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What You Need To Know About Lymphocyte-Depleted Hodgkin Lymphoma: Symptoms, Treatment, and Prognosis

Posted on April 06, 2022
Medically reviewed by
Todd Gersten, M.D.
Article written by
Amanda Agazio, Ph.D.

Lymphocyte-depleted Hodgkin lymphoma (LDHL) is a rare type of classical Hodgkin lymphoma. Hodgkin lymphoma is a type of cancer that affects the lymphatic system. It occurs when certain immune cells, known as lymphocytes or white blood cells, grow out of control. Doctors characterize LDHL when someone has both cancerous lymphocytes and low levels of normal lymphocytes. Symptoms like night sweats, fever, and weight loss (called B symptoms) may occur in someone with LDHL. Typically LDHL can be more difficult to diagnose and treat compared to other types of classical Hodgkin lymphoma.

What Is Classical Hodgkin Lymphoma?

Doctors divide Hodgkin lymphoma into two main types, classical Hodgkin lymphoma and nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). These two variants are defined by the type of neoplastic cells (tumor-forming cells) a person has. Reed-Sternberg cells appear commonly in someone with classical Hodgkin lymphoma. The cancerous cells in those with NLPHL are similar to Reed-Sternberg cells, but contain only one nucleus. Another point of difference is that people with NLPHL have “popcorn” cells. (This nickname suits because under a microscope these cancerous cells look like popped kernels of corn.)

Classical Hodgkin lymphoma occurs more commonly than NLPHL. In fact, the Leukemia & Lymphoma Society notes about 95 percent of all Hodgkin lymphoma cases fall into the classical category.

In addition to lymphocyte-depleted Hodgkin lymphoma, classical Hodgkin lymphoma includes several other subtypes, such as:

  • Nodular sclerosis
  • Mixed cellularity
  • Lymphocyte-rich

What Is Lymphocyte-Depleted Hodgkin Lymphoma?

The rarest form of classical Hodgkin lymphoma is LDHL. According to the authors of “Lymphocyte-depleted Hodgkin Lymphoma,” LDHL makes up approximately 1.5 percent of all classical Hodgkin lymphoma cases in the Western world. In developing countries, though, LDHL may be more common. Typically people diagnosed with LDHL fall between 30 to 37 years of age. Males get diagnosed with LDHL twice as often as females.

Two things characterize LDHL in particular: the substantial growth of cancerous Reed-Sternberg cells and loss of normal lymphocytes. And, in addition to showing up in the tissues of the lymphatic system, cancer cells commonly occur in the bone marrow of a person with LDHL. Everyone’s white blood cells (the soldiers of the immune system) come from our bone marrow. When too many cancer cells occur in someone’s bone marrow, the level of their blood cells drop (a state called cytopenia), which leads to an unhealthy imbalance. When cytopenia takes place in someone with LDHL, the bone marrow can’t make enough white blood cells.

What Are the Symptoms of LDHL?

People with LDHL typically display symptoms referred to as B symptoms. These include:

  • Unexplained fever greater than 100.4 F
  • Unexplained loss of 10 percent or more of total body weight (over six months or less)
  • Drenching night sweats

Other symptoms may include:

  • Swollen lymph nodes
  • Fatigue
  • Severe itching
  • Loss of appetite
  • Increased sensitivity to alcohol

People with LDHL may also develop abdominal pain due to cancer cell growth in their abdominal organs and lymph nodes.

Causes and Risk Factors for LDHL

There can be many causes for LDHL, and these vary among people with the condition. In general, most cancers are due to abnormalities in a person’s genes. Atypical genes can affect how a person’s cells act and whether or not cells survive. When a cell doesn’t work as it should, cancerous cells can develop.

Overactive cell signaling may be another factor. (Scientists use the term “cell signaling” to describe when one cell communicates with another cell and prompts the second cell into action.) If the body’s networks of proteins that affect cell activity and survival experience overactive signaling, that could spur the production of cancer cells.

Other factors that appear to play a role in the risk of LDHL include the following.

Epstein-Barr Virus Infection

The Epstein-Barr virus infection is known for causing mononucleosis (mono). In some cases, Epstein-Barr may lead to the development of some forms of classical Hodgkin lymphoma.

HIV Infection

The human immunodeficiency virus (HIV) can lead to the chronic activation of so-called B cells. Such abnormal cell activity could be responsible for spurring LDHL to develop in some people. Estimates say 15 percent of people with LDHL also have HIV.

Other Risk Factors

Other factors that may increase the risk of LDHL include being male, having a family history of lymphoma, and being immune-compromised.

How Is LDHL Diagnosed?

To diagnose LDHL, a doctor takes samples of tissue and screens those for cancerous cells. (This sample-and-study procedure is called a biopsy.) Sometimes a doctor will perform an excisional biopsy, which means they remove an entire mass. In the case of LDHL, they could remove an entire lymph node. Diseases can be identified by the substances (“markers”) in or on a person’s cells. (The ID process is called immunophenotyping.) To confirm an LDHL diagnosis, a hematopathologist (doctor who specializes in cancers of the blood) looks for the markers named CD30, CD15, and PAX5.

How Is LDHL Typically Treated?

Treatment for LDHL can include chemotherapy, radiation therapy, and stem cell transplantation. Which of these (or combination of these) a doctor prescribes depends on the risk factors a person with LDHL has.

The chemotherapy regimen referred to as ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) is often used to treat people with the classical forms of Hodgkin lymphoma, including LDHL. This regimen is sometimes combined with radiation therapy. People with advanced stages of LDHL often undergo multiple cycles of ABVD to treat their disease.

People with LDHL that returns after their initial treatment may undergo a stem cell transplant. This involves using high doses of chemotherapy to destroy their cancerous blood cells and then replacing those with healthy new ones. In treating someone with a blood disease, a doctor replaces dead, diseased cells with healthy stem cells transferred into the person’s bone marrow or bloodstream. Healthy stem cells can come from the person undergoing treatment or a donor. To use someone with LDHL’s own stem cells, they must be collected before they undergo chemotherapy. The harvested matter then gets filtered to remove cancerous cells.

What’s the Prognosis for LDHL?

Compared to other forms of classical Hodgkin lymphoma, LDHL can be more challenging to diagnose and treat. An elusive diagnosis gives a disease a longer window to develop and advance. One study in particular shows this. A group of Japanese scientists reported on a pool of 600 people with classical Hodgkin lymphoma — over 80 had LDHL. The researchers found that 64 percent of those with LDHL had an advanced-stage disease (stages 3 or 4) at the time of their diagnoses. Also, LDHL is typically a more progressive disease and has a poorer prognosis (forecast of outcome) compared to other types of classical Hodgkin lymphoma. Overall survival rates in people with LDHL is lower than that seen in other forms of classical Hodgkin lymphoma.

Talk With Others Who Understand

On MyLymphomaTeam, the social network for people with LDHL and their loved ones, more than 11,000 members come together to ask questions, give advice, and share their experiences living with lymphoma.

Do you have experience with Lymphocyte-Depleted Hodgkin Lymphoma? How old were you when you were diagnosed with LDHL? Share in the comments below or start a discussion on MyLymphomaTeam.

All updates must be accompanied by text or a picture.
Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Amanda Agazio, Ph.D. completed her doctorate in immunology at the University of Colorado Anschutz Medical Campus. Her studies focused on the antibody response and autoimmunity. Learn more about her here.

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