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| '''For patient information click [[{{PAGENAME}} (patient information)|here]]'''
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| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = Non-Hodgkin's Lymphoma | | | Name = Non-Hodgkin's Lymphoma | |
| Image = lymphoma_tungsten.jpg| | | Image = lymphoma_tungsten.jpg| |
| Caption = Malignant lymphoma, high grade B cell, not otherwise specified (Courtesy of Ed Uthman, MD) | | | Caption = Malignant lymphoma, high grade B cell, not otherwise specified (Courtesy of Ed Uthman, MD) | |
| DiseasesDB = 9065 |
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| ICD10 = {{ICD10|C|82||c|81}}-{{ICD10|C|85||c|81}} |
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| ICD9 = {{ICD9|200}}, {{ICD9|202}} |
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| ICDO = 9591/3 |
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| OMIM = 605027 |
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| MedlinePlus = 000581 |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| eMedicine_mult = |
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| MeshID = D008228 |
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| }} | | }} |
| {{SI}}
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| {{CMG}}
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| {{Non-Hodgkin lymphoma}} | | {{Non-Hodgkin lymphoma}} |
| ==Overview==
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| '''Non-Hodgkin lymphoma''' (NHL) describes a group of [[cancer]]s arising from [[lymphocyte]]s, a type of [[white blood cell]]. It is distinct from [[Hodgkin lymphoma]] in its [[pathology|pathologic features]], [[epidemiology]], common sites of involvement, clinical behavior, and treatment. The non-Hodgkin lymphomas are a diverse group of diseases with varying courses, treatments, and [[prognosis|prognoses]].
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| [[Image:|frame|left|Malignant lymphoma, high grade B cell, not otherwise specified Courtesy of Ed Uthman, MD]] | | '''For patient information click [[{{PAGENAME}} (patient information)|here]]''' |
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| Non-Hodgkin lymphoma may develop in any organ associated with the lymphatic system (e.g. [[spleen]], [[lymph node]]s, or [[tonsils]]). Most cases start with infiltration of lymph nodes, but some subtypes may be restricted to other lymphatic organs.
| | {{CMG}}; {{AE}} {{Preeti}} {{UA}} |
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| The diagnosis of non-Hodgkin lymphoma requires a [[biopsy]] of involved tissue. The numerous subtypes of non-Hodgkin lymphoma are typically grouped into three distinct categories based on their aggressiveness, or histologic grade. These categories are ''indolent'' (or low-grade), ''aggressive'' (or intermediate-grade), and ''highly aggressive'' (or high-grade). The treatment of indolent or low-grade lymphoma may initially involve a period of observation, while aggressive or highly aggressive non-Hodgkin lymphoma is typically treated with [[chemotherapy]] and/or [[radiation therapy]].
| | {{SK}} NHL; Non-Hodgkin's disease; B-cell NHLs; T-cell and NK–cell NHLs |
| | ==[[Non-Hodgkin lymphoma overview|Overview]]== |
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| == Symptoms == | | ==[[Non-Hodgkin lymphoma historical perspective|Historical Perspective]]== |
| {{see also|B symptoms}}
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| The most common symptom of non-Hodgkin's lymphoma is a painless swelling of the lymph nodes in the neck, underarm (axilla), or groin.
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| Other symptoms may include the following:
| | ==[[Non-Hodgkin lymphoma classification|Classification]]== |
| * Unexplained [[fever]]
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| * Unexplained [[weight loss]] and [[anorexia (symptom)|anorexia]] (poor appetite)
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| * Unexplained night sweats
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| * Constant [[Fatigue (physical)|fatigue]]
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| * [[Pruritis|Itchy skin]]
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| * Reddened patches on the skin
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| Such symptoms are non-specific and may be caused by other, less serious conditions.
| | ==[[Non-Hodgkin lymphoma pathophysiology|Pathophysiology]]== |
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| == Diagnosis == | | ==[[Non-Hodgkin lymphoma causes|Causes]]== |
| If non-Hodgkin's lymphoma is suspected, the doctor asks about the person's medical history and performs a physical exam. The exam includes feeling to see if the lymph nodes in the neck, underarm, or groin are [[lymphadenopathy|enlarged]]. In addition to checking general signs of health, the doctor may perform blood tests.
