STEP 3: Diagnosis, staging, and treatment planning
Step 3 outlines the process for confirming the diagnosis of CAYA acute leukaemia and for planning subsequent treatment. The guiding principle is that interaction between appropriate multidisciplinary team members should determine the treatment plan.
All CAYA with acute leukaemia should be managed by a specialist cancer service.
Urgent pathway
Some patients may present with oncological emergencies including, but not limited to, hyperleucocytosis, tumour lysis syndrome, mediastinal mass, sepsis and coagulopathies.
For these patients, urgent, immediate emergency assessment and diagnostic investigations need to be completed to allow early commencement of therapy. These patients may require initial intensive care support during their inpatient admission to a tertiary oncology/haematology centre.
Standard pathway
For clinically stable patients with a new diagnosis of acute leukaemia, the diagnostic interventions can be planned for the next business day. These patients still will require inpatient admission to a tertiary oncology/haematology centre.
The diagnostic evaluation is a critical time for these patients. It should provide a complete diagnosis according to the most recent classification system (Swerdlow et al. 2017), assess the presence of and manage any comorbidities, plus identify any predisposition syndrome.
This is essential to ensure accurate diagnosis, accurately classify the subtype of leukaemia, inform prognosis and ensure treatment decisions are evidence-based.
To achieve this the treatment team should perform a series of investigations, outlined below. Pre-treatment laboratory examinations include:
- full blood count and blood film review (note: morphological assessment of the blood film to identify acute promyelocytic leukaemia [APL] should be conducted immediately and the result conveyed to the treating physician)
- urea and creatinine, electrolytes including calcium and phosphate, liver function tests
- uric acid and lactate dehydrogenase
- blood group, antibody screen and red blood cell phenotype
- coagulation studies
- consideration of pharmacogenomic testing (e.g. TPMT and G6PD)
- haemoglobin electrophoresis
- immunoglobulins and T- and B-cell subsets
- for relevant or appropriate groups, pregnancy tests (urine or blood BHCG).
Pre-treatment medical imaging includes a chest x-ray to exclude a mediastinal mass.
Diagnostic laboratory investigations include work-up tests performed on bone marrow and/or trephine biopsy and, at times, also on peripheral blood morphology:
- immunophenotyping, karyotyping and FISH analysis
- molecular genetic analysis
- minimal residual disease (MRD) sample (either PCR-MRD or FLOW or by NGS). Other tests may include:
- DNA microarray (or chromosomal microarray)
- biobanking
- other investigations dictated by clinical trial
Lumbar puncture (LP) is performed to establish if there is any CNS disease. Most paediatric acute leukaemia protocols and adolescent and young adult (AYA) ALL protocols currently recommend that a diagnostic LP should occur before starting systemic chemotherapy. Some patients cannot have an LP before therapy such as those with coagulopathies. Therapy should be performed
with adequate platelet cover and performed by an experienced clinician to reduce the risk of a traumatic tap contaminating the CSF with blasts. To further minimise this complication, intrathecal chemotherapy should be given at the same time as the diagnostic LP.
In children and adolescents, diagnostic tests should be organised to reduce the number of procedures requiring general anaesthesia. For example, use peripheral blood flow cytometry to confirm the immunophenotype to allow central line placement, diagnostic LP and bone marrow (including collection for clinical trial enrolment), all under the same general anaesthetic.
Infection screening
It is important that infection screening is undertaken at diagnosis and before blood product support and definitive treatment. The purpose of this screening is to establish a baseline before administering blood products and to investigate serostatus to herpes family viruses, which may reactivate in immunosuppressed patients.
This screening should include routine serology – HBV, HCV, HIV, HTLV, HSV, VZV, EBV, CMV, syphilis and toxoplasma. For patients born or who have travelled overseas, particularly to tropical regions
or tuberculosis-endemic countries, consultation with infectious diseases should be sought. Other investigations are as clinically indicated and on discussion with the infectious diseases service (e.g. malaria screen, melioidosis serology in patients from Far North Queensland and the Top End of the Northern Territory).
Biobanking
Consent for biobanking of diagnostic material should be sought. In many upfront clinical trials in leukaemia, biobanking is a prerequisite to enrolment.
Measurable/minimal residual disease
An MRD level is a strong and independent predictor of relapse in CAYA acute leukaemia and widely used for risk stratification (Cave et al. 1998; Van Dongen et al. 1998). This requires a diagnostic marrow or peripheral blood specimen to enable identification of leukaemia-specific marker or leukaemia associated immunophenotype.
Clinical trial investigations
Further laboratory tests may be required for enrolment into clinical trials.
