Chronic Lymphocytic Leukemia Prognosis In Older Adults

  • Nastassia Ventura M.Sc., B.Sc. Biological Sciences, University of Konstanz, Germany

Get our weekly health related email

Your privacy is important to us. Any information you provide to us via this website may be placed by us on servers located in countries outside of the EU. If you do not agree to these placements, please do not provide the information.

Best Milk Alternative


Chronic lymphocytic leukaemia (CLL) is a type of cancer which affects the blood and bone marrow. All cells originate from the bone marrow as stem cells before differentiating into specific cell types. The bone marrow contains blood stem cells that develop into myeloid stem cells or lymphoid stem cells. Myeloid stem cells become red blood cells, granulocytes and platelets, while lymphoid stem cells become T-lymphocytes, B-lymphocytes and natural killer cells

Stem cells can produce abnormal lymphocytes, known as leukaemia cells. When too many leukaemia cells are produced, they take up the space of healthy lymphocytes, red blood cells and platelets. This can, in turn, lead to bleeding, anaemia, and increased infections, as well as leukaemias such as CLL.

CLL in older adults

CLL is mainly diagnosed in older patients, with the average age of diagnosis being 70.1 Treatment options are based on careful risk assessments as there may be other comorbidities present, taking into account the physical and cognitive capacity and life expectancy of the patient. Clinical staging and evaluation of various prognostic factors, such as genetic mutations, should also be considered.1

Importance of prognosis

CLL is a form of blood cancer that is typically uncurable. However, with treatment, it can be effectively managed and controlled.  CLL usually progresses slowly, and some people do not require treatment for several years, if at all. For others, it can progress quickly and requires more immediate and intensive treatment. Each patient’s prognosis varies depending on several prognostic factors. Adverse prognostic factors are linked with shorter survival time and favourable prognostic factors predict longer survival.

Doctors perform tests to see how far the condition has developed to guide treatment and give a prognosis; this is known as staging. There are two staging systems for CLL: Rai staging and Binet staging.2

Prognostic factors in older adults

Binet staging

Binet staging is mainly used in Europe and focuses on red blood cells, white blood cells and platelets and how many areas in which lymph nodes are enlarged.2 It has three stages:

  • Stage A: Fewer than three areas of enlarged lymph nodes present with no anaemia or thrombocytopenia
  • Stage B: Three or more areas of enlarged lymph nodes with no anaemia or thrombocytopenia
  • Stage C: Any number of lymph nodes may be enlarged. Anaemia or thrombocytopenia may be present

Rai staging

Rai staging is more commonly used in America and is based on lymphocytosis.2 Rai staging consists of 5 stages:

  • Stage 0: Lymphocytosis, with no enlargement of the lymph nodes, liver, or spleen and with near normal red blood cell and platelet counts
  • Stage 1: Lymphocytosis and enlarged lymph nodes. The spleen and liver are not enlarged and the red blood cell and platelet counts are near normal
  • Stage 2: Lymphocytosis in combination with an enlarged spleen and possibly an enlarged liver. The lymph nodes may or may not be enlarged and red blood cell and platelet counts are near normal
  • Stage 3: Lymphocytosis and anaemia (low red blood cell count). The lymph nodes, spleen and liver, may or may not be enlarged. Platelet counts are near normal
  • Stage 4: lymphocytosis and thrombocytopenia (low platelet count). The lymph nodes, spleen or liver may be enlarged. Anaemia may be present or red blood cell count may be normal

Stage 0 is low risk, Stages 1 and 2 are intermediate risk and stages 3 and 4 are high risk.

Key prognostic factors

  • Del(17p) and TP53 mutation: TP53 is a tumour suppressor gene, and patients with mutations in TP53 or specific mutations in chromosome 17 (del(17p)) are associated with a poor prognostic outcome.2 This is because these patients are usually more resistant to chemotherapy and should be treated with targeted agents2
  • IGHV mutation status: IGHV is a gene that, when mutated, gives a more favourable prognosis to CLL patients. Unmutated IGHV predicts an unfavourable response to chemoimmunotherapy.3 Patients with unmutated IgHV should be considered for novel therapies and closely monitored3
  • Beta-2 microglobulin levels: Beta-2 microglobulin (B2M) levels are a strong predictor of CLL patients’ overall and treatment-free survival. A low B2M level indicates a more favourable prognosis4
  • ZAP-70 expression: Zeta-chain-associated protein kinase 70 (ZAP-70) is linked to IGHV mutational status as well as survival and disease progression. High levels of ZAP-70 are associated with aggressive disease and IGHV unmutated cells5
  • CD38 expression: The expression of CD38 indicates an unfavourable prognosis in CLL patients and is seen as an indicator of cell proliferation6

Prognosis in older adults

84% of all patients with CLL will survive their leukaemia for five years or more after being diagnosed.7  In patients below 60 years of age, the survival rate five years after diagnosis is higher at 95%.7 However, for patients aged 80 or over, the survival rate drops to around 65% five years after diagnosis.

