Understanding Childhood Non-Hodgkin Lymphoma A Guide for Patients, Survivors and Loved Ones First Edition Understanding Childhood Non-Hodgkin Lymphoma A Guide for Patients, Survivors and Loved Ones First Edition This guide is an educational resource compiled by the Lymphoma Research Foundation providing general information on childhood non-Hodgkin lymphoma. Publication of this information is not intended to take the place of medical care or the advice of your physician. Patients are strongly encouraged to talk to their physician for complete information on how their disease should be treated and followed. Before starting treatment, patients should discuss the potential benefits and side effects of cancer therapy with their physician. National Headquarters 115 Broadway, 13th Floor New York, NY 10006 (212) 349-2910 phone (212) 349-2886 fax Helpline:(800) 500-9976 [email protected] Website: lymphoma.org Email: [email protected] This project is supported through Cooperative Agreement Number 1U58DP001110 from the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention. © 2010 Lymphoma Research Foundation Information contained herein is the property of the Lymphoma Research Foundation (LRF). Any portion may be reprinted or reproduced provided that LRF is acknowledged to be the author. ACKNOWLEDGMENTS The Lymphoma Research Foundation wishes to acknowledge those individuals listed below who have given generously of their time and expertise. We thank them for their contributions, editorial wisdom and advice, which have truly enhanced this publication. Without their dedication and efforts this publication would not have been possible. We hope those in the lymphoma community will now be better informed and have a better understanding of their illness because of the gracious efforts of those involved in the planning and execution of this comprehensive disease guide. Editorial Board Laura J. Eisenberg, BSN, MN, ARNP, Seattle Children’s Anna R. Franklin, MD, MD Anderson Cancer Center Melanie Goldish, SuperSibs! Rebecca H. Johnson, MD, Seattle Children’s Barbara L. Jones, PhD, University of Texas at Austin School of Social Work Jennifer Mills, LMSW, MPH, New York University School of Social Work Sandi Ring, MS, CCLS, SuperSibs! Stuart E. Siegal, MD, Childrens Hospital Los Angeles James Testaverde, BS, Lymphoma Research Foundation Brian Tomlinson, MPA, BSW, Lymphoma Research Foundation Tim Walker, MA, National Marrow Donor Program ii Understanding Childhood Non-Hodgkin Lymphoma Table of Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Chapter 1 Cancer Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Lymphoma Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Non-Hodgkin Lymphoma Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Common Types of Childhood Non-Hodgkin Lymphoma . . . . . . . . . . . . . . . . . . . . The Causes of Non-Hodgkin Lymphoma in Children . . . . . . . . . . . . . . . . . . . . . . . 3 3 6 7 9 Chapter 2 Diagnosing Childhood Non-Hodgkin Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . Use of Conscious Sedation When Performing Diagnostic Tests . . . . . . . . . . . . . Common Diagnostic Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 11 12 15 Chapter 3 Childhood Cancer Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Unique Features of Childhood Cancer Clinical Trials . . . . . . . . . . . . . . . . . . . . . . Enrolling Children in Clinical Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Understanding the Clinical Trial Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Use of a Placebo in Phase III Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 17 18 20 21 Chapter 4 Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Radiation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . What Happens If Relapse Occurs? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 23 27 27 Chapter 5 Supportive Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Side Effects of Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35 Chapter 6 Coping with Childhood Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . What Children Need and Hope For After a Lymphoma Diagnosis . . . . . . . . . . . . Emotional Coping for Parents, Adult Family Members and Friends . . . . . . . . . . Support for Siblings of Children with Lymphoma . . . . . . . . . . . . . . . . . . . . . . . . 41 41 43 44 Chapter 7 Long-Term and Late Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Glossary of Medical Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Childhood Cancer Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 Young Adult Cancer Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 About the Lymphoma Research Foundation . . . . . . . . . . . . . . . . . . . . . . . . . . . 69 Donate Now . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Understanding Childhood Non-Hodgkin Lymphoma iii Please refer to our website for additional and updated information. lymphoma.org iv Understanding Childhood Non-Hodgkin Lymphoma Introduction This guide is designed for parents and loved ones of children and teens diagnosed with non-Hodgkin lymphoma (NHL) below the age of 18. If you are looking for resources on adults diagnosed with lymphoma, please refer to the Lymphoma Research Foundation’s comprehensive guides on adult lymphomas (www.lymphoma.org/ aboutlymphoma). If you are looking for resources on children diagnosed with Hodgkin lymphoma, please visit the Leukemia and Lymphoma Society’s website (www.lls.org.). Since the 1970’s research has led to significant improvements in outcome for children with NHL. With appropriate medical therapy, childhood NHLs are curable for over 80 percent of patients. Recent data suggests cure rates as high as 90 percent to 95 percent, depending on the type of tumor. Even for those children who develop recurrent disease, cures can often be achieved. It is important to remember that childhood NHLs are very different from other types of cancer in this respect. Furthermore, childhood cancers, as a group, have better outcomes than adult cancers. Because of the significant differences that exist between adult NHL and childhood NHL, it is crucial to find a designated pediatric cancer center for advice and treatment and to use childhood-specific NHL information for reference. This guide is divided into seven chapters. The material provides an overview of lymphoma and discusses: the different subtypes of lymphoma most common among children and teens, how lymphoma is diagnosed, the importance of clinical trials, available treatment options, supportive care issues, how to cope with the diagnosis, and the long-term and late effects that result from lymphoma treatments. Understanding Childhood Non-Hodgkin Lymphoma 1 Please refer to our website for additional and updated information. lymphoma.org 2 Understanding Childhood Non-Hodgkin Lymphoma 1 Chapter 1 Cancer Overview This chapter will present a broad overview of cancer and, more specifically, non-Hodgkin lymphoma. Childhood lymphomas are divided into two categories: Hodgkin lymphoma (HL) and nonHodgkin lymphoma (NHL). This chapter will focus exclusively on describing the biology of NHL in childhood. Cancer Overview The human body is composed of millions of cells that grow and divide in an orderly fashion to support thousands of biological functions. Cells divide routinely to replace cells that are damaged or dying. Cancer results from an uncontrolled growth and spread of abnormal cells. Cancer cells develop when there is damage to the cell’s DNA (the hereditary material found in every cell). This damage can be caused by an inherited genetic abnormality and/or exposure to something in the environment, such as smoking. The body’s immune system usually destroys damaged cells, but sometimes these abnormal cells evade the body’s defenses and grow uncontrollably, eventually forming a cancerous tumor. Lymphoma Overview Lymphoma, a type of blood cancer, is more common in adults than in children. Approximately 98 percent of all NHLs occur in adults, with only 1.7 percent occurring in those under the age of 20. In children, lymphoma is the third most common cancer. Lymphoma usually develops when a genetic error, or mutation, occurs within a lymphocyte (a white blood cell), causing the abnormal lymphocyte to duplicate faster, or live longer, than a normal lymphocyte. Cancerous lymphocytes can travel to many parts of the body, through the blood stream and the lymphatic system, and form tumors. Understanding Childhood Non-Hodgkin Lymphoma 3 Anatomy of the Immune System The immune system is the body’s defense against outside invaders. Tonsils and adenoids Lymph nodes Thymus Lymph nodes Lymph nodes (epitrochlear) Spleen Peyer’s patches (inside the abdomen) Appendix Bone marrow Lymph nodes Lymphatic vessels 4 Understanding Childhood Non-Hodgkin Lymphoma 1 Immune System Invaders Many of these invaders come from outside the body. The immune system is the body’s defense. It acts like a shield to detect and defeat these invaders. Bacteria Viruses Parasites Fungi Pollution Toxins How Cancer Forms Inside the body Sometimes the threat comes from within the body. Cancer occurs when abnormal cells cannot be controlled and continue to grow and multiply. Abnormal Cells Evade the Immune System Abnormal Cells Multiply (Cancer) Tumors May Form (Groups of Abnormal Cells) Understanding Childhood Non-Hodgkin Lymphoma 5 The Lymphatic System The lymphatic system is a circulatory system made up of a series of thin tubes called lymph vessels, which branch out like blood vessels into all tissues of the body. Lymph vessels carry lymph, a fluid that contains lymphocytes. Within this vast network of vessels are groups of small, bean-shaped organs called lymph nodes. Thousands of lymph nodes are found throughout the body, including the neck, armpits, groin and elbows. Lymph fluid flows through lymph nodes and specialized lymph tissues, such as the spleen, tonsils, bone marrow and thymus gland. Lymph nodes filter lymph fluid, removing bacteria, viruses and other foreign substances from the body. How Lymphocytes Work Lymphocytes, a type of white blood cell, are made in the bone marrow, spleen and lymph nodes, and circulate in the blood and lymph vessels. There are two main types of lymphocytes: B-lymphocytes and T-lymphocytes. Each type of lymphocyte plays a role in helping the body fight infections. Non-Hodgkin Lymphoma Overview The two main forms of lymphoma are Hodgkin lymphoma and non-Hodgkin lymphoma (NHL). The World Health Organization has identified six types of Hodgkin lymphoma and 61 types of NHL. Although the various types of NHL have some things in common, such as their lymphatic origin, they differ in their appearance under the microscope, the proteins found on the surface of the cancer cells, their growth patterns and their impact on the body. Different forms of NHL require different therapies. Non-Hodgkin lymphoma has grown from being a relatively uncommon disease to being the fifth most common cancer in the United States, nearly doubling in incidence since the early 1970s. According to the American Cancer Society, over 65,000 new cases of NHL are diagnosed annually in the United States. 6 Understanding Childhood Non-Hodgkin Lymphoma 1 Non-Hodgkin lymphoma is divided into two major groups: B-cell lymphomas and T-cell lymphomas. B-cell lymphomas develop from abnormal B-lymphocytes (“B” because B-lymphocytes come from the bone marrow) and account for 85 percent of all NHLs. T-cell lymphomas develop from abnormal T-lymphocytes (“T” because normally T-lymphocytes spend part of their lifespan in the thymus gland, a small organ in the chest) and account for the remaining 15 percent of NHLs. Common Types of Childhood Non-Hodgkin Lymphoma There are many different types of NHL. Correctly identifying or diagnosing the type of lymphoma a child has is critical because an accurate diagnosis allows the physician to select the most appropriate treatment for the child. (Diagnostic tests are described in Chapter 2.) Childhood NHLs can be broadly divided into four categories: 1. Lymphoblastic Lymphoma Lymphoblastic lymphoma is a type of NHL. However, this disease is often treated using protocols originally developed for a specific type of leukemia (a different form of blood cancer), called acute lymphoblastic leukemia. The survival rate for children with advanced stage lymphoblastic lymphoma is 60 percent to 80 percent. 2. Mature B-cell NHL Burkitt Lymphoma Burkitt lymphoma is an aggressive B-cell NHL that occurs in children and young adults far more commonly than in older adults. It accounts for approximately 50 percent of childhood NHL in the United States. There are three main types of Burkitt lymphoma: sporadic, endemic and immunodeficiency-related disease. While sporadic Burkitt lymphoma occurs throughout most of the world, endemic Burkitt lymphoma is found mostly in Africa, with the vast majority of cases associated with the Epstein-Barr virus (EBV). Immunodeficiencyrelated Burkitt lymphoma is diagnosed most often in people with Understanding Childhood Non-Hodgkin Lymphoma 7 Common Types of Childhood Non-Hodgkin Lymphoma Childhood NHL Lymphoblastic Lymphoma Mature B-Cell Lymphoma Diffuse Large BCell Lymphoma (DLBCL) Anaplastic Large Cell Lymphoma (ALCL) Other Rare Subtypes: (PTCL/NK) Burkitt Lymphoma congenital immunodeficiency or those infected with HIV. Common sites of disease include the jaw, central nervous system, bone marrow, bowel, kidneys, ovaries and testes. Burkitt lymphoma is considered one of the fastest growing cancers—the number of tumor cells doubles every 24 hours. Despite its fast growth, this type of lymphoma is often very responsive to chemotherapy. This is because the faster a tumor cell divides the more likely it is to be killed by treatment. Therefore, the treatments are usually very intense, with only a short time interval between courses of chemotherapy, so that tumors do not re-grow. The overall survival rate for children diagnosed with Burkitt lymphoma in the United States is 90 percent. Diffuse Large B-cell Lymphoma Diffuse large B-cell lymphoma (DLBCL) is the most common form of NHL in adults, but it is relatively rare in children. The disease is an aggressive (fast-growing) lymphoma and can arise in the lymph nodes or outside of the lymphatic system. It may be localized or generalized (spread throughout the body). Despite being an aggressive lymphoma, DLBCL is usually curable. Survival rates are extremely high for children diagnosed with DLBCL. 