Patient Information

Diffuse large B-cell lymphoma in adults

Diffuse large B-cell lymphoma in adults
Arnold S Freedman, MD
Jonathan W Friedberg, MD
Section Editor
Andrew Lister, MD, FRCP, FRCPath, FRCR
Deputy Editor
Rebecca F Connor, MD
Last literature review version 19.3: Fri Sep 30 00:00:00 GMT 2011 | This topic last updated: Thu Jan 27 00:00:00 GMT 2011 (More)

DIFFUSE LARGE B-CELL LYMPHOMA OVERVIEW — Lymphoma is a cancer of lymphocytes, a type of white blood cell. Lymphocytes circulate in the body through a network referred to as the lymphatic system, which includes the bone marrow, spleen, thymus, and lymph nodes. The organs and vessels of the lymphatic system work together to produce and store cells that fight infection (figure 1).

There are two main types of lymphoma:


  • Hodgkin lymphoma (HL)
  • Non-Hodgkin lymphoma (NHL)


Non-Hodgkin lymphoma (NHL) is the most common type of lymphoma. Although there are more than 30 types of NHL, diffuse large B-cell lymphoma (DLBCL) is the most common type, making up about 30 percent of all lymphomas. In the United States, DLBCL affects about 7 out of 100,000 people each year.

DLBCL is a fast-growing, aggressive form of NHL. DLBCL is fatal if left untreated, but with timely and appropriate treatment, over half of all patients can be cured. The following discussion will review the risk factors, classification, symptoms, treatment, and prognosis of this type of non-Hodgkin lymphoma.

DIFFUSE LARGE B-CELL LYMPHOMA RISK FACTORS — Age, gender, and ethnicity affect a person’s likelihood of developing DLBCL. Although DLBCL has been found in people of all age groups, it is found most commonly in people who are middle-aged or elderly. The average age at the time of diagnosis is 64 years. Men are slightly more likely to develop DLBCL than women. In the United States, white people are more likely to develop this type of lymphoma than are Asians or Blacks.

WHAT IS DIFFUSE LARGE B-CELL LYMPHOMA? — The lymph organs include the bone marrow, thymus, spleen, and lymph nodes. These help to fight infection throughout the body. The organs of the lymphatic systems are connected by a network of lymphatic and blood vessels, through which lymphatic fluid flows (figure 1). Lymphatic fluid contains white blood cells called lymphocytes.

There are two primary types of lymphocytes: B-cells and T-cells. Diffuse large B-cell lymphoma is a cancer of B lymphocytes. Almost all lymphocytes begin growing in the bone marrow or lymph nodes. T-cells leave the bone marrow before they are completely matured, and finish maturing in the thymus gland. B-cells instead continue to develop and mature in the bone marrow and lymph nodes. In DLBCL, the abnormal B-cell lymphocytes are larger than normal, and they have stopped responding to signals that usually limit the growth and reproduction of cells.

DLBCL can either develop as a transformation from a less aggressive form of lymphoma or as a first occurrence of lymphoma (called de novo).

DIFFUSE LARGE B-CELL LYMPHOMA SYMPTOMS — The first sign of DLBCL is often a quickly growing, non-painful mass in a lymph node in the neck, groin, or abdomen. Patients may also experience fever, weight loss, drenching night sweats, or other symptoms.

Extranodal disease — In about 40 percent of cases, the cancer does not begin in the lymph nodes, but instead develops elsewhere. This is called extranodal disease. The most common site of extranodal involvement is the stomach or gastrointestinal tract, but the disease can arise in virtually any tissue.

Advanced versus localized disease — Most patients (about 60 percent) are not diagnosed with DLBCL until the disease is advanced (stage III or IV). In the remaining 40 percent of patients, the disease is confined to one side of the diaphragm (above or below the diaphragm). This is called localized disease.