Sometimes, a scale called the Chronic Lymphocytic Leukaemia International Prognostic Index (CLL-IPI) is used to predict a patient’s outlook. CLL-IPI takes into account the patient's age, the stage of their disease and other prognostic factors such as the presence of any mutations. A point is given for each risk factor, and patients are subsequently divided into four groups from low to very high risk.1,2

Treatment approaches in older adults

Watchful waiting

Some patients whose CLL is at an early stage and may be slow growing, as well as those who don’t have any symptoms, are not treated immediately. Instead, they are closely monitored until their condition worsens or they develop symptoms. 


Chemoimmunotherapy is the standard treatment for CLL. It is a combination of chemotherapy drugs and immunotherapy drugs such as monoclonal antibodies.8,9 However, a patient’s age and comorbidities need to be considered as they can be aggressive, especially in older patients and those with poor kidney function.9

Targeted therapies

Targeted therapy focuses on specific proteins in leukaemia cells in order to inhibit their growth. Common drugs used in targeted therapy are Bruton tyrosine kinase (BTK) inhibitors, Phosphatidylinositol 3-kinases (PI3K) inhibitors and BCL-2 inhibitors.8,10 

Targeted treatment is usually given to CLL patients together with chemotherapy or other forms of targeted therapies. Target treatments focus on key proteins in B-lymphocytes.

Using these treatments may lead to mild or more severe side effects, and additional drugs may need to be used to combat them.

Stem cell transplantation

A stem cell transplant is usually only recommended for use in younger patients or for those whose CLL has returned quickly and require higher doses of chemotherapy.10  The patient is first treated with high doses of chemotherapy and sometimes radiation therapy. Following this, they receive a stem cell transplant to restore the bone marrow.

Supportive care

CLL and its treatment affect the immune system. Supportive care manages any symptoms of CLL or those caused by its treatment. Patients with CLL are more at risk of infections, some of which can be life-threatening. Treatment includes antibiotics as well as antiviral and antifungal drugs.

Patients may also need to be treated with drugs to prevent infections, such as being given immunoglobulins if they have low antibody levels in their blood. Growth factors can increase the number of white blood cells and stem cells. Certain vaccines should be administered to prevent infections, including flu and coronavirus vaccines, as well as vaccines to prevent pneumonia and streptococcus infections. Due to low platelet counts or anaemia, patients may also require platelet or blood transfusions.

Challenges for older adults

Comorbidities and health status

Most patients with CLL are older patients who are “less fit” with nearly 90% having comorbidities and many are not able to tolerate chemoimmunotherapy as it is too aggressive.10 Elderly patients are also often ineligible for clinical trials as there is usually an age cutoff or due to decreased organ function. Additionally, any interactions with other medications the patient might be taking for other conditions must be considered.

Treatment tolerance and toxicity

When caring for elderly patients, it is crucial to consider their ability to tolerate the treatment and the impact of any prior treatments’ toxicity on their organs as some of the treatments can cause severe side effects in frailer patients. The Cancer and Ageing Research Group (CARG) score and Chemotherapy Risk Assessment Scale for High-Age patients (CRASH) score are used to predict severe toxicity in older patients.11

Geriatric assessment and supportive care

Geriatric assessment (GA) tools can evaluate an elderly patient's best treatment options as they can predict outcomes in older patients with cancer. GA includes the evaluation of the patient’s cognition, emotion, nutrition, mobility, basic and instrumental activities of daily living (IADL) and social functioning.1 One study showed a link between impaired physical and cognitive capacity and overall survival rate, but it did not include patients treated with chemoimmunotherapy or targeted drugs.1 However, GA is recommended by the Society of Geriatric Oncology for routine use in cancer patients. It may identify age-related health problems and alter planned cancer treatment.1

Current research and future directions

There are several recent advances in CLL treatments, and some are summarised below:

  • The safety and efficacy of combining several targeted therapies are being studied, such as BCL-2 and BTK inhibitor combinations or combinations with CD2012,13
  • Next-generation BTK inhibitors, which aim to reduce resistance development and make them more tolerable for patients, are also being trialled13
  • Minimal Residual Disease (MRD) guided approaches where patients who have a low MRD score after treatment induction can have treatment dosage reduced or stopped entirely13
  • Treatment with bispecific antibodies, which allow for the targeting of two proteins instead of just one, is also being looked into13
  • CAR T-cell therapy is being studied in the treatment of recurrent or refractory (non-response to treatment or response lasting less than six months) CLL13

A personalised approach that uses different biomarkers to identify patients whose disease will progress rapidly and require early intervention is likely to aid in Progression-free survival. For older patients, it is important to provide supportive care to manage any side effects of treatment.  


Chronic lymphocytic leukaemia is a blood cancer which mainly develops in older adults. It often develops slowly, and although it is not curable, it is possible to live with it for many years. The management of elderly patients is more complex due to a higher likelihood of comorbidities, lower physical capabilities and reduced organ function. The best treatment is carefully selected depending on different prognostic factors and staging. The effect of treatment on the quality of life of the patient is also an important consideration.