8 Understanding Childhood Non-Hodgkin Lymphoma 1 3. Anaplastic Large Cell Lymphoma Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma comprising 10 percent to 30 percent of all lymphomas in children and 3 percent of all lymphomas in adults. It is the most common T-cell malignancy in children. Anaplastic large-cell lymphoma can appear in the skin or in other organs throughout the body, also known as systemic ALCL. Patients with systemic ALCL are divided into two groups, depending on the expression of a protein called anaplastic lymphoma kinase (ALK). The prognosis is different based on whether a patient is ALK positive (expresses the protein) or ALK negative (does not express the protein). While both subtypes are treated with chemotherapy, ALK positive disease often responds permanently to chemotherapy, putting most patients in long-term remission or cure. A larger percentage of patients with ALK negative ALCL will relapse and potentially require more aggressive chemotherapy. 4. Other Rare Subtypes Other rare subtypes of childhood NHL exist. For more information on these rare subtypes, consult a physician specializing in pediatric lymphomas. The Causes of Non-Hodgkin Lymphoma in Children Although the exact causes of NHL remain unknown, some common factors appear to have an impact on risk. The disease is more common among people with depressed immune systems and those exposed to environmental carcinogens, pesticides, herbicides, viruses and certain bacteria. The risk for developing lymphoma may be higher in individuals who: •have a family history of NHL •are immune-deficient due to either an inherited immunodeficiency (such as common variable immunodeficiency or autoimmune lymphoproliferative syndrome, also known as ALPS) or an infection (such as human T-lymphotropic virus type 1, also known as HTLV-1, or HIV/AIDS) Understanding Childhood Non-Hodgkin Lymphoma 9 •have received an organ transplant •have been exposed to chemicals such as pesticides, fertilizers or organic solvents for a long period •have been infected with viruses such as Epstein-Barr (which causes mononucleosis), which is associated with Burkitt lymphoma It is important to note that having one or more of these risk factors does not mean a person will develop NHL. In fact, most people with risk factors never develop the disease, and most of those diagnosed with lymphoma have never been exposed to clearly identifiable risk factors. While researchers do not know why NHL develops, they do know that it cannot be caused by injury or caught from someone who has the disease. Please refer to our website for additional and updated information. lymphoma.org 10 Understanding Childhood Non-Hodgkin Lymphoma 2 Chapter 2 Diagnosing Childhood NHL Determining what type of lymphoma a patient has and where it is located in the body is important information for both the physician and the patient. An accurate diagnosis of childhood non-Hodgkin lymphoma (NHL) requires a number of tests. Physicians may use some or all of the following tests as well as the patient’s medical history and results from the physical examination to assess the best course of treatment: (1) blood tests, (2) biopsy, (3) imaging tests, (4) bone marrow examination and (5) lumbar puncture. Why these tests are needed and how they are performed will be described in this chapter. Use of Conscious Sedation When Performing Diagnostic Tests Some of the tests described below can be painful, including biopsies, bone marrow biopsies and lumbar punctures (note that blood work does not involve pain beyond a needle prick). To prevent children from suffering, some physicians use a technique called “conscious sedation.” Conscious sedation drugs create an altered state of consciousness, like sleeping lightly, to minimize pain and discomfort. During conscious sedation, a patient can usually speak and respond to verbal cues. Patients that are given these drugs usually experience a brief period of amnesia, erasing any memory of the procedure. Parents should note that these drugs are administered only by physicians with specific training in conscious sedation. Pediatricians, oncologists or anesthesiologists may perform the sedation. These healthcare professionals carefully monitor breathing and vital signs throughout the procedure. Children undergoing conscious sedation will never be left unmonitored. Understanding Childhood Non-Hodgkin Lymphoma 11 What You Should Know If Your Child Receives Conscious Sedation Planning for Conscious Sedation •Children should not eat anything several hours before receiving conscious sedation. The exact number of hours varies by institution. Your child’s oncologist will inform you of the instructions. What to Expect After Conscious Sedation •Your child will not remember anything from the procedures. •Most children wake up quickly, and recovery from conscious sedation is fairly rapid. Most children recover in one hour or less. •Children can resume eating immediately after conscious sedation. Common Diagnostic Tests Blood Tests A complete blood count (CBC) may be performed to determine whether different types of blood cells, including red blood cells, white blood cells and platelets, are normal in number and appearance when viewed under the microscope. Abnormalities in these blood cells may be the first sign of lymphoma. Various blood tests may also be performed to determine whether lymphoma is affecting certain tissues or organs, such as the liver or kidneys, or to identify specific substances circulating in the blood that may help physicians select the most appropriate treatment option. For example, levels of the enzyme lactate dehydrogenase (LDH) and/or the protein beta (2) microglobulin (B2M) are commonly measured because higher levels of either or both suggest that the lymphoma may be more aggressive, indicating that a more intensive treatment may be needed. Biopsy A biopsy is a procedure in which a piece of tissue from an area of suspected disease is removed from the body and examined under a 12 Understanding Childhood Non-Hodgkin Lymphoma microscope in order to determine which type of cancer the patient has. The type of biopsy performed often depends on the location of the lymphoma. Excisional Biopsy During an excisional biopsy, an entire lymph node or a large portion of it is surgically removed. This technique is often preferred because attempting to make a diagnosis from a small tissue specimen may lead to errors in diagnosis and sub-optimal therapy. Surgery may be necessary to obtain a sufficient sample of the tumor for examination. Needle Biopsy When tumors or lymph nodes are in locations that are difficult to biopsy (e.g., deep in the chest or abdomen), a needle biopsy (also called a core biopsy) may be performed. For this type of biopsy, a needle is inserted into a lymph node suspected of being cancerous and a small tissue sample is removed. Fine Needle Aspirate A fine needle aspirate (FNA) uses a very small gauge needle to collect a sample of cells from a cancerous lymph node. Such needle biopsies are more often used to confirm a relapse rather than an initial diagnosis because they generally do not produce sufficient tissue to establish a precise diagnosis. After a biopsy is performed, the sample is examined by a pathologist (a physician who studies tissues and cells to identify diseases) who develops a report. The oncologist uses this report along with results from other tests to confirm the diagnosis. However, if the pathologist’s interpretation of the biopsy is uncertain, the report should be reviewed by a hematopathologist (a pathologist who focuses on the identification of hematologic malignancies). Bone Marrow Biopsy Lymphoma is often found in the bone marrow, a material found within bones, which contains cells that develop into red blood cells, Understanding Childhood Non-Hodgkin Lymphoma 13 2 white blood cells and platelets. To determine whether lymphoma is present in the bone marrow, a physician will insert a hollow needle into an area of the pelvic bone and extract a small tissue sample. The sample is then studied for signs of lymphoma by a pathologist. Lumbar Puncture NHL can sometimes spread to the nervous system. When this happens, the fluid present around the spinal cord and the brain (cerebrospinal fluid) may be abnormal and contain cancer cells. To determine whether this has occurred, the physician may recommend a test called a spinal tap or a lumbar puncture, in which a thin needle is inserted into the lower back. A small sample of fluid is then removed, and the cerebrospinal fluid is examined for chemical content and abnormal cells. Imaging Tests Physicians will often order imaging tests that provide pictures of areas inside the body. Most of these tests are painless. Some young children will be sedated if they are not able to lie completely still for the scans. Several types of imaging procedures may be needed to help best evaluate lymphoma, including the following: X-rays X-rays use radiation to take pictures of areas inside the body. For children with NHL, a chest X-ray is the most common type of X-ray. CT (computerized axial tomography) Scan A CT scan takes X-rays from different angles around the body. The pictures obtained are then combined using a computer to give a detailed image. People with NHL often have CT scans of the neck, chest, abdomen and pelvis. These tests are useful in determining how many lymph nodes are involved, how large they are and whether internal organs are affected by the disease. 14 Understanding Childhood Non-Hodgkin Lymphoma MRI (magnetic resonance imaging) An MRI is similar to a CT scan, but uses magnets and radiofrequency waves instead of X-rays. An MRI can provide important information about tissues and organs, particularly the nervous system, which is not available from other imaging techniques. Because this testing technique creates clear images of the bones, brain and spinal cord, an MRI may be ordered to see whether the lymphoma has spread in these areas. PET (positron emission tomography) Scan PET scans have largely replaced gallium scans (in which radioactive gallium was injected into the body) in many cancer centers, because the technique is more convenient and more sensitive. This test evaluates NHL activity in all parts of the body. To perform the test, a radioactive substance is first injected into the body. A positron camera is then used to detect the radioactivity and produce cross-sectional images of the body. Unlike gallium scans, which are used primarily to detect response to treatment, PET scans are useful for both determining how much disease is present (staging) and how well it is responding to treatment. While CT scans show the size of a lymph node, gallium and PET scans show if the lymph node is active (still has disease). Today, CT and PET scans are often being combined into one test (CT/PET). Ultrasound Exam An ultrasound utilizes high-energy sound waves to create an image called a sonogram. This technique can be used for examining the abdomen. Staging Childhood NHL is divided into four stages, based on how far the disease has spread in the body. Staging the disease helps physicians predict outcome (prognosis) and determine the most appropriate treatment approach. Understanding Childhood Non-Hodgkin Lymphoma 15 2 Staging Stage Description IThe lymphoma is found in one group of lymph nodes or one area outside the lymph nodes. To be identified as Stage I, the lymphoma cannot appear in the abdomen or mediastinum (the area between the lungs). IIThe lymphoma is found in: (1) one group of lymph nodes and lymph nodes nearby; (2) two or more areas on the same side of the diaphragm; or (3) the stomach or intestines, but can be completely removed through surgery. IIIThe lymphoma is found: (1) on both sides of the diaphragm; (2) in the chest; (3) in the abdomen, but cannot be completely removed through surgery; or (4) near the spine. IVThe lymphoma is found in the: (1) bone marrow; (2) brain; or (3) cerebrospinal fluid. Childhood NHL may also be categorized and treated according to the ABC grouping system. The number of chemotherapy cycles administered may differ by group. •Group A: Tumors that can be completely removed. •Group B: Tumors occurring in the chest or abdomen that cannot be surgically removed. •Group C: Tumors occurring in the bone, bone marrow, brain or other location outside of the lymphatic system. 