Treatments for relapsed or refractory chronic lymphocytic leukemia

Relapsed, or recurrent, chronic lymphocytic leukemia (CLL) means the cancer has come back after treatment and reaching remission.

Refractory disease means the leukemia did not respond to treatment.

The following are treatment options for relapsed and refractory CLL. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan.

Watchful waiting

Watchful waiting is also called active surveillance. You may be offered watchful waiting for relapsed or refractory CLL. Treatment is started if there are signs that the disease is progressing or if you develop new symptoms.


You may be offered chemotherapy for relapsed or refractory CLL. If CLL relapses, you may be given the same chemotherapy drugs again if the leukemia had a good response to them the first time. If the disease becomes resistant to the chemotherapy, other drugs may be given.

Chemotherapy drugs used alone or in combination include:

  • fludarabine (Fludara)
  • bendamustine (Treanda)
  • cladribine (Leustatin)
  • chlorambucil (Leukeran)
  • cyclophosphamide (Cytoxan, Procytox)
  • pentostatin (deoxycoformycin, Nipent)
  • vincristine (Oncovin)
  • doxorubicin (Adriamycin)
  • mitoxantrone (Novantrone)

A steroid such as prednisone or dexamethasone (Decadron, Dexasone) may be used in combination with chemotherapy.

Targeted therapy

You may be offered targeted therapy for relapsed or refractory CLL. Targeted therapy may be used in combination with chemotherapy drugs.

The targeted therapy drugs that may be used include:

  • rituximab (Rituxan)
  • alemtuzumab (Campath)
  • ofatumumab (Arzerra)
  • ibrutinib (Imbruvica)
  • idelalisib (Zydelig)


You may be offered surgery to remove the spleen (called a splenectomy). It can improve red blood cell or platelet counts. It can also relieve discomfort when the enlarged spleen puts pressure on other organs.

Radiation therapy

You may be offered low-dose external beam radiation therapy for relapsed or refractory CLL. It is used to shrink an enlarged spleen or swollen lymph nodes in one area of the body.

Supportive therapy

Supportive therapy is an important part of treatment for relapsed or refractory CLL. It is used to treat the complications that usually happen with treatment for CLL and the disease itself.

Supportive therapies may include:

  • antibiotics, antivirals or antifungals to prevent or fight infections
  • infusion of immunoglobulins (IVIG) to prevent recurrent infections
  • growth factors to help the bone marrow recover from chemotherapy (chemotherapy can affect the bone marrow so it doesn’t make enough healthy blood cells, which can increase the risk for infection)
  • transfusions of red blood cells, platelets, fresh frozen plasma and cryoprecipitate (a product that replaces clotting factors) as needed
  • drugs to bring down high levels of some chemicals in the blood that increase when many cancer cells die at the beginning of treatment (called tumour lysis syndrome)
  • leukapheresis to remove large numbers of white blood cells from the blood

Clinical trials

You may be asked if you want to join a clinical trial for CLL. Find out more about clinical trials.

Expert review and references

  • American Cancer Society. Leukemia - Chronic Lymphocytic. Atlanta, GA: American Cancer Society; 2013:
  • American Society of Clinical Oncology (ASCO). Leukemia - Chronic Lymphocytic - CLL: Treatment Options. Alexandria, VA.: American Society of Clinical Oncology (ASCO); 2014:
  • Borthakur G, O'Brien S . Treatment of chronic lymphocytic leukemia and related disorders. Wiernik PH, Goldman JM, Dutcher JP & Kyle RA (eds.). Neoplastic Diseases of the Blood. 5th ed. Springer; 2013: 9: pp. 121-119.
  • Health Canada. Drugs and Health Products: Zydelig. Ottawa, ON: Health Canada; 2015:
  • Mir Muhammad A . Chronic lymphocytic leukemia treatment & management. WebMD LLC; 2014.
  • National Cancer Institute. Chronic lymphocytic leukemia Treatment (PDQ®) Health Professional Version. Bethesda, MD: National Cancer Institute; 2014.
  • Wierda WG, O'Brien S . Chronic lymphocytic leukemia. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles & Practice of Oncology. 9th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins; 2014: 134: pp. 1973-1987.