Module information

Module details

Title
Haematological Malignancies 1
Type
Specialist
Module code
S-CG-S2
Credits
10
Phase
2
Requirement
Compulsory

Aim of this module

This module will provide the trainees with the knowledge and understanding of the role of genomic testing in the diagnosis, classification, monitoring and management of haematological malignancies.

This module will focus on patients with chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and acute lymphoblastic leukaemia (ALL), as exemplars. Trainees will develop the skills to recognise the sample diagnostic pathway, the relevant testing strategies, the urgency of testing and follow up testing, including minimal residual disease and post-transplant monitoring.

Work-based content

Training activities

# Learning outcome Training activity Type Action
# 1 Learning outcome 1 Training activities

Receive samples and referral information for a range of haematological malignancies

Type ETA Action View
# 2 Learning outcome 2,3,6 Training activities

Interpret haematological assays to inform testing strategies, to include:

  • CML
  • AML
  • MPN
  • ALL
Type ETA Action View
# 3 Learning outcome 2,3 Training activities

Select laboratory molecular assays for patients referred for haematological malignancies investigation, to include:

  • CML
  • AML
  • MPN
  • ALL
Type ETA Action View
# 4 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for appropriate assays for suspected myeloproliferative neoplasms, including:

  • PV
  • ET
  • MF
Type ETA Action View
# 5 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for the detection of MRD monitoring for two of the following:

  • BCR-ABL
  • PML-RARA
  • CBFB-MYH11
  • RUNX1-RUN1T1
  • IGH/TR
Type ETA Action View
# 6 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for the genetic analysis for the identification of sequence variants within the ABL1 tyrosine kinase domains for patients with sub-optimal response to CML treatment

Type DTA Action View
# 7 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for rapid testing for urgent treatment decisions for AML and/or ALL, to include:

  • FLT3
  • IDH1/2
Type ETA Action View
# 8 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for diagnosis and risk stratification of ALL, to include:

 

  • Gene fusion detection
  • Copy number assessment (ploidy and specific genes)
Type ETA Action View
# 9 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for the cytogenetic analysis of:

  • Triple neg MPN
  • AML
Type DTA Action View
# 10 Learning outcome 4,5,6 Training activities

Analyse, interpret and draft a clinical report for monitoring of patients after allogenic haematopoetic stem cell transplantation

Type DTA Action View
# 11 Learning outcome 4,6 Training activities

Assist with the preparation of cases to be discussed and reviewed in a multidisciplinary team meeting or GTAB meeting with other healthcare professionals

Type DTA Action View

Assessments

Complete 2 Case-Based Discussions

Complete 2 DOPS or OCEs

Direct Observation of Practical Skills Titles

  • Interpret RT-PCR for the detection of fusion genes
  • Risk stratify a patient with CML, AML, MPN or ALL on the basis of all the molecular investigations
  • Interpret FISH analysis for a CML, AML, or ALL case
  • Interpret a somatic variant in MPN and discuss the relevance for diagnosis
  • Analyse the results of post-transplant chimerism monitoring

Observed Clinical Event Titles

  • Advise another healthcare professional on the appropriate acceptance criteria for a sample for investigation for haematological malignancies
  • Notify another healthcare professional of authorised results for CML, AML, MPN or ALL
  • Inform another healthcare professional of a delay in results or a need for additional or confirmatory testing for CML, AML, MPN or ALL

Learning outcomes

# Learning outcome
1

Apply the appropriate sample acceptance criteria for investigation of haematological malignancies for a variety of sample types.

2

Select the relevant testing strategy for commonly referred haematological malignancies, including CML, AML, MPN and ALL.

3

Evaluate the urgency of testing for particular haematological malignancies to inform management decisions.

4

Analyse, interpret and prepare interpretive reports for common haematological malignancies, including results for somatic variants, kinase domain mutations, minimal residual disease and post-transplant monitoring.

5

Interpret the associated IQC and EQA of the laboratory tests for investigation of haematological malignancies.

6

Practice with the relevant specialities for the diagnosis, monitoring and management of haematological malignancies.

Clinical experiences

Clinical experiences help you to develop insight into your practice and a greater understanding of your specialty's impact on patient care. Clinical experiences should be included in your training plan and you may be asked to help organise your experiences. Reflections and observations from your experiences may help you to advance your practice and can be used to develop evidence to demonstrate your awareness and appreciation of your specialty.