16 Understanding Childhood Non-Hodgkin Lymphoma Chapter 3 Childhood Cancer Clinical Trials Clinical trials are research studies designed by physicians and researchers to answer questions about new treatments or new ways of using existing treatments. The majority of children with cancer are treated in clinical trials. Over the past several decades, high clinical trial enrollment has led to rapid increases in the survival rates of children and teens with cancer. This chapter will discuss the unique features of childhood cancer clinical trials, describe the process of enrolling children in clinical trials, provide an overview of clinical trials and identify resources for more information. Unique Features of Childhood Cancer Clinical Trials Today, over 80 percent of children diagnosed with cancer will be cured. This is a stark contrast to 50 years ago, when few children survived childhood cancer. Several strategic decisions within the scientific community led to this rapid increase in survival rates, including the following: •Collaboration: Progress in research only occurs when adequate numbers of patients are enrolled in clinical trials. For example, because childhood cancers are so rare, if one institution tried to enroll the relatively small number of patients with Burkitt lymphoma into a trial it would take decades before enough patients could be enrolled. Therefore, to make significant advances in the understanding and treatment of childhood cancers more quickly, the decision was made to establish strong clinical trial collaborations across institutions and countries. •Design: Clinical trials for children are based on what physicians and researchers know to be the “gold standard” of care for a particular subtype. Therefore, each clinical trial is designed to improve on the Understanding Childhood Non-Hodgkin Lymphoma 17 3 best therapies that modern medicine currently has to offer. Improvements may include how to give smaller doses or how to maximize effectiveness by adding an additional drug to an already effective regimen. •Consistency of Treatment: Due to the collaboration described above, the majority of children with the same type of non-Hodgkin lymphoma (NHL) will receive the same treatment regimen. For example, a child diagnosed with DLBCL in Kansas will likely receive the same treatment as a child diagnosed with DLBCL in Washington. When all children with lymphoma are treated as a group, researchers can learn things more quickly. Children’s Oncology Group Trials The success of the strategies listed above serves as the foundation for how children diagnosed with lymphoma are treated today. The Children’s Oncology Group (COG) consists of 5,000 childhood cancer experts from more than 200 institutions throughout the United States. COG designs, implements and evaluates the large-scale clinical trials conducted with children diagnosed with cancer today. Therefore, it is very likely that a child diagnosed with lymphoma will be treated on a protocol (term used to describe the details of a research study) designed by COG. It is important to note that COG trials for lymphoma often continue for five to ten years after they are initiated. Therefore, it is likely that the majority of children treated within a specific time period will receive the same treatment. Enrolling Children in Clinical Trials Pediatric hematologists/oncologists will discuss the details of the specific trial and why it is most appropriate for the patient. Once the physician has explained the details of the trial, the parent(s) will be asked to give “informed consent” for their child to be “enrolled” in the study. These details will include: 18 Understanding Childhood Non-Hodgkin Lymphoma •Name of the trial •Drugs used in the trial 3 •Schedule of treatment •What to expect during treatment •Long-term effects of treatment For children under the age of 18 years, parents must provide consent for treatment. At some institutions, children over the age of 14 must also consent to receiving treatment. This also applies to children as young as seven at some institutions. It is important to remember that hundreds of physicians from around the country come together to design each trial and participants are carefully monitored while enrolled. Every trial must be approved by institutional review boards (IRBs) to ensure that the trial is ethical and that patients are kept safe. Clinical Trial Process Diagnostic Tests Conducted and Evaluated Physician Evaluates Which Clinical Trial is Most Appropriate Children are Closely Monitored Throughout Treatment Treatment Begins Physician Discusses Details of Clinical Trial with Parents (process known as “informed consent”) Parents Consent on Behalf of Their Children Understanding Childhood Non-Hodgkin Lymphoma 19 Understanding the Clinical Trial Process There are hundreds of NHL clinical trials now underway in hospitals, cancer centers and physicians’ offices around the country. The government, pharmaceutical and biotechnology companies, universities and physician groups often sponsor clinical trials. However, in childhood lymphoma trials, the majority are coordinated through the COG, as described above. Clinical Trial Phases Clinical trials are divided into three phases, as described below. Phase I Phase I studies (first in human studies) are designed to assess the maximum tolerated dose (MTD), frequency of treatment and overall safety of the drug in a small number of patients. Phase II Once the therapy dose is determined and shown to be safe in a phase I trial, it is then ready to be tested in a phase II study. Phase II studies aim to establish whether the therapies have any evidence of effectiveness in a larger group of patients with a particular type of cancer (e.g., Burkitt lymphoma). Phase II studies might be used to generate preliminary data on a drug or to confirm data to obtain United States Food and Drug Administration (FDA) approval. Phase II studies also investigate whether a therapy already approved for one type of disease is effective treatment for another. Phase III Phase III trials are performed to determine whether the treatments developed in phase I and II studies are better than what is currently considered the “standard of care” for a specific disease. Phase III studies often require a large number of patients. Once a patient elects to enroll in a phase III study, he or she is assigned to one of two groups in a process called “randomization.” In randomization, a computer assigns 20 Understanding Childhood Non-Hodgkin Lymphoma the treatment the patient is to receive. One group receives the standard therapy and the other group receives the experimental treatment. It is important to remember that this randomization process is done so that each treatment arm will have patients with similar characteristics and be free of bias. The randomization in phase III trials allows researchers to determine whether or not the new treatment is more effective or less toxic than the standard of care. Use of a Placebo in Phase III Trials A placebo, or sugar pill, is an inactive ingredient that is used is some types of clinical trials to ensure that the test results are unbiased. It is important to note that clinical trial participants will never receive a placebo in a phase III trial if standard therapy exists. Patients would only potentially receive a placebo if there were no standard therapies to test against. Placebo-controlled trials are never done in a manner to deny patients an effective therapy. In trials that include placebo medications for some patients, all patients are notified in advance about the possibility of receiving a placebo. The Cost of Being in a Clinical Trial Clinical trials are very expensive undertakings for the study sponsor. In children’s cancer the sponsor is usually the Children’s Oncology Group (i.e., funded by the federal government). Patient costs vary depending on the study, who is sponsoring the trial, what portion of the trial-related expenses the sponsor will cover and the patient’s health insurance coverage. Some health insurance and managed healthcare providers will pay for the basic medical procedures associated with the trial, such as lab tests, scans and hospitalization when required, while others may define clinical trials as “experimental” or “investigational” and not cover some of the routine costs, such as physician visits, tests or treatments. The costs vary depending on the study and the health plan. Medicare provides coverage for patient care associated with government-sponsored clinical trials. Understanding Childhood Non-Hodgkin Lymphoma 21 3 If a patient is taking part in a National Cancer Institute (NCI) trial being conducted at the National Institutes of Health (NIH) in Bethesda, Maryland, the NCI will pay for the study drug and the costs related to the study. A stipend for travel, food and lodging is also provided. Some cancer centers provide financial assistance or discounted rates for room and board and have special research units that will pay for study-related costs. Some organizations provide financial assistance for treatment-related expenses. Parents or patients should ask the physician what clinical trials would be most appropriate. Here are some additional ways to find information: •Contact the Lymphoma Helpline at the Lymphoma Research Foundation at (800) 500-9976 to request a clinical trial search. •Cancer centers in your area may also have information about trials. •Coalition of Cancer Cooperative Groups (CancerTrialsHelp.org). •NIH websites (Cancer.gov and Clinicaltrials.gov). Please refer to our website for additional and updated information. lymphoma.org 22 Understanding Childhood Non-Hodgkin Lymphoma Chapter 4 Treatment Treatment options for children with non-Hodgkin lymphoma (NHL) are quite different from those used to treat adults with NHL. The most common treatment option for children with NHL is chemotherapy. As described in the previous chapter, because of the rarity of childhood cancers, most children diagnosed at any given point in time are treated in a similar manner on a specific clinical trial (also known as a “protocol”). This chapter will discuss information parents need to know about common childhood NHL chemotherapy regimens, including how it is given and what to expect. Other treatment options will be presented. Chemotherapy Chemotherapy (“chemo”) is treatment with drugs (as opposed to radiation, for example). Combining Chemotherapy Drugs Chemotherapy for NHL often consists of giving several drugs together (combination chemotherapy) in a defined way (schedule), called a treatment regimen. Drug combinations are used because different medications damage or kill cancer cells in different ways, making them more vulnerable to the treatment. Combining chemotherapy drugs provides a more effective way to kill tumor cells, because using the drugs together greatly augments the impact of each drug (called synergism). In addition, when some drugs are added together in lower doses, it helps reduce the likelihood of side effects without reducing the overall amount of effective chemotherapy. For example, the combination of three drugs (cyclophosphamide, vincristine, and prednisone) is referred to as COP. This combination uses drugs that are given in somewhat less toxic amounts while sustaining a full or Understanding Childhood Non-Hodgkin Lymphoma 23 4 augmented (synergistic) capacity to destroy NHL. Another reason for combination chemotherapy is to prevent the emergence of drug resistance. Chemotherapy Cycles Chemotherapy is usually given in cycles in which each treatment is followed by a period of rest and recovery. Together, each period of treatment and non-treatment is called a “chemotherapy cycle.” Clinical trials have determined how often chemotherapy should be given to kill the most tumor cells while minimizing side effects. However, timing may vary depending on the specific treatment. Most childhood chemotherapy cycles are given every three to four weeks. Also, most regimens include frequent vincristine (Oncovin) as well as oral steroids within the three week cycles. Chemotherapy Cycles Most children present with symptoms and advanced disease Draw blood on initial visit Scans Child allowed to go home and come to clinic for chemotherapy (goal: maintain as much normalcy as possible) Admitted to hospital and given initial chemotherapy 24 Understanding Childhood Non-Hodgkin Lymphoma How Chemotherapy Is Given Depending on the regimen, chemotherapy may be administered in pill form, as an injection or as an intravenous drip. For patients receiving intravenous drugs (ones that are given through a vein) for multiple cycles, an intravenous catheter may be inserted to make it easier to give drugs. Catheters may be left in place temporarily or permanently. There are several types of implanted catheters, which are inserted using a minor surgical procedure. One type, called a Hickman-Broviac catheter, consists of one to three tubes inserted through the chest wall into a vein. Six to twelve inches of tubing remain outside the skin. The main advantage of this type of catheter is that blood tests can be drawn and drugs given without having to pierce the skin. Disadvantages include: (1) the possibility of infection if the catheter is exposed to any bacteria found on a needle during a blood draw or if the catheter is not cared for properly, and (2) the tubes on the outside of the body make it more obvious that a catheter is in place. Patients with catheters will receive specific instructions from their healthcare team regarding proper care and cleaning. Where Chemotherapy is Given Some chemotherapy is given in the hospital (referred to as in-patient) and some is given on an out-patient basis where the child lives at home and comes to a clinic to receive the treatment. The goal is to maintain as much normalcy as possible in the lives of children living with NHL. Common Types of Chemotherapy Regimens Used to Treat Childhood NHL The most common types of chemotherapy regimens currently used to treat childhood NHL are presented in the table on the next page. It is important to remember that today’s science is moving very fast. Therefore the chart in this chapter may not be entirely comprehensive or accurate depending on when this information is being read (i.e., please refer to the date of print of this publication). Parents should speak to their child’s oncologist to see if any trials have closed or if any new trials have opened. Understanding Childhood Non-Hodgkin Lymphoma 25 4 Lymphoma Subtype Protocol Name Drugs Used Lymphoblastic lymphoma 1.Berlin-FrankfurtMunster (BFM) Study 1.BFM Study • Vincristine • Corticosteroids • Anthracyclines • L-asparaginase • 6-thioguanine 2.COPG A5971: A randomized Phase III study for the treatment of newly diagnosed disseminated lymphoblastic lymphoma or localized lymphoblastic lymphoma 2.COPG A5971 • Vincristine • Daunorubicin • L-asparaginase • Cytarabine • Methotrexate • Prednisone • 6-Mercaptopurine • Cyclophosphamide • Thioguanine • Doxorubicin • Dexamethasone 1.Berlin-FrankfurtMunster (BFM) Study 1.BFM Study • Vincristine • Corticosteroids • Anthracyclines • L-asparaginase • 6-thioguanine 2.French LMB 2.French LMB (COPAD or COPAD-M) • Cyclophosphamide • Vincristine • Prednisone • Methotrexate • Doxorubicin • Hydrocortisone • Cytarabine • Leucovorin Anaplastic large cell lymphoma Treatment protocols may vary by institution. One potential combination: • Vincristine • Doxorubicin • Methotrexate • Prednisone • 6-Mercaptopurine Rare Subtypes Treatment protocols may vary by institution. Diffuse large B-cell lymphoma and Burkitt lymphoma 26 Understanding Childhood Non-Hodgkin Lymphoma Details No Children’s Oncology Group (COG) clinical trials were open at the time of this guide’s printing. COG recently completed a pilot study incorporating rituximab (Rituxan) into the LMB backbone. Treatment can range from 24 months to several years. Discuss treatment options with physician. Radiation Radiation is not a common treatment option for children with NHL. Most subtypes of NHL seen in children are “chemo-sensitive,” which means they respond well to chemotherapy and do not require radiation. What Happens If Relapse Occurs? Secondary Therapies Every parent’s concern during their child’s treatment is “what happens if this treatment does not work?” This is a very normal fear, and one that is shared by most people who care for someone undergoing cancer treatment. The fact is that the large majority of children diagnosed with NHL today will be cured by the first treatment regimen they are given. If a child does not respond to the first treatment regimen they receive, their disease may be considered “refractory” (resistant to treatment). A “relapse” (sometimes called a recurrence) is when a child’s disease returns after treatment. Most relapses happen shortly after treatment, decreasing in frequency as time passes after the completion of therapy. If a relapse is going to occur in a child with B-cell NHL, it will generally happen within the first 18 months. If a relapse is going to occur in a child with T-cell NHL, it will generally happen early. However, there are some children who may experience a recurrence three to four years later. Close monitoring and early identification of relapse is important. All patients will be carefully watched for five years following diagnosis. Parents whose child experiences a relapse or refractory diagnosis should not lose hope. Complete remission may still be achieved following a diagnosis of relapsed or refractory lymphoma. The type of treatment used for children who relapse or have refractory disease depends on two factors: (1) the disease type (e.g., Burkitt, anaplastic large cell lymphoma) and (2) stage. Treatments used after the first treatment (also known as primary treatment) are often referred to as “second line” or “secondary” treatments. These treatments are described on the following pages. Understanding Childhood Non-Hodgkin Lymphoma 27 4 Chemotherapy Plus Rituximab (Rituxan) For children with B-cell NHL, most secondary treatment options include a combination of chemotherapies plus rituximab (Rituxan), which is a monoclonal antibody—a drug that selectively targets specific cancerous B-cells within the body. A commonly used secondary treatment option is RICE, which includes rituximab (Rituxan) plus a combination of chemotherapies (ifosfamide, carboplatin, etoposide). Rituximab (Rituxan) was the first monoclonal antibody approved for cancer therapy by the United States Food and Drug Administration (FDA) as a single agent in the treatment of relapsed or refractory adult lymphoma patients with CD20 positive, B-cell non-Hodgkin lymphoma. This drug was subsequently approved for additional indications by the FDA. It has not yet been approved for use in children, but may be used to treat relapsed or refractory disease in children with NHL. Stem Cell Transplantation Current Perspectives on Transplantation in Children with NHL Physicians may consider stem cell transplants as a treatment option for children who have relapsed or refractory NHL. Factors affecting the success of transplants include: (1) type of disease and (2) disease status. One of the largest transplant-specific studies to date examined the records of 182 relapsed or refractory NHL patients who had received either an autologous (using a child’s own stem cells) or allogeneic (using cells from a sibling or unrelated donor). The study found no difference between autologous and allogeneic transplantation for children with Burkitt, DLBCL or ALCL. Therefore, autologous transplants are more commonly used than allogeneic to treat these three diseases. Some debate exists regarding which transplant is most effective for lymphoblastic lymphoma and currently, either type may be used, depending on an individual’s specific situation. 28 Understanding Childhood Non-Hodgkin Lymphoma Understanding Transplantation Bone marrow transplants are now called stem cell transplants because they use three types of blood-forming stem cells: •Bone marrow •Peripheral (circulating) blood (also called peripheral blood stem cells or PBSC) •Cells collected from an umbilical cord after a baby is born A transplant using any one of these cells can replace a child’s damaged marrow with healthy blood-forming cells, resulting in a new blood and immune system. With these new cells working in the child’s bone marrow (the spongy material found inside our bones) the marrow can once again form healthy: •Red blood cells, which carry oxygen to all parts of the body •White blood cells, which fight infections •Platelets, which control bleeding by helping blood to clot To get the child’s body ready for a transplant, he/she will receive chemotherapy and/or radiation. This will destroy or suppress the immune system. Physicians call this a preparative regimen, or conditioning. The new stem cells grow in the body, and take over the blood-forming machinery in the marrow. Because a transplant places great strain on a patient’s body, it is not an option for everyone. Among the things to consider are age, medical history, cancer stage, current medical condition and response to previous therapy. In some patients, a reduced-intensity conditioning regimen can be used, which lowers the strain on the body. There are two types of stem cell transplants: allogeneic, in which patients receive stem cells from another person, and autologous, in which patients receive their own cells. Understanding Childhood Non-Hodgkin Lymphoma 29 4 •Autologous Transplantation: In this procedure, a patient’s own stem cells are removed—while the patient is in remission—and frozen. When it is time for the transplant, the patient will receive very high-dose chemotherapy and/or radiation, after which the thawed stem cells are re-infused back into the patient’s body. The cells go into the bloodstream, where they make their way to the bone marrow where they belong. •Allogeneic Transplantation: In allogeneic transplantation, a donor’s stem cells are used. Finding a compatible donor is important because the body will reject stem cells if they are too different from the patient’s own cells. The new cells may also react against the patient’s body, a condition called graft-versus-host disease (GVHD). However, allogeneic transplants have one important potential advantage: the donor’s immune cells can destroy any lymphoma cells in the body not killed by the conditioning regimen. Very sensitive tests are used to see if someone is a suitable transplant donor. The best candidates are siblings, but there is only a one in four chance that a sibling will be a close enough match for a transplant. If no family members are a match, a search for an unrelated donor (or a cord blood unit) in a large registry of volunteers can be initiated. For more information on transplantation, please visit the National Marrow Donor Program’s website at marrow.org. 30 Understanding Childhood Non-Hodgkin Lymphoma How Transplants Are Done Transplants are performed in four steps: Step 1: Collecting stem cells Stem cells are collected (harvested) in one of three ways: • Bone Marrow - To harvest bone marrow, physicians use a hollow needle inserted into the hip bone. This is done in an operating room and the donor receives general anesthesia. Once the marrow is harvested, it is either quickly transported to the waiting patient receiving an allogeneic transplant or frozen until needed for an autologous transplant. • Peripheral Blood Stem Cells (PBSC) - The second, and now more common way to collect stem cells from an adult, is by harvesting PBSCs from the blood. In this case, the donor takes a drug called a growth factor that causes the stem cells in the marrow to move into the peripheral blood. The stem cells are then removed from the donor’s blood using a process called apheresis. Blood is taken from a vein in one of the donor’s arms and passes through an apheresis machine, which separates out the stem cells. The rest of the blood, minus the stem cells, is returned to the donor through a different vein. This is done while the donor (in an allogeneic transplant) or patient (in an autologous transplant) is awake. • Cord Blood - Cord blood is collected at birth from a newborn’s umbilical cord. After the delivery is complete, trained technicians pierce the base of the cord with a sterile needle and drain the blood into a collection bag. The cord blood cells are then processed, tested and frozen until needed for a patient. Step 2: Processing or preserving stem cells In autologous transplants, marrow and PBSC collections are frozen for later re-infusion. In allogeneic transplants, cells undergo minimal processing and are given to the waiting patient as soon as possible. Cord blood cells (almost exclusively used in allogeneic transplants) are shipped frozen to the patient’s hospital, where they are kept until the patient is conditioned and ready to receive them. Step 3: Pre-transplant conditioning Before receiving the cells, patients are conditioned with chemotherapy and/or radiation. High-dose conditioning is always used in autologous transplants. In allogeneic transplants, the type and dose of the conditioning depends on the stage and type of disease, whether it is a recurrence and the condition of the patient. Step 4: Infusing the stem cells When the patient is ready, the stem cells are infused into the patient’s bloodstream through a needle inserted into a vein in one arm. The infused cells travel through the bloodstream, pass through the bones and implant themselves in the marrow. There, they slowly begin to make healthy new blood cells. Over time, the marrow produces enough healthy cells to completely restore the patient’s blood and immune system. Until these new cells are created, patients are more susceptible to infections. Understanding Childhood Non-Hodgkin Lymphoma 31 4 Novel Therapies It is an exciting time in lymphoma drug development. Now, more than ever before, drugs are being approved by the United States Food and Drug Administration (FDA) to treat lymphoma in adults. Many of the new drug approvals are not chemotherapy agents, but rather attack the lymphoma using novel techniques. The differences in biology between children and adults make it difficult to rely on data from drugs investigated only with adult populations. Therefore, studies are now underway to examine many of the novel therapies (already approved and those still under investigation) specifically with children. Some trials specifically designed for adults will lower their minimum age limit to sometimes include children over the age of 12, as well. The following chart describes some of these treatment options. It is critical to remember that today’s science is moving very fast. Therefore, the charts in this chapter may not be entirely comprehensive or accurate depending on when this information is being read. Some treatments may be found to be ineffective. Others may advance to the front-line setting. Please check with the Lymphoma Research Foundation or your physician for additional information and recent updates. 