STEP 6: Managing refractory, relapsed, residual or progressive disease
Patients who present with relapsed or refractory disease should be managed by a multidisciplinary team and offered timely referral to appropriate physical, practical and emotional support.
Step 6 is concerned with managing relapsed or refractory disease in CAYA acute leukaemia.
Despite approximately 90 per cent of CAYA with ALL being cured of their disease, relapse remains the most common cause of treatment failure, occurring in 15–20 per cent of all patients. Of children who relapse, cure only occurs in about 50 per cent of patients, with survival in AYA with relapsed ALL being dismal (Hunger & Raetz 2020; Sellar et al. 2018). Significant improvements in survival have been achieved with incorporating newer targeted therapies into salvage regimens (Brown et al. 2021; Locatelli et al. 2021; Maude et al. 2018).
Refractory ALL in the frontline setting also confers a poor prognosis. Children with induction failure have a 10-year survival of 32 per cent (Schrappe 2012).
In AML, 30 per cent of all patients will relapse, and recent studies show only 30–40 per cent of those patients survive (Hoffman et al 2021).
Some patients may present with symptoms of relapsed disease after a previous cancer diagnosis. The relapse may be discovered by the patient or by surveillance in the post-treatment period.
Access to the best available therapies, including clinical trials, as well as treatment overseen by a multidisciplinary team, are crucial to achieving the best outcomes for anyone with relapsed or refractory disease.
There should be an immediate referral to a leukaemia multidisciplinary team specialist cancer service for all patients with suspected or confirmed relapse.
All CAYA with relapsed or refractory acute leukaemia should be managed by a specialist cancer service.
From the time of diagnosis, the team should offer patients appropriate psychosocial care, supportive care, advance care planning and symptom-related interventions as part of their routine care. The approach should be personalised to meet the patient’s individual needs, values and preferences. The full complement of supportive care measures as described throughout the optimal care pathway and in Appendices A, B and C should be offered to assist patients and their families and carers to cope. These measures should be updated as the patient’s circumstances change.
Survivorship issues should be considered as part of routine care. Health professionals should therefore be ready to change and adapt treatment strategies according to disease status, prior treatment tolerance/toxicities and the patient’s quality of life, in addition to the patient’s priorities and life plans.
If there is an indication that a patient’s cancer has returned, care should be provided under the guidance of a treating specialist.
There should be an immediate referral to a leukaemia multidisciplinary team within a CAYA cancer service for all with suspected or confirmed relapse. As with frontline therapy, routine involvement of allied health (e.g. social work, psychology) within the team is required. The team may include new members such as palliative care specialists.
Treatment will depend on the timing of relapse, location of relapse (isolated bone marrow relapse, isolated extramedullary relapse, combined relapse), immunophenotype in ALL (B-cell vs T-cell), previous management, response to salvage therapy (including MRD response in ALL), number of previous relapses and the patient’s preferences.
CAYA with relapsed ALL are often eligible for enrolment in clinical trials for relapsed disease. These typically involve systemic chemotherapy, newer targeted agents and/or immunotherapy, together with HSCT for selected patients.
In relapsed AML, achieving rapid remission via systemic chemotherapy, targeted therapies and/or immunotherapy followed by HSCT is currently the most effective curative strategy.
Immunotherapy or immune effector cell therapy is used in certain relapsed acute leukaemia patients. Current examples of immunotherapy used in acute leukaemia include BiTEs (e.g. blinatumomab), antibody drug conjugates (e.g. gemtuzumab, inotuzumab) and CAR T-cells (e.g. tisagenlecleucel).
A number of additional immunotherapies are currently under investigation in CAYA acute leukaemia.
Access to new therapies that have not yet been approved by the Pharmaceutical Benefits Scheme may sometimes be challenging. This highlights the importance of enrolling CAYA with relapsed/ refractory disease onto clinical trials wherever possible.
The potential goals of treatment should be discussed, respecting the patient’s cultural values. Wherever possible, written information should be provided.
