Lymphocyte-depleted Hodgkin lymphoma (LDHL) is a rare and aggressive subtype of classical Hodgkin lymphoma. Hodgkin lymphoma is a type of blood cancer that affects the lymphatic system, which is part of the body’s immune system. This condition develops when certain white blood cells, called lymphocytes, begin to grow out of control.

LDHL is characterized by the presence of cancerous lymphocytes and low levels of normal lymphocytes. People with LDHL may experience symptoms like night sweats, fever, and weight loss — known as B symptoms. Compared with other forms of classical Hodgkin lymphoma, LDHL can be more difficult to diagnose and treat.

What Is Classical Hodgkin Lymphoma?

Doctors divide Hodgkin lymphoma into two main types — classical Hodgkin lymphoma and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). These types are defined by the characteristics of the cancerous cells, also called neoplastic cells.

Classical Hodgkin lymphoma is distinguished by the presence of Reed-Sternberg cells. These large, abnormal lymphocytes often have more than one nucleus and a distinctive appearance under the microscope. In contrast, NLPHL involves cancerous cells that resemble Reed-Sternberg cells but usually have only one nucleus. These cells are sometimes called “popcorn cells” because, when viewed under a microscope, their shape resembles popped kernels of corn.

Classical Hodgkin lymphoma is far more common than NLPHL. About 95 percent of all cases of Hodgkin lymphoma fall into the classical category, according to the Leukemia & Lymphoma Society.

In addition to lymphocyte-depleted Hodgkin lymphoma, subtypes of classical Hodgkin lymphoma include:

• Nodular sclerosis
• Mixed cellularity
• Lymphocyte-rich

What Is Lymphocyte-Depleted Hodgkin Lymphoma?

Lymphocyte-depleted Hodgkin lymphoma is the rarest form of classical Hodgkin lymphoma, accounting for about 1.5 percent of all classical Hodgkin lymphoma cases in Western countries. However, in developing countries, LDHL may be more common. LDHL is most often diagnosed between ages 30 and 40. Men are affected about twice as often as women, according to StatPearls, a professional medical education resource.

LDHL is primarily characterized by two key features — the growth of cancerous Reed-Sternberg cells and a loss of normal lymphocytes. In addition to appearing in lymphatic tissues such as lymph nodes and the spleen, cancer cells in LDHL commonly involve the bone marrow.

The bone marrow is responsible for producing white blood cells, which play a critical role in the body’s immune defenses. When LDHL spreads to the bone marrow, it can interfere with normal blood cell production, leading to a condition called cytopenia (a decrease in blood cells, including white blood cells). This can cause an imbalance in the immune system, making it harder for the body to fight infections.

Does Hodgkin Lymphoma Cause Low Lymphocytes?

Some Hodgkin lymphoma subtypes may cause low levels of normal, noncancerous lymphocytes, which doctors can detect using blood tests. LDHL is one lymphoma type in which this occurs, which is why its name includes “lymphocyte-depleted.” Lymphocytopenia (low lymphocyte levels) can cause symptoms such as frequent or long-lasting infections, joint pain or swelling, swollen lymph nodes, skin issues, or an enlarged spleen. However, not everyone with low lymphocytes (called lymphocytopenia) experiences symptoms.

Symptoms of Lymphocyte-Depleted Hodgkin Lymphoma

People with LDHL often experience what are known as B symptoms. These may include:

• Unexplained fever higher than 100.4 Fahrenheit
• Unexplained weight loss of at least 10 percent of total body weight within six months or less
• Drenching night sweats

Other common Hodgkin lymphoma symptoms can include:

• Swollen lymph nodes
• Fatigue
• Severe itching

People with LDHL sometimes develop abdominal pain due to a buildup of cancer cells in abdominal lymph nodes and organs such as the spleen or liver.

