Chronic lymphocytic leukemia (CLL), like all leukemias, is a cancer of the blood cells. CLL affects a certain type of white blood cell, called a B lymphocyte. This disease is also called B-cell chronic lymphocytic leukemia. B cells originate in the bone marrow, mature in the lymph nodes, and then circulate in the blood to help fight infections.
In CLL, malignant (cancerous) B cells grow into mature cells, but they don’t work properly. These defective B cells fight infections poorly and they can crowd out the normal lymphocytes in the marrow and lymph nodes.
CLL is primarily an adult disease; it is very rare in children and young adults. The median age of diagnosis is 72 years, and about 60% of all people getting CLL are male. In the United States, about 15,000 people are diagnosed with CLL each year. (Data from the National Cancer Institute.)
CLL symptoms and diagnosis
CLL often develops slowly, and some people with CLL do not have any signs or symptoms of the disease at all. These people may find out they have CLL after a routine blood test shows specific changes in the blood. For others, CLL is suspected when a person experiences:
- Enlarged, but painless, lymph nodes
- Enlarged liver
- Enlarged spleen
- Night sweats
- Weight loss
- Frequent infections
Because these symptoms are common to other diseases, a hematologist (a doctor specializing in blood diseases) may order a complete blood count (CBC) to help establish a CLL diagnosis.
If a CBC shows abnormal blood counts, then a doctor may also order a bone marrow biopsy in which a small sample of marrow is removed from the body and studied. Other tests that can tell apart different types of leukemia cells may also be used to diagnose CLL.
Treatment options for CLL
Treatment for CLL varies from no treatment at all ("watch and wait") when the disease is mild, to more intensive treatments such as chemotherapy and bone marrow or cord blood transplantation. Which treatment is chosen depends on the stage of the disease, how fast it is growing, the patient’s age, and the physical health of the patient.
Patients with slow-growing CLL will be watched carefully, and may have frequent blood tests. They will usually not be treated, because these patients may live many years before the disease begins to cause difficulties.
Treatments usually begin when a person with CLL has an advanced form of the disease or has serious or bothersome symptoms such as very enlarged lymph nodes or a rapidly rising number of lymphocytes in the blood.
In these instances, CLL patients may be treated with chemotherapy drugs such as fludarabine, cyclophosphamide, and rituximab. These drugs may be given separately or in combinations. Fludarabine is the chemotherapy drug used most often.
Bone marrow or cord blood transplantation usually becomes a treatment option when a patient with CLL relapses after chemotherapy. You may hear a doctor use the terms "high risk" or "poor prognosis" to describe CLL patients who have become chemotherapy resistant or who have relapsed despite chemotherapy.
Whichever treatment you and your doctor choose, you may be asked to be part of a clinical trial. Even standard treatments continue to be studied in clinical trials. These studies help doctors learn more about which treatments work best for which patients.
Drug therapy for CLL
The most common drug treatment for CLL is the chemotherapy drug fludarabine, which is given intravenously (by vein). Fatigue is the most common side effect from fludarabine, and this is typically mild to moderate in most patients.
Other medications used to treat CLL include steroids such as prednisone and other chemotherapy drugs such as cyclophosphamide (Cytoxan). Often different medications are combined to increase their effectiveness.
Two other drugs used to treat CLL, rituximab and alemtuzumab, are a newer class of drug called monoclonal antibodies. These drugs are designed to take advantage of specific weaknesses in cancerous CLL cells. They work by homing in on specific proteins on the surface of CLL cells. These antibody drugs are most often used in combination with chemotherapy drugs.
To date, none of the various drug treatments has been definitely proven to be better than the others. Your doctor may therefore choose to use drugs with the fewest side effects.
While drugs can ease the symptoms of CLL and can often slow the progress of the disease, they cannot cure CLL. Only a bone marrow or cord blood transplant has the potential to produce long-term, stable remissions in CLL patients. [1,2]
Bone marrow or cord blood transplant for CLL
Allogeneic transplants for CLL
The type of bone marrow or cord blood transplant that is most often used to treat CLL is called an allogeneic transplant. An allogeneic transplant replaces the abnormal cells in the patient’s bone marrow with healthy blood-forming cells from a family member, unrelated donor or cord blood unit. See Learning about Bone Marrow or Cord Blood Transplants for more information on the sources of the blood-forming cells used in transplantation.
The first step in an allogeneic transplant is finding a matching donor – someone who can donate marrow or peripheral blood – or a cord blood unit to provide these blood-forming cells.
Choosing a donor or cord blood unit
If an allogeneic transplant is an option for you, your doctor will do a test to find out your HLA tissue type. HLA stands for human leukocyte antigen, and refers to the specific types of proteins (called antigens) that are on the surface of your body’s cells.
For a transplant to succeed, the donated cells must be a very close HLA match to the patient’s cells, otherwise the donated cells will not be accepted by the patient’s body.