DIFFUSE LARGE B-CELL LYMPHOMA DIAGNOSIS — The diagnosis of DLBCL is confirmed by removing part or all of an enlarged lymph node with a biopsy. This procedure may be performed with local anesthesia if the involved tissue is relatively close to the skin’s surface. If the node is deeper, general anesthesia is required. The cells from the tissue are then examined in detail using a microscope and other techniques.

Staging — Once the diagnosis is confirmed, additional tests are performed to obtain more information about the extent to which the disease has spread in the body. This process is called staging. The results of these tests will help determine the most effective course of treatment.

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History and physical exam — A careful interview and physical examination will help determine the extent of the disease. The physical exam may reveal swollen lymph nodes in various locations (figure 1).

Staging tests — A number of tests are available to help determine which areas of the body have been affected by follicular lymphoma. Tests that may be done include:


  • Blood tests
  • Bone marrow biopsy
  • CT scan
  • PET scan


Staging terms — The following are terms used in the staging criteria:


  • Lymph node regions: An area of lymph nodes and the surrounding tissue. Examples include the cervical nodes in the neck (figure 2), the axillary nodes in the armpit, the inguinal nodes in the groin, or the mediastinal nodes in the chest (figure 1).
  • Lymph structures: Organs or structures that are part of the lymphatic system, such as the lymph nodes, spleen, and thymus gland.
  • Diaphragm: A large muscle that separates the chest cavity from the abdominal cavity.


Stage grouping — Staging involves dividing patients into groups (stages) based upon how much of the lymphatic system is involved at the time of diagnosis. Staging helps determine a person’s prognosis and treatment options (table 1).

Here is how the stages of lymphoma are defined:


  • Stage I — Only one lymph node region is involved, or only one lymph structure is involved.
  • Stage II — Two or more lymph node regions or lymph node structures on the same side of the diaphragm are involved.
  • Stage III — Lymph node regions or structures on both sides of the diaphragm are involved.
  • Stage IV — There is widespread involvement of a number of organs or tissues other than lymph node regions or structures, such as the liver, lung, or bone marrow.


When a stage is assigned, it also includes a letter, A or B, to denote whether fever, weight loss, or night sweats are present. “A” means these symptoms are not present; “B” means they are. For example, a person with stage 1B disease has evidence of cancer in one lymph node region and has “B” symptoms (fever, weight loss, or night sweats). (See ‘Diffuse large B-cell lymphoma symptoms’ above.)

DIFFUSE LARGE B-CELL LYMPHOMA TREATMENT — The treatment of DLBCL depends upon whether the disease is advanced or localized.

Advanced disease — The standard treatment of advanced DLBCL is combination chemotherapy plus immunotherapy.

Chemotherapy drugs work by interfering with the ability of rapidly growing cells (like cancer cells) to divide or reproduce themselves. Because most of an adult’s normal cells are not actively growing, they are less affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal tract.

Immunotherapy uses antibodies that target a specific group of cells (usually cancer cells). Rituximab is an antibody that targets B lymphocytes.

The most common chemotherapy regimen for advanced DLBCL is called R-CHOP. R-CHOP includes rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. The first four drugs are given into a vein (IV) over the course of one day, while prednisone is taken by mouth for five days. In the United States, this regimen is given every three weeks for 6 to 8 cycles.

A cycle of chemotherapy refers to the time it takes to give the treatment and then allow the body to recover from the effects. Thus, 8 cycles of treatment would last 24 weeks (approximately 5 months). During this time, patients are closely monitored for signs of drug toxicity and side effects.

Side effects of chemotherapy — Most patients who are treated with R-CHOP develop side effects, with the most common including:


  • Fever and low blood count — A potentially life-threatening side effect of chemotherapy is fever and lowered levels of a type of white blood cell, called neutrophils (the condition is called febrile neutropenia).

    Anyone who is getting chemotherapy and who develops a temperature higher than 100.4ºF (38ºC) should immediately call his or her healthcare provider. This condition is a medical emergency and requires prompt treatment, usually with admission to a hospital and antibiotics by vein (IV).

