Haematological Malignancies 2

Module details

Title

Haematological Malignancies 2

Type

Specialist

Module code

SLS431

Credits

15

Requirement

Compulsory

Aim of this module

This module provides trainees with an in-depth knowledge of the diagnosis, prognosis and molecular monitoring of patients with a range of complex haematological malignancies. It builds on the concepts and approaches identified in the haematological malignancies 1 module by investigating more complex and heterogeneous haematological neoplasms including myeloid (AML, MDS) and lymphoid malignancies (CLL, large B cell lymphomas). Trainees will appreciate the importance of the role of molecular genetics approaches for the correct classification of heterogeneous disorders such as AML and Diffuse large B-cell lymphoma (DLBCL). The trainee will acquire the skills required to diagnose and monitor patients with AML, MDS and certain lymphoid malignancies. These skills will also be applicable for other haematological malignancies such as acute lymphoblastic leukaemia, myeloma and less common lymphoid malignancies. At the end of this module the trainee will be able to understand and appreciate the interaction between the laboratory and the clinic for the management of these disorders.

Competencies

#	Learning outcome	Competency	Action
# 1	Learning outcome 1,2,3	Competency Receive samples and decide on the appropriate diagnostic pathway for patients with a suspected diagnosis of the following conditions :  AML MDS CLL Large B cell lymphoma	Action View
# 2	Learning outcome 3,5	Competency Assist with the preparation of samples for analysis, selecting the correct sample processing pathway(s) : AML MDS CLL Large B cell lymphoma	Action View
# 3	Learning outcome 3,7	Competency Analyse samples for clinically significant gene fusions	Action View
# 4	Learning outcome 3,7	Competency Analyse samples for genomic rearrangements and or copy number variation (CNV) using standard laboratory methodology for patients referred at diagnosis	Action View
# 5	Learning outcome 3,7	Competency Perform the appropriate genetic investigations for patients referred with CLL	Action View
# 6	Learning outcome 3,5,7	Competency  Perform the appropriate genetic investigations for patients referred with large B-cell lymphoma	Action View
# 7	Learning outcome 5,7	Competency Analyse and interpret the result of Lymphoid clonality assessment (IG gene rearrangement) to aid the diagnosis of mature lymphoid malignancies	Action View
# 8	Learning outcome 3,4,5,7	Competency Analyse samples for a range of sequence variants to aid diagnosis and prognosis.	Action View
# 9	Learning outcome 6,7	Competency Prepare clinical reports for patients being investigated for a range of examples including : AML MDS CLL Large B cell lymphoma	Action View
# 10	Learning outcome 3,4	Competency Analyse and interpret appropriate genetic investigations for the monitoring of patients (eg AML)	Action View
# 11	Learning outcome 3,6	Competency Perform and interpret appropriate genetic investigations for the monitoring of patients after bone marrow transplantation	Action View
# 12	Learning outcome 1,7	Competency Assist with the preparation of cases to be discussed and reviewed in an MDT meeting with other healthcare professionals	Action View
# 13	Learning outcome 1	Competency Observe a clinic where a patient is being given results of laboratory tests that include genetic analysis. Reflect on this experience and present to colleagues	Action View

Assessments

You must complete:

• 3 case-based discussion(s)
• 3 of the following DOPS/ OCEs:

Perform and interpret FISH in a case of AML or MDS.	DOPS
Perform and interpret FISH in a case of CLL or large B cell lymphoma	DOPS
Interpret the results of a molecular genetic assay for the detection of acquired mutations.	DOPS
Use bioinformatics tools to analyse the results of a next generation sequencing	DOPS
Analyse the results of post transplant chimerism testing	DOPS
Prepare a report for a patient diagnosed with AML, MDS, CLL or large B cell lymphoma	DOPS
Carry out morphological assessment for a patient with AML, MDS, CLL or large B cell lymphoma	DOPS
Prepare a draft report for an inappropriate referral	DOPS
Discuss patient results with a healthcare professional telephone or in person	OCE
Discuss implications of receiving an unlabeled sample with a healthcare professional.	OCE
Discuss an inapparopriate referral with a healthcare professaional	OCE
Participate in an MDT meeting with other healthcare professionals	OCE

