Large Granular Lymphocyte (LGL) leukemia is a rare disease whose etiology is currently not known. There are two types of LGL leukemia: T-cell LGL leukemia and Natural Killer (NK) LGL leukemia. We have established this national registry to collect and store blood and tissue samples on patients with LGL leukemia. In addition to blood and tissue samples, we are also studying each participant's medical and family history. Every participant enrolled into this registry provides an important contribution to our research on the pathogenesis of this rare disease.
Enrollment into the LGL leukemia registry involves signing consent, completing the standard enrollment forms, and submitting blood samples to our laboratory twice a year. Each participant's medical history is reviewed to assist with confirming the LGL leukemia diagnosis. Correlation is being made between experimental results and clinical history of disease to gain insight into how LGL leukemia cells are able to survive and proliferate. We are currently studying cellular pathways that may be involved in the dysregulated apoptosis or cell death of LGL leukemia cells. We are also investigating whether an unknown infection may play a role in the development of LGL leukemia. The knowledge gained in the laboratory may lead to new treatments and diagnostic testing for this disease. Without this registry, our research would not be possible.
- Ayodele Ayoola, M.D., Penn State Cancer Institute at St. Joseph Medical Center
- David Claxton, M.D.
- Christopher Ehmann, M.D.
- Michael Evans, M.D.
- Jeffrey Pu, M.D.
- Witold Rybka, M.D.
- Kamal Sharma, M.D., Penn State Cancer Institute at State College
- Marc Rovito, M.D., Penn State Cancer Institute at St. Joseph Medical Center
- Giampaolo Talamo, M.D.
What is the Large Granular Lymphocyte Leukemia Registry?
The Large Granular Lymphocyte (LGL) Leukemia Registry is a national registry that collects, manages, and analyzes information on people with LGL leukemia. It also maintains a bank of blood and tissue samples from people with LGL leukemia. The registry is maintained at the Penn State Cancer Institute located at the Penn State Milton S. Hershey Medical Center in Hershey, Pennsylvania.
What are the goals of the registry?
There are two goals of the registry:
- To collect and study information on people with Large Granular Lymphocyte (LGL) leukemia over an extended period of time. This information includes blood counts, symptoms, treatment, patient medical history, and family medical history. By collecting information on people with LGL leukemia twice a year, we are able to gain valuable information about the progression and treatment of this disease.
- To collect and store blood and tissue from people with LGL leukemia. This blood and tissue will be studied in the future and may be used to develop new diagnostic tests, therapies, or treatments for this disease.
What are the scientific objectives of the registry?
The scientific objectives of the registry are:
To determine the natural history and pathogenesis of this disorder and correlate clinical outcomes with laboratory parameters. We will test the hypothesis that systemic symptoms are a poor prognostic feature. By using a comparative analysis of results from patients exhibiting varying symptoms and forms of LGL leukemia we hope to find the cause of this disease and to grasp a better understanding of it.
To determine if clonal progression or spontaneous remission occurs in LGL leukemia. There have been reports of patients achieving a spontaneous remission, and even reports of a few patients showing complete loss of the T-cell LGL clone. During the course of our research, we would like to find out why and how these results were achieved. We have several clinical trials open that use different treatment regimens; we hope these trials will aid in finding the answers to those questions.
Who is eligible to be in the registry?
Any person who is suspected to have LGL leukemia is eligible to enroll in the national database.
What will I be asked to do if I participate in the registry?
Participation in the registry involves the effort of both the person with LGL leukemia and his/her doctor.
The person with LGL leukemia will be asked to:
- Read, understand, and sign Informed Consent Forms. These forms explain the purpose of the research and tell exactly what will be asked of him/her if he/she decides to participate.
- Complete a questionnaire. This questionnaire asks questions such as "on what date were you born?" "What is your current job?" and "do you have any family members with cancer?"
- Provide samples of blood. Once every six months, about 3 ounces of blood will be drawn and sent to the Penn State Cancer Institute for processing, research analysis, and storage.
The person's doctor will be asked to:
- Review the Informed Consent Forms with the person with LGL leukemia and answer any questions he/she might have. The person with LGL must be consented by an investigator at Penn State. This can take place over the phone.
- Complete 2 questionnaires. The first questionnaire asks for general information (address, fax number, phone number) about the physician. The second questionnaire asks questions about the medical history of the person with LGL leukemia, including blood counts, symptoms, treatments, serological findings, etc.
