Hydroxyurea/hydroxycarbamide is frequently used in the first few weeks to reduce the WBC count and/or the platelet count to safer levels. Hydroxyurea should be switched to a TKI as soon as the patient has decided which TKI to take.

In cases with markedly elevated platelet counts it may be necessary to use anagrelide for the first few days or weeks before an appropriate TKI is selected.

The mainstay of therapy for chronic phase CML is TKI therapy. There are currently three TKIs approved and reimbursed for first-line therapy in Australia: imatinib, nilotinib and dasatinib. All three represent excellent choices, but the preferred TKI for each patient will depend on a combination of CML risk score (ELTS), comorbidity assessment (including Framingham risk score or equivalent) and the patient’s motivation to achieve treatment-free remission. Ideally, the choice of TKI should be a shared decision between the clinician and patient after an in-depth discussion of the advantages and disadvantages of each drug and to consider any available clinical trials that may be available.

It’s important not to rush this decision to give the patient time to consider the advantages and disadvantages of each option.

Ideally TKI therapy should start within the first four weeks, unless there is a specific indication to delay.

Blast phase may be present at diagnosis of CML, or it may develop after a period of chronic and/or accelerated phase CML.

Once diagnosed, the treatment approach for blast phase CML should be similar to that taken for acute myeloid leukaemia if in myeloid blast phase, or acute lymphoblastic leukaemia if in lymphoid blast phase, except that TKI therapy will generally be used alongside chemotherapy.

An allogeneic stem cell transplant is almost always indicated for patients with good performance status who achieve a second chronic phase.

The treatment pathway is complex for patients who are potential candidates for an allogeneic stem cell transplant. They should be admitted to a hospital with expertise in managing acute leukaemia that is accredited to undertake allogeneic stem cell transplants, or has close links to a hospital with this capability.

TKI-related side effects can significantly affect quality of life and have the potential to be life-threatening.

Comprehensive side effect management is essential since lifelong treatment may be required, and treatment with TKIs can impact physical, psychological, nutritional and general wellbeing.

From the time of diagnosis, the treating team should offer patients appropriate psychosocial and supportive care and symptom-related interventions as part of routine care. The approach should be personalised to meet each patient’s needs, values and preferences.

Managing side effects may be complex and requires optimal communication between the treating clinician, patient, general practitioner and appropriate specialties in the multidisciplinary team.

Patients who achieve deep molecular response that is maintained for at least 24 months have the option to consider ceasing treatment. It’s important to have a frank discussion about what discontinuing TKI therapy entails, including the chance of success, the frequency of molecular

monitoring required, the risk of TKI-withdrawal syndrome and the impact of restarting therapy if that becomes necessary. Before ceasing treatment, strict processes need to be in place to ensure that molecular monitoring is timely and results are acted on promptly.

For more information, see Table 8 in the European LeukemiaNet 2020 recommendations for treating CML

Systemic therapy (cytotoxic agents) is only indicated in cases of blast phase CML.

Timeframes for starting treatment

Initiating therapy is urgent in blast phase CML. Ideally chemotherapy and/or TKI therapy should be started within one week of diagnosis.

Training and experience required of the appropriate specialists

Haematologists must have training and experience of this standard:

• Fellow of the Royal Australian College of Physicians (or equivalent)
• adequate training and experience that enables institutional credentialing and agreed scope of practice within this area (ACSQHC 2015).

Cancer nurses should have accredited training in these areas:

• anti-cancer treatment administration
• specialised nursing care for patients undergoing cancer treatments, including side effects and symptom management
• the handling and disposal of cytotoxic waste (ACSQHC 2020).

Systemic therapy should be prepared by a pharmacist whose background includes this experience:

• adequate training in systemic therapy medication, including dosing calculations according to protocols, formulations and/or preparation.

In a setting where no haematologist is locally available (e.g. regional or remote areas), some components of less complex therapies may be delivered by a general practitioner or nurse with training and experience that enables credentialing and agreed scope of practice within this area. This should be in accordance with a detailed treatment plan or agreed protocol, and with communication as agreed with the medical oncologist or as clinically required.

The training and experience of the appropriate specialist should be documented.

Health service characteristics

To provide safe and quality care for patients having systemic therapy, health services should have these features:

• a clearly defined path to emergency care and advice after hours
• access to diagnostic pathology including basic haematology and biochemistry, and imaging
• cytotoxic drugs prepared in a pharmacy with appropriate facilities
• occupational health and safety guidelines regarding handling of cytotoxic drugs, including preparation, waste procedures and spill kits (eviQ 2019)
• guidelines and protocols to deliver treatment safely (including dealing with extravasation of drugs)
• coordination for combined therapy with radiation therapy, especially where facilities are not co-located
• appropriate molecular pathology access.