Diffuse Large B-cell Lymphoma

Synonyms

2

Overview

Diffuse large B-cell lymphoma (DLBCL or DLBL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. It is the most common type of non-Hodgkin lymphoma among adults,with an annual incidence of 7–8 cases per 100,000 people per year. This cancer occurs primarily in older individuals, with a median age of diagnosis at approximately 70 years of age, though it can also occur in children and young adults in rare cases. DLBCL is an aggressive tumor which can arise in virtually any part of the body, and the first sign of this illness is typically the observation of a rapidly growing mass, sometimes associated with fever, weight loss, and night sweats.

The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma or leukemia. An underlying immunodeficiency is a significant risk factor. Infection with Epstein–Barr virus has also been found to contribute to the development of some subgroups of DLBCL.

Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis. Several subtypes of DLBCL have been identified, each having a different clinical presentation and prognosis. However, the usual treatment for each of these is chemotherapy, often in combination with an antibody targeted at the tumor cells.Through these treatments, more than half of patients with DLBCL can be cured, and the overall five-year survival rate for older adults is around 58%.

Symptoms

The most typical symptom at the time of diagnosis is a mass that is rapidly enlarging and located in a part of the body with multiple lymph nodes.

Causes

The causes of diffuse large B-cell lymphoma are unknown. Diffuse large B-cell lymphoma, like other cancers, is not infectious and cannot be passed on to other people.

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

Diagnosis

A diagnosis is made by removing an enlarged lymph node, or part of it, and examining the cells under the microscope (biopsy). It is a very small operation and may be done under local or general anaesthetic. Biopsies may also be taken from other body tissues.

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.

History and physical exam:

A careful interview and physical examination will begin to determine the extent of the disease. The physical exam may reveal swollen lymph nodes in various locations.

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 (not performed if a combined PET/CT is used)
  • PET/CT scan

Lymphoma is divided into 4 stages based on its severity:

  • Stage I :Only one lymph node region is involved, only one lymph structure is involved, or only one extranodal site (IE) 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.

Prognosis

The germinal center subtype has the best prognosis, with 66.6% of treated patients surviving more than five years. The IPI score is used in prognosis in clinical practice. Lenalidomide has been recently shown to improve outcomes in the non-germinal center subtype. Ratios of immune effectors such as CD4 and CD8 to immune checkpoints such as PD-L1 and M2 macrophages are independent of and additive to the cell of origin and IPI in DLBCL, and are applicable to paraffin-embedded biopsy specimens. These findings might have potential implications for selection of patients for checkpoint blockade and/or lenalidomide within clinical trials.

For children with diffuse large B-cell lymphomas, most studies have found 5-year survival rates ranging from about 70% to more than 90%.

Treatment

Chemotherapy

Current treatment typically includes R-CHOP, which consists of the traditional CHOP, to which rituximab has been added. This regimen has increased the rate of complete response for DLBCL patients, particularly in elderly patients. R-CHOP is a combination of one monoclonal antibody (rituximab), three chemotherapy agents (cyclophosphamide, doxorubicin, vincristine), and one steroid (prednisone). These drugs administered intravenously, and the regimen is most effective when it is administered multiple times over a period of months. People often receive this type of chemotherapy through a PICC line (peripherally inserted central catheter) in their arm near the elbow or a surgically implanted venous access port. The number of cycles of chemotherapy given depends on the stage of the disease — patients with limited disease typically receive three cycles of chemotherapy, while patients with extensive disease may need to undergo six to eight cycles. A recent approach involves obtaining a PET scan after the completion of two cycles of chemotherapy, to assist the treatment team in making further decisions about the future course of treatment. Older people often have more difficulty tolerating therapy than younger people. Lower intensity regimens have been attempted in this age group.

Radiation therapy

Radiation therapy is often part of the treatment for DLBCL. It is commonly used after the completion of chemotherapy. Radiation therapy alone is not an effective treatment for this disease.