Non-Hodgkin’s lymphoma

WHAT IS NON-HODGKIN’S LYMPHOMA?

The lymph system is part of the immune system. Lymph system is made up of the following:

Lymph: Colorless, watery fluid that travels through the lymph system and carries white blood cells called lymphocytes. Lymphocytes protect the body against infections and the growth of tumors.
Lymph vessels: A network of thin tubes that collect lymph from different parts of the body and return it to the bloodstream.
Lymph nodes: Small, bean-shaped structures that filter substances in lymph and help fight infection and disease. Lymph nodes are located along the network of lymph vessels found throughout the body. Clusters of lymph nodes are found in the underarm, pelvis, neck, abdomen, and groin.
Spleen: An organ that produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.
Thymus: An organ in which lymphocytes grow and multiply. The thymus is in the chest behind the breastbone.
Tonsils: Two small masses of lymph tissue at the back of the throat. The tonsils produce lymphocytes.
Bone marrow: The soft, spongy tissue in the center of large bones. Bone marrow produces white blood cells, red blood cells, and platelets.
There are many different types of lymphoma.

Lymphomas are divided into two general types: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. For information about other types of lymphoma, refer to the following PDQ summaries:

Adult Acute Lymphoblastic Leukemia Treatment
Adult Hodgkin’s Lymphoma Treatment
AIDS-Related Lymphoma Treatment
Chronic Lymphocytic Leukemia Treatment
Hairy Cell Leukemia Treatment
Multiple Myeloma and Other Plasma Cell Neoplasms Treatment
Mycosis Fungoides and the Sézary Syndrome Treatment
Non-Hodgkin’s Lymphoma During Pregnancy
Primary CNS Lymphoma Treatment
Non-Hodgkin’s lymphoma is a disease in which malignant (cancer) cells form in the lymph system.

Non-Hodgkin’s lymphomas (NHLs) are a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment.

Because lymph tissue is found throughout the body, NHLs can begin in almost any part of the body. Cancer can spread to the liver and many other organs and tissues.

Unlike Hodgkin’s lymphoma, NHL is much less predictable than Hodgkin’s lymphoma and has a far greater predilection to disseminate to extranodal sites. The prognosis depends on the histologic type, stage, and treatment.

Non-Hodgkin’s lymphoma can occur in both adults and children. Treatment for children, however, is different than treatment for adults.



WHAT ARE THE RISK FACTORS OF NHLs?

Age, gender, and a weakened immune system can affect the risk of developing adult non-Hodgkin’s lymphoma.

Risk factors include the following:

Being older, male, or white.
Having one of the following medical conditions:
An inherited immune disorder.
An autoimmune disease.
HIV/AIDS.
Human T-lymphotrophic virus type I or Epstein-Barr virus.
A history of Helicobacter pylori infection.
Taking immunosuppressant drugs after an organ transplant.
Being exposed to certain pesticides.
A diet high in meats and fat.
Past treatment for Hodgkin’s lymphoma or with radiation.


HOW TO DETECT NHL’s?

Possible signs of NHL’s include fever, sweating, fatigue, and weight loss.

These and other symptoms may be caused by adult NHLs or by other conditions.The following problems suggest the possibility of NHLs:

Painless swelling in the lymph nodes in the neck, underarm, groin, or stomach.
Fever (unexplained).
Drenching night sweats.
Constant tiredness.
Weight loss (unexplained) in the past 6 months.
Skin rash or itchy skin.
Pain in the chest, abdomen, or bones (unexplained).
Tests that examine the body and lymph system are used to help detect (find) and diagnose adult non-Hodgkin’s lymphoma.

