Haematological Malignancies 1 —
Training activity: 8

Details

Interpret and draft clinical reports for NGS for the diagnosis and treatment decisions of myeloid disorders

Type

Entrustable training activity (ETA)

Evidence requirements

Evidence the activity has been undertaken by the trainee repeatedly, consistently, and effectively over time, in a range of situations. This may include occasions where the trainee has not successfully achieved the outcome of the activity themselves. For example, because it was not appropriate to undertake the task in the circumstances or the trainees recognised their own limitations and sought help or advice to ensure the activity reached an appropriate conclusion. ​

Reflection at multiple timepoints on the trainee learning journey for this activity.

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

What does success look like?

• Identify what is expected of you in relation to interpreting complex NGS data and drafting reports for myeloid disorders (e.g., MDS, MPN overlap).
• Consider how the learning outcomes apply, specifically in relation to report preparation, interpreting somatic variants, and collaborating with relevant specialties.
• Discuss with your training officer to gain clarity of what is expected of you in relation to expectations for distinguishing true malignancy from clonal haematopoiesis of indeterminate potential (CHIP).

What is your prior experience of this activity?

• Think about your knowledge of NGS for myeloid malignancies, relevant genes, and the interpretation of clonal haematopoiesis.
• Consider possible challenges you might face during the activity, such as distinguishing somatic mutations indicative of malignancy from age-related clonal haematopoiesis (CHIP) or interpreting multiple concurrent sub clonal variants.
• Recognise the scope of your own practice for this activity i.e. know when you will need to seek advice or help, and from whom. You will need to seek advice from your Training Officer when required, for example when distinguishing CHIP from malignancy requires correlation with bone marrow morphology or when assessing the prognostic impact of specific co-mutations.
• Acknowledge how you feel about interpreting complex myeloid data that dictates prognosis and risk.

What do you anticipate you will learn from the experience?

• Consider the specific skills you want to develop, such as accurately interpreting variant calls and integrating genomic findings with clinical context specific to myeloid disorders.
• Identify the specific insights you hope to gain into the genomic landscape of myeloid malignancies, including the significance of specific mutations and clonal evolution.

What additional considerations do you need to make?

• Consult actions identified following previous experiences of NGS data interpretation.
• Identify important information you need to consider before embarking on the activity, such as the patient’s current clinical presentation and morphology data, which are critical for interpreting myeloid NGS results.

In action

Is anything unexpected occurring?

• Are you noticing anything surprising or different from what you anticipate whilst interpreting complex NGS data for myeloid disorders?
• Are you encountering situations such as:
  • A borderline allele frequency for a variant (e.g., DNMT3A) that suggests Clonal Haematopoiesis of Indeterminate Potential (CHIP)?
  • Unexpected NGS findings that point to a specific WHO or ICC classification e.g. NPM mutant AML ?
  • Difficulty interpreting multiple concurrent sub clonal variants?
  • Conflicting data between NGS findings and cytogenetics?

How are you reacting to the unexpected development?

• How is this impacting your actions? For example, are you responding to the situation appropriately? Are you adapting or changing your approach by immediately consulting the patient’s pathology report to correlate NGS with morphology?
• Consider the steps you are taking in the moment, such as integrating NGS findings with other data (e.g., cytogenetics) or immediately seeking expert advice to determine prognostic algorithms.
• How are you feeling in that moment? For instance, are you finding it difficult to distinguish malignancy from age-related changes? Is it affecting your confidence in translating findings into clinically actionable statements?

What is the conclusion or outcome?

• Identify how you are working within your scope of practice. For example, are you successfully integrating NGS and cytogenetic findings to inform diagnosis and treatment decisions? Or are you needing support because the interpretation of multiple sub clonal variants requires specialist input to determine prognostic impact?
• What are you learning as a result of the unexpected development? For example, are you gaining insight into the nuanced interpretation of allele frequency and its relevance for distinguishing CHIP from malignancy?

On action

What happened?

• Begin by summarising the key steps you took when interpreting the NGS data and drafting the clinical report for the myeloid disorder case(s).
• Consider specific events, actions, or interactions which felt important, such as identifying the specific genes or variants relevant to diagnosis, prognosis, or treatment decisions, or how the NGS results informed prognostic information.
• Include any ‘reflect-in-action’ moments where you had to adapt to the situation as it unfolded, for instance, immediately correlating low allele frequency variants (e.g., DNMT3A) with the patient’s age and morphology to distinguish malignancy from Clonal Haematopoiesis of Indeterminate Potential (CHIP).
• How did you feel during this experience, e.g., did you feel highly focused on allele frequencies and clinical context or challenged by the necessity of interpreting multiple concurrent sub clonal variants?