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| [[Image:Malignant lymphoma, high grade B cell 1.jpg|thumb|left|Excisional biopsy NHL specimen]] | | ==[[Non-Hodgkin lymphoma differential diagnosis|Differentiating Non-Hodgkin lymphoma from other Diseases]]== |
| The doctor may also order [[medical imaging|tests that produce pictures of the inside of the body]]. These may include:
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| *[[X-ray]]s: Pictures of areas inside the body created by high-energy radiation.
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| *[[CT scan]] (computed [[Tomographic reconstruction|tomography]] scan, also known as a "CAT scan"): A series of detailed pictures of areas inside the body. The pictures are created by a computer linked to an x-ray machine.
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| *[[PET scan]] (positron emission tomography scan): This is an imaging test that detects uptake of a radioactive tracer by the tumor. More often, the PET scan can be combined with the CT scan.
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| *MRI ([[magnetic resonance imaging]]): Detailed pictures of areas inside the body produced with a powerful magnet linked to a computer.
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| ===Less commonly used=== | | ==[[Non-Hodgkin lymphoma epidemiology and demographics|Epidemiology and Demographics]]== |
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| *[[Lymphangiogram]]: Pictures of the lymphatic system taken with x-rays after a special dye is injected to outline the lymph nodes and vessels. This test is not used as often because of the adoption of CT scan and the PET scan technologies.
| | ==[[Non-Hodgkin lymphoma risk factors|Risk Factors]]== |
| *[[Gallium scan]]: Gallium is a rare metal that behaves in the body in a fashion similar to iron, so that it concentrates in areas of inflammation or rapid cell-division, and hence is useful for imaging the entire lymphatic system for staging of lymphoma once the presence of the disease has been confirmed. PET scans have supplanted gallium scans for evaluation and follow up of NHL.
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| ===Biopsy=== | |
| A [[biopsy]] is needed to make a diagnosis. A surgeon removes a sample of tissue, which a [[pathologist]] can examine under a microscope to check for cancer cells. A biopsy for non-Hodgkin's lymphoma is usually taken from lymph nodes that are enlarged, but other tissues may be sampled as well. Biopsies in internal lymph nodes can also taken as needle biopsies under the guidance of CT scans. Rarely, an operation called a [[laparotomy]] may be performed. During this operation, a surgeon cuts into the abdomen and removes samples of tissue to be checked under a microscope.
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| == Types of non-Hodgkin's lymphoma == | | ==[[Non-Hodgkin lymphoma screening|Screening]]== |
| Over the years, doctors have used a variety of terms to classify the many different types of non-Hodgkin's lymphoma . Most often, they are grouped by how the cancer cells look under a [[microscope]] and how quickly they are likely to grow and spread. Current lymphoma classification is complex.
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| [[MeSH]] includes four different criteria for classifying NHL. (It is possible to be classified under more than one.) | | ==[[Non-Hodgkin lymphoma natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| * ''High-grade vs. intermediate vs. low-grade'': Aggressive lymphomas, also known as intermediate and high-grade lymphomas, tend to grow and spread quickly and cause severe symptoms. Indolent lymphomas, also referred to as low-grade lymphomas, tend to grow quite slowly and cause fewer symptoms. One of the paradoxes of non-Hodgkin's lymphoma is that the indolent lymphomas generally cannot be cured by [[chemotherapy]], while in a significant number of cases aggressive lymphomas can be.
| | ==Diagnosis== |
| | [[Non-Hodgkin lymphoma diagnostic study of choice|Diagnostic Study of Choice]] | [[Non-Hodgkin lymphoma staging|Staging]] | [[Non-Hodgkin lymphoma history and symptoms|History and Symptoms]] | [[ Non-Hodgkin lymphoma physical examination | Physical Examination]] | [[Non-Hodgkin lymphoma laboratory findings|Laboratory Findings]] | [[Non-Hodgkin lymphoma electrocardiogram|Electrocardiogram]] | [[Non-Hodgkin lymphoma chest x ray|Chest X Ray]] | [[Non-Hodgkin lymphoma CT|CT]] | [[Non-Hodgkin lymphoma MRI|MRI]] | [[Non-Hodgkin lymphoma ultrasound|Ultrasound]] | [[Non-Hodgkin lymphoma biopsy|Biopsy]] | [[Non-Hodgkin lymphoma other imaging findings|Other Imaging Findings]] | [[Non-Hodgkin lymphoma other diagnostic studies|Other Diagnostic Studies]] |
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| * ''Diffuse vs. follicular'': [[Follicular lymphoma]] tends to be indolent, and [[diffuse lymphoma]] tends to be aggressive.