32 Understanding Childhood Non-Hodgkin Lymphoma Agent Predominant Mechanism of Action Comments Monoclonal Antibodies Rituximab (Rituxan) CD20 monoclonal antibody Approved for B-cell NHL in adults; under investigation in children Epratuzumab CD22 monoclonal antibody Ongoing clinical trials in adults with NHL and children with acute lymphoblastic leukemia (ALL) SGN-35 CD30 monoclonal antibody Ongoing separate clinical trials in adults and children Nelarabine Nucleoside analog Ongoing clinical trials in adults and children with lymphoblastic lymphoma Clofarabine Deoxyadenosine analog Clinical trials completed as well as ongoing in children and adults with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) Forodesine hydrochloride Purine nucleotide phosphorylase inhibitor Phase I study complete in children with T-cell cancers; being studied in other B-and T-cell NHLs Bortezomib (Velcade) Proteasome inhibitor Approved for relapsed/refractory mantle cell lymphoma in adults; under investigation in children Other * For more information on any of the drugs included in this chart, visit lymphoma.org/booklets to read the Understanding Non-Hodgkin Lymphoma: A Guide for Patients, Survivors and Loved Ones or call the Lymphoma Research Foundation at (800) 500-9976. Understanding Childhood Non-Hodgkin Lymphoma 33 4 Please refer to our website for additional and updated information. lymphoma.org 34 Understanding Childhood Non-Hodgkin Lymphoma Chapter 5 Supportive Care Children with non-Hodgkin lymphoma (NHL) may have side effects, also called toxicity, from the cancer treatment they receive. Fortunately, there are many effective ways to make them more tolerable. Parents and patients should ask their healthcare team about possible treatment side effects and inform the physician if the patient experiences any. In many cases, side effects can be lessened with medications or lifestyle changes. This chapter discusses some of the more common treatment-related side effects and how they are treated. Side Effects of Treatment Some of the most common side effects of NHL treatment are described below, along with strategies for minimizing their affect on children. Decreased Blood Cell Production Red blood cells, white blood cells and platelets are constantly being produced in the bone marrow. Both chemotherapy and chemoimmunotherapy treatment may temporarily interfere with the ability of the bone marrow to produce adequate numbers of blood cells. When this occurs, it is called myelosuppression. Anemia is the term used when myelosuppression causes a reduction in the number of red blood cells. Anemia can cause people to feel very tired, get headaches and have shortness of breath. Mild or moderate anemia is common with many chemotherapy regimens, and treatment with red blood cell transfusions may be necessary, depending on the degree of anemia. Neutropenia is the term used when myelosuppression causes a decrease in neutrophils—the primary type of white blood cells found in the blood. Because neutrophils play a very important role in fighting Understanding Childhood Non-Hodgkin Lymphoma 35 5 infection, a low count increases a patient’s risk for developing a serious or even life-threatening infection that may require hospitalization or antibiotic therapy. If the absolute neutrophil count (ANC) is too low, the chemotherapy dosage may need to be reduced or treatment may be delayed rather than risk infection. The first sign of infection may include fevers, chills or a general “unwell” appearance. To prevent and control neutropenia, physicians will check patients’ white blood cell and neutrophil counts before and during each chemotherapy cycle. When neutropenia threatens a patient’s ability to receive the planned dose of chemotherapy, drugs such as filgrastim (Neupogen), pegfilgrastim (Neulasta) or sargramostim (Leukine) can be given after chemotherapy to reduce the duration and severity of neutropenia. These drugs can sometimes cause bone pain. By keeping the white blood count from dipping too low, these medications can help keep chemotherapy doses on schedule. Thrombocytopenia is the term used when myelosuppression depletes the number of platelets in the blood. Platelets help start the clotting process when bleeding occurs. If platelet counts are low, patients may bruise easily. A low platelet count may also cause prolonged or excessive bleeding from cuts, nose bleeds, bleeding from the gums or bleeding without a previous injury. A platelet transfusion may be needed in some cases. Mucositis (Mouth Sores) The membranes of the mouth may become red, sore or irritated during chemotherapy, which is referred to as mucositis. Infections of the mouth and throat caused by viruses, bacteria or fungi may also occur. If throat soreness occurs, the healthcare provider will examine the throat and may do a swab (called a culture) to check for infection. If an infection is present, several medications are available to treat it. Pain medication may be recommended if it becomes difficult to eat or drink, and occasionally a child will need to receive intravenous fluids to stay hydrated while the sores heal. 36 Understanding Childhood Non-Hodgkin Lymphoma Nausea or Vomiting Chemotherapy can cause nausea or vomiting. Fortunately, advances over the last few decades have made it much easier to prevent nausea. Drugs that prevent vomiting (called antiemetics) commonly used with children undergoing chemotherapy include: •Aprepitant (Emend) (for children over 10 years of age) •Benadryl 5 •Granisetron (Kytril) •Lorazepam (Ativan) •Metoclopramide (Reglan) •Ondansetron (Zofran) •Promethazine (Phenergan) •Scopolamine patch (for children over 10 years of age) Because nausea is more easily prevented than controlled, physicians will likely prescribe one of the above medications before chemotherapy to prevent nausea from occurring at all. In most cases, these drugs can partially or completely prevent nausea and vomiting. Treatment-Induced Diabetes Sometimes the steroids that are given as part of the chemotherapy regimen can cause treatment-induced diabetes. This means that during treatment, some children may develop temporary diabetes. This happens most often to children who are pre-diabetic, though children with no risk factors for developing diabetes may also be affected. Treatment-induced diabetes occurs because the steroids affect the body’s ability to handle sugar. If frequent urination occurs or the child is unusually thirsty, the physician will check the child’s blood sugar levels. Most treatment-induced diabetes can be managed by decreasing the amount of sugar and carbohydrates the child eats and drinks, for example, eliminating soda and fruit juice. Insulin may be given if Understanding Childhood Non-Hodgkin Lymphoma 37 limiting sugar intake does not work. It is important to note that the vast majority of children who experience treatment-induced diabetes will return to their normal blood sugar levels once the steroids have ended. This means that if a child had to receive insulin, the child may be able to stop taking insulin shortly after the steroid treatment has stopped. Treatment-Induced Hypertension Hypertension (high blood pressure) can occur in children with NHL while they are receiving treatment. The steroids given in most treatment regimens cause the body to hold onto salt, which results in water retention and extra fluid in the bloodstream. The causes of hypertension include: •Lymphoma in the kidneys •Hyperuricemia, which is a build up of uric acid in the kidneys that can cause the kidneys to become blocked. A drug called allopurinol (Zyloprim) may be given to treat hyperuricemia. Infection Most children with NHL will be at an increased risk for getting infections while they are receiving chemotherapy. The immune system does not work as well as it does in a healthy person, making it easier for viruses, fungi and bacteria to invade the body. Infections may happen from the following: •Exposure to people with colds or flu •Bacteria that normally live in our bodies enter the blood stream from sores in the mouth or along the gut •Bacteria can enter the body from a cut in the skin •Bacteria that enter the bloodstream from a Hickman catheter, PICC line or through the skin after accessing a Port-a-Cath •Complications following a viral illness, such as pneumonia 38 Understanding Childhood Non-Hodgkin Lymphoma Infections can happen suddenly, and can be very serious. Most children will develop a fever or chills with a serious infection. It is important to call your child’s health care provider immediately and report any signs of infection. Most infections can be treated effectively with antibiotics, either in the hospital or as an outpatient, if treatment is started promptly. Constipation Vincristine (Oncovin) is a chemotherapy drug frequently used in the treatment of NHL. Vincristine (Oncovin) can affect the nerves that line the inside of the colon, resulting in the colon’s inability to contract and push stool along, leading to constipation. It is important to drink extra fluids, remain active and increase dietary fiber to help prevent constipation. It may be necessary to take a stool softener such as colace, or a laxative such as miralax. Cardiac Issues Anthracycline drugs, such as doxorubicin (Adriamycin), can damage the heart. The impact on the heart is usually not clinically significant until a specific amount of the drug has been given. However, some children are more sensitive to anthracycline drugs and experience problems at a lower dose. Therefore, children will be carefully monitored during and after treatment with echocardiograms or radionuclide scans. The goal is to identify signs that the drugs may be affecting the heart before the problem becomes severe. Occasionally, the dose of anthracycline may need to be reduced or held off. Cardiac muscle failure can occur, but only in a small number of children. Rarely does anthracycline cause heart arrhythmias (changes in the heart rhythm). If this does occur, the drug can be stopped or anti-arrhythmic drugs can be administered. The drug dexrazoxane (Zinecard) may also be given along with anthracycline drugs to protect the heart. Understanding Childhood Non-Hodgkin Lymphoma 39 5 Please refer to our website for additional and updated information. lymphoma.org 40 Understanding Childhood Non-Hodgkin Lymphoma Chapter 6 Coping with Childhood Lymphoma Lymphoma not only affects the child, but also the child’s siblings, friends, parents and extended family. This chapter will discuss the common experiences of children with lymphoma and ways parents can help both the child and their siblings cope with the diagnosis. Strategies for acknowledging and alleviating challenges as a parent caring for a child with lymphoma will also be presented. What Children Need and Hope For After a Lymphoma Diagnosis Unless they have had experiences with cancer, children may not immediately know the meaning of the words “cancer” or “lymphoma.” Therefore, at first, they may not be as scared or worried about the words or diagnosis itself. Often, it is the reactions of adults around them that inform their response, making them feel safe or scared. Strategies for sharing information about their diagnosis may vary by age. Keeping messages hopeful and grounded in simple facts can help the child feel safe. Numerous resources exist to help parents with this communication. (To find some available resources, refer to the Resource chapter of this guide). Practical Aspects of Lymphoma from the Eyes of a Child Practical Medical Concerns Children may be more concerned about the practical rather than theoretical issues (e.g., what will having cancer today mean for me 10 years from now). Common questions running through the mind of a child with cancer include: •Will this hurt? •Am I going to be alone? •Is it going to be scary? Understanding Childhood Non-Hodgkin Lymphoma 41 6 Establishing ways to reinforce their safety and letting them know that they will not be alone will help. For example, in preparation for receiving chemotherapy, explain to the child what to expect, including the physical and practical pieces. Describe what they will feel during and after chemotherapy. Make it clear that every step will be taken to minimize pain or the “ouchies.” Children do not like surprises. Tell them details such as: •What will happen first, second, third, etc. •Who will be in the room when they get specific tests/procedures •Mom and/or dad will be there the whole time The more they can be prepared for what to expect, the better. When they are not told, they may be concerned that adults are lying to them and lose trust in future medical situations. Children can often tell when adults are being honest or trying to hide things. Tell them that the physician and adults will be honest with them. Work with the child to identify how much information they like to receive before each procedure and how involved they would like to be in their own treatment. Some children want everything explained to them step by step, while others may just want to “get it over with.” The Benefit of Routine It is a common reaction for parents of children with cancer to want to relax rules and routines for their sick child and well siblings. This sometimes helps temporarily minimize guilt for the parent and stress on the child. However, developmentally, children thrive with structure and routines. It makes them feel safe because they are able to anticipate what to do, how to do it and what is expected of them. Suspending rules and routines may make the child concerned that they are much sicker than everyone is telling them. Reasonable changes to help the child feel more comfortable if they become nauseous, fatigued, etc. can help, but extreme changes should be made with caution. 42 Understanding Childhood Non-Hodgkin Lymphoma Social Workers and Child Life Specialists Social workers and child life specialists are skilled at helping parents with children affected by cancer. They are there to serve as partners for parents during and after lymphoma treatment. Numerous books, web-based resources and tools exist to help parents communicate with their children about cancer, as well as ways for them to cope. Speaking with a social worker or child life specialist can help save time because they have access to the most appropriate resources for families, based on the child’s age and other specific needs. Emotional Coping for Parents, Adult Family Members and Friends As a parent of a child with cancer, it is completely understandable and reasonable to be sad and scared. The following specific strategies may help parents and children at the same time: •Children sense what their parent is feeling. Therefore, it is best to be honest and say something like, “Yes, Mommy is worried, but that is okay. Here is what we are going to do (lay out a plan).” This acknowledges what the child instinctually senses and also quickly makes them feel secure and that the parent is in control. •Emotional breakdowns and feeling overwhelmed may happen frequently or come on all at once for a parent. The important thing to do is to find a suitable outlet or source of support to help. Rely on friends and family members for emotional support. This will help ensure that when the parent interacts with their child they are not overwhelmed with their own emotions and are fully supportive and nurturing. Coping with Guilt Parents often believe that they can protect their children from everything. This feeling is natural and expected. It is critical to recognize that feeling frustrated, tired and guilty is inevitable. The causes of lymphoma are not known, so nothing anyone “did” caused the disease. Childhood cancers in general are very rare and out of the ordinary experiences of Understanding Childhood Non-Hodgkin Lymphoma 43 6 parenthood. However, due to recent treatment advances, the large majority of children will survive their lymphoma diagnosis and grow into healthy adults. Furthermore, research shows that many childhood cancer survivors experience something referred to