- Submit the blood samples drawn from the person with LGL leukemia to the Penn State Cancer Institute.
- Complete a questionnaire once a year, beginning the year after the person with LGL leukemia is entered into the registry. This form asks questions regarding the medical condition of the person with LGL leukemia including blood counts, symptoms, treatments, serological findings, etc.
What else is involved in participating?
Occasionally, research questions related to LGL leukemia will arise. In order to answer these questions, the LGL Leukemia Registry may contact the doctor of the person with LGL leukemia to request additional blood or tissue samples. It is up to the person and their doctor to decide if they want to provide the registry with these samples.
What should I do if I want to participate?
If you, or someone you know, have been diagnosed with LGL leukemia, we ask that you have the doctor of that person contact the LGL Leukemia Registry. Together they will determine if the person is eligible to enter into the registry and start the entry process. The entry process will be completed by the LGL Leukemia Registrar, Kendall Thomas Baab.
Are there clinical trials for people with LGL Leukemia?
A clinical trial is a study conducted on people with a particular type of disease, often to evaluate a new treatment for that disease. Through clinical trials researchers can learn which treatments are most effective. There is no standard therapy for LGL leukemia, each individual is assessed by their physician to determine what treatment best suits them. However, patients entered into the LGL Leukemia Registry will have access to ongoing clinical trials designed to establish the best treatment for LGL leukemia. In most cases, such treatment can be given by the patient's own doctor in their hometown.
Disclaimer: The information below is for informative purposes only. If you have a health-related problem, please consult a physician.
What is Large Granular Lymphocyte (LGL) Leukemia?
Blood consists of three types of cells:
- White blood cells which fight infection and disease
- Red blood cells which carry oxygen to the blood
- Platelets which help the blood to clot
There are several types of white blood cells:
- Granulocytes (including neutrophils, eosinophils, and basophils)
- Lymphocytes (including B-cells, T-cells, and NK-cells)
Because people with LGL leukemia can report having no symptoms or many symptoms (including night sweats, weakness, dizziness, frequent fevers, fatigue, anemia, enlarged spleen, etc.), there is no ‘typical' treatment. Therapy often includes blood transfusions to treat anemia (less than normal number of red blood cells) and antibiotics to treat infections. A splenectomy (removal of the spleen) may have a benefit in some patients. Treatment with medicines which turn off or suppress the immune system (immunosuppressants) are most often used. The cause of LGL leukemia is not currently known.
LGL leukemia is divided into two categories (depending on which type of LGL is increased in the blood): (1) T-cell LGL leukemia and (2) NK-cell LGL leukemia. Below are some facts about each of these types of LGL leukemia.
In normal blood 10%-15% of the lymphocytes are large granular lymphocytes (LGL's). LGL's have a characteristic appearance as shown in the above figure. They are larger than normal lymphocytes and contain pink granules. LGL's may either be a T-cell or NK-cell type of lymphocyte. LGL's are part of the normal immune system and are killer cells, which fight viruses. Large granular lymphocyte leukemia occurs when there are too many LGL's and not enough of the other types of blood cells, especially the neutrophils. In some cases, the total number of lymphocytes is not greater than normal; however, the proportion or percentage of LGL's in your lymphocytes is higher than normal.
LGL leukemia can be diagnosed by employing several different clinical tests. These can include:
- CBC (Complete Blood Count)
- Flow cytometry with an LGL Panel
- TCR (T-cell Receptor Gene Rearrangement)
- Bone Marrow Biopsy
- Splenectomy and spleen analysis
The hallmark of LGL leukemia is a high lymphocyte count and a low neutrophil count. This would be detected by the CBC and is usually the first indication that there might be something out of the ordinary. The flow cytometry is one of the main diagnostic tests. It employs an array of activation markers that will indicate if a certain level of LGL's are present and what type of LGL's. This will help to narrow down the type of LGL a person might have. Unfortunately, not all hospitals have flow cytometry available and even those that do may not be familiar with the panel of markers that are commonly used for LGL leukemia. These activation markers include CD3, CD8, CD56, CD16, and CD57. The NK form of LGL leukemia may show CD16+, CD56+, and CD3-. The T-cell form will usually show CD3+/CD8+ and CD57+.
The TCR test is usually done after a person has had the flow cytometry. This helps to narrow the field even further with regards to if there is a clone of the T-cell and if so, which type. There are two types of T-cell clones.