  • Nausea and vomiting — Between 30 and 90 percent of patients develop nausea and vomiting after R-CHOP. Several medications may be given before and after chemotherapy to reduce its severity. This often includes dexamethasone and aprepitant (Emend®), and a 5-HT3 receptor antagonist (eg, ondansetron/Zofran®, granisetron/Kytril®, dolasetron/Anzemet®, palonosetron/Aloxi®, or tropisetron/Navoban®).
  • Hypersensitivity reaction — Hypersensitivity reactions may occur the first time a chemotherapy or immunotherapy drug is given, causing flushing; itching; chest, back or abdominal pain; fever; nausea; dizziness; and other symptoms. It is not clear why this type of reaction occurs. Several medications are usually given before chemotherapy to reduce the severity of these symptoms, including acetaminophen (Tylenol®), diphenhydramine (Benadryl®), hydrocortisone (a steroid), and a stomach-acid-reducing medication, such as ranitidine (Zantac®).
  • Tumor lysis syndrome — Tumor lysis syndrome is a serious, potentially life-threatening condition that can occur after beginning treatment with chemotherapy. It happens because the tumor cells die quickly and release toxic break-down products into the bloodstream. Symptoms can include nausea, vomiting, diarrhea, lack of appetite, lethargy, blood in the urine, heart problems, seizures, muscle cramps, and others. Preventive treatments are usually given before chemotherapy to reduce the risk of developing tumor lysis syndrome, including IV fluids and medications. In addition, blood tests are often done during and after treatment to monitor for the condition.
  • Other potential complications — Other potential complications of chemotherapy include damage to the heart (called cardiotoxicity) or the nerves (called neurotoxicity), or loss of the ability to have children (infertility). These risks, as well as ways to manage or monitor for them, should be discussed with a healthcare provider before beginning treatment.


Localized disease — Patients with localized disease may be treated with fewer cycles (usually three cycles) of R-CHOP chemotherapy in combination with radiation therapy to the involved area.

Radiation therapy — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays over several days. This prevents the cancer cells from growing further and causes them to eventually die.

RT for lymphoma is usually given as external-beam RT, meaning that the radiation beam is generated by a machine that is outside the patient. Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, RT is given daily, five days per week, for approximately 3 to 4 weeks.

SURVIVING DIFFUSE LARGE B-CELL LYMPHOMA — The chance of surviving DLBCL depends upon many factors. The following factors are known to reduce the chances of survival:


  • Age older than 60
  • Lactate dehydrogenase level higher than normal (lactate dehydrogenase is a protein found in blood whose levels increase when tissues have been damaged)
  • Poor general health status (ECOG performance status score of 2 or greater) (table 2)
  • Stage III or IV disease (table 1)
  • More than one involved extranodal disease site


A scoring system, known as the International Prognostic Index (IPI), gives one point for each of the above characteristics, for a total score ranging from zero to five, representing three risk groups [1]:


  • Low risk — IPI score of 0 or 1 (91 percent of people in this risk group are still alive at three years)
  • Low to intermediate risk — IPI score of 2 (81 percent of people in this risk group are still alive at three years)
  • High to intermediate risk — IPI score of 3 (65 percent of people in this risk group are still alive at three years)
  • High risk — IPI score of 4 or more (59 percent of people in this risk group are still alive at three years)



Response evaluation — After finishing the planned course of treatment, the patient will have a medical history, physical examination, and laboratory testing to gauge his or her response to treatment.

A radiologic imaging test (PET/CT) is recommended, either six to eight weeks after finishing chemotherapy or 12 weeks after finishing radiation therapy.