as “post-traumatic growth,” and report that their lives were positively impacted by their cancer experience. For example, teenagers often say that they quickly realized what is important in life, as compared to their cancer-free peers. Many of the positive aspects occur years later. Parents are encouraged to engage children in conversations about their experience as they are going through it so that they are supported in the present and prepared for the future. While parents are actively supporting their children through lymphoma treatment, they need to do their best to also be compassionate to themselves. Ask for and receive practical support from friends, neighbors and healthcare providers. Talk to a social worker and ask for resources. Support for Siblings of Children with Lymphoma Childhood lymphoma affects more than the child diagnosed. Fear, sadness and extra tasks enter the daily lives of family members and friends. Brothers and sisters of the child diagnosed with lymphoma are uniquely impacted. Siblings of sick children may feel neglected, angry, sad, scared, like their needs do not matter and are often forced to grow up quicker than normal. Parents should remain aware of all children in the family and look out for changes in behavior. One unique resource for siblings of children with cancer is a nationwide non-profit organization called SuperSibs!. The organization is dedicated to ensuring that the brothers and sisters of children with cancer are honored, supported and recognized. They do this by providing free, ongoing comfort and care support to children between the ages of 4 and 18, who reside in the United States and Canada, and who have (or have had) a brother or sister with cancer. (See the 44 Understanding Childhood Non-Hodgkin Lymphoma Resource section of this guide for contact information.) In addition to this direct support, SuperSibs! works with hospitals, clinics and organizations across the country to provide the most effective tools and resources so that sibling awareness and support can be a part of the help that families receive from their medical, social and emotional support staff. A few strategies may help siblings better cope with their brother or sister’s cancer: •Try to assess the child’s awareness of cancer and what it is. Simply ask, “Have you heard of cancer? What do you know about it?” Aim to deliver age-appropriate descriptions. Numerous resources exist to help parents do this. •Spend one-on-one time with the well sibling(s). Do an activity of their choice that opens up the possibility for talking about how they are doing. Siblings of children with lymphoma may quickly diminish their needs to “accommodate” their sibling’s needs. Therefore, it is critical that you ask them about their day, their dreams and what they would like to do. Listening is even more important than asking. Take in what your child says and ask more questions. •Gently ask hospital staff and other people to refer to the sibling by their name, as opposed to “the patient’s brother or sister.” This will help remind them that their identity matters too. •Siblings often take on extra responsibility. Be careful of asking the sibling to do more than they should at their age. For example, babysitting younger siblings may not be appropriate before a certain age. This should not change even with a sick child. •Ask siblings if they want to be involved. If the answer is yes, then find ways they can contribute. Being in charge of daily communication with family, for example, may help the sibling feel connected, but not overburdened. Understanding Childhood Non-Hodgkin Lymphoma 45 6 Talking to Siblings About Cancer By Age Ages 2-5 For this age group it is very important to keep things very simple. One example for explaining lymphoma: “Tommy’s blood is very sick. The doctors are going to give him some medicine to help his blood get better. Sometimes Tommy will have to get his medicine at the hospital and sometimes Tommy will take the medicine at home. The doctors are going to do everything they can to make Tommy’s blood get better.” Kids this age just want to be close to their parents. It is important to help your kids feel connected. Some suggestions include: • Record several of the child’s favorite books and songs on tape for them to listen to and hear your voice. • Make picture frames together and put a picture of yourself inside. • Make a blanket together or pick one out together and identify it as the item that can “HUG” you while mom and dad have to be away. Ages 6-10 For this school age group, you can use the actual words. One example for explaining lymphoma: “Tommy has cancer. Have you ever heard that word before? There are different kinds of cancer and Tommy has a kind called lymphoma. That means the cancer is in his lymphatic system, which helps the body fight off infections and germs. The doctors are going to give Tommy a very strong medicine called chemotherapy. You can call it “chemo” for short. The chemo will help to make the lymphoma go away.” (Re-iterating): “The doctors and nurses are going to do everything they can to make the lymphoma go away.” Questions to Spark Conversation: • What do you know about lymphoma or cancer? • Do you think someone did something “bad” to cause lymphoma or cancer? (That’s not what causes cancer!) • Do you think you can catch cancer from someone else? (No, it’s not “catchy!”) • How is your life different now? • What is the biggest change in your life? • What do you want/need from us grownups? • How do you know you are loved? 46 Understanding Childhood Non-Hodgkin Lymphoma AGES 11 - 18 Start with the basics and elaborate, depending on how much information your teen wants to hear. Some want a lot of information, some want to read it themselves and some want it kept to only what they NEED to know. Questions to Spark Conversation: • What do you know about lymphoma or cancer? • Do you think cancer is contagious? (It’s not!) • Do you think cancer is caused by something that someone did? (It’s not!) • How is your life different now? • What additional things do you have to do at home now? • What do you want/need from us, your parents? • What do you want/need from your friends? • What do you want/need from school? The information from this section was adapted from the SuperSibs! new parent toolkit. If you have not received a new parent toolkit, contact SuperSibs! at 866-444-SIBS(7427) or supersibs.org. Understanding Childhood Non-Hodgkin Lymphoma 47 6 Please refer to our website for additional and updated information. lymphoma.org 48 Understanding Childhood Non-Hodgkin Lymphoma Chapter 7 Long-Term and Late Effects Survival rates for children with lymphoma are extremely high, resulting in a growing number of childhood lymphoma survivors. Some of these survivors are at risk of developing treatment-related health problems that could occur months, or even years, following their last treatment. Lymphoma treatments are designed to destroy cancer cells. However, some of these treatments unintentionally damage healthy cells in the process. This damage can effect the development and proper functioning of various tissues and organs and could result in the development of secondary cancers later in life. Most childhood lymphoma survivors do not develop treatmentrelated health problems. For those who do, the effects are generally mild. However, a limited number of childhood lymphoma survivors may experience severe or chronic effects. There are several factors that can affect the risk of developing treatment-related health problems, including: •The type and amount of treatment the child receives •The age at which the child is treated •What area of the body is treated •The child’s gender •The child’s overall health Treatment-related health problems are placed into two categories. Those that continue for months or years following treatment are called “long-term effects” and those that do not appear until months or years after treatment are called “late effects.” Understanding Childhood Non-Hodgkin Lymphoma 49 7 Long-term and late effects vary by treatment. Some treatments may: •Cause cognitive impairment, such as difficulties learning, problem solving and concentrating •Affect the proper functioning of organs, such as the lungs, kidneys, liver, thyroid and spleen •Damage the digestive, musculoskeletal and central nervous systems •Affect the reproductive system, resulting in the delay of puberty, low sperm count, irregular periods, ovarian failure, premature menopause and infertility •Cause damage to the heart •Result in the development of secondary cancers, such as breast and thyroid cancer The following are examples of some common therapies and their potential long-term or late effects: •Anthracyclines: Anthracyclines, a form of chemotherapy, may increase the risk of developing heart damage and heart failure. Examples of anthracyclines include doxorubicin (Adriamycin) and daunorubicin (Daunomycin). •Alkylating agents: Alkylating agents, a form of chemotherapy, may increase the risk of developing heart failure and acute myelogenous leukemia (AML). A commonly used alkylating agent includes cyclophosphamide (Cytoxan) and ifosfamide (Ifex). •Radiation: Radiation to the head and neck may cause vision or hearing problems and could affect the thyroid. Radiation to the chest and abdomen could impair the heart (with severe cases resulting in heart failure) and lungs, and could increase the risk of developing breast and thyroid cancer. 50 Understanding Childhood Non-Hodgkin Lymphoma Due to the various medical conditions that can result from treatment, it is important that parents discuss the potential risks of all treatment options with their child’s oncologist before treatment. Once a treatment is completed, parents and the child’s oncologist should create a “follow-up care plan” that: •Provides a treatment summary, which includes information such as age and date of diagnosis, staging, the types of chemotherapy drugs administered, and response to treatment. •Indicates the type and frequency of medical tests that a survivor should routinely undergo over their lifespan. This follow-up care plan should be written and provided to the parent upon completion of treatment. As children grow up and move around, this document will serve as a history for their primary care physician. The follow-up care plan also ensures that any late effects will be diagnosed and treated as early as possible. Childhood lymphoma survivors should receive regular medical exams from a physician who is familiar with their medical history as well as the treatments they have received. Survivors and their caregivers are encouraged to keep copies of all medical records and test results as well as information on the types, amounts and duration of all treatments received. This documentation will be important for keeping track of, and treating, any late effects resulting from treatment. Scientific investigators are constantly testing new treatments and varying amounts of old treatments in hopes of reducing the long-term and late effects of lymphoma treatment or eliminating them altogether. Because greater numbers of children with lymphomas are now surviving for many decades following cancer treatment, new discoveries about the late effects of cancer are frequently being made. Guidelines are periodically updated to reflect this new information. Understanding Childhood Non-Hodgkin Lymphoma 51 7 The Children’s Oncology Group has created a document for physicians, which provides recommendations for managing the late effects of treatment, entitled Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. To view the document, visit survivorshipguidelines.org Resources Please refer to our website for additional and updated information. lymphoma.org 52 Understanding Childhood Non-Hodgkin Lymphoma Glossary of Medical Terms Absolute neutrophil count (ANC): A measurement of the number of mature neutrophils (a type of white blood cell) that are available for fighting infection. A low ANC increases the risk for infection. Advanced disease: Disease that has spread to multiple locations. Aggressive lymphomas: Lymphomas that are fast growing and generally need to be treated immediately. Also called intermediate-grade or high-grade lymphomas. Allogeneic transplant: A procedure in which a patient receives bone marrow or stem cells donated by another person. Alopecia: Hair loss. Alopecia from chemotherapy is almost always temporary; hair grows back when therapy is finished. Anemia: A shortage of red blood cells, causing weakness and fatigue. Angiogenesis: The process of developing new blood vessels. Antiangiogenesis therapies: Drugs that prevent tumors from developing new blood vessels, thereby stopping or limiting tumor growth. Antibody: A substance made by B-lymphocytes that reacts with antigens on toxins, bacteria and some cancer cells and either kills or marks them for removal. Antiemetic: A drug that reduces or prevents nausea and vomiting. Antigen: Identifying proteins located on the surface of all cells. The immune system uses antigens to determine whether cells are a necessary part of the body or need to be destroyed. Apheresis: The part of the stem cell transplantation procedure in which stem cells are removed from the blood. Autologous transplant: A type of bone marrow or stem cell transplantation in which a patient receives his or her own cells. Beta (2) microglobulin (B2M): A protein found in the blood. Higher levels of B2M suggest that the lymphoma may be more aggressive. ChildhoodLymphoma Lymphoma 53 UnderstandingUnderstanding Childhood Non-Hodgkin Biologic therapy: Treatment that uses or stimulates the immune system or other body systems to fight infection and disease. Biopsy: Removal of a small piece of tissue for evaluation under a microscope. Bone marrow: Spongy material found inside the bones containing stem cells that develop into three types of cells: red blood cells that deliver oxygen to the body and take away carbon dioxide; white blood cells that protect the body from infection; and platelets that help the blood to clot. Bulky tumor: A large tumor, usually greater than five, seven or ten centimeters. Cancer: Abnormal cell growth that cannot be controlled by the body’s natural defenses. Cancerous cells can grow and eventually form tumors. Catheter (intravenous access): A device that is temporarily or permanently put into a vein that makes it easier to give medications. Cerebrospinal fluid: Fluid that is present around the spine and brain. It may be examined to determine if NHL has spread to these parts of the body. Chemotherapy: Treatment with drugs to stop the growth of rapidly dividing cancer cells, including lymphoma cells. Chemotherapy cycle: Term used to describe the process in which chemotherapy is given, followed by a period of rest in which the body is allowed to recover. Chemotherapy regimen: Combinations of anticancer drugs given at a certain dose in a specific sequence according to a strict schedule. Clinical trial: A research study in which a new treatment is given to patients to determine whether it is safe, more effective or less toxic than current therapies. Combination chemotherapy: Several drugs given together to increase response rate of certain tumors. 