How has this experience contributed to your developing practice?

• Identify what learning you can take from this experience regarding NGS interpretation for myeloid disorders. What strengths did you demonstrate, e.g., ability to interpret age-related clonal haematopoiesis?
• What skills and/or knowledge gaps were evident, e.g., unfamiliarity with complex gene interactions determining prognosis in MDS?
• Compare this experience against previous engagement with similar activities – were any previously identified actions for development achieved? Has your practice improved in your understanding of using NGS for myeloid disorders and ability to interpret NGS variants and prognostic information?
• Identify any challenges you experienced, such as needing to seek advice or clarification on scope of practice regarding the required commentary on the prognostic risk score (e.g., IPSS-R and IPSS-M) in the report, and how you reacted to this.

What will you take from the experience moving forward?

• Identify the actions or ‘next steps’ you will now take to support the assimilation of what you have learnt, including from any feedback you have received, with regards to enhancing your NGS interpretation and reporting skills for myeloid disorders.
• What will you do differently next time you approach myeloid NGS interpretation, for instance, by proactively reviewing external prognostic scoring systems (e.g., IPSS-M) before interpreting the results to aid clinical correlation?
• Do you need to practise any aspect of the activity further, such as reviewing specific NGS variants and their clinical significance in myeloid malignancies or key knowledge outcomes related to distinguishing CHIP from malignancy?

Beyond action

Have you revisited the experiences?

• How have your subsequent experiences of interpreting and reporting complex NGS data for myeloid disorders since completing this specific training activity led you to revisit your initial approach or decisions during that activity? For example, how an instance where a subsequent MDS case required careful differentiation of disease-related mutations from Clonal Haematopoiesis of Indeterminate Potential (CHIP) forced you to re-evaluate the diligence of your allele frequency analysis and clinical correlation process you applied during your first attempt at this training activity?
• Considering what you understand about CHIP distinction, sub clonal variant interpretation, and prognostic scoring systems now, were the actions or considerations you identified after your initial reflection on this training activity sufficient? How have you since implemented or adapted improvements in your NGS interpretation methodology based on further learning and experiences? For example, how you proactively reviewed and integrated the prognostic criteria based on mutation presence (e.g., TP53 status) to inform risk in myeloid reports?
• Has discussing ambiguous CHIP vs. MDS cases or the impact of inaccurate sub clonal variant reporting on patient prognosis with colleagues, peers, or supervisors changed how you now view your initial experience in this training activity? For example, how professional storytelling with a senior colleague about a report that initially missed a critical sub clonal SRSF2 mutation refined your understanding of the critical nature of low allele frequency variant reporting in myeloid disorders?

How have these experiences impacted upon current practice?

• How has the learning from this initial training activity, in combination with subsequent experiences, contributed to your overall confidence and competence in myeloid NGS interpretation and reporting, particularly in preparing for assessments like CBDs? For example, how your accumulated ability in distinguishing actionable variants from background CHIP now enables you to confidently discuss prognostic classification during a CBD assessment?
• How has reflecting back on this specific training activity, combined with everything you’ve learned since, shaped your current approach to myeloid NGS reporting? How does this evolved understanding help you identify when something is beyond your scope of practice or requires escalation? For example, how your evolved approach means you now routinely seek advice immediately when NGS reveals a complex pattern of clonal evolution requiring detailed risk stratification commentary?
• Looking holistically at your training journey, how has this initial NGS reporting experience, revisited with your current perspective, contributed to your development in analysing and interpreting complex somatic variants and ensuring reports are clinically relevant for prognostic scoring?

Relevant learning outcomes

#	Outcome
# 4	Outcome Analyse, interpret and prepare interpretive reports for common haematological malignancies, including results for somatic variants, kinase domain mutations, measurable residual disease and post-transplant monitoring.
# 5	Outcome Interpret the associated IQC and EQA of the laboratory tests for investigation of haematological malignancies.
# 6	Outcome Practice with the relevant specialities for the diagnosis, monitoring and management of haematological malignancies.