STEP 4: Treatment

Step 4 outlines the optimal treatments for CAYA acute leukaemia, the training and experience required of the treating clinicians and the health service characteristics required for optimal cancer care.

All health services must have clinical governance systems that meet the following integral requirements:

  • identifying safety and quality measures
  • monitoring and reporting on performance and outcomes
  • identifying areas for improvement in safety and quality (ACSQHC 2020).

The intent at diagnosis for all CAYA with acute leukaemia is cure. Patients who develop refractory or relapsed disease are discussed in Step 6: Managing refractory, relapsed, residual or progressive disease.

The treatment intent should be established in a multidisciplinary setting, documented in the patient’s medical record and conveyed to the patient and carer as appropriate.

The lead clinician should discuss the advantages and disadvantages of each treatment and associated potential side effects with the patient and their carer or family before treatment consent is obtained and begins so the patient can make an informed decision. Supportive care services including community support organisations should also be considered during this decision- making process. Patients and carers should be asked about their use of (current or intended) complementary therapies (see Appendix D).

Timeframes for starting treatment should be informed by evidence-based guidelines where they exist. The treatment team should recognise that shorter timeframes for appropriate consultations and treatment can promote a better experience for patients.

Where appropriate, initiate advance care planning discussions with patients before treatment begins (this could include appointing a substitute decision-maker and completing an advance care directive). Formally involving a palliative care team/service may benefit any patient, so it is important to know and respect each person’s preference (Australian Government Department of Health 2021a).

Treatment options – newly diagnosed acute lymphoblastic leukaemia (ALL)

Advances in treating CAYA ALL have been achieved through successive well-designed international clinical trials (Pui et al. 2015). It is considered standard of care to enrol CAYA ALL patients into an open clinical trial for newly diagnosed ALL.

Most treatments for CAYA acute leukaemia patients start as inpatient; however, standard- risk leukaemia treatment can be delivered in an outpatient setting. Currently, treatment lasts approximately two years and the treatment plan depends on risk stratification. Treatment includes CNS-directed therapy.

All AYA with ALL should be treated according to a paediatric (or paediatric-inspired) protocol because there is consistent and compelling evidence that these confer superior survival outcomes (Siegel et al. 2018; Stock et al. 2019).

MRD is an important test for measuring response to treatment in CAYA ALL. The general principles for MRD monitoring for CAYA ALL are:

  • diagnostic (baseline MRD panel) specimen
  • end of induction therapy
  • end of consolidation for those who are positive at end of induction
  • end of induction therapy in relapsed disease
  • prior to a transplant for patients preceding HSCT
  • additional timepoints may be required in patients receiving novel/cellular immunotherapies, including CAR T-cell therapy.

These time points will vary according to the clinical protocol and the requirements of clinical trials.

Treatment options – acute myeloid leukaemia (AML)

Systemic chemotherapy-based treatment is the backbone of AML therapy and is divided into two phases: induction therapy to achieve remission and consolidation therapy once a remission has been achieved to maintain ongoing remission or as a bridge to HSCT in some patients. Currently, total duration is four to six months, depending on risk stratification. Treatment is risk-stratified based on cytogenetics and response using MRD. CNS-directed therapy is given during treatment.

MRD is an important test for measuring response to treatment in CAYA AML. The general principles for MRD monitoring for CAYA AML are:

  • diagnostic (baseline MRD panel) specimen
  • end of the first course of induction
  • consideration at end of subsequent course, if positive at end of

These time points will vary according to the clinical protocol and the requirements of clinical trials.

Treatment options – infant leukaemia

Infants diagnosed with ALL are at high risk of relapse and have significantly inferior outcomes that school-aged children (Kotecha et al. 2014; Pieters et al. 2009; 2019). Current event-free survival remains at 50 per cent, despite best-practice international collaborative trials. Treatment is intensive and predominantly inpatient-based. New therapies are examining the addition of specific targeted therapies (Clesham et al. 2020) because current treatment regimens have reached dose-limiting toxicities.

MRD is an important test for measuring response to treatment in infant ALL. The general principles for MRD monitoring for infant ALL are as per section 4.2.1. MRD at the end of induction may identify some infants that would benefit from AML-like consolidation (Stutterheim et al. 2021).

It is important that infants with a leukaemia diagnosis are enrolled in clinical trials, wherever possible.