54 Understanding UnderstandingChildhood ChildhoodLymphoma Non-Hodgkin Lymphoma 54 Complete remission (CR): Term used when all signs of the disease have disappeared after treatment. About LRF **Insert from other booklets** CT or CAT (computerized axial tomography) scan: This imaging test provides a series of detailed pictures of inside the body using an X-ray machine linked to a computer. Cure: There are no signs or symptoms of lymphoma, and a significant period of time (usually defined by years) has passed during which there are no relapses. Decreased blood cell production: A decrease in the production of red blood cells, white blood cells and platelets that may occur as a side effect of cancer or cancer therapies. Also called myelosuppression. Diaphragm: The muscle below the lungs and heart that separates the abdomen from the chest. Disease progression: The term used if the disease worsens despite treatment (also called treatment failure). DNA: Abbreviation for deoxyribonucleic acid, an essential component of genes. Dose intensity: A term used to describe giving the highest possible doses of drugs over a specific period of time with acceptable side effects. Durable remission: When a complete response lasts for years. Dysgeusia: When familiar foods taste differently. Echocardiogram: Use of ultrasound to examine the heart. It is ordered when potential cardiotoxic chemotherapy is used. Etiology: The study of the causes of a disease. Extranodal disease: NHL that has spread outside the lymphatic system. Fatigue: A decreased capacity for activity that is often accompanied by feelings of weariness, sleepiness or irritability. Understanding Childhood Non-Hodgkin Lymphoma 55 Gallium (radioisotope) scan: When injected into the body, radioactive gallium is a chemical that collects in some tumors. The body is then scanned to see whether the gallium has collected in a tumor. Generalized disease: A cancer that has spread throughout the body. Genes: The basic building blocks of heredity that are present in all cells. Genes are comprised of DNA and other materials. Gene therapy: Therapy approaches that alter the genetic structure of tumor cells, making them more susceptible to either the immune system or chemotherapy drugs. Grade: A method of classifying a tumor on the basis of how aggressively it is growing. Graft versus host disease (GVHD): Occurs when a donor’s bone marrow (graft) recognizes the recipient of the marrow (the host) as foreign. In response, the immune cells in the donor marrow attack the foreign cells in the host. Harvesting: A procedure in which stem cells are obtained from the blood or bone marrow for use in repopulating the body’s cells after high-dose chemotherapy. Hematologist: A physician who specializes in treating diseases of the blood and blood-forming tissues. Histology: The study of tissue characteristics that may lead to identifying a specific type of tumor. Hodgkin lymphoma: One of the two major types of lymphoma that begin in the lymph nodes and tissues of the lymphatic system. All other lymphomas are classified as non-Hodgkin lymphomas. Hodgkin lymphoma has a characteristic cell, the Reed-Sternberg cell, seen by the pathologist under the microscope when looking at the tissue from the biopsy. Hypogeusia: When the flavors of foods are not as strong as normal. 56 Understanding UnderstandingChildhood ChildhoodLymphoma Non-Hodgkin Lymphoma Hypothyroidism: A condition in which there is lower than normal production of thyroid hormone. Low thyroid levels can lead to a variety of effects, including mild weight gain, dry skin, fatigue and sleepiness. Idiotype: A unique “fingerprint” portion of an antibody present on the surface of B-cells. Idiotype vaccine: A lymphoma vaccine that is custom-made to attack an individual patient’s lymphoma and contains idiotype (unique) tumor material and an immune stimulant. Immune system: One of the body’s defense mechanisms. All lymphomas are diseases of the immune system. Immunological tests: Blood tests that detect the presence of diagnostic proteins or antigens on a tumor. Immunotherapy: See biologic therapy. Improvement: This term is used if a tumor shrinks following therapy but is still more than one-half of its original size. Indolent lymphoma: Lymphoma that is slow growing and has few symptoms. Also called low-grade lymphoma. Lactate dehydrogenase (LDH): An enzyme found in the blood. Higher levels of LDH suggest that the lymphoma may be more aggressive. Laparoscopy: Passing a tube through the abdominal wall to obtain a small sample of tissue for examination under the microscope. Leukemia: Disease generally characterized by the overproduction of abnormal or immature white blood cells that circulate or are present in the blood. Leukopenia: A shortage of white blood cells, resulting in the inability to fight infecting organisms such as bacteria, fungi and viruses. Localized disease: A cancer that is only present in a limited part of the body, for example, the neck or armpits. Understanding Childhood Non-Hodgkin Lymphoma 57 Local therapy: A therapy that only affects a small area. Low-grade lymphoma: Lymphoma that grows slowly and has few symptoms. Also called indolent lymphoma. Lymph: The watery fluid in the lymph system that contains white blood cells (lymphocytes). Lymph nodes: Small bean-shaped glands located in the small vessels of the lymphatic system. There are thousands of lymph nodes located throughout the body, with clusters of them in the neck, under the arms, the chest, abdomen and groin. Lymph nodes filter lymph fluid, trapping and destroying potentially harmful bacteria and viruses. Lymphatic system: The channels, tissues and organs that store and carry lymphocytes that fight infection and other diseases. Lymphocyte: A type of white blood cell. Lymphocytes, carried along by the lymph fluid, are part of the immune system and fight infection. Lymphoma: A malignant disease that begins in the lymph nodes, organs and tissues of the lymphatic system (immune system). Hodgkin lymphoma is one type of lymphoma; the other major type is called non-Hodgkin lymphoma. There are approximately 61 types of non-Hodgkin lymphoma. Malignant: Cancerous—a malignant tumor is a cancerous tumor. Medical oncologist: A physician who specializes in the use of chemotherapy, hormone therapy and many other types of biologic therapies to treat cancer. Memory cells: Memory cells are types of B-lymphocytes and T-lymphocytes. After a foreign invader or unwanted cell has been destroyed, surviving B- and T-lymphocytes develop into specialized memory cells that remain on watch and can provide protection if the invader is encountered in the future. 58 Understanding UnderstandingCLL/SLL Childhood Non-Hodgkin Lymphoma Metastasize: To spread to other organs of the body. Cancer may spread from its primary site to other sites or organs. Monoclonal antibodies: Biologic therapies that act specifically against a particular antigen. Scientists can produce large amounts of antibody that can be directed to a single target (or antigen) on the cell’s surface. Monoclonal antibodies have been developed to help combat specific cancers, including some forms of non-Hodgkin lymphoma. MRI (magnetic resonance imaging): MRI uses magnets and radio frequency waves to produce images of inside the body. MRIs can provide information about tissues and organs that is not available from other imaging techniques. Mucositis: Inflammation of the lining of tissues and organs. In the mouth, it is characterized by sores or inflammation. Myelosuppresion: A reduction in the bone marrow’s ability to make red blood cells, white blood cells and platelets. Neutropenia: An abnormally low level of neutrophils (the white blood cells responsible for fighting bacterial infections). Neutrophils: The primary type of white blood cells found in the blood that fight bacteria, etc. Non-bulky tumor: A small tumor, usually less than five centimeters (approximately two inches) Non-Hodgkin lymphoma (NHL): A group of several closely related cancers that arise from the lymphatic system. Although the different types of NHL have some things in common, they differ in what the cancer cell looks like under a microscope, how the cells grow and how the tumor affects the body. Oncologist: A physician who specializes in treating cancer. Some specialize in chemotherapy (medical oncologists), radiotherapy (radiation oncologists) or surgery (surgical oncologists). Understanding Childhood Non-Hodgkin Lymphoma 59 Palliation: Treatment that is given to remove or relieve symptoms. Para-aortic: The area close to the aorta. The aorta is the largest vessel in the body and rises from the heart. Partial remission (PR): The term used when a cancer has shrunk in size by at least half but has not totally disappeared. The cancer can still be detected, and other treatments may be recommended. Pathologist: A physician who specializes in studying disease through microscopic evaluation of body tissues and organs. Any tissue suspected of being cancerous must first be examined by a pathologist to confirm the diagnosis. PCR (polymerase chain reaction): A molecular test that can identify small amounts of genetic material. This test is done if looking for minimal residual disease. Performance status: A term used to describe a person’s ability to follow a typical lifestyle. Peripheral neuropathy: Damage to the nerves. This condition can be caused by some drugs and is usually characterized by tingling and weakness or numbness in the extremities. PET (positron emission tomography) scan: A type of test that may be used instead of gallium scans to identify areas in the body that are affected by non-Hodgkin lymphoma. This test evaluates metabolic activity in different parts of the body using a radioisotope. Plasma cell: A mature B-cell that makes antibodies—these antibodies help the body destroy or remove toxins, bacteria and some cancer cells. Primary therapy: The first therapy given after a diagnosis of cancer. Prognosis: The likely outcome of a disease, including the chance of recovery. 60 Understanding Childhood Non-Hodgkin Lymphoma Pulmonary function test: A procedure for determining the capacity of the lungs to exchange oxygen and carbon dioxide efficiently. Radiation field: The part of the body that receives radiation therapy. Radiation oncologist: A physician who specializes in treating cancer with radiation. Radiation therapy: The use of radiation beams (X-rays) to treat a cancer. High doses of high-energy radiation beams carefully focused on a tumor will kill cancer cells. Radiation therapy (with or without chemotherapy) is used to treat certain lymphomas. Radioimmunotherapy: A therapy that is prepared by attaching a radioactive isotope to a monoclonal antibody. Radionuclide tests: Tests that use radioactive substances to help evaluate the function of tissues. Refractory disease: A cancer that is resistant to treatment. Regimen: A specific combination of drugs (chemotherapy), their doses and their schedules of administration. A regimen may also include radiotherapy. Relapse: The return of cancer after treatment. Lymphoma may recur in the area where it first started, or it may occur in another place. Remission: The absence of disease. A patient is considered in remission when the lymphoma has been treated and tumors have diminished by at least 50 percent (partial) or have totally disappeared (complete). Remission does not necessarily mean cure. Patients with intermediate or aggressive lymphomas must achieve a complete remission and maintain it for a period of time, usually five or more years, before there is consideration of cure. Patients with low-grade tumors are usually not considered cured because the disease can reappear even with a long remission of many years. Patients may have a complete or partial remission. Understanding Childhood Non-Hodgkin Lymphoma 61 Risk factors: Factors that may increase the chance that a person will develop NHL. It is important to note that most people with risk factors never develop lymphoma, and many who are diagnosed have no identifiable risk factors. Salvage therapy: Therapy that is given if the primary therapy is not successful or if the disease disappears and then comes back. Spleen: An organ on the left side of the upper abdomen, near the stomach. A key component of the lymphatic system, the spleen produces and stores lymphocytes and releases them when required as part of the body’s response to infections and other stimuli. The spleen may store blood and remove old blood cells from circulation. Stable disease: The disease does not get better or worse following therapy. Stage: The extent of cancer in the body, including whether the disease has spread from the original site to other body parts. Standard therapy: The most widely