STEP 3: Diagnosis, staging, and treatment planning
Step 3 outlines the process for confirming the diagnosis of CML and for planning subsequent treatment. The guiding principle is that interaction between appropriate multidisciplinary team members should determine the treatment plan.
The treatment team, after taking a thorough medical history and making a thorough medical examination of the patient, including specifically documenting spleen size, should undertake the following investigations under the guidance of a specialist.
Minimum established tests:
- real-time quantitative RT-PCR test to detect and measure the level of BCR-ABL1 on the international scale
- biochemistry screen including liver function tests, electrolytes, renal function tests, urate, lipase and amylase, blood sugar level
- HIV, hepatitis B and hepatitis C serology
- electrocardiogram.
Investigations that should be done in most circumstances:
- bone marrow aspiration including cytogenetics, immunophenotyping/flow cytometry and morphology (exceptions can be made for frail or very elderly patients)
- fasting lipids (not essential if the patient will receive frontline imatinib)
- chest x-ray (not essential for young, healthy patients).
The following tests are important in cases where a second-generation tyrosine kinase inhibitor (TKI) is being considered in a patient who may have a high risk of vascular disease (based on age or other factors):
- ankle brachial index
- Doppler study of neck and leg arteries
- cardiac echocardiogram.
Specialist assessments should generally be completed within two weeks from the first haematologist appointment. However, the ankle brachial index, Doppler study and cardio echocardiogram tests that are recommended in selected cases are less time-critical and should be completed within six weeks.
Determining the phase of disease is a critical element of treatment planning and should be clearly documented in the patient’s medical record.
There are three phases of CML: chronic, accelerated and blast phase. They are described in more detail in the European LeukemiaNet 2020 recommendations for treating CML (Hochhaus et al. 2020).
More than 90 per cent of patients are diagnosed in the chronic phase (Hochhaus et al. 2017). The following tests are used to determine the phase of CML:
- investigations for extramedullary disease
- percentage of blasts, basophils and platelet count in the peripheral blood
- bone marrow morphology – a report should specifically state the phase of disease.
Patients with chronic phase CML should have their risk category assessed using an accepted scoring system. Currently, the EUTOS long-term survival (ELTS) score is preferred (Hochhaus et al. 2020).
The ELTS factors in age, spleen size, blasts in peripheral blood and platelet count to predict long-term survival and support treatment selection (European LeukaemiaNet 2020).
The treating haematologist should discuss and develop a treatment plan with the patient within two weeks of completing investigations.
Participation in clinical trials, patient registries and tissue banking, where available, is encouraged
for patients with CML. Cross-referral between clinical trials centres should be encouraged to facilitate participation.
For more information visit:
- Cancer Australia
- Australian New Zealand Clinical Trials Registry
- Australasian Leukaemia & Lymphoma Group
- ClinicalTrials.gov for an international view.
Participation in clinical trials, patient registries and tissue banking, where available, is encouraged for patients with cml. Cross-referral between clinical trials centres should be encouraged to facilitate participation.
For more information visit:
Cancer prehabilitation uses a multidisciplinary approach combining exercise, nutrition and psychological strategies to prepare patients for the challenges of cancer treatment such as systemic therapy and radiation therapy. Prehabilitation is indicated for patients with blast phase CML where chemotherapy and possibly allogeneic stem cell transplant are part of the therapy plan.
Team members may include anaesthetists, oncologists, surgeons, haematologists, clinical psychologists, exercise physiologists, physiotherapists and dietitians, among others.
Patient performance status is a central factor in cancer care and should be frequently assessed. All patients should be screened for malnutrition using a validated tool, such as the Malnutrition Screening Tool (MST). The lead clinician may refer obese or malnourished patients to a dietitian preoperatively or before other treatments begin.
Patients who currently smoke should be encouraged to stop smoking before receiving treatment. This should include an offer of referral to Quitline in addition to smoking cessation pharmacotherapy if clinically appropriate.