A complete response has been achieved if all of the following criteria are met:


  • The patient is well
  • There is no evidence of disease or disease-related symptoms on history and physical examination
  • The spleen and liver cannot be felt during the physical examination
  • Any abnormalities seen on the CT scan do not “light up” on the PET scan
  • If a pretreatment bone marrow biopsy was positive, a repeat bone marrow biopsy must be negative


Patients who do not have a complete response are treated for refractory disease. (See ‘Recurrent or refractory diffuse large B-cell lymphoma treatment’ below.)

Surveillance for relapse — Patients who achieve a complete response must be evaluated on a regular basis after treatment. The visits usually include a medical history and physical examination, blood tests, and may include a radiologic imaging test, such as a CT scan. The purpose of these visits is to monitor for treatment complications and possible relapse. If there are new signs of a relapse, a biopsy must be done to confirm the diagnosis.

The frequency of these visits depends upon the comfort of both the patient and physician. When deciding how often these visits should occur, the patient and physician must consider the following:


  • The majority of relapses occur during the first two years after finishing treatment.
  • Relapses usually cause the person to have symptoms and are rarely found solely on the basis of routine radiologic imaging tests.
  • If a relapse is picked up a few weeks earlier because of more intense monitoring, it is unlikely to improve outcome.
  • The number of CT scans should be limited, particularly in younger individuals, to limit radiation exposure and the risk for second cancers.


One approach is to schedule patient visits every three months during the first year, every three to six months during the second year, every six months starting two years after a complete response, and then once yearly after the third year.

RECURRENT OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA TREATMENT — Recurrent disease is the term used to describe disease that returns after an initial remission. Refractory disease is the term used to describe disease that does not fully respond to treatment in the first place. (See ‘Response evaluation’ above.)

Patients who have refractory or recurrent disease have only a small chance of cure. Depending upon the person’s age and underlying medical problems, treatment may include one or more chemotherapy medications given over several days.

If the person responds to chemotherapy and is healthy enough, high-dose chemotherapy and a specific kind of bone marrow transplant called autologous hematopoietic stem cell transplantation may be recommended. This type of bone marrow transplant uses a person’s own cells to “rescue” his or her bone marrow from intensive chemotherapy. (See “Patient information: Bone marrow transplantation (stem cell transplantation)”.)

CLINICAL TRIALS — A clinical trial is an approved research study that is designed to determine the best treatment for a particular disease. Clinical trials are especially important in diffuse large B-cell lymphoma, since there no treatment program capable of curing all patients with this disease.

Enrollment in a clinical trial, if available, is always recommended. Ask your doctor for more information, or read about clinical trials at:


  • National Cancer Institute




  • National Library of Medicine



WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed every four months on our Web site (

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Bone marrow transplantation (stem cell transplantation)

Professional Level Information:

Classification of the hematopoietic neoplasms
Clinical presentation and diagnosis of non-Hodgkin lymphoma
Initial evaluation and staging of non-Hodgkin lymphoma
Hematopoietic cell transplantation in follicular lymphoma
Initial treatment of follicular lymphoma
Initial treatment of mantle cell lymphoma
Natural killer (NK) cell large granular lymphocyte leukemia
Pathobiology of diffuse large B cell lymphoma and primary mediastinal large B cell lymphoma
Treatment of large granular lymphocyte leukemia
Treatment and prognosis of Waldenstrom macroglobulinemia
Treatment of advanced stage (IIB to IV) mycosis fungoides and Sézary syndrome
Treatment of early stage (IA to IIA) mycosis fungoides
Treatment of hairy cell leukemia
Treatment of marginal zone (MALT) lymphoma
Treatment of relapsed or refractory diffuse large B cell lymphoma
Treatment of relapsed or refractory mantle cell lymphoma

The following organizations also provide reliable health information.


  • American Cancer Society




  • National Cancer Institute




  • National Library of Medicine




  • The Leukemia & Lymphoma Society





  1. Ziepert M, Hasenclever D, Kuhnt E, et al. Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol 2010; 28:2373.
  2. American Cancer Society. What is non-Hodgkin’s lymphoma? (Accessed 3/7/05).