Staging is not clinically relevant in CAYA acute leukaemias other than for the presence of CNS disease and, in boys, testicular disease. However, appropriate prognostic assessment and risk stratification is a critical element in treatment planning and should be clearly documented in the patient’s medical record. This should be evidence-based to ensure patients at the highest risk of relapse receive appropriately intensified therapy while those with more favourable prognosis (the lowest risk of relapse) receive therapy of reduced intensity to reduce complications.
The most important current factors for prognostic assessment and risk stratification are cytogenetics and response to treatment using MRD. Newer molecular markers with prognostic and potentially therapeutic relevance in acute leukaemia will become clinically routine in the near future (Pui et al. 2018; Tasian & Hunger 2017).
Patient performance status is a central factor in cancer care and should be clearly documented in the patient’s medical record.
Performance status should be measured and recorded using an established scale such as the Karnofsky/Lansky scale or the Eastern Cooperative Oncology Group (ECOG) scale.
New diagnostic techniques in the biology of CAYA acute leukaemia continue to develop rapidly. The multidisciplinary team needs to be aware of these changes and advances and ensure they are translated to clinical management. CAYA acute leukaemia patients being enrolled in clinical trials
is important and associated with superior outcome. The team must know which suitable clinical trials are available for CAYA acute leukaemia. If there is no open clinical trial then every specialist CAYA acute leukaemia service should have a predefined, peer-reviewed treatment model that the multidisciplinary team has endorsed.
A number of factors should be considered at this stage:
- the patient’s overall condition, life expectancy, personal preferences and decision-making capacity
- discussing the multidisciplinary team approach to care with the patient
- appropriate and timely referral to an MDM
- pregnancy and fertility
- support with travel and accommodation
- teleconferencing or videoconferencing as required
- educational
More information
For more information see the Victorian paediatric oncology care pathways: Providing optimal care for children and adolescents – acute leukaemia, central nervous system tumours and solid tumours (May 2019)
Induction treatment is often required before a full MDM ratifies details for the ongoing management plan. All CAYA will be inpatients when treatment starts, allowing their initial multidisciplinary management to be performed on the ward.
All CAYA acute leukaemia should be discussed as soon as possible after diagnosis at an appropriate MDM, with further discussions at the time of response assessment or final risk stratification.
All CAYA acute leukaemia should also be discussed at suitable MDMs that will include psychosocial and supportive care assessment.
Results of all relevant tests and access to images should be available for the MDM. Information about the patient’s concerns, preferences and social and cultural circumstances should also be available.
Participation in clinical trials, patient registries and tissue banking, where available, is encouraged for patients with CAYA acute leukaemia. The most important factor contributing to the improvement in survival in childhood leukaemia over the past 50 years has been the widespread participation in well- conducted phase 3 clinical trials (Pui et al. 2015). Clinical trial protocols are rigorously peer reviewed and are a means to ensure CAYA are receiving the best available treatment. These are expected to continue to be important in increasing survival rates for future generations. Enrolment in a clinical trial should be considered the standard of care for CAYA acute leukaemia, whenever possible.
For more information visit:
- Cancer Australia
- Australian New Zealand Clinical Trials Registry
- Australasian Leukaemia and Lymphoma Group
- Australian & New Zealand Childrens Haematology/Oncology Group
- ClinTrial Refer <www.clintrial.org.au>
- Clinical Trialsfor an international view.
For more information see the Victorian paediatric oncology care pathways: Providing optimal care for children and adolescents – acute leukaemia, central nervous system tumours and solid tumours (May 2019)
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. 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. The lead clinician may refer obese or malnourished patients to a dietitian.
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 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 CAYA acute leukaemia, 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.
Following completion of primary cancer treatment, rehabilitation programs have considerable potential to enhance physical function.
Cancer and cancer treatment may cause fertility problems. 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 and carers need to be advised about and 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 males and females. Fertility preservation options
are different for males and females and may be specific to a patient’s age. The need for ongoing contraception applies to 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 also the Victorian paediatric oncology care pathways: Providing optimal care for children and adolescents – acute leukaemia, central nervous system tumours and solid tumours (May 2019)
See validated screening tools mentioned in Principle 4 ‘Supportive care’.
