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Advanced Stage Chronic Lymphocytic Leukemia (CLL) : Symptoms & Treatment

Chronic lymphocytic leukemia (CLL) is a type of blood cancer that affects the body’s white blood cells, known as lymphocytes, and starts in the bone marrow. Most people with Chronic lymphocytic leukemia (CLL) are usually diagnosed before the cancer spreads and reaches an advanced stage. It typically takes several months and sometimes even years to reach an advanced stage. However, once the disease moves into an advanced stage, it could cause more serious problems, including low platelet count, anemia, and an enlarged spleen and liver. Read on to find out all you need to know about advanced stage Chronic lymphocytic leukemia (CLL).

Advanced Stage Chronic Lymphocytic Leukemia (CLL)

What is Chronic Lymphocytic Leukemia (CLL)?

Chronic lymphocytic leukemia (CLL) is a type of blood cancer. It typically starts in the bone marrow and is known to affect the white blood cells known as lymphocytes. Lymphocytes are an important part of your immune system, and they help the body fight against infection. Chronic lymphocytic leukemia (CLL) is known as the most common type of blood cancer in adults, and this type of leukemia is known to be chronic. This means that it typically develops gradually over a long period of time. Most people who have this type of cancer don’t experience any signs or symptoms of the same for several years. However, in some rare cases, though, the cancer can grow faster and also be aggressive.(1, 2, 3, 4)

Most people who have chronic lymphocytic leukemia get diagnosed before the cancer reaches an advanced stage. However, it may take a couple of months and sometimes even years to reach the advanced stage. And when the cancer transforms into the later stages, the Chronic lymphocytic leukemia (CLL) cells start crowding out the healthy cells present in the bone marrow. This can lead to many other problems, including low platelet count, anemia, as well as an enlarged spleen and liver.(5)

Once the cancer reaches a later stage, you are likely to experience symptoms like fatigue, enlargement of the lymph nodes, fever, chills, unexplained weight loss, night sweats, and weakness.

Understanding the Early Symptoms of Chronic Lymphocytic Leukemia

It is important that you know about the early symptoms of Chronic lymphocytic leukemia (CLL) so that the cancer is detected before it reaches an advanced stage. In most cases, people who are diagnosed with CLL in the early stages do not experience any symptoms of the disease.

Chronic lymphocytic leukemia (CLL) is a type of leukemia that might be found when a doctor prescribes some routine blood tests during your annual check-up or for an unrelated health condition. If there is a high number of lymphocytes found on your blood test report, it will cause your doctor to suspect blood cancer.(6)

There is, however, a small number of people who experience symptoms of CLL in the early stages of the disease. The symptoms at this stage are usually subtle and likely to be confused for being any another more common condition.(7)

These early symptoms of Chronic lymphocytic leukemia (CLL) may include:

  • Weakness
  • Unexplained weight loss
  • Chills
  • Fever
  • Fatigue
  • Painless lumps or swelling underneath the skin

Another symptom of early stage Chronic lymphocytic leukemia (CLL) that some people may notice before the symptoms become apparent is a painless swelling of the lymph nodes. Some of the common lymph nodes that may be swollen are the ones in the groin and underarms. Some people also feel pain, heaviness, or fullness in the stomach. However, this only happens when the Chronic lymphocytic leukemia progresses further and causes the spleen to become enlarged.

It is important to schedule an appointment with your doctor if you find any changes, such as swelling or lumps on the skin, or any other symptoms that tend to persist.

Remember that the doctor will enquire about how long and how frequently you have been experiencing these symptoms, so it is good to keep track of these points. You should also inform your doctor if you have had any recent infections, unexplained weight loss, or fever.

