Chronic Lymphocytic Leukemia

Chronic Lymphocytic Leukemia

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Chronic Lymphocytic Leukemia is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • CLL
  • chronic lymphoid leukemia
  • SLL (small lymphocytic lymphoma)

Disorder Subdivisions

  • Ig-mutated CLL
  • Ig-unmutated CLL

General Discussion

Chronic lymphocytic leukemia (CLL) is a malignant blood disorder in which there are an increased number of white blood cells in the lymphoid tissue. In CLL, the abnormal lymphocytes, also called leukemic cells, are produced instead of healthy white blood cells, and then accumulate over time. As the number of unhealthy blood cells grows, there is less room for healthy cells. The combination of fewer healthy cells, and the fact that the CLL lymphocytes are poor at fighting infections can lead to frequent infection, anemia, and easy bleeding. This disease progresses slowly, and the uncontrolled buildup and enlargement of lymphoid tissue can occur in various sites of the body such as the lymph nodes, spleen, bone marrow, and lungs. CLL is the most common type of leukemia in adults and very rarely occurs in children.



In the majority of cases, chronic lymphocytic leukemia is the result of a rapid production of B lymphocyte cells (a short-lived type of white blood cell that is responsible for the production of vertebrate serum proteins that include antibodies). What was previously called CLL derived from T lymphocytes has been renamed as another disorder, T cell prolymphocytic leukemia. The overgrowth of cells in this T-cell disease tends to be much faster.



The ability to distinguish between cells that have unmutated IgVH (Ig-unmutated CLL) and mutated IgVH (Ig-mutated CLL) has become very important in predicting the course of the disease (prognosis). Patients who have Ig-unmutated CLL have a much shorter average survival period of about 7 years compared to Ig-mutated CLL patients, whose average survival period is about 25 years. These survival times however are based on older data and likely longer now, with improved therapies. A protein called ZAP-70 is correlated with the IGVH status about 75% of the time but also provides independent prognostic information. Determining the subset of CLL based on IGVH status is important because it predicts prognosis. Because CLL usually progresses so slowly, many patients do not need immediate treatment and some do not even require it in their lifetime. Treatment is still based primarily on symptoms or worsening blood counts, not on these prognostic factors.

Symptoms

Approximately 50-75% of the patients with chronic lymphocytic leukemia have no symptoms when first diagnosed. The disease is discovered during a routine exam or blood test. Symptoms between the two subdivisions of CLL, Ig-mutated and Ig-unmutated, will experience the same symptoms, however, Ig-unmutated CLL progresses much faster.



Early signs of chronic lymphocytic leukemia may be fatigue, weight loss, loss of appetite (anorexia), labored breathing, low-grade fever, a feeling of fullness in the abdomen due to an enlarged spleen, and night sweats. Bacterial infections such as skin infections, fluid and inflammation of the lungs (pneumonia), and inflammation of the sinuses (sinusitis) often occur. As the disorder advances, the patient loses the ability to fight off infections. Viral infections become an increasing concern.



In the later stages of the disorder, the liver, spleen, and lymph nodes may steadily increase in size. Chronic lymphocytic leukemia may also invade other tissues such as the skin, eye socket (orbit), mucous membrane that lines the inside of the eyelids (conjunctivae), lungs, sacs that line the chest (pleura), heart, and gastrointestinal tract. Swelling and a yellow pigment of the skin (jaundice) may also occur.



The National Cancer Institute has published a six-step description of the staging of this disorder. The staging determines the treatment and management plan.



Stage 0: An abundance of lymphocytes in blood but no other sign of leukemia; lymph nodes, spleen, liver, red blood cells and platelets are normal.



Stage I: Too many lymphocytes; lymph nodes swollen; spleen and liver are normal as are erythrocytes and platelets.



Stage II: Too many lymphocytes; lymph nodes, spleen and/or liver swollen.



Stage III: Too many lymphocytes; too few red blood cells (anemia); lymph nodes swollen; spleen and/or liver may be swollen.



Stage IV: Too many lymphocytes; too few platelets (difficult blood clotting); lymph nodes, spleen and liver may be swollen; too few red blood cells (anemia).



Refractory: CLL does not respond to standard treatments.

Causes

The exact cause of chronic lymphocytic leukemia is not known. Multiple genetic mutations occur in the DNA of blood-producing cells. This mutation causes the blood cells to produce abnormal lymphocytes, which are not effective at fighting infection.



Usually, an abnormal chromosome is present in a patient with CLL. Most often this abnormality is a deletion, or the loss of part of a chromosome. The loss of part of chromosome 13 is the most common deletion, as well as chromosome 11 and 17 deletions. Sometimes there is an extra chromosome 12 (trisomy 12). Other rare chromosome abnormalities have also been reported. Scientists know these abnormalities are important in the causation of CLL, but it's not yet clear which genes are involved in the development of CLL. The common chromosomal abnormalities are important prognostically, however, with deletions of chromosomes 11 and 17 predicting rapid disease progression.

First-degree relatives of someone who has been diagnosed with CLL have a 5-7 times greater chance of developing CLL.