A number of specific challenges and needs may arise for patients and carers 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
- management of physical symptoms such as pain and fatigue (Australian Adult Cancer Pain Management Guideline Working Party 2019), including pain management for mucositis or peripheral neuropathy
- physiotherapy/exercise support in managing chemotherapy induced peripheral neuropathy and muscle weakness
- neuropsychology supports: referral to neuropsychology should be considered for patients who have experienced potential neurocognitive insult from triggers such as CNS-directed therapy (cranial radiation and intrathecal chemotherapy), those patients receiving high-dose methotrexate and patients who experience any significant CNS morbidity during treatment such as cerebral bleed, stroke, acute meningitis and encephalopathies
- nutritional assessment at diagnosis and subsequently for all This should include malnutrition or undernutrition, noting that many patients with a high BMI (obese patients) may also be malnourished (WHO 2018)
- education and school support (where applicable)
- support for families or carers who are distressed with the patient’s cancer diagnosis (including support for siblings where applicable)
- 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
A number of supportive therapies may be necessary at this time including:
- managing acute symptoms in newly diagnosed patients
- providing blood product support and managing electrolyte abnormalities, including tumour lysis syndrome
- managing clinical symptoms at diagnosis due to extramedullary disease
- management and prevention of
For more information on supportive care and needs that may arise for different population groups, see Appendices A, B and C.
Communication with patients should always be tailored to their age and developmental stage. For adolescents, and some children, it is important to involve them in the discussion rather than just speaking to their parent/carer. Similarly, the participation of young adults’ parent or support person should also be encouraged (Osborn et al. 2019).
In discussion with the patient and their families and carers, the lead clinician should undertake the following:
- establish if the patient has a regular or preferred general practitioner and if the patient does not have one, then encourage them to find one
- provide written information appropriate to the health literacy of the patient about the diagnosis and treatment to the patient and carer and refer the patient to the Guide to best cancer care (consumer optimal care pathway) for CAYA acute leukaemia, as well as to relevant websites and support groups as appropriate
- provide a treatment care plan including contact details for the treating team and information on when to call the hospital
- discuss a timeframe for diagnosis and treatment with the patient and carer
- discuss the benefits of multidisciplinary care and gain the patient’s or carer’s consent before presenting their case at an MDM
- provide brief advice and refer to Quitline (13 7848) for behavioural intervention if the patient currently smokes (or has recently quit), and prescribe smoking cessation pharmacotherapy, if clinically appropriate
- recommend an ‘integrated approach’ throughout treatment regarding nutrition, exercise and minimal or no alcohol consumption among other considerations
- communicate the benefits of continued engagement with primary care during treatment for managing comorbid disease, health promotion, care coordination and holistic care and supporting the family
- where appropriate, review fertility needs with the patient and refer for specialist fertility management (including fertility preservation, contraception, management during pregnancy and of future pregnancies)
- be open to and encourage discussion about the diagnosis, prognosis (if the patient or carer wishes to know) and survivorship and palliative care while clarifying the patient or carer’s preferences and needs, personal and cultural beliefs and expectations, and their ability to comprehend the communication
- encourage young adult patients to participate in advance care planning including considering appointing one or more substitute decision-makers, or a legal guardian, and completing an advance care directive to clearly document their treatment preferences (each state and territory has different terminology and legislation surrounding advance care directives and substitute decision-makers)
- discuss clinical trials (if available), explaining how this may differ from standard therapy and providing adequate information and time to enable an informed decision about participation (sites without open clinical trials may consider referring the patient to a site that does)
- refer 15–25-year-old patients to the jurisdiction’s Youth Cancer Service for psychosocial support
- offer referral to community support organisations such as Canteen, Camp Quality, Leukaemia Foundation, Redkite and other state-based NGOs; these frequently help support parents and siblings too.
Additionally, patients, family and carers should be provided with both verbal and written information on the following topics:
- management of fever and neutropenia
- side effects of treatment
- central line care
- caring for the child at home
- orientation to the hospital and overview of the healthcare team (key members)
- blood counts
- follow-up
Information specifically targeted to children with acute leukaemia immediately following diagnosis includes neutropenia precautions, medication adherence, chemotherapy side effects, bleeding precautions, managing procedures, nutrition and anaemia.
Verbal education to families and patients, where appropriate, should be paced throughout the initial admission and time allowed to process the diagnosis. Education should not be left to the moment of discharge, and families and patients, where appropriate, should be aware that education is ongoing and accessible throughout treatment.
Written and/or audio-visual educational information should be provided as part of the discharge plan following diagnosis and should also include information targeted to CAYA.
More information
For more information see the Victorian paediatric oncology care pathways: Providing optimal care for children and adolescents – acute leukaemia, central nervous system tumours and solid tumours (May 2019)
The lead clinician has these communication responsibilities:
- involving the general practitioner from the point of diagnosis
- ensuring regular and timely communication with the general practitioner about the diagnosis, treatment plan and recommendations from MDMs and inviting them to participate in MDMs (consider using virtual mechanisms)
- supporting the role of general practice both during and after treatment
- discussing shared or team care arrangements with general practitioners or regional cancer specialists, or both, together with the patient.
More information
Refer to Principle 6 ‘Communication’ for communication skills training programs and resources.