Symptoms of Advanced Chronic Lymphocytic Leukemia

As Chronic lymphocytic leukemia progresses to an advanced stage, or in cases of faster developing CLL, you may notice some more noticeable and serious signs and symptoms. These symptoms of Chronic lymphocytic leukemia as the disease progresses may include:

  • Severe or Persistent Fatigue: Since Chronic lymphocytic leukemia can cause anemia, which is a shortage of red blood cells, along with low oxygen levels, this can cause severe or ongoing fatigue.(8)
  • Frequent or Recurring Infections: Advanced stage Chronic lymphocytic leukemia might cause frequent lower and upper respiratory tract infections. This is believed to happen because this type of blood cancer triggers a shortage of white blood cells in the body that help fight off infection, a condition known as leukopenia. You may also get repeated skin infections. It is also possible to develop more severe infections of the kidneys, lungs, and other organs.(9)
  • Abnormal or Easy Bruising Or Bleeding: Chronic lymphocytic leukemia is a type of cancer that can also cause thrombocytopenia, which is a condition that causes reduced blood platelets in about two to five percent of people who have this type of blood cancer.(10) Low levels of platelets in the body will impact how well the blood clots. This can lead to abnormal or more bleeding and bruising, and you may experience more frequent nosebleeds and bleeding gums.(11)
  • Severe Anemia: In advanced stages of Chronic lymphocytic leukemia, patients may develop more serious types of anemia, known as autoimmune hemolytic anemia. This happens in about seven to ten percent of all people who have this type of blood cancer.(10) This happens because, at this stage, the cancer starts to produce abnormal antibodies that start attacking the body’s red blood cells. This may cause severe low levels of oxygen-carrying red blood cells in the body.(12)
  • Headaches and Other Neurological Symptoms: In more advanced but rare cases, Chronic lymphocytic leukemia can impact the central nervous system. This can cause a variety of nervous and brain symptoms, including:(13, 14)
    • Headaches
    • Seizures
    • Behavioral changes
    • Weakness
    • Numbness
    • Walking issues or change in gait
    • Night sweats
    • Fever
  • Other cancers: Some people with advanced stage Chronic lymphocytic leukemia have a greater risk of developing other types of cancers as well, such as lung cancer, skin cancer, and cancers of the digestive system. In rare cases, some people with CLL may also develop a very aggressive type of cancer known as Richter’s syndrome or diffuse large B-cell lymphoma.(15, 16)

Are There Any Treatment Options For Advanced Stage Chronic Lymphocytic Leukemia (CLL)?

It might be difficult to treat cancer once it reaches the advanced stage. However, in cases of Chronic lymphocytic leukemia, people may still benefit from treatment at an advanced stage. There are combination and single drug therapies that a doctor may recommend for treating advanced stage Chronic lymphocytic leukemia. You may have to go through a couple of different medications or even think about joining a clinical trial to find out the best possible treatment for you at this stage.

When you have advanced stage Chronic lymphocytic leukemia, you should make sure to let your doctor know about any and every change you experience in your symptoms. You can also talk to your doctor about the overall treatment goals, your concerns and tell them how you are feeling. You should also share with them if you are not feeling well emotionally, apart from physically. Your doctor will be the right person to guide you on new clinical trials, different therapies, or even if you want to stop your treatment altogether.


Chronic lymphocytic leukemia is a type of blood cancer that impacts the white blood cells in the body, known as lymphocytes. This is one of the most common types of blood cancer that happens in older adults. Many people do not realize they have Chronic lymphocytic leukemia in the early stages because they are unlikely to cause any signs and symptoms at the start, or the symptoms may be confusing and mistaken for another condition.

In other people, though, the cancer may advance rapidly, causing more severe symptoms and other potential complications. However, the nature of this cancer is such that early-stage Chronic lymphocytic leukemia may even take several years to progress. In some people, though, it may progress faster. This is why you should always let your doctor know if you notice any unusual symptoms or symptoms that continue to persist.


