Haematological Malignancies 1

Details

Title

Haematological Malignancies 1

Type

Specialist

Module code

S-CG-S2-2

Credits

10

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 myelodysplastic syndromes (MDS), 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 measurable residual disease and post-transplant monitoring.

Competencies

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 MDS on the basis of all the molecular investigations
• Interpret FISH analysis for a CML, AML, or MDS 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 MDS
• Inform another healthcare professional of a delay in results or a need for additional or confirmatory testing for CML, AML, MPN or MDS

Learning outcomes

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 myelodysplastic syndromes (MDS) , 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 myelodysplastic syndromes (MDS).
4. Summarise the natural history and clinical management of chronic myeloid leukaemia (CML), acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS).
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 measurable 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.
• The underlying pathogenesis of MPNS, MDS, and AML
• 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.
• 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.
• An understanding of age related clonal haematopoiesis with regard to the molecular diagnosis of myelodysplastic syndromes.
• Introduction to the classification of haematological malignancies according to the relevant guidelines e.g WHO, ICC
• Current laboratory pathways and international guidelines for diagnosis of myeloid malignancies (BSH, ELN, WHO).
• Characteristic features for the diagnosis of CML, AML and MDS.
• 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 MDS.
• 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 MDS.
• 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).

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.