Lymphoproliferative Disorders

What are lymphoproliferative disorders?

Lymphoproliferative disorders (LPDs) are groups of rare diseases that happen when lymphocytes, a type of white blood cell, don’t work as they should. Your lymphocytes help your body’s immune system fight intruders like cancer, viruses and bacteria.

Some LPDs are immunologic, meaning they affect how your immune system reacts to intruders. Other types are lymphoid blood cancers, like leukemia and lymphoma, which are serious illnesses that happen when abnormal lymphocytes multiply uncontrollably. In all, more than a dozen different diseases are lymphoproliferative disorders.

What are the types of lymphoproliferative disorders?

There are two groups of lymphoproliferative disorders: immunologic disorders and lymphoid blood cancers. Lymphoid blood cancers include B-cell and T-cell cancers.

Immunologic disorders

Immunologic disorders affect how your immune system reacts to intruders. People with these LPDs have an increased risk of developing lymphoma:

• X-linked lymphoproliferative disorder (XLP): If you have this disorder, exposure to Epstein-Barr virus may lead to lymphoma.
• Autoimmune lymphoproliferative syndrome (ALPS): In ALPS, large numbers of lymphocytes build up in your lymph nodes, spleen and liver, making your lymph nodes, spleen and liver get bigger.
• Post-transplant lymphoproliferative disorders (PTLD): PTLDs are rare but serious complications of solid organ transplants or allogeneic (donated) stem cell transplantations that can happen if you or the organ or stem cell donor have B-cells with Epstein-Barr virus.

Lymphoid blood cancers

These disorders happen when white blood cells change and become abnormal cells that multiply in your bone marrow and blood. These cells are B-cells, T-cells and natural killer cells. Healthcare providers may call these conditions lymphocytic disorders. In some cases, diseases involving these white blood cells are curable. But they’re serious illnesses that may be life-threatening.

B-cell non-Hodgkin lymphomas

Some common non-Hodgkin lymphomas that are lymphoproliferative disorders include:

• Diffuse large B-cell lymphoma.
• Follicular lymphoma.
• Mantle cell lymphoma.

B-cell lymphocytic leukemias

These disorders include:

• Chronic lymphocytic leukemia (CLL): Normal B-cells in your bone marrow multiply, crowding out healthy blood cells and platelets.
• B-cell prolymphocytic leukemia: Abnormal B-cells form in your bone marrow so there’s no room for healthy blood cells and platelets.
• Hairy cell leukemia: Your bone marrow makes abnormal white blood cells that multiply. The abnormal cells appear hairy when viewed under a microscope.

T-cell non-Hodgkin lymphomas

T-cell lymphocytic disorders are generally divided into systemic and cutaneous T-cell disorders:

• Systemic T-cell lymphomas affect your lymph nodes, spleen, bone marrow, blood and other organs in your body.
• Cutaneous T-cell lymphomas mainly affect your skin, but in some cases, can involve lymph nodes, blood, bone marrow and other internal organs.

Systemic T-cell lymphomas

There are many kinds of systemic T-cell lymphomas. Common types include:

• Peripheral T-cell lymphoma not otherwise specified (PTCL NOS).
• Angioimmunoblastic T-cell lymphoma (AITL).
• Anaplastic large cell lymphoma.
• Follicular helper T-cell lymphoma (FHTCL).
• Follicular T-cell lymphoma (FTCL).

Some rare types include:

• Hepatosplenic T-cell lymphoma (HSTCL).
• Enteropathy-associated T-cell lymphoma (EATL).
• Monomorphic epithelioid tropic intestinal T-cell lymphoma (MEITL).

Some systemic T-cell lymphomas are called chronic T-cell leukemias. Examples are:

• T-cell prolymphocytic leukemia (T-PLL).
• T-cell large granular lymphocytic leukemia (T-LGL).

Cutaneous T-cell lymphomas

The two most common subtypes of cutaneous T-cell lymphoma are:

• Mycosis fungoides.
• Sézary syndrome.

NK-cell lymphocytic disorders

These are very rare disorders that affect NK cells. They include:

• Extranodal NK T-cell lymphoma nasal type.
• Aggressive NK-cell leukemia (AKNL).
• NK-cell large granular lymphocytic leukemia (NK-LGL).