used primary therapy. Synergism: The term used when two or more drugs given together provide a better anti-cancer effect than expected from the additive effects from the medications alone. Systemic symptoms: Symptoms that affect the entire body. Examples of these include fever, night sweats and weight loss. Thrombocytopenia: A shortage of platelets in the blood, which reduces the ability of the blood to clot. Thymus gland: A gland located behind the sternum (breastbone) that enhances the reproduction and development of lymphocytes. T-lymphocytes are processed in the thymus. Toxicities: The unwanted side effects of cancer therapies, such as a decrease in blood cells, nausea and vomiting, and hair loss. 62 Understanding Childhood Non-Hodgkin Lymphoma Tumor: An abnormal mass or swelling of tissue. Tumors may occur anywhere in the body. A tumor may be benign (non-cancerous) or malignant (cancerous). Vaccine: A substance or group of substances meant to cause the immune system to respond. A vaccine can help the body recognize and destroy cancer cells. Lymphoma vaccines often combine cancer antigens with a substance to stimulate the patient’s own natural defenses to fight the disease. These vaccines in lymphoma are custom-made for each patient, using a sample of tumor obtained from the patient’s lymph nodes. VEGF (Vascular Endothelial Growth Factor): One of a number of substances that stimulate angiogenesis, blood vessel formation—a process necessary for tumor growth. Watchful waiting: An approach in which no immediate medical, surgical or radiation therapy is given. Patients are followed closely to make sure the cancer does not progress. Watchful waiting is an appropriate option for some patients with indolent (slow-growing) non-Hodgkin lymphoma. Xerostomia: A temporary reduction in the production of saliva or “dry mouth.” X-ray: Radiation that is used in low doses to provide images of the inside of the body and in high doses to treat cancer. Understanding Childhood Non-Hodgkin Lymphoma 63 Please refer to our website for additional and updated information. lymphoma.org 64 Understanding Childhood Non-Hodgkin Lymphoma Resources Childhood Cancer Resources Candlelighters Childhood Cancer Foundation (CCCF) (800) 366-2223 candlelighters.org CCCF is a national non-profit organization whose mission is to educate, support, serve and advocate for families whose children have been diagnosed with cancer, survivors of childhood cancer, and the professionals who care for them. Children’s Cancer Association (CCA) (503) 244-3141 childrenscancerassociation.org The Children’s Cancer Association is a one-of-a-kind nonprofit organization bringing support, resources, award-winning programs and above all, joy to seriously ill kids/teens and their families in Oregon, SW Washington and nationally. CureSearch (800) 458-6223 curesearch.org CureSearch unites the world’s largest childhood cancer research organization, the Children’s Oncology Group, and the National Childhood Cancer Foundation to cure childhood cancer. CureSearch also provides advocacy, public education, referrals and clinical trial information. Understanding Childhood Non-Hodgkin Lymphoma 65 National Children’s Cancer Society (NCCS) (314) 241-1600 children-cancer.org The NCCS provides financial assistance, advocacy, emotional support and education to families who have children diagnosed with cancer. Pediatric Oncology Resource Center acor.org/ped-onc The Pediatric Oncology Resource Center provides a website by parents of children with cancer for parents of children with cancer. This website offers patient-friendly resources as well as links to various support groups. Special Love, Inc. (888) 930-2707 speciallove.org Special Love, Inc. sponsors Camp Fantastic and 19 other events for children with cancer and their families in the Mid-Atlantic region. Starlight Children’s Foundation (800) 315-2580 starlight.org Starlight Children’s Foundation is an international non-profit organization dedicated to improving the quality of life for seriously ill children and their families through a variety of in-hospital and outpatient programs and services. 66 Understanding Childhood Non-Hodgkin Lymphoma SuperSibs! (866) 444-SIBS (7427) supersibs.org SuperSibs! provides services free of charge to honor, support and recognize brothers and sisters of children, teens and young adults with cancer. Young Adult Cancer Resources Camp Mak-A-Dream (406) 549-5987 campdream.org Camp Mak-A-Dream is a medically supervised, cost-free Montana experience, in an intimate community setting, for children, young adults and families affected by cancer. Lance Armstrong Foundation LIVESTRONG Young Adult Alliance (866) 673-7205 livestrong.org/yaa The LIVESTRONG Young Adult Alliance is a coalition of organizations with the goal to improve the survival rates and quality of life for young adults with cancer between the ages of 15 and 40. This website provides access to the websites of all member organizations. Lymphoma Research Foundation (800) 500-9976 lymphoma.org/youngadults The Lymphoma Research Foundation offers a wide array of webcasts and podcasts for individuals affected by lymphoma in their teens, 20s and 30s, including topics specifically designed to help friends and family. Understanding Childhood Non-Hodgkin Lymphoma 67 Planet Cancer planetcancer.org Planet Cancer’s website is a 24 hour, 7 days a week online community providing peer support, information and humor for young adult cancer patients and survivors. Teens Living with Cancer teenslivingwithcancer.org TLC focuses on teen issues, presents information about cancer and treatment written at teens’ level of interest, provides opportunities to interact with other teens living with cancer and offers links to relevant sites. Ulman Cancer Fund for Young Adults (888) 393-3863 ulmanfund.org Ulman Cancer Fund focuses on how cancer affects young adults. The Ulman Cancer Fund offers scholarships, community grants, advocacy services and a guidebook. 68 Understanding Childhood Non-Hodgkin Lymphoma About the Lymphoma Research Foundation The Lymphoma Research Foundation (LRF) is the nation’s largest lymphoma-focused nonprofit health organization devoted exclusively to funding lymphoma research and providing patients and healthcare professionals with the most current information on the disease. The Foundation’s mission is to eradicate lymphoma and serve those touched by this disease. The Lymphoma Research Foundation was formed in 2001 with the merger of the Cure For Lymphoma Foundation (CFL) and the Lymphoma Research Foundation of America (LRFA). Both organizations were founded by lymphoma advocates who wanted to turn a life-altering diagnosis into a positive experience for others with the disease. Ellen Glesby Cohen founded LRFA in Los Angeles in 1991. Until her death in 2000, Ellen was a tireless champion for patients and their families who created new education and support programs and served as a staunch advocate for improved government legislation. Jerry and Barbara Freundlich founded CFL in 1994 in New York City. Jerry is a long-term survivor of non-Hodgkin lymphoma. Resources for Patients, Survivors and Loved Ones Receiving a diagnosis of lymphoma can be challenging. Whether you or someone you love is newly diagnosed or a long-term survivor, understanding the latest medical information and accessing appropriate support services may help. The Lymphoma Research Foundation offers a wide array of programs and support services to assist you from the point of diagnosis through long-term survivorship. Understanding Childhood Non-Hodgkin Lymphoma 69 Patient Services and Support Lymphoma Helpline and Clinical Trials Information Service Through this phone and email service, trained staff members are available to answer your questions and provide individual support to you and your loved ones. Services are available in any language. Lymphoma Support Network (LSN) This national one-to-one peer support program matches lymphoma patients or caregivers with volunteers who have had similar lymphoma-related experiences. Lymphoma Newsline Lymphoma-related news can be distributed to you directly through this free electronic news services. Sign up by clicking on the “register” icon on LRF’s homepage at lymphoma.org. In-Person Patient Education Programs North American Educational Forum on Lymphoma This two-day national forum is held annually and provides critical information about the latest in lymphoma research, making the best decisions about treatment options and patient support issues. Lymphoma Workshop: Understanding Lymphoma Basics and Current Treatment Options These regional, full-day educational programs provide the latest information about lymphoma, current treatment options and patient support issues. Multimedia Programs Because LRF understands that information about lymphoma continually changes throughout the year, the ongoing production of webcasts, podcasts and teleconferences enable you to access the latest information on specific topics anywhere, anytime. 70 Understanding Childhood Non-Hodgkin Lymphoma Webcasts Webcast programs offer you the opportunity to navigate through a synchronized audio and slide presentation. Podcasts Podcasts (video format) can be viewed on LRF’s website. Teleconferences Teleconferences are hour-long interactive telephone programs that provide an opportunity to learn more about lymphoma, treatments and promising research from leading lymphoma experts. These are conducted live, and the archived version is available after the program. Publications Patient Guides In addition to this publication, LRF also produces Understanding Non-Hodgkin Lymphoma: A Guide for Patients, Survivors and Loved Ones, Understanding Hodgkin Lymphoma: A Guide for Patients, Survivors and Loved Ones, and Understanding CLL/SLL: A Guide for Patients, Survivors and Loved Ones. Fact Sheets Fact sheets with the latest disease- and treatment-specific information are available in either hard copy or in PDF on LRF’s website. New topics are added on a regular basis; check to see if the topic you are looking for is available. Newsletters To keep you abreast of LRF research and news in the wider lymphoma community, you can sign up to receive any of LRF’s regular newsletters either electronically or via mail. Any of LRF’s publications may be ordered by visiting lymphoma.org. Individual and bulk copies are available free of charge. Understanding Childhood Non-Hodgkin Lymphoma 71 How to Access Programs and Services Many of the aforementioned programs are available on LRF’s website at lymphoma.org. For additional information about these resources, call (800) 500-9976 or email us at [email protected]. If you would like to order additional copies of Understanding Childhood Non-Hodgkin Lymphoma: A Guide for Patients, Survivors and Loved Ones, please call (800) 500-9976 or visit lymphoma.org. 72 Understanding Childhood Non-Hodgkin Lymphoma How to Get Involved and Give BACK Take Action to Make a Difference The LRF Advocacy Program is a network of people and programs dedicated to increasing awareness and support for the lymphoma community. The Advocacy Program focuses on taking action on laws, policies and positions that affect every lymphoma patient and survivor. By contacting elected officials via phone calls, email and letters in support of these priorities, local advocates help LRF to make lymphoma a national health priority. To become involved, visit lymphoma.org/advocacy. Start or Join a Local Chapter Chapter volunteers work tirelessly to educate people about lymphoma, conduct outreach, raise funds for research and participate in public policy and advocacy initiatives. To learn more about a chapter in your area or how to start one, please visit lymphoma.org/chapters. Raise Funds and Awareness Raise funds and awareness by participating in a variety of events being held across the country such as Lymphomathon walks, bike rides, golf tournaments, galas, lunches, young professional social events and much more! Visit lymphoma.org/events for more information. Join Team LRF Team LRF is a program through which people across the country raise much-needed funds and awareness for lymphoma research through sporting events such as marathons, half marathons, triathlons, hiking adventures, bowling tournaments, soccer matches, bike rides, lacrosse tournaments, paddling events, dance-a-thons, spin-a-thons, yoga-athons and much more. Join Team LRF in an existing LRF-partnered event in your area, or join Team LRF Teammates Across the Country if you wish to raise funds by starting your own event or by participating in an event in which LRF does not have official charity entries. For more information, visit lymphoma.org/teamlrf. Understanding Childhood Non-Hodgkin Lymphoma 73 Please refer to our website for additional and updated information. lymphoma.org 74 Understanding Childhood Non-Hodgkin Lymphoma Donate Now The Lymphoma Research Foundation (LRF) is a nonprofit health organization with 501(c)(3) status. If you would like to support LRF, your generous gift will help us move closer to finding a cure, while helping those affected by the disease. Three easy ways to give: Website: lymphoma.org/donatenow Call: (800) 235-6848 Mail: Cut out this form and mail it to Lymphoma Research Foundation, 115 Broadway, 13th Floor, New York, New York 10006 or FAX Fax: (212) 349-2886 Amount of donation $ Make checks payable to the Lymphoma Research Foundation. Charge my n Amex n Visa n MasterCard Credit Card # Exp. Date Name Address City State Telephone (day) (evening) Zip Code Email address Understanding Childhood Non-Hodgkin Lymphoma 75 Please refer to our website for additional and updated information. lymphoma.org 76 Understanding Childhood Non-Hodgkin Lymphoma Understanding Non-Hodgkin Lymphoma 77 This project is supported through Cooperative Agreement Number 1U58DP001110 from the Centers for Disease Control and Prevention. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.
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