A bone marrow biopsy is another test that can show LGL's present. Flow cytometry tests can be run on the bone marrow as well as immunoperoxidase staining to show whether the markers employed in the flow cytometry are present.
In some cases of LGL leukemia, the patient may exhibit splenomegaly which is enlargement of the spleen. If this occurs the patient's physician may consider performing a splenectomy (removal of the spleen.) If the physician deems this necessary, subsequent analysis of the spleen may be done to see if there was an infiltration of LGL's. This is an invasive surgical procedure and should only be done after careful consideration by the physician and the patient.
Facts about T-cell LGL leukemia:
- T-cell LGL leukemia is a "chronic", or slowly progressing, disease.
- It usually occurs in people between the ages of 50 and 60.
- About the same number of men and women get T-cell LGL leukemia.
- About half of patients have anemia (less than normal amount of RBC).
- About half of patients have an enlarged spleen (splenomegaly).
- Bacterial infections are common and reoccur.
- Rheumatoid arthritis is common.
- Neutropenia (less than normal amount of neutrophils) is common.
Facts about NK-cell LGL leukemia:
- NK-cell LGL leukemia has two forms: Acute and Chronic.
Acute form of NK-cell LGL leukemia:
- There is a rapid increase in the number of LGLs over a few weeks time.
- Unlike T-cell LGL leukemia, it can occur in a younger group of people.
- About the same number of men and women get NK-cell LGL leukemia.
- Systemic symptoms (such as fever and weight loss) are common.
- Massive enlargement of the liver & spleen (hepatosplenomegaly) is common.
- Most patients with the acute form die within 2 months of diagnosis.
- Almost all patients have anemia (less than normal amount of red blood cells).
- Severe neutropenia (less than normal amount of neutrophils) is common.
Chronic form of NK-cell LGL leukemia:
- The clinical features of chronic NK LGL leukemia are very similar to those seen in T-LGL leukemia.
- It is a chronic illness and is different than the acute form of NK LGL leukemia.
- The chronic form does NOT change to the acute form.
Large Granular Lymphocyte (LGL) Leukemia is a clonal disorder of LGL associated with autoimmune diseases (Blood 82:1-14, 1993, Cancer Control Journal 5: 25-33, 1998). The disorder may arise from either NK-cells or T-cells. The disease should be suspected in patients with cytopenia, lymphocytosis, or autoimmune diseases, particularly rheumatoid arthritis. The LGL Leukemia Registry was formed in order to collect data regarding the natural history of this disease. The registry will assist in establishing or confirming the diagnosis of LGL leukemia.
Once the diagnosis is established, the patient will be offered entry into clinical trials should they meet the established criteria. Since there is no standard therapy for this disease, such trials will be important in establishing effective treatment.
Another aspect of the registry is to form an LGL leukemia tumor bank. Such samples will support ongoing laboratory research on this disease. Current hypotheses being investigated in the laboratory include: (1) LGL leukemia is associated with infection with an HTLV-like virus; (2) leukemic LGL represent activated cytotoxic T lymphocytes; and (3) dysregulated apoptosis underlies the pathogenesis of LGL leukemia. Support of such laboratory research is important, as the etiology of LGL leukemia is not known.
Sources of Information about LGL Leukemia:
For more information on how you can join the LGL Leukemia Registry, please see the below contact information:
Kendall Thomas Baab
Research Studies Coordinator
Penn State Cancer Institute
500 University Dr. M.C. CH56
Hershey, PA 17033
- Penn State Cancer Institute Website and Open Clinical Trials
- The National Cancer Institute designated cancer centers in the U.S.A. There are only approximately 40 of the centers in the nation. These institutes would be able to provide patients with physicians who have open clinical trials for various diseases and are widely recognized to be the best standard of care treatment facilities in the nation.
- There is an online support group dedicated to LGL Leukemia. In order to register with the Yahoo Group, you must have a Yahoo I.D. login and password. Then click the link to "Groups" and search for Large_Granular_Lymphocyte. This is just a forum for patients to speak to each other about their disease and is not monitored by a physician, nor is any of the information exchanged from a physician.
Kendall Thomas Baab
LGL Leukemia Registrar/Research Studies Coordinator
Penn State Cancer Institute
500 University Dr. M.C. CH56
Hershey, PA 17033
Phone - 717-531-6308
Fax - 717-531-1649