| | ==Treatment== |
| | [[Non-Hodgkin lymphoma medical therapy|Medical Therapy]] | [[Non-Hodgkin lymphoma surgery |Surgery]] | [[Non-Hodgkin lymphoma primary prevention|Primary Prevention]] | [[Non-Hodgkin lymphoma secondary prevention|Secondary Prevention]] | [[Non-Hodgkin lymphoma cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Non-Hodgkin lymphoma future or investigational therapies|Future or Investigational Therapies]] |
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| * ''[[T-cell lymphoma]] vs. [[B-cell lymphoma]]''
| | ==Case Studies== |
| ** [[Gluten-sensitive_enteropathy_associated_conditions#GSEA_Lymphoma|Gluten-sensitive enteropathy associated T-cell lymphoma]] or EATL
| | [[Non-Hodgkin lymphoma case study one|Case #1]] |
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| * ''Large cell lymphoma (such as [[anaplastic large cell lymphoma]]) vs. [[Small cell lymphoma]] vs. Mixed cell lymphoma
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| Details of the most popular classifications of lymphoma can be found in the [[lymphoma]] page.
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| ==Causes== | |
| The [[etiology]], or cause, of most lymphomas is not known. Some types of lymphomas are associated with [[virus|viruses]]. [[Burkitt's lymphoma]], extranodal NK/T cell lymphoma, classical [[Hodgkin's disease]] and most [[AIDS-related lymphoma]] are associated with [[Epstein-Barr virus]]. Adult T-cell lymphoma/[[leukemia]], endemic in parts of Japan and the Caribbean, is caused by the [[HTLV-1]] virus. Lymphoma of the stomach (extranodal marginal zone B-cell lymphoma) is often caused by the [[Helicobacter]] bacteria.
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| The incidence of non-Hodgkin's lymphoma has increased dramatically over the last couple of decades. This disease has gone from being relatively rare to being the fifth most common cancer in the United States. At this time, little is known about the reasons for this increase or about exactly what causes non-Hodgkin's lymphoma.
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| Doctors can seldom explain why one person gets non-Hodgkin's lymphoma and another does not. It is clear, however, that cancer is not caused by an injury, and is not contagious; no one can "catch" non-Hodgkin's lymphoma from another person.
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| By studying patterns of cancer in the population, researchers have found certain risk factors that are more common in people who get non-Hodgkin's lymphoma than in those who do not. However, most people with these risk factors do not get non-Hodgkin's lymphoma, and many who do get this disease have none of the known risk factors.
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| The following are some of the risk factors associated with this disease:
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| *Age/sex. The likelihood of getting non-Hodgkin's lymphoma increases with age and is more common in men than in women.
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| *Weakened immune system ([[AIDS-related lymphoma]]). Non-Hodgkin's lymphoma is more common among people with inherited immune deficiencies, [[autoimmune disease]]s, or HIV/[[AIDS]], and among people taking [[immunosuppressant]] drugs following [[organ transplant]]s. (see [[Post-transplant lymphoproliferative disorder]])
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| *Viruses. Human T-lymphotropic virus type I ([[HTLV-1]]) and [[Epstein-Barr virus]] are two infectious agents that increase the chance of developing non-Hodgkin's lymphoma.
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| *Environment. People who work extensively with or are otherwise exposed to certain chemicals, such as pesticides, solvents, or fertilizers, have a greater chance of developing non-Hodgkin's lymphoma.
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| People who are concerned about non-Hodgkin's lymphoma should talk with their doctor about the disease, the symptoms to watch for, and an appropriate schedule for checkups. The doctor's advice will be based on the person's age, medical history, and other factors.