Advance care planning is important for all patients with a cancer diagnosis but especially those with advanced disease. Where appropriate, patients, their family or carer should be encouraged to think and talk about their healthcare values and preferences and consider developing an advance care directive to convey their preferences for future health care (Australian Government Department of Health 2021a). The lead oncologist, haematologist, palliative care team or general practitioner are best placed to assist with a CAYA-centred approach and assist in developing an advance care directive.
More information
Refer to section 4.3 ‘More information’ for links to resources.
Refer patients and carers to Advance Care Planning Australia or to the Advance Care Planning National Phone Advisory Service on 1300 208 582.
Refer patients, their family or carer to the Thinking ahead framework or call (03) 9345 5522.
Early referral to palliative care can improve the quality of life for people with cancer and in some cases may be associated with survival benefits (Haines 2011; Temel et al. 2010; Zimmermann et al. 2014). The treatment team should emphasise the value of palliative care in improving symptom management and quality of life to patients and their carers. Refer to section 4.3 for more detailed information.
CAYA with an uncertain prognosis and a high symptom burden should be able to access palliative care support alongside curative-intent therapies.
Cases of relapse should trigger a referral to palliative care services.
The lead clinician should ensure timely and appropriate referral to paediatric palliative care services. Referral to palliative care services should be based on the patient’s need and potential for benefit, not prognosis.
More information
Refer to the end of section 4.3 ‘Palliative care’ for links to resources.
The treatment team should support the patient to participate in research and clinical trials where available and appropriate.
For additional information visit:
See validated screening tools mentioned in Principle 4 ‘Supportive care’.
A number of specific challenges and needs may arise at this time for patients, carers and families:
- assistance for dealing with emotional and psychological distress resulting from fear of death or dying, existential concerns, anticipatory grief, communicating wishes to loved ones, interpersonal problems and sexuality concerns
- potential isolation from normal support networks, particularly for rural patients who are staying away from home for treatment
- cognitive changes as a result of treatment and disease progression such as altered memory, attention and concentration (a patient may appoint someone to make medical, financial and legal decisions on their behalf – a substitute decision-maker – before and in case they experience cognitive decline)
- management of physical symptoms
- decline in mobility or functional status as a result of recurrent disease and treatments (referral to physiotherapy or occupational therapy may be required)
- coping with hair loss and changes in physical appearance (refer to the Look Good, Feel Better program – see ‘Resource list’)
- appointing a substitute decision-maker and completing an advance care directive
- financial issues as a result of disease recurrence such as gaining early access to superannuation and insurance
- legal issues (completing a will, care of dependent children) and making an insurance, superannuation or social security claim on the basis of terminal illness or permanent disability. financial and employment issues (e.g. loss of income and assistance with returning to work, and the cost of treatment, travel and accommodation)
- referral to supportive care services and community support
Treatment for relapsed acute leukaemia has a high-risk of treatment-related morbidity and mortality, particularly infectious complications. HSCT, novel agents and cell therapies used in refractory leukaemia may also be associated with significant treatment-related side effects. Families and patients from regional centres may need to move closer to the specialist cancer service due to
the toxicity of therapy. Support of the patient and family, including access to information, should be managed under the family-centred care principles discussed in Principle 4 ‘Supportive care’.
Rehabilitation may be required at any point of the care pathway, from preparing for treatment through to palliative care. Issues that may need to be dealt with include managing cancer-related fatigue, improving physical endurance, achieving independence in daily tasks, returning to work and ongoing adjustment to cancer and its consequences.
Exercise is a safe and effective intervention that improves the physical and emotional health and wellbeing of cancer patients. Exercise should be embedded as part of standard practice in cancer care and be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment.
The lead clinician should ensure there is adequate discussion with patients and carers about the diagnosis and recommended treatment, including treatment intent and possible outcomes, likely adverse effects and the supportive care options available.
More information
Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.