The following tests are helpful to diagnose NHLs:

Physical exam and history
Complete blood count: A sample of blood is drawn and checked for the following:
The number of red blood cells, white blood cells, and platelets.
The amount of hemoglobin in the red blood cells.
The portion of the sample made up of red blood cells.
Blood chemistry studies: A procedure in which a blood sample is checked to measure the amounts of certain substances released into the blood by organs and tissues in the body. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that produces it.
Lymph node biopsy: One of the following types of biopsies may be done:
Excisional biopsy: The removal of an entire lymph node.
Incisional biopsy: The removal of part of a lymph node.
Core biopsy: The removal of part of a lymph node using a wide needle.
Needle biopsy: The removal of part of a lymph node using a thin needle. This procedure is also called a fine-needle aspiration biopsy.
Bone marrow biopsy: The removal of a small piece of bone and bone marrow by inserting a needle into the hipbone or breastbone, to look for signs of cancer.
Stage Information

Stage is important in selecting a treatment for patients with non-Hodgkin’s lymphoma (NHL). The majority of patients with NHL present with advanced (stage III or IV) disease that can often be identified with limited staging procedures such as CT scanning and biopsies of the bone marrow and other accessible sites of involvement. Laparoscopic biopsy or laparotomy is not required for staging but may be necessary to establish a diagnosis or histologic type. Positron emission tomography with fluorine-18-fluorodeoxyglucose can be used for initial staging and for follow-up after therapy as a supplement to CT scanning.

Staging subclassification system

Stage I: involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE).
Stage II: involvement of 2 or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph nodes with or without other lymph node regions on the same side of the diaphragm (IIE).
Stage III: involvement of lymph node regions on both sides of the diaphragm (III) that may also be accompanied by localized involvement of an extralymphatic organ or site (IIIE), by involvement of the spleen (IIIS), or both (IIIS+E).
Stage IV: disseminated (multifocal) involvement of 1 or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement.
The designation “E” is used when extranodal lymphoid malignancies arise in tissues separate from, but near, the major lymphatic aggregates. Stage IV refers to disease that is diffusely spread throughout an extranodal site, such as the liver.



HOW TO TREAT NHLs?

Treatment Option Overview

Treatment of non-Hodgkin’s lymphoma (NHL) depends on the histologic type and stage. Even though standard treatment in patients with lymphomas can cure a significant fraction, numerous clinical trials that explore improvements in treatment are in progress. If possible, patients should be given some new drugs.

Late effects of treatment of NHL have been observed. Pelvic irradiation and large cumulative doses of cyclophosphamide have been associated with a high risk of permanent sterility. For up to 2 decades after diagnosis, patients are at significantly elevated risk of second primary cancers, especially lung, brain, kidney, and bladder cancers and melanoma, Hodgkin’s lymphoma, and acute nonlymphocytic leukemia. Left ventricular dysfunction was a significant late effect identified in 8 of 57 long-term survivors of high-grade NHL who received more than 200 milligrams per meter squared of doxorubicin. Myelodysplastic syndrome and acute myelogenous leukemia are late complications of myeloablative therapy with autologous bone marrow or peripheral blood stem cell support, as well as conventional chemotherapy-containing alkylating agents; Most of these patients show clonal hematopoiesis even before the transplantation, suggesting that the hematologic injury usually occurs during induction or reinduction chemotherapy. Successful pregnancies with children born free of congenital abnormalities have been reported in young women after autologous bone marrow transplantation.

Radiation techniques differ somewhat from those used in the treatment of Hodgkin’s lymphoma. The dose of radiation therapy usually varies from 2,500 cGy to 5,000 cGy and is dependent on factors that include the histologic type of lymphoma, the patient’s stage and overall condition, the goal of treatment (curative or palliative), the proximity of sensitive surrounding organs, and whether the patient is being treated with radiation therapy alone or in combination with chemotherapy. Given the patterns of disease presentations and relapse, treatment may need to include unusual sites such as Waldeyer’s ring, epitrochlear, or mesenteric nodes. However, the associated morbidity of the treatment must be considered carefully. The majority of patients who receive radiation are usually treated on only 1 side of the diaphragm. Localized presentations of extranodal NHL may be treated with involved-field techniques with significant (>50%) success.