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| == Staging ==
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| If non-Hodgkin's lymphoma is diagnosed, the doctor needs to learn the stage, or extent, of the disease. [[Cancer staging|Staging]] is a careful attempt to find out whether the cancer has spread and, if so, what parts of the body are affected. Treatment decisions depend on these findings.<ref>{{cite web | title=Staging NHL | work=Cancer Research UK 2002 | url=http://www.cancerhelp.org.uk/help/default.asp?page=3044 | accessdate=April 25| accessyear=2005}}</ref>
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| The doctor considers the following to determine the stage of non-Hodgkin's lymphoma:
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| *The number and location of affected lymph nodes;
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| *Whether the affected lymph nodes are above, below, or on both sides of the diaphragm (the thin muscle under the lungs and heart that separates the chest from the abdomen);
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| *Whether the disease has spread to the bone marrow, spleen, or to organs outside the lymphatic system, such as the liver;
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| and the testes.
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| *Whether [[B symptoms]] (systemic symptoms) such as fever, chills, night sweats, or weight loss are present.
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| In staging, the doctor may use some of the same tests used for the diagnosis of non-Hodgkin's lymphoma. Other staging procedures may include additional biopsies of lymph nodes, the liver, bone marrow, or other tissue. A bone marrow biopsy involves removing a sample of bone marrow through a needle inserted into the hip or another large bone. A pathologist examines the sample under a microscope to check for cancer cells.
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| ===Stages of NHL===
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| The various stages of NHL (the [[Ann Arbor staging]] classification, developed for Hodgkin's lymphoma) are based on how far the cancer has spread throughout and beyond the lymphatic system, and whether constitutional symptoms (fever, night sweats, or weight loss) are present.
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| ;Stage I:"Stage I" indicates that the cancer is located in a single region, usually one lymph node and the surrounding area. Stage I often will not have outward symptoms.
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| ;Stage II:"Stage II" indicates that the cancer is located in two separate regions, an affected lymph node or organ within the lymphatic system and a second affected area, and that both affected areas are confined to one side of the diaphragm - that is, both are above the diaphragm, or both are below the diaphragm.
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| ;Stage III:"Stage III" indicates that the cancer has spread to both sides of the diaphragm, including one organ or area near the lymph nodes or the spleen.
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| ;Stage IV:"Stage IV" indicates that the cancer has spread beyond the lymphatic system and involves one or more major organs, possibly including the bone marrow or skin.
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| The absence of constitutional symptoms is denoted by adding an "A" to the stage; the presence is denoted by adding a "B" to the stage (hence the name [[B symptoms]]).
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| Staging in non-Hodgkin's lymphomas is far less significant in determining therapy than it is in Hodgkin's lymphoma
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| ==Prognosis==
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| {{see also|International Prognostic Index}}
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| The most significant factor in overall [[prognosis]] is the grade, or aggressiveness, of the lymphoma. Indolent (low-grade) non-Hodgkin's lymphoma is generally not curable, but is typically slowly progressive and responds temporarily to therapy. Aggressive and highly aggressive (intermediate- and high-grade) NHL's are potentially curable with combination [[chemotherapy]]. Long-term survival or cure rates for these diseases vary with a number of prognostic factors.
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| ===International Prognostic Index===
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| The [[International Prognostic Index]], or IPI, is the most widely used prognostic system for non-Hodgkin's lymphoma. This system uses 5 factors:
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| :*Age
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| :*[[Lactate dehydrogenase]] level (a blood test)
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| :*Performance status
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| :*Clinical stage
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| :*Sites of extranodal disease
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| However, it should be noted that the IPI was developed prior to the introduction of [[rituximab]]. As [[rituximab]] has become a standard part of therapy for [[B-cell]] NHL's, the impact on the prognostic value of the IPI is unclear.
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| ====FLIPI====
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| For the subtype of NHL known as [[follicular lymphoma]], a modified version of the IPI called the FLIPI ([[International Prognostic Index|follicular lymphoma international prognostic index]]) has been developed. The factors which figure into the FLIPI are age, clinical stage, [[lactate dehydrogenase]] level, [[hemoglobin]] level, and number of nodal sites involved. As with the IPI, the FLIPI was developed and validated prior to the widespread use of [[rituximab]], so the same caveats apply as were mentioned with the IPI above.
