Patient Information: Diffuse Large B Cell Lymphoma
Lymphomas are a blood cancer arising from T and B lymphocytes — types of white blood cells — present in the lymphatic system. Lymphomas are divided into two main categories: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). Hodgkin lymphoma is named after the English physician who first discovered the type of abnormal B lymphocytes that occur in HL specifically. NHL accounts for 90% of lymphomas and consists of around 60 different lymphoma subtypes. Lymphoma is the most prevalent blood cancer and accounts for approximately 3–4% of all cancer diagnoses.
What is diffuse large B cell lymphoma?
Diffuse large B cell lymphoma (DLBCL) is the most commonly occurring subtype of non-Hodgkin lymphoma and accounts for around 30% of lymphomas. Arising from B cells in lymph nodes (nodal disease) and other organs (extranodal disease), DLBCL is named for the appearance of affected lymph nodes under microscopic examination. This shows large B cells spread throughout the lymph node. 60% of cases are nodal disease with extranodal disease arising from other sites such as the stomach and spleen. The site(s) where DLBCL occurs is one of the criteria used to stage the disease. Biomarker testing may be used to determine the type of B cell from which the cancer originates which, in turn, may have a bearing on prognosis and treatment options. Biomarker testing is typically used to distinguish between two types of DLBCL:
- Germinal center B-cell-like (GCB) subtype;
- Activated B-cell-like (ABC) subtype
There is evidence to suggest that ABC DLBCL is less responsive to current standard of care. Biomarker testing for DLBCL is not yet widely available although its use is increasingly being advocated.
Although DLBCL can occur at any age it is more common in older patients with around half of diagnoses made in patients over the age of 60. It is aggressive and, if untreated, rapidly fatal.
What are the symptoms of diffuse large B cell lymphoma?
Symptoms can vary depending on where in the body the lymphoma arises and the effect the rapidly expanding lymphoid tissue has on surrounding structures. Apart from a rapidly growing mass, which typically is a lymph node in the neck, groin or abdomen, the following symptoms may also be reported:
- Fever
- Night sweats
- Unexplained weight loss
- Fatigue
- Loss of appetite
- Shortness of breath
- Pain
How is diffuse large B cell lymphoma diagnosed?
DLBCL is diagnosed in two steps. The first is a tissue biopsy of an affected lymph node and examination under a microscope to confirm the diagnosis. After that a number of different tests are used to look for DLBCL in other sites in the body. The results of these tests, along with physical examination findings, are then used to determine the stage of DLBCL. Staging may include the following tests:
- Blood tests e.g. complete blood count (CBC), lactate dehydrogenase level
- Whole body CT scan
- Positron emission tomography scan(PET)/CT scan
- Lumbar puncture
- Bone marrow biopsy
What are the stages of diffuse large B cell lymphoma?
DLBCL is classified into four different stages depending on the extent to which it has spread through the body:
- Stage I — disease in a single lymph node region/lymph structure/extranodal site
- Stage II — disease in two or more lymph node regions on the same side of the diaphragm
- Stage III — disease in lymph node regions or structures on both sides of the diaphragm
- Stage IV — disease in a number of organs/tissue other than lymph node regions or structures, such as liver and bone marrow
Stage I and II are referred to as localized disease while stage III and IV are considered to be advanced disease. 60% of patients with DLBCL present with advanced disease.
What is the survival rate for diffuse large B cell lymphoma?
The International Prognostic Index (IPI) is used to determine the prognosis of aggressive lymphomas, including DLCBL. It looks at a combination of factors in order to determine a patient’s prognosis. The IPI combines factors that are considered to indicate a poor prognosis. Each factor is assigned a score of 1 as follows:
DLBCL poor prognostic factors
The total score is then used to divide patients into four risk groups:
IPI score
What are diffuse large B cell lymphoma treatment guidelines?
There are different treatment options for DLBCL. Organizations such as the Lymphoma Research Foundation and National Comprehensive Cancer Network outline guidance on treatment based on the stage of disease. The first-line treatment used depends on whether there is advanced or localized disease. Around 40% of patients with DLBCL go on to develop refractory disease (not responsive to treatment) or relapse (disease returns after treatment). Second-line treatments may be suitable for only a select group of these patients.
Advanced diffuse large B cell lymphoma
As previously mentioned, the majority of patients with DLBCL present with advanced disease. Standard first-line treatment for these patients is a combination of:
- Chemotherapy — drugs that preferably interfere with cells that are rapidly growing and making copies of themselves as compared to normal cells. This mostly impacts cancer cells, but as a side effect, also rapidly dividing cells such as those found in bone marrow, hair and the gastrointestinal tract’s lining.
- Immunotherapy — drugs that are made up of antibodies that target specific types of cells. In the case of DLBCL this is B cells.
The combination of the above that is most commonly used to treat advanced DLBCL is called RCHOP. Rituximab (an immunotherapy drug) given with cyclophosphamide, doxorubicin and vincristine (chemotherapy drugs) and prednisone. RCHOP is usually given every 3 weeks six to eight times (cycles). There is a risk of complications, such as infection, because of a low level of another type of white blood cell type known as neutrophils.
Localized diffuse large B cell lymphoma
Patients with localized DLBCL may receive RCHOP as first-line therapy as well, but using fewer cycles. In addition, radiation therapy (RT) may also be used. RT uses X-rays that contain a large amount of energy to damage the DNA of rapidly dividing cancer cells, thereby stopping their growth. The X-ray beam is targeted on the tumor in order to minimize damage to surrounding normal cells, but it may still occur.
Refractory/relapsed diffuse large B cell lymphoma
Second-line treatment is used to treat these patients. For those suitable, this involves high-dose chemotherapy along with hematopoietic stem cell transplantation (HCT). In HCT stem cells from the patient’s own bone marrow (or a donor) are transplanted into the patient after high-dose chemotherapy or radiotherapy has been used to destroy cancer cells. It also completely destroys other normal cells in the bone marrow.
Older patients, as well as those with other medical problems, may not be able to tolerate the intense second-line treatment regimen. Some of these patients may opt for supportive care and palliation alone. Others, wanting to continue to pursue treatment options, may look to clinical trials.
The role of clinical trials in diffuse large B cell lymphoma
The National Comprehensive Cancer Network’s guidelines recommend, among others, clinical trials as a treatment option for patients with advanced DLBCL, as well as for those with refractory or relapsed DLBCL. There are quite a few active clinical trials investigating drugs with a number of different targets and modes of action. Providing timely and accurate information to patients and physicians may play a role in shared decision-making that is part of the process of considering, and potentially accessing treatment options.