Aggressive, Recurrent Adult Non-Hodgkin’s Lymphoma

In general, retreatment with standard agents rarely produces a cure in patients whose lymphomas relapse. Reports indicate that regimens using continuous-infusion chemotherapy may be more efficacious than bolus administration. Other salvage chemotherapy regimens are available.

Bone marrow transplantation is the treatment of choice for patients whose lymphoma has relapsed. Preliminary studies indicate that approximately 20% to 40% of patients will have a long-term disease-free status. In a prospective randomized study, in the 5-year median follow-up, the event-free survival was significantly improved with transplantation (46% vs. 12%). Overall survival was also significantly better with transplantation (53% vs. 32%).

Peripheral stem cell transplantation has yielded results equivalent to standard autologous transplantation. Even patients who never experienced complete remission with conventional chemotherapy may have prolonged progression-free survival (31% at 5 years) after high-dose chemotherapy and hematopoietic stem cell transplantation if they retain chemosensitivity to reinduction therapy. Some patients who relapse after a previous autologous transplantation can have durable remissions after myeloablative or nonmyeloablative allogeneic stem cell transplantation.

Rituximab, the anti-CD20 monoclonal antibody, can induce responses in one third of patients with relapsing aggressive lymphoma of appropriate phenotype (CD20 positive).

Radiolabeled anti-CD20 monoclonal antibodies, such as iodine-131 tositumomab and yttrium-90 ibritumomab, induce 60% to 80% response rates in patients with relapsed or refractory B-cell lymphoma.



HOW ABOUT THE PROGNOSIS OF NHLs?

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

The stage of the cancer.
The type of non-Hodgkin's lymphoma.
The patient’s age and general health.
Whether the lymphoma has just been diagnosed or has recurred (come back).
The NHLs can be divided into 2 prognostic groups:

Indolent lymphomas: Indolent NHL types have a relatively good prognosis, with median survival as long as 10 years, but they usually are not curable in advanced clinical stages. Early-stage (I and II) indolent NHL can be effectively treated with radiation therapy alone. Most of the indolent types are nodular (or follicular) in morphology.

While indolent NHL is responsive to radiation therapy and chemotherapy, a continuous rate of relapse is usually seen in advanced stages. However, patients can often be retreated with considerable success as long as the disease histology remains low grade. Patients who present with or convert to aggressive forms of NHL may have sustained complete remissions with combination chemotherapy regimens or aggressive consolidation with marrow or stem cell support.

In asymptomatic patients with indolent forms of advanced NHL, treatment may be deferred until the patient becomes symptomatic as the disease progresses. When treatment is deferred, the clinical course of patients with indolent NHL varies; frequent and careful observation is required so that effective treatment can be initiated when the clinical course of the disease accelerates. Some patients have a prolonged indolent course, but others have disease that rapidly evolves into more aggressive types of NHL that require immediate treatment.

Aggressive lymphomas:The aggressive type of NHL has a shorter natural history, but a significant number of these patients can be cured with intensive combination chemotherapy regimens. In general, with modern treatment of patients with NHL, overall survival at 5 years is approximately 50% to 60%. Thirty percent to 60% of patients with aggressive NHL can be cured. The vast majority of relapses occur in the first 2 years after therapy.

A number of other factors that are not included in the above staging system are important for the staging and prognoses of patients with NHL. These factors include age, performance status, tumor size, lactate dehydrogenase (LDH) values, and number of extranodal sites. The model was suggested which identifies 5 significant risk factors prognostic of overall survival as below:

age (<60 years vs. >60 years)
serum LDH (normal vs. elevated)
performance status (0 or 1 vs. 2-4)
stage (I or II vs. III or IV)
extranodal site involvement (0 or 1 vs. 2-4).
Patients with 2 or more risk factors have less than a 50% chance of relapse-free and overall survival at 5 years.