  1. Chiorazzi, N., Rai, K.R. and Ferrarini, M., 2005. Chronic lymphocytic leukemia. New England Journal of Medicine, 352(8), pp.804-815.
  2. Rozman, C. and Montserrat, E., 1995. Chronic lymphocytic leukemia. New England Journal of Medicine, 333(16), pp.1052-1057.
  3. Byrd, J.C., Stilgenbauer, S. and Flinn, I.W., 2004. Chronic lymphocytic leukemia. ASH Education Program Book, 2004(1), pp.163-183.
  4. Keating, M.J., 1999, October. Chronic lymphocytic leukemia. In Seminars in oncology (Vol. 26, No. 5 Suppl 14, pp. 107-114).
  5. Rai, K.R., Sawitsky, A., Cronkite, E.P., Chanana, A.D., Levy, R.N. and Pasternack, B.S., 1975. Clinical staging of chronic lymphocytic leukemia.
  6. Nabhan, C. and Rosen, S.T., 2014. Chronic lymphocytic leukemia: a clinical review. Jama, 312(21), pp.2265-2276.
  7. Shanafelt, T.D., Byrd, J.C., Call, T.G., Zent, C.S. and Kay, N.E., 2006. Narrative review: initial management of newly diagnosed, early-stage chronic lymphocytic leukemia. Annals of internal medicine, 145(6), pp.435-447.
  8. Westbrook, T.D., Maddocks, K. and Andersen, B.L., 2016. The relation of illness perceptions to stress, depression, and fatigue in patients with chronic lymphocytic leukaemia. Psychology & health, 31(7), pp.891-902.
  9. Hilal, T., Gea-Banacloche, J.C. and Leis, J.F., 2018. Chronic lymphocytic leukemia and infection risk in the era of targeted therapies: linking mechanisms with infections. Blood reviews, 32(5), pp.387-399.
  10. Ghia, P. and Hallek, M., 2014. Management of chronic lymphocytic leukemia. Haematologica, 99(6), p.965.
  11. Visco, C., Ruggeri, M., Laura Evangelista, M., Stasi, R., Zanotti, R., Giaretta, I., Ambrosetti, A., Madeo, D., Pizzolo, G. and Rodeghiero, F., 2008. Impact of immune thrombocytopenia on the clinical course of chronic lymphocytic leukemia. Blood, The Journal of the American Society of Hematology, 111(3), pp.1110-1116.
  12. Mauro, F.R., Foa, R., Cerretti, R., Giannarelli, D., Coluzzi, S., Mandelli, F. and Girelli, G., 2000. Autoimmune hemolytic anemia in chronic lymphocytic leukemia: clinical, therapeutic, and prognostic features. Blood, The Journal of the American Society of Hematology, 95(9), pp.2786-2792.
  13. Cramer, S.C., Glaspy, J.A., Efird, J.T. and Louis, D.N., 1996. Chronic lymphocytic leukemia and the central nervous system: a clinical and pathological study. Neurology, 46(1), pp.19-25.
  14. Strati, P., Uhm, J.H., Kaufmann, T.J., Nabhan, C., Parikh, S.A., Hanson, C.A., Chaffee, K.G., Call, T.G. and Shanafelt, T.D., 2016. Prevalence and characteristics of central nervous system involvement by chronic lymphocytic leukemia. Haematologica, 101(4), p.458.
  15. Giles, F.J., O’Brien, S.M. and Keating, M.J., 1998, February. Chronic lymphocytic leukemia in (Richter’s) transformation. In Seminars in oncology (Vol. 25, No. 1, pp. 117-125).
  16. Jain, P. and O’Brien, S., 2012. Richter’s transformation in chronic lymphocytic leukemia. Oncology, 26(12), pp.1146-1146.
Pramod Kerkar, M.D., FFARCSI, DA
Pramod Kerkar, M.D., FFARCSI, DA
Written, Edited or Reviewed By: Pramod Kerkar, M.D., FFARCSI, DA Pain Assist Inc. This article does not provide medical advice. See disclaimer
Last Modified On:October 19, 2022

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