Affected Populations

Chronic lymphocytic leukemia is the most common type of leukemia found in multiple family members. It is twice as common in males as in females and the average age of onset in patients is 72. It is also more common in people that are white, or of Russian and Eastern European Jewish heritage. The rate of incidence of the disorder increases with age. CLL almost never affects children and is rare under the age of thirty. In the United States, it is thought that three out of every 100,000 people will develop CLL, but this may be an underestimate.

Standard Therapies

Diagnosis

CLL is most commonly discovered when an abnormally high white blood cell count is noticed in routine blood work. A diagnosis can be made with one of the following tests:



1. Complete blood cell count-This test will measure the count of every type of blood cell, white blood cells, red blood cells, and platelets. A high number of B-cells, a certain type of white blood cell, may indicate CLL.



2. Flow cytometry-In this test, blood cells are examined with antibodies to determine if they are malignant (cancerous). This test establishes the diagnosis of CLL vs other related diseases.



3. Bone marrow biopsy-This test is conducted by removing a sample of bone marrow and examining it to determine what time of leukemia is present.



4. Lymph node biopsy-A biopsy of the lymph nodes can determine whether cancer has spread to the lymphatic system.



To predict the likely course of CLL, your doctor may also recommend more specialized tests. Specialized tests can determine the need for treatment vs. observation, and predict response to treatment and the likelihood of relapse.



Clinical Testing and Work-Up

Regular blood tests and physical exams are used to carefully watch for signs of progression because early-stage CLL may take years to progress,. It is also important to know the stage the CLL to know what treatment is appropriate. Generally just blood tests and physical exams are all that is required for routine disease monitoring, along with blood chemistries and antibody tests.



Treatment

Treatment for CLL is based on the stage of the disease, symptoms, and prognosis.Patients with CLL may show no symptoms for years, and don't require special care. However, in later stages of the disease, chemotherapy is a common choice of treatment. Another treatment option is monoclonal antibody therapy, which binds proteins to cancer cells, activating a mechanism that destroys them. Using both of these therapies together usually produces the highest treatment response.



In especially aggressive or recurrent cases of CLL, a blood and marrow stem cell transplant has shown promise.



Treatment of chronic lymphocytic leukemia includes platelet transfusions which are used for bleeding associated with a persistent decrease in the number blood platelets (thrombocytopenia). When anemia is present, transfusions of packed red blood cells are usually given. Antibiotics are used to combat bacterial infections usually related to a decrease in the number of leukocytes (lymphopenia) and a low level of gammaglobulin in the blood.



The FDA approved the anti-cancer drug Rituxan (rituximab) in 2010 to treat certain patients with chronic lymphocytic leukemia. Rituxan is intended for patients with CLL who are beginning chemotherapy for the first time and for those who have not responded to other cancer drugs for chronic lymphocytic leukemia. Rituxan is administered with two other chemotherapy drugs, fludarabine and cyclophosphamide.



For more information, please contact:



Genentech, Inc.

One DNA Way

South San Francisco, CA 94080-4990

Phone: (650) 225-1000



Treanda (Bendamustine hydrochloride) has been approved by the FDA for treating CLL. It has been shown that Treanda can be effective when administered once every four weeks, similar to other chemotherapies for CLL. For more information please contact:



Cephalon, Inc.

41 Moores Road

Frazer, PA 19355 USA

Phone: 1-610-344-0200



The monoclonal antibody CAMPATH (alemtuzumab) has been approved by the FDA for the treatment of chronic lymphocytic leukemia. For more information, contact:



Genzyme Corporation

A Sanofi Company

877-4-CAMPATH (877-422-6728



The FDA has also approved Arzerra (Ofatumumab) to combat CLL. This drug is usually only used when other treatments have not been successful because it can cause serious viral infections in the brain. To be sure that this medication is not causing harm, blood cell, kidney, and liver function need to be testing even after administration has stopped. For more information please contact:



Global Community Partnerships

GlaxoSmithKline

Phone: 1-888-593-5977

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Contact for additional information about chronic lymphocytic leukemia:



Jennifer R. Brown, MD, PhD

617-632-4564

References

TEXTBOOKS

Rai KR, Stephenson J, Waldman H. Campath-1H: Emerging Frontline Therapy in Chronic Lymphocytic Leukemia. CRC Press - Parthenon Publishing. 2001;128.



Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:949-51.



Berkow R., ed. The Merck Manual-Home Edition. Whitehouse Station, NJ: Merck Research Laboratories; 1997:765-67.



Larson DE. ed. Mayo Clinic Family Health Book. New York, NY: William Morrow and Company, Inc; 1996:966-67.



JOURNAL ARTICLES

Wiestner A, Rosenwald A, Barry TS, et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003: 15;101(12):4944-51. http://www.ncbi.nlm.nih.gov/pubmed/12595313



Kipps TJ. Advances in classification and therapy of indolent B-cell malignancies. Semin Oncol. 2002;29(1 Suppl 2):98-104.



Nabhan C, Rosen ST. Conceptual aspects of combining rituximab and Campath-1H in the treatment of chronic lymphocytic leukemia. 2002;29(1 Suppl 2):75-80.