Your doctor will test possible donors in your family, primarily brothers and sisters, to see if any one matches you. If you do not have a suitable donor in your family, your doctor can work with the National Marrow Donor Program® to search for an unrelated donor or cord blood unit for you from our Be The Match Registry® and other registries around the world. To save time, your doctor may check for potential donors on the registry at the same time he or she is testing for donors in your family.
The closeness of the donor match can affect a patient's chances of a good transplant outcome. In general, transplants using matched sibling donors have had the best results. However, outcomes for unrelated donor transplants have improved in the last decade. For some groups of patients, outcomes for sibling donor and unrelated donor transplants are comparable.
Reduced-intensity and non-myeloablative transplants
For some people with CLL, an allogeneic transplant may offer the best chance for a long-term remission.
In a standard transplant, patients get very high doses of chemotherapy and/or radiation before the transplant. This is called the pre-transplant conditioning regimen.
A high-dose conditioning regimen has two goals: 1) to wipe out as many cancerous CLL cells in the patient’s marrow and bloodstream, and 2) to prevent rejection of the donated cells by the patient's immune system. But such high doses can also damage organs such as the liver, kidneys and heart.
The median age of patients with CLL is 72 years; many patients would not tolerate a standard transplant. For an older patient with CLL, a transplant doctor may suggest a transplant that uses lower doses of chemotherapy and may not use radiation at all. This type of transplant is called a reduced-intensity or non-myeloablative transplant. These less intense conditioning regimens have been in use for more than 10 years and results are equal to and sometimes better than transplants using standard conditioning regimens. 
Autologous transplants for CLL
Autologous transplantation is not as common as allogeneic transplantation in treating CLL. In an autologous transplant, a patient receives his or her own blood-forming cells.
These cells are collected from the patient’s blood or marrow, preferably when he or she is in remission, and then frozen and stored. The patient then receives a very high-dose conditioning regimen, after which the thawed cells are given back to the patient intravenously (through an IV).
Autologous transplant recipients have been shown to experience remissions of 5-6 years, so it remains a possible treatment option for some patients with CLL. [4,5]
Transplant risks and benefits
Both allogeneic and autologous transplants have risks of serious complications, but both options can offer many patients the best chance for a long-term remission.
Autologous transplants have risks of serious side effects, but these risks are lower than for allogeneic transplants. For example, autologous transplant recipients cannot develop graft-versus-host disease, which is a common complication of allogeneic transplants.
However, autologous patients have a higher risk of relapse (a return of their leukemia) than allogeneic patients have. This is because CLL cells may be returned to the autologous patient along with his or her blood-forming cells.
If transplant is an option for you, your doctor can talk with you about the possible risks and benefits of a transplant in your specific situation. The chance a transplant will succeed depends on many factors, including your age, your overall health, whether you are in remission, how fast your disease is progressing, and whether you’ve received chemotherapy or not. In addition, the closeness of the donor match can affect transplant outcomes.
Making treatment decisions
CLL is a chronic disease, which means that it typically progresses slowly, although this is not always the case. If you and your doctor agree that transplant may be a treatment option for you, it’s important to talk to a transplant doctor sooner rather than later. Getting a transplant at the right time in the course of your disease may offer the best chance of a cure.
It’s always best to start a search for unrelated donors at the same time family members are tested to see if any are HLA-matched with you. By starting a search of the Be The Match Registry soon after being diagnosed with CLL, you and your doctor will increase the chance of having a donor or cord blood unit ready for an allogeneic transplant.
For patients with CLL, the choice among allogeneic transplant, autologous transplant and chemotherapy depends on many different factors. It is important to talk about your treatment options with a doctor who is experienced in treating CLL and who knows your specific medical condition.
More information on CLL
You can get further information about CLL from disease-specific organizations, such as:
- Delgado J, Milligan DW, Dreger P. Allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: ready for prime time? Blood. 2009; 114(13): 2581-2588.
- Pavletic SZ, Khouri IF, Haagenson M, et al. Unrelated donor marrow transplantation for B-cell chronic lymphocytic leukemia after using myeloablative conditioning: results from the Center for International Blood and Marrow Transplant Research. J Clin Oncol. 2005; 23(24): 5788-5794.
- Peres E, Braun T, Krijanovski O, et al. Reduced intensity versus full myeloablative stem cell transplant for advanced CLL. Bone Marrow Transplant. 2009; 44(9): 579–583.
- Tam CS, Khouri I. The role of stem cell transplantation in the management of chronic lymphocytic leukaemia. Hematological Oncology. 2009; 27(2): 53-60.
- Dreger P, Stilgenbauer S, Benner A, et al. The prognostic impact of autologous stem cell transplantation in patients with chronic lymphocytic leukemia: a risk-matched analysis based on the VH gene mutational status. Blood. 2004; 103(7): 2850-2858.
Willis Navarro, M.D., Medical Director, National Marrow Donor Program, Minneapolis, Minn.