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| == Treatment ==
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| The doctor develops a treatment plan to fit each patient's needs. Treatment for non-Hodgkin's lymphoma depends on the stage of the disease, the type of cells involved, whether they are indolent or aggressive, and the age and general health of the patient.
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| Non-Hodgkin's lymphoma is often treated by a team of specialists that may include a [[hematologist]], medical oncologist, and/or radiation oncologist. Non-Hodgkin's lymphoma is usually treated with [[chemotherapy]], [[radiation therapy]], or a combination of these treatments. In some cases, [[bone marrow transplantation]], biological therapies, or surgery may be options. For indolent lymphomas, the doctor may decide to wait until the disease causes symptoms before starting treatment. Often, this approach is called "watchful waiting."
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| Taking part in a clinical trial (research study) to evaluate promising new ways to treat non-Hodgkin's lymphoma is an important option for many people with this disease.
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| ===Chemotherapy and radiation therapy===
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| [[Chemotherapy]] and [[radiation therapy]] are the most common treatments for non-Hodgkin's lymphoma, although bone marrow transplantation, biological therapies, or surgery are sometimes used. [[CHOP]], with [[rituximab]] added in certain circumstances, is the most commonly used combination of chemotherapy.
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| [[Rituximab]] is an antibody-based therapy. Zevalin and Bexxar are government-approved options, requiring a Nuclear Medicine facility, but only two shots 1 week apart. There is mounting evidence that more patients have long-term remission if they use radioimmunotherapy first.
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| Radiation therapy (also called radiotherapy) is the use of high-energy rays to kill cancer cells. Treatment with radiation may be given alone or with chemotherapy. Radiation therapy is local treatment; it affects cancer cells only in the treated area. Radiation therapy for Non Hodgkin's lymphoma comes from a machine that aims the high-energy rays at a specific area of the body. There is no radioactivity in the body when the treatment is over.
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| Sometimes patients are given chemotherapy and/or radiation therapy to kill undetected cancer cells that may be present in the central nervous system (CNS). In this treatment, called central nervous system prophylaxis, the doctor injects anticancer drugs directly into the cerebrospinal fluid.
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| ===Hematopoietic stem cell transplantation===
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| [[Hematopoietic stem cell transplantation]] (HSCT), or [[Bone marrow transplantation]] (BMT) may also be a treatment option, especially for patients whose non-Hodgkin's lymphoma has recurred (come back). BMT provides the patient with healthy stem cells (very immature cells, found in the marrow, that produce blood cells), the function of which is to replace white blood cells that are damaged or destroyed by treatment with very high doses of chemotherapy and/or radiation therapy. The healthy bone marrow may come from a donor, or it may be "autologous" (marrow that was removed from the patient, stored, and then given back to the person following the high-dose treatment). Autologous transplants are preferred, as the recipient is less likely to reject the cells, the origins of which were the same entity. However, in order for an autologous transplant to be performed, certain physiological conditions must be optimal within the patient. If these conditions are not present, transplanted stem cells can come from other donors. Until the transplanted bone marrow begins to produce enough white blood cells, patients have to be carefully protected from infection due to the virtual elimination of the auto-immune system resulting from the high-intensity treatment. Without the introduction of the stem cells following the high dose treatment, the patient will not survive as the body will be unable to produce infection-fighting white blood cells. Patients usually stay in the hospital for several weeks and will be monitored for transplant rejection and overall health.
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| ===Immunotherapy===
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| Biological therapy (also called [[immunotherapy]]) is a form of treatment that uses the body's immune system, either directly or indirectly, to fight cancer or to lessen the side effects that can be caused by some cancer treatments. It uses materials made by the body or made in a laboratory to boost, direct, or restore the body's natural defenses against disease. This approach is under close investigation. Biological therapy is sometimes also called biological response modifier therapy.
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| ===Measuring response to treatment===
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| After treatment for non-Hodgkin's lymphoma, the response is classified as follows:
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| :*''Complete Response (CR)''. This indicates the disappearance of all detectable disease.
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| :*''Partial Response (PR)''. A reduction in the bulk of disease by at least 50%, but with some remaining disease.
