exitoso, es esencial que exista una estrecha coincidencia entre los marcadores HLA del donante y del pacient e.

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