Evidence indicates that patients who respond well to prehabilitation may have fewer complications after treatment. For example, those who were exercising before diagnosis and patients who use prehabilitation before starting treatment may improve their physical or psychological outcomes, or both, and this helps patients to function at a higher level throughout their cancer treatment (Cormie et al. 2017; Silver 2015).
For patients with CML in the blast phase, the multidisciplinary team should consider these specific prehabilitation assessments and interventions for treatment-related complications or major side effects:
- conducting a physical and psychological assessment to establish a baseline function level
- identifying impairments and providing targeted interventions to improve the patient’s function level (Silver & Baima 2013)
- reviewing the patient’s medication to ensure optimisation and to improve adherence to medicine used for comorbid conditions.
After completing primary cancer treatment, rehabilitation programs have considerable potential to enhance physical function.
For men taking the TKIs imatinib, dasatinib and nilotinib, there is no significant impact on fertility and no increased risk of congenital abnormalities in their offspring. Therefore, they can continue
taking these TKIs and father children. There is less data on fertility with the other TKIs, ponatinib and asciminib (Hochhaus et al. 2020).
For women, TKIs have been shown to cause birth defects in the fetus, or fetal death. Therefore, women of childbearing age are advised to use at least one highly effective method of birth control to prevent pregnancy while taking TKIs.
Women who may want to have children in the future should be referred to a fertility clinic within the first two weeks to discuss the possibility of egg or embryo storage before starting treatment with hydroxyurea or TKIs. Women should be informed about potential risks associated with delaying TKI therapy to enable storage of eggs/embryos and should discuss this with their haematologist.
If a woman becomes pregnant while taking TKIs, she should cease the TKI immediately and have a fetal ultrasonography urgently. Options for continuing treatment, as well as continuing or discontinuing the pregnancy, should be discussed thoroughly.
TKIs are secreted in breast milk, therefore women are advised not to take TKIs while breastfeeding.
Males do not routinely need to store sperm if they are in chronic phase CML. However, if they are in blast or accelerated phase, or if they respond poorly to initial therapy and may proceed to an allograft, sperm storage should be discussed and considered.
Cytotoxic treatment for blast phase CML may cause fertility problems. However, this will depend on the age of the patient, the type of cancer and the treatment received. Infertility can range from difficulty having a child to the inability to have a child. Infertility after treatment may be temporary, lasting months to years, or permanent (AYA Cancer Fertility Preservation Guidance Working Group 2014).
Patients need to be advised about and potentially referred for discussion about fertility preservation before starting treatment and need advice about contraception before, during and after treatment. Patients and their family should be aware of the ongoing costs involved in optimising fertility. Fertility management may apply in both men and women.The potential for impaired fertility should be discussed and reinforced at different time points as appropriate throughout the diagnosis, treatment, surveillance and survivorship phases of care. These ongoing discussions will enable the patient and, if applicable, the family to make informed decisions. All discussions should be documented in the patient’s medical record.
More information
See the Cancer Council website for more information.
See validated screening tools mentioned in Principle 4 ‘Supportive care’.
A number of specific challenges and needs may arise for patients at this time:
- assistance for dealing with psychological and emotional distress while adjusting to the diagnosis; treatment phobias; existential concerns; stress; difficulties making treatment decisions; anxiety or depression or both; psychosexual issues such as potential loss of fertility and premature menopause; history of sexual abuse; and interpersonal problems
- diaries, reminders or other tools to aid with oral medication adherence
- management of physical symptoms such as pain and fatigue (Australian Adult Cancer Pain Management Guideline Working Party 2019)
- malnutrition or undernutrition, identified using a validated nutrition screening tool such as the MST (note that many patients with a high BMI [obese patients] may also be malnourished [WHO 2018])
- support for families or carers who are distressed with the patient’s cancer diagnosis
- support for families/relatives who may be distressed after learning of a genetically linked cancer diagnosis
- specific spiritual needs that may benefit from the involvement of pastoral/spiritual care. Additionally, palliative care may be required at this stage.
For more information on supportive care and needs that may arise for different population groups, see Appendices A, B and C.