Van BeslenK, Keralavarma B, Devine S, et al. Allogenic and autologous transplantation for chronic lymphocytic leukemia. Leukemia. 2001;15:1317-25.



Syrigos KN, Pliarchopoulou K, Harrington KJ. The development of monoclonal antibody therapy in leukemias. Hybridoma. 2001;20:145-48.



Monni O, Knuutila S. 11q deletions in hematological malignancies. Leuk Lymphoma. 2001;40:259-66.



Robak T. Cladribine in the treatment of chronic lymphocytic leukemia. Leuk Lymphoma. 2001;40:551-64.



Caligaris-Cappio F. Biology of chronic lymphocytic leukemia. Rev Clin Exp Hematal. 2000;4:5-21.



Stilgenbauer S, Lichter P, Dohner H. Genetic features of B-cell chronic lymphocytic leukemia. Rev Clin Exp Hematal. 2000;4:48-72.



FROM THE INTERNET

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; http://omim.org/entry/151400 ; Last Update: 6/3/11.

Mayo Clinic. Chronic Lymphocytic Leukemia. http://www.mayoclinic.com/health/chronic-lymphocytic-leukemia/DS00565 Accessed 7/26/11.



National Cancer Institute. Chronic Lymphocytic Leukemia. http://www.cancer.gov/cancertopics/pdq/treatment/CLL/Patient/page1

Accessed 7/26/2011.



Drugs.com. Ofatumumab. http://www.drugs.com/mtm/ofatumumab.html. Revision Date: 12/15/2010 Accessed 7/27/2011.



American Cancer Society. Leukemia-Chronic Lymphocytic. http://www.cancer.org/Cancer/Leukemia-ChronicLymphocyticCLL/DetailedGuide/leukemia-chronic-lymphocytic-what-causes Last Revised: 06/23/2011. Accessed 7/26/2011.



Vachani, C. Oncolink.com. Chronic Lymphocytic Leukemia. http://www.oncolink.org/types/article.cfm?c=8&s=29&ss=763&id=9590&p=4 Last Modified: August 22, 2007. Accessed 7/28/2011.

Resources

Leukemia & Lymphoma Society

1311 Mamaroneck Avenue

Suite 310

White Plains, NY 10605

Tel: (914)949-5213

Fax: (914)949-6691

Tel: (800)955-4572

Email: infocenter@LLS.org

Internet: http://www.LLS.org



American Cancer Society, Inc.

250 Williams NW St

Ste 6000

Atlanta, GA 30303

USA

Tel: (404)320-3333

Tel: (800)227-2345

TDD: (866)228-4327

Internet: http://www.cancer.org



National Cancer Institute

6116 Executive Blvd Suite 300

Bethesda, MD 20892-8322

USA

Tel: (301)435-3848

Tel: (800)422-6237

TDD: (800)332-8615

Email: cancergovstaff@mail.nih.gov

Internet: http://www.cancer.gov



OncoLink: The University of Pennsylvania Cancer Center Resource

3400 Spruce Street

2 Donner

Philadelphia, PA 19104-4283

USA

Tel: (215)349-8895

Fax: (215)349-5445

Email: hampshire@uphs.upenn.edu

Internet: http://www.oncolink.upenn.edu



Children's Leukemia Research Association

585 Stewart Avenue, Suite 18

Garden City, NY 11530

Tel: (516)222-1944

Fax: (516)222-0457

Email: info@childrensleukemia.org

Internet: http://www.childrensleukemia.org



Lymphoma Research Foundation

115 Broadway

Suite 1301

New York, NY 10006

USA

Tel: (212)349-2910

Fax: (212)349-2886

Tel: (800)235-6848

Email: LRF@lymphoma.org

Internet: http://www.lymphoma.org



Cancer Research UK

Angel Building

407 St John Street

London, EC1V 4AD

United Kingdom

Tel: 020 7242 0200

Fax: 02071216700

Email: cancerhelpuk@cancer.org.uk

Internet: http://www.cancerresearchuk.org/cancer-help/



Rare Cancer Alliance

1649 North Pacana Way

Green Valley, AZ 85614

USA

Internet: http://www.rare-cancer.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



Friends of Cancer Research

1800 M Street NW

Suite 1050 South

Washington, DC 22202

Tel: (202)944-6700

Email: info@focr.org

Internet: http://www.focr.org



Cancer.Net

American Society of Clinical Oncology

2318 Mill Road Suite 800

Alexandria, VA 22314

Tel: (571)483-1780

Fax: (571)366-9537

Tel: (888)651-3038

Email: contactus@cancer.net

Internet: http://www.cancer.net/



Cancer Support Community

1050 17th St NW Suite 500

Washington, DC 20036

Tel: (202)659-9709

Fax: (202)974-7999

Tel: (888)793-9355

Internet: http://www.cancersupportcommunity.org/



Lance Armstrong Foundation

2201 E. Sixth Street

Austin, TX 78702

Tel: (512)236-8820

Fax: (512)236-8482

Tel: (877)236-8820

Email: media@livestrong.org

Internet: http://www.livestrong.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.