  1. Stauder R, Eichhorst B, Hamaker ME, Kaplanov K, Morrison VA, Österborg A, et al. Management of chronic lymphocytic leukaemia (CLL) in the elderly: a position paper from an International Society of Geriatric Oncology (Siog) Task Force. Annals of Oncology [Internet]. 2017 Feb 1 [cited 2023 Jun 30];28(2):218–27. Available from:
  2. Hallek M, Al‐Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. American J Hematol [Internet]. 2021 Dec [cited 2023 Jun 28];96(12):1679–705. Available from:
  3. Crombie J, Davids MS. ighv mutational status testing in chronic lymphocytic leukaemia. Am J Hematol [Internet]. 2017 Dec [cited 2023 Jun 30];92(12):1393–7. Available from:
  4. Delgado J, Pratt G, Phillips N, Briones J, Fegan C, Nomdedeu J, et al. Beta 2 -microglobulin is a better predictor of treatment-free survival in patients with chronic lymphocytic leukaemia if adjusted according to glomerular filtration rate. British Journal of Haematology [Internet]. 2009 Jun [cited 2023 Jun 30];145(6):801–5. Available from:
  5. Dielschneider RF, Xiao W, Yoon JY, Noh E, Banerji V, Li H, et al. Gefitinib targets ZAP-70-expressing chronic lymphocytic leukaemia cells and inhibits B-cell receptor signalling. Cell Death Dis [Internet]. 2014 Oct [cited 2023 Jun 30];5(10):e1439. Available from:
  6. Malavasi F, Deaglio S, Damle R, Cutrona G, Ferrarini M, Chiorazzi N. CD38 and chronic lymphocytic leukaemia: a decade later. Blood. 2011 Sep 29;118(13):3470–8. Available from:
  7. HMRN - Survival. Accessed 16 Jan. 2024.
  8. Kajüter H, Wellmann I, Khil L, Jöckel KH, Zhang C, Fink AM, et al. Survival of patients with chronic lymphocytic leukaemia before and after the introduction of chemoimmunotherapy in Germany. Blood Cancer J [Internet]. 2021 Oct 29 [cited 2023 Jun 30];11(10):1–4. Available from:
  9. Lamanna, Nicole. ‘The Evolving Role of Chemoimmunotherapy in Chronic Lymphocytic Leukemia’. Clinical Advances in Hematology & Oncology, vol. 14, no. 10, 2016, pp. 756–58, Available from:
  10. Schuh AH, Parry-Jones N, Appleby N, Bloor A, Dearden CE, Fegan C, et al. Guideline for the treatment of chronic lymphocytic leukaemia: a British society for haematology guideline. Br J Haematol [Internet]. 2018 Aug [cited 2023 Jun 30];182(3):344–59. Available from:
  11. Ortland I, Mendel Ott M, Kowar M, Sippel C, Jaehde U, Jacobs AH, et al. Comparing the performance of the CARG and the CRASH score for predicting toxicity in older patients with cancer. Journal of Geriatric Oncology [Internet]. 2020 Jul [cited 2023 Jun 30];11(6):997–1005. Available from:
  12. Walewska R, Parry‐Jones N, Eyre TA, Follows G, Martinez‐Calle N, McCarthy H, et al. Guideline for the treatment of chronic lymphocytic leukaemia. Br J Haematol [Internet]. 2022 Jun [cited 2023 Jun 30];197(5):544–57. Available from:
  13. Patel K, Pagel JM. Current and future treatment strategies in chronic lymphocytic leukaemia. J Hematol Oncol [Internet]. 2021 Apr 26 [cited 2023 Jun 30];14(1):69. Available from:

Get our weekly health related email

Your privacy is important to us. Any information you provide to us via this website may be placed by us on servers located in countries outside of the EU. If you do not agree to these placements, please do not provide the information.

Best Milk Alternative
[optin-monster-inline slug="yw0fgpzdy6fjeb0bbekx"]
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

Get our health newsletter

Get daily health and wellness advice from our medical team.
Your privacy is important to us. Any information you provide to this website may be placed by us on our servers. If you do not agree do not provide the information.

Nastassia Ventura

M.Sc., B.Sc. Biological Sciences, University of Konstanz, Germany

After graduating Nastassia spent several years working for large healthcare and scientific companies in scientific customer service, order management and medical sales.

Nastassia has always had a keen interest in health topics and enjoys educating others about them. Having taken time out to raise a young family, she is currently a medical writer for Klarity and working towards a career in medical communications. presents all health information in line with our terms and conditions. It is essential to understand that the medical information available on our platform is not intended to substitute the relationship between a patient and their physician or doctor, as well as any medical guidance they offer. Always consult with a healthcare professional before making any decisions based on the information found on our website.
Klarity is a citizen-centric health data management platform that enables citizens to securely access, control and share their own health data. Klarity Health Library aims to provide clear and evidence-based health and wellness related informative articles. 
Klarity / Managed Self Ltd
Alum House
5 Alum Chine Road
Westbourne Bournemouth BH4 8DT
VAT Number: 362 5758 74
Company Number: 10696687

Phone Number:

 +44 20 3239 9818