Learning outcomes

1. Interact with relevant disciplines and apply appropriate approaches for the diagnosis and treatment of heterogeneous myeloid and lymphoid malignancies
2. Recognise the main clinical features and morphological characteristics of AML, MDS, CLL and large B cell lymphomas
3. Apply the appropriate testing strategy for a range of complex myeloid malignancies including AML, MDS, considering the approach for subclassification and prognosis of disease
4. Implement the appropriate strategy for monitoring residual disease in patients with acute myeloid leukaemia
5. Implement the appropriate testing strategy for a range of lymphoid malignancies including CLL and large B cell lymphomas, including assessment of lymphoid clonality 
6. Appreciate the role of stem cell transplantation and monitor the presence of donor material by ‘chimerism analysis’
7. Interpret and report on the relevant laboratory procedures for the diagnosis of a range of myeloid and lymphoid malignancies

Learning outcomes

1. Describe the underlying pathogenesis of myeloid malignancies and germinal centre B cell malignancies
2. Classify heterogeneous myeloid and lymphoid malignancies using international standards eg WHO
3. Understand the importance of molecular genetic analysis for sub-classification of disorders
4. Determine the laboratory approaches for the diagnosis, classification and prognosis of a range of myeloid and mature lymphoid malignancies
5. Summarise the approaches taken to treat a range of haematological malignancies (including myeloid and lymphoid disorders and the use of stem cell transplantation and clinical trials
6. Evaluate the methods available for monitoring of residual disease including molecular genetic approaches and multi-parametric flow cytometry selecting the most appropriate technique for each disorder

Indicative content

Pathogenesis of haematological malignancies

• 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 spliceosomes in myelodysplastic syndromes
• Role of epigenetic modifiers
• Oncogenes and tumour suppressor gene function including TP53 Mechanism of generation of oncogenes eg translocation
• The clonal nature of haematological malignancies and development of resistant clones during treatment

Classification of haematological malignancies (WHO) and molecular genetic analysis

• Classification of myeloid malignancies according to the WHO Classification of mature lymphoid malignancies according to the WHO Integration of a multidisciplinary approach for correct classification
• Classification of disorders according to molecular genetic investigations – increasing role of molecular genetic and cytogenetic analysis, for example :
  • AML – NPM1; CEBPA; RUNX1; fusion genes MDS – SF3B1; Karyotype analysis
  • High grade B cell lymphoma – MYC, BCL2, BCL6
• The importance of molecular genetic and cytogenetic data to provide prognostic information that would influence treatment decisions
• An understanding of age related clonal haematopoiesis with regard to the molecular diagnosis of myelodysplastic syndrome

 Laboratory approaches for the diagnosis and prognostic stratification of a range of haematological malignancies

• Current laboratory pathways and international guidelines for diagnosis of myeloid and lymphoid malignancies (BCSH, ELN, WHO)
• Characteristic morphology and immunophenotype of AML, MDS, CLL and large B cell lymphomas Flow cytometry techniques and approaches
• Immunohistochemistry techniques and approaches Use of FISH and G-banding techniques
• DNA and RNA extraction (including FFPE and fresh material)
• A range of single gene mutation assessment procedures (eg Sanger sequencing, allele specific PCR, pyrosequencing, high resolution melt analysis, fragment analysis, droplet PCR and others)
• RT-PCR for fusion transcripts
• Lymphoid clonality (IG gene rearrangement) approaches to aid the diagnosis of lymphoid malignancies Sensitivity and specificity of these techniques
• Role of next generation sequencing for multi-gene analysis including both DNA and RNA approaches
• Role of array CGH
• Use of bioinformatic tools to analyse data including international resources (eg COSMIC) Interaction of multiple gene abnormalities and into prognostic algorithms

 Treatment of haematological malignancies

• Current approaches to treatment of haematological malignancies, including chemotherapy, immunotherapy, targeted therapy and stem cell transplant
• Importance of clinical trials
• Importance of and procedures for monitoring residual disease during treatment

Activities

• Attend multidisciplinary team meetings in myeloid and lymphoid malignancies at which the results of the molecular investigations are discussed, along with other laboratory and clinical information Reflect on the impact of the laboratory investigations on patient treatment and management
• Attend ‘leukemia’ and/or ‘lymphoma’ clinics and review the work of the clinics and interaction with other disciplines
• Identify the main clinical and haematological symptoms associated with myeloid malignancies, CLL and large B cell lymphomas
• Attend a follow up appointment and reflect on the different types of treatment available for patients with myeloid malignancies, CLL or large B cell lymphomas
• Visit a clinical trials unit and discuss the importance of trials in the development of new treatments for patients Observe and reflect on the techniques used for flow cytometry assessment of acute myeloid leukaemia and CLL
• Observe the preparation and analysis of G-banded chromosomes in the relevant disorders Reflect on the clinically significant chromosome rearrangements that are commonly detected