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| :*''Stable Disease''. Less than a partial remission, but no progression of disease and no new sites of disease.
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| :*''Progressive Disease''. Growth in bulk of disease by >50%, or the appearance of new sites of disease.
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| If a complete remission is achieved, the patient is watched closely for any evidence of recurrent disease. Standard guidelines dictate that a patient be monitored for relapse every three months in the first year following a complete remission, every six months in the second year, and finally once annually in the third and later years. Diffuse large b-cell lymphoma is the most common type of lymphoma that is considered curable. Currently, if a patient maintains a complete remission for 3 years, the patient is considered cured. Generally most relapses of diffuse large b-cell lymphoma occur within the first year after a complete remission is obtained. Reoccurences after 3 years are rare but they do occur. The effect of Rituximab on relapse rates for diffuse large b-cell lymphoma is still largely unknown, though initial relapse rates since 2003 have been much lower than expected.
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| Patients with follicular lymphoma are generally not considered cured. Instead, they are categorized as in ongoing complete remission. Relapses occur steadily over time. Relapse rates are estimated to be 33%, 66%, and 100% for follicular lymphoma's Grades I, II, and III respectively.
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| Research has indicated that relapse rates can be lowered on patients with follicular lymphoma by giving supplemental radiation therapy, however, it is known that this additional therapy increases the chances of a second malignancy of unknown type later in life.
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| If the response to treatment falls short of a complete response, more treatment may be administered (using a different [[chemotherapy]] regimen), or watchful waiting may be utilized, depending on the goals of treatment.
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| ===Nutrition during treatment===
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| Eating well during cancer treatment means getting enough [[food energy]] and [[protein]] to help prevent weight loss and regain strength. Good nutrition often helps people feel better and have more energy.
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| Some people with cancer find it hard to eat a balanced diet because they may lose their appetite. In addition, common side effects of treatment, such as nausea, vomiting, or mouth sores, can make eating difficult. Often, foods may taste or smell different. Also, people being treated for cancer may not feel like eating when they are uncomfortable or tired.
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| Doctors, nurses, and dietitians can offer advice on how to get enough food energy and protein during cancer treatment. Patients and their families also may want to read the [[National Cancer Institute]] (USA) booklet ''Eating Hints for Cancer Patients'', which contains many useful suggestions.<ref> {{cite web|url=http://www.cancer.gov/cancertopics/eatinghints |title=Eating Hints for Cancer Patients: Before, During, and After Treatment |accessdate=2007-07-15 |publisher=National Cancer Institute }}</ref>
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| == Followup care ==
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| People who have had non-Hodgkin's lymphoma should have regular followup examinations after their treatment is over. Followup care is an important part of the overall treatment plan, and people should not hesitate to discuss it with their health care provider. Regular followup care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between followup appointments, people who have had Non Hodgkin's lymphoma should report any health problems as soon as they appear.
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| ==References==
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| <references/>
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| ==External links==
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| *{{cite web | title=What You Need to Know About Non-Hodgkin's Lymphoma | work=NIH Publication No. 99-1567 | url=http://www.cancer.gov/cancerinfo/wyntk/non-hodgkins-lymphoma | accessdate=January 22 | accessyear=2002}}
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| *[http://www.lymphoma.org/site/pp.asp?c=chKOI6PEImE&b=1573289 Lymphoma Research Foundation]
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| *[http://www.mantlecelllymphoma.org/ Mantle Cell Lymphoma Consortium]
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| *[http://www.leukemia-lymphoma.org/all_page?item_id=7087 The Leukemia & Lymphoma Society]
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| *[http://lymphoma.ie/Non-Hodgkins-Lymphoma-NHL/What-is-it?/Non-Hodgkins-Lymphoma/ Understanding Non Hodgkin's Lymphoma from Lymphoma Support Ireland]
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| *[http://www.lymphomainfo.net/lymphoma.html Lymphoma Information Network]
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| *[http://www.nonhodgkinslymphomastudy.com/ Non-Hodgkin's Lymphoma Clinical Research Study] (commercial, sponsored by Genentech)
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| {{Hematology}}
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| {{Hematological malignancy histology}}
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