What are symptoms of lymphoproliferative disorders?

The symptoms vary widely depending on the type of lymphoproliferative disorder you have. Some common symptoms of LPDs are:

• Drenching night sweats.
• Enlarged or swollen lymph nodes, liver or spleen.
• Excessive or unusual bleeding and bruising.
• Fatigue.
• Fever.
• Frequent viral infections.
• Loss of appetite.
• Unexplained weight loss.

What causes lymphoproliferative disorders?

There’s no single cause for most lymphoproliferative disorders. Potential causes of LPDs include:

• Infections: Epstein-Barr virus or H. pylori may cause some types of lymphoproliferative disorders.
• Certain autoimmune diseases: Rheumatoid arthritis or lupus may cause some types of marginal zone lymphomas.
• Medication: Immunosuppressant drugs may lead to hepatosplenic T-cell lymphoma.
• Certain genetic mutations: Rarely, you may inherit a mutation that causes a lymphoproliferative disorder. For example, people with X-linked lymphoproliferative disorder carry one of two genetic mutations that cause them to have an unusually severe reaction to the Epstein-Barr virus that can lead to lymphoma. Likewise, genetic mutations that affect white blood cell growth play a role in lymphoma and leukemia.

How are lymphoproliferative disorders diagnosed?

There are many different types of LPDs, so the diagnosis process focuses on finding out which disorder is causing your symptoms.

To do that, a healthcare provider will consider symptoms like swollen lymph nodes and signs that your liver or spleen is bigger than normal. They’ll also ask about your medical history.

They may order the following tests:

• Biopsy: Your provider may order a bone marrow biopsy to look for signs of blood cancer like leukemia or lymphoma.
• Blood tests: Blood tests may include a complete blood count (CBC), comprehensive metabolic panel (CMP), Epstein-Barr antibody test, hepatitis test, human immunodeficiency virus HIV test or lactate dehydrogenase (LDH) test.
• Imaging tests: Tests may include computed tomography (CT) scans and positron emission tomography (PET) scans.
• Lab tests: Your provider may order a flow cytometry test to help diagnose specific disorders.

How are lymphoproliferative disorders treated?

LPD treatment depends on the specific disorder. For example, if you have a type of leukemia or lymphoma, your treatments may include:

• Chemotherapy.
• Immunotherapy.
• Radiation therapy.
• Stem cell (bone marrow) transplant.
• Targeted therapy.

What can I expect if I have a lymphoproliferative disorder?

It depends. There are many types of LPDs and many factors that may affect your prognosis, or what you can expect after treatment.

Can lymphoproliferative disorders be cured?

That depends on the type of disorder that you have. For example, chemo-immunotherapy may cure certain lymphomas like large B-cell lymphoma, Burkitt lymphoma and Hodgkin lymphoma. If you have X-linked lymphoproliferative disorder, a stem cell transplant may cure the condition.

In some cases, treatment may put certain lymphomas into remission but can’t cure the disease. Remission means you don’t have symptoms and tests don’t find signs or evidence of disease. But some LPDs can come back months or years after you finish treatment.

It’s understandable that you’d want to know about a cure or how long you may live. If you have a type of LPD, ask your healthcare provider what you can expect. They’re your best resource for information because they know you and your situation.

How do I take care of myself?

Lymphoproliferative disorders are serious illnesses. While there are treatments that ease symptoms and may cure the conditions, you might find some challenges as you go through treatment. Here are some suggestions that may help you:

• Ask about palliative care. If you have an LPD, you may need help managing symptoms and treatment side effects. Your palliative care team will have recommendations and suggestions.
• Eat well. Being sick and/or undergoing treatment can affect your appetite. If that’s your situation, ask a nutritionist for suggestions.
• Get some exercise. Light exercise may help you deal with the stress that can come with having a serious illness. But be sure to talk to your healthcare provider before starting a new exercise program.
• Protect against infection. Your immune system may be weak from illness or treatment. Ask your healthcare provider about ways to avoid viral infections.

When should I see my healthcare provider?

If you’re receiving treatment for a lymphoproliferative disorder, ask your healthcare provider to explain the kinds of changes in your body that may be signs that your condition is getting worse, like having a fever that won’t go away. That way, you’ll know when you should contact them.