Activities

  1. Observe flow cytometry and the work of specialist haematology to appreciate the diagnostic pathway.
  2. Observe laboratory procedures for the analysis of haematological malignancies, to include PCR, RNA based MRD, and FISH.
  3. Attend a morphology review meeting to appreciate the role of cancer genomics in the patient pathway.
  4. Attend a multidisciplinary team meeting where patient results are discussed and treatment plans devised to appreciate the role of cancer genomics in the patient pathway.
  5. Attend a bone marrow clinic and observe a sample being obtained to appreciate the patient experience.

Academic content (MSc in Clinical Science)

Important information

The academic parts of this module will be detailed and communicated to you by your university. Please contact them if you have questions regarding this module and its assessments. The module titles in your MSc may not be exactly identical to the work-based modules shown in the e-portfolio. Your modules will be aligned, however, to ensure that your academic and work-based learning are complimentary.

Learning outcomes

On successful completion of this module the trainee will be able to:

  1. Apply integrative knowledge of the pathogenesis of chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and acute lymphoblastic leukaemia (ALL), including the mechanism of activation of oncogenes through genomic variation.
  2. Classify haematological malignancies as defined by international guidelines.
  3. Determine the laboratory approaches used to diagnose chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and acute lymphoblastic leukaemia (ALL).
  4. Summarise the natural history and clinical management of chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and acute lymphoblastic leukaemia (ALL).
  5. Evaluate the use of targeted therapies in the treatment of patients.
  6. Critically appraise the role of molecular monitoring to assess response to therapy, detection of minimal residual disease, causes of drug resistance and choice of therapy.
  7. Examine the role of post-transplant monitoring to identify successful engraftment or impending graft rejection.

Indicative content

  • Haemtopoietic stem cells.
  • Signal transduction pathways in myeloid cells and in myeloid malignancies.
  • Role of transcription factors in myeloid cell development and leukaemia.
  • Role of epigenetic modifiers.
  • Oncogenes and tumour suppressor gene function.
  • Translocations giving rise to MYC deregulation through IG-MYC.
  • Translocation giving rise to BCR-ABL1 oncogene (Philadelphia chromosome).
  • Pathogenic variants within MPNs (including JAK2 p.V617F, CALR and MPL mutations).
  • Molecular consequences of dysregulation of signal transduction pathways in MPNs as a result of mutational processes.
  • The clonal nature of haematological malignancies and development of resistant clones during treatment.
  • Introduction to the classification of haematological malignancies according to the WHO guidelines.
  • Characteristic features for the diagnosis of CML, AML and ALL.
  • Characteristic features for the diagnosis of the MPNs (focusing on CML, PV, ET and PMF).
  • Introduction to less common myeloid disorders related to the MPNs:
    • Chronic neutrophilic leukaemia.
    • Mastocytosis
    • Atypical chronic myeloid leukaemia.
    • Other tyrosine kinase gene fusions (e.g. PDGFRA, PDGFRB, FGFR1, and PCM1-JAK2).
  • Characteristic morphology and and/or immunophenotype of CML, AML, MPN and ALL.
  • Appropriate immunohistochemistry and/or flow cytometry techniques approaches.
  • Use of FISH and G-banding techniques.
  • Appropriate molecular genetic techniques for the detection of pathogenetic variants.
  • Sensitivity and specificity of these techniques.
  • Role of next generation sequencing and approaches to assesses copy number variation.
  • Current approaches to the treatment of CML, AML, MPN and ALL.
  • Mechanism of action of targeted therapies relevant for these disorders.
  • Definitions of response in CML according to current guidelines (e.g. ELN guidelines).
  • Use of appropriate BCR-ABL1 quantification techniques for monitoring residual disease.
  • International guidelines for inter-laboratory comparison of BCR-ABL1 quantification techniques.
  • Mechanisms of resistance to first line therapy in CML:
    • Evaluation of BCR-ABL1 kinase domain mutation.
    • Choice of second and third line therapy.
  • Appropriate approaches for quantitative monitoring of other relevant mutations (e.g. JAK2 p.V617F).

Module assigned to

Specialties

Specialty code Specialty title Action
Specialty code SLS4-3-23 Specialty title Cancer Genomics [2023] Action View
Specialty code SLS4-3-22 Specialty title Cancer Genomics [2022] Action View
Specialty code SLS4-3-24 Specialty title Cancer Genomics [2024] Action View