Causes of Lymphocyte-Depleted Hodgkin Lymphoma

There are several possible causes of lymphocyte-depleted Hodgkin lymphoma (LDHL), and they can vary from person to person. In general, most cancers are due to abnormalities in a person’s genes, which may be present at birth or develop over time. When certain genes are altered, they can affect how cells grow, function, or die. If a cell no longer behaves normally, it may become cancerous.

Overactive cell signaling may be another factor. “Cell signaling” refers to the process of one cell communicating with another to trigger a specific response. If the body overproduces proteins that cause overactive signaling, it can lead to uncontrolled cell division and the growth of cancerous cells.

Several additional factors may raise the risk of LDHL. Epstein-Barr virus infection — best known for causing mononucleosis (mono) — has been linked to some types of classical Hodgkin lymphoma, including LDHL. Another important risk factor is infection with the human immunodeficiency virus (HIV), which can cause chronic activation of B cells, a type of white blood cell. This abnormal cell activity may contribute to the development of LDHL. Estimates suggest that 15 percent of people diagnosed with LDHL also have HIV.

Other factors that may increase the risk of Hodgkin lymphoma in general include being male and having a family history of lymphoma, according to Mayo Clinic.

Diagnosis of Lymphocyte-Depleted Hodgkin Lymphoma

Diagnosing lymphocyte-depleted Hodgkin lymphoma begins with a biopsy, a procedure in which a doctor removes a sample of tissue to examine it for cancer cells. In some cases, an excisional biopsy — removing an entire mass, such as a lymph node — may be done to get a clearer view of the disease.

Doctors use specialized tests to identify cancer cells based on substances, or markers, found in or on the surface of the cells. This process, known as immunohistochemistry or immunophenotyping, helps confirm the type of lymphoma. To diagnose LDHL specifically, a hematopathologist (a doctor who specializes in blood cancers) looks for markers such as CD30, CD15, and PAX5.

Treatment of Lymphocyte-Depleted Hodgkin Lymphoma

LDHL treatment may include chemotherapy, radiation therapy, and stem cell transplantation. The specific approach depends on several factors, including the stage of the disease, the person’s overall health, and individual risk factors.

One of the most commonly used chemotherapy regimens for LDHL is called ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine). This regimen is sometimes combined with radiation therapy, especially in early-stage disease. In more advanced stages, multiple cycles of ABVD may be needed to control the disease.

People with LDHL that returns after initial treatment may undergo a bone marrow transplant. This typically involves giving high doses of chemotherapy to destroy their cancerous blood cells and replacing them with healthy new ones. To treat someone with a blood disease, a doctor replaces damaged or diseased cells with healthy ones transferred into the person’s bone marrow or bloodstream.

Healthy cells can come from the person undergoing treatment or from a donor. If the cells come from the person with LDHL, they must be collected before chemotherapy begins, then processed to remove any cancerous cells before being reintroduced into the bloodstream.

Prognosis for Lymphocyte-Depleted Hodgkin Lymphoma

Compared to other forms of classical Hodgkin lymphoma, lymphocyte-depleted Hodgkin lymphoma can be more challenging to diagnose and treat. A delayed diagnosis gives the disease more time to progress and advance.

One study of people with LDHL found that 64 percent had advanced-stage disease (stage 3 or 4) at the time of diagnosis. LDHL also tends to be a more aggressive disease and is generally associated with a poorer prognosis (expected outcome) than other types of classical Hodgkin lymphoma. Overall survival rates in people with LDHL are lower than those seen in other forms of classical Hodgkin lymphoma. Talk to your oncology team to get a personalized prognosis based on your specific stage of disease and other individual factors.

Talk With Others Who Understand

On MyLymphomaTeam, the social network for people with lymphocyte-depleted Hodgkin lymphoma and their loved ones, more than 21,000 members come together to ask questions, give advice, and share their experiences living with lymphoma.

Have you or a loved one been diagnosed with LDHL? What has your experience been so far? Share in the comments below, or start a discussion on your Activities page.