Treatment options – acute promyelocytic leukaemia

Although CAYA APL is rare, many patients at diagnosis have significant coagulopathy. The presentation of APL is a medical emergency because of the high risk of death as a result of the associated coagulopathy. If APL is suspected, treatment should start without delay. These patients are managed at diagnosis as inpatients in specialist centres with ready access to intensive care and blood products to manage the life-threatening coagulopathy. These patients do not get a diagnostic LP because of the coagulopathy. Patients undergo molecular monitoring to guide treatment (e.g. quantitative molecular

MRD for PML-RARA gene fusion). Consolidation therapy after induction can usually be outpatient-based.

Timeframes for starting treatment Urgent pathway

Treatment should begin on the day of presentation immediately following diagnostic interventions. Urgent patients include, but are not limited to, those who present with hyperleucocytosis, tumour lysis syndrome, mediastinal mass and coagulopathies.

Standard pathway

Treatment for should start by the next business day following diagnosis. In clinically stable patients, clinical trial requirements and the level of institutional resources available on the day to provide optimal care should guide timings.

‘After-hours’ admission of newly diagnosed patients

The timing of diagnostic and therapeutic interventions should be flexible and reflect clinical need, particularly for patients who present with oncological emergencies.

Chemotherapy is the key component for treating CAYA acute leukaemia. Due to the complexity and toxicity of administering cytotoxic agents to patients, adherence to medication safety standards (e.g. mini-bag vincristine infusions) and the demands for supportive care, intravenous chemotherapy should be delivered via a central venous access device.

Urgent pathway

Central venous access should be established on the day of presentation, if possible.

Standard pathway

Insertion of a central venous access device should be undertaken before initial treatment, if possible. However, this may vary and institutional guidelines should be followed.

Training and experience required of the appropriate specialists

Paediatric or adult haematologist/oncologists treating CAYA acute leukaemia 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 and demonstrate competency 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 medical oncologist 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

Treatment for CAYA acute leukaemia is administered by a specialist cancer service.

Consideration for supportive care and some aspects of treatment such as administering chemotherapy in shared care centres outside the specialist cancer service and referral to community support organisations should be made after consultation with the patient’s multidisciplinary team.

Episodes of chemotherapy in regional shared care centres should be conducted via telehealth between the local health service and the child’s oncologist or haematologist.

Palliative care is a multidisciplinary approach to symptom management and psychosocial support and helps identify care goals for patients with serious illness and their families. Note, a significant number of patients with CAYA acute leukaemia are cured.

Paediatric palliative care services can also support and provide care coordination with other care providers such as schools, NDIS providers, equipment services and community services to enhance care of the patient and their family. Sibling support and grandparent support can also be provided. Bereavement care, including anticipatory grief, is a core element of paediatric palliative care.

Early referral to palliative care can improve the quality of life for people with cancer (Haines 2011; Temel et al. 2010; Zimmermann et al. 2014). This is particularly true for cancer with poor prognosis.

The lead clinician should ensure patients receive timely and appropriate referral to paediatric palliative care services. Referral should be based on need rather than prognosis. When given an evidence- based process to safely address these confronting issues, young people and their families are highly engaged. Addressing the value of palliative care and advance care planning with young people has been shown to reduce their anxiety, does not affect depression, improves symptom management and quality of life for patients and their carers (Wiener et al. 2008; 2012).

The ‘Dying to Talk’ resource may help health professionals, where appropriate, initiating discussions with patients, family or carer about future care needs (see ‘More information’). Ensure that carers and families receive information, support and guidance about their role in palliative care (Palliative Care Australia 2018).

Where appropriate, patients, their family or carer should be encouraged to initiate advance care planning. Advance care planning discussions can be triggered at the time of diagnosis to ensure care is informed by respect and knowledge of the patient or caregiver’s preferences.

Therapies such as HSCT, treatment for high-risk AML and targeted therapies within the context of clinical trials can result in high levels of physical, psychological and existential distress, despite having curative intent. CAYA with an uncertain prognosis and high symptom burden should be able to access palliative care support alongside curative-intent therapies.

Discussion should be held within a CAYA acute leukaemia MDM to offer the family referral to palliative care services where there is a likely need to escalate care to manage symptoms and distress in

high-risk curative regimens such as HSCT, as well as support when cure is no longer the intent of the multidisciplinary team.

Refer to Step 6 for a more detailed description of managing patients with refractory, relapsed, residual or progressive or refractory disease.

More information

These online resources are useful:

The team should support the patient to participate in research or clinical trials where available and appropriate. Many emerging treatments are only available on clinical trials that may require referral to certain trial centres.

For more information visit: