10. Haematology II: Leukaemia & Lymphomas Flashcards
LOs
1.
what is leukaemia?
2.
what does it result in?
1
- Malignant neoplasms of haemopoietic stem cells
2
- Result in diffuse replacement of bone marrow and normal blood precursor cells by neoplastic cells
- Bone marrow failure leads to anaemia, neutropenia and thrombocytopenia
- Leukaemic cells spill over into blood and may infiltrate organs
how leukaemias classified?
classified based on cell type involved and its maturity:
- cell type
- maturity
what are the classes of leukaemia split into?
- Cell type
~ Myeloid cell line
~ Lymphoid cell line - Maturity
~ Acute > 50% myeloblasts or lymphoblasts in
bone marrow at clinical presentation
~ Chronic cells are more differentiated
myeloid cell line?
lymphoid cell line?
how are leukaemias diagnosed?
- BLOOD FILM
~ Suggests diagnosis
~ Due to presence of Abnormal WCC (white cells)
~ Presence of blasts - BONE MARROW
~ usually confirms diagnosis
~ Hypercellular
~ Numerous blast cells
what can blood film test and bone marrow aspirate tell us?
- Important prognostic indicators
~ Leukaemia type
~ Cell phenotype
~ Chromosomal abnormalities
aetiology of leukaemias
- Ionizing radiation
- Chemicals including benzene and alkylating agents
- Viruses (e.g.. HTLV – human T-cell leukaemic virus)
- Genetic factors (e.g.. Down’s syndrome)
- Acquired haematological disorders such as aplastic anaemia
what can bone marrow infiltration result in?
- can result in failure of other important cell lines
- this can result in:
~ anaemias
~ impacted immune system
~ impact coagulation and platelet function - these over all can thus then cause:
- pallor
- malaise
- fever + infection
- bleeding
- bruising / petechiae
- why may tissue infiltration occur?
- what can tissue infiltration result in/ cause?
1
- neoplastic cells may spill out of the bone marrow into the peripheral blood
- this can lead to infiltration of other organs
2
- Lymphadenopathy
- Hepatosplenomegaly
- Central nervous system
- Bone and joint pain (ALL)
- Testicular swelling (ALL)
- Gingival hypertrophy (AML) (important for dentistry)
names of acute and chronic leukaemias?
ACUTE (immature cell lines) (could be myeloid or lymphoid depending on type of cell)
- Myeloid (AML = acute myeloid leukaemia)
- Lymphoid (ALL = acute lymphoblastic leukaemia)
CHRONIC (typically more mature cells)
- Myeloid (CML = chronic myeloid leukaemia)
- Lymphoid (CLL = chronic lymphocytic leukaemia)
ALL - Acute lymphoblastic leukaemia
1
age of peak incidence
2
management
1
Children - peak incidence 4-5 years
2
- Remission induced with non-myelosuppressive chemotherapy
- 2-12 years >60% cure rate with chemotherapy
- Adults 20% cure rate
- Combination chemotherapy to induce remission
- CNS treatment performed prophylactically
- Maintenance therapy for up to 2 years increases disease-free survival
AML - Acute myeloid leukaemia
1
incidence at what age most likely?
2
management?
1
- Most common leukaemia in adults
- Increasing incidence with age
- X400 higher incidence in children with Down’s syndrome
2 Management
- >80% cure rate with intensive chemotherapy in young patients
- 15% resistant disease
- 4-5 courses of intensive chemotherapy (each lasting 5-10 days)
- No maintenance therapy
- Autologous and allogenic stem cell transplant (if fail chemotherapy)
CLL - Chronic lymphocytic leukaemia
1
common age?
Male : female incidence?
2
clinical features
1
- 25 % of all leukaemias
- Elderly (>60years)
- M:F ~ 2:1
2
- Constitutional symptoms
- Lymphadenopathy
- Splenomegaly
- Recurrent infections
- Abnormal FBC (anaemia, thrombocytopenia)
- Hypogammaglobinaemia
CLL - Chronic lymphocytic leukaemia
treatment?
- Asymptomatic patients do not require treatment (monitoring only)
- 30% of patients with early stage disease die of unrelated cause
- Chemotherapy typically effective
- Median survival 10-12 years
- Mortality usually due to infection or bone marrow failure
- Bone marrow transplantation occasionally attempted in younger patients with poor prognostic disease
CML - Chronic myeloid leukaemia
1
median onset age?
more common in M or F?
2
clinical features
1
- < 20% of all leukaemias
- Median age of onset 40-50 years
- Slight male predominance
- Chronic phase for years – no treatment
- Accelerated phase and then blast crisis - require treatment
2
- Bone marrow failure (anaemia, thrombocytopenia)
- Hypermetabolism (anorexia, weight loss, night sweats)
- Splenomegaly
- Leucostasis (visual disturbances, priapism)
- Hyperuricaemia (gout, renal failure)
CML - Chronic myeloid leukaemia
what is philadelphia chromosome?
what did it lead to?
- > 90% have ‘Philadelphia chromosome’
- ‘Balanced translocation’ between 9 and 22
- Resultant oncogene with tyrosine kinase activity
- Lead to first targeted therapy for leukaemia – imatinib (tyrosine kinase inhibitor)
classifications of lymphomas
- Hodgkin’s disease
- non-Hodgkin’s disease
features of Hodgkin’s disease lymphomas
- Nodal (involves lymph nodes)
- Contiguous (applies to serial lymph nodes)
- Good outcome
- Not associated with immunodeficiency
features of non-Hodgkin’s disease lymphomas?
- Extranodal
- Non-contiguous
- Variable outcome
- Associated with immunodeficiency
Hodgkin’s disease lymphomas
1
peak incidence age?
2
annual incidence (M + F)?
3
aetiology?
1
- Peak incidence in third decade
- Possible bimodal age with second peak adults> 60yrs)
2
Annual incidence
Male - 3 per 100,000
Female - 1.8 per 100,000
3
Aetiology unknown
EBV (infectious mononucleosis) suggested
Hodgkin’s disease lymphomas clinical features?
- Lymphadenopathy
(particularly cervical lymph chain)
~ Cervical and contiguous
~ Painless, non-tender, rubbery
~ Alcohol induced pain - Constitutional ‘B’ symptoms
~ Fever
~ Night sweats
~ Weight loss >10% in 6 month period - Anorexia and fatigue
- Pruritus and erythematous rash
- Mediastinal lymph node involvement
~ Hilar lymphadenopathy
~ Bronchial compression
~ SVC obstruction - Hepatosplenomegaly
how is Hodgkin’s disease lymphomas staged?
- staged based on Ann Arbor system
- I Single LN region
- II Two LN regions
- III Groups on both sides of
diaphragm - IV Widespread disease outside
lymphatic tissues - B symptoms
~ Weight loss
~ Night sweats
~ Unexplained fever
Hodgkin’s disease lymphomas management?
1
investigations
2
treatment
1
- FBC (full blood count) (normochromic normocytic anaemia)
- Elevated ESR (inflam markers)
- LFTs / U&Es / bone profile / LDH (liver+renal blood test)
- CXR / CT
- Lymph node biopsy (Reed-Sternberg cells presence?)
- Rarely bone marrow examination
2
treatment (curative)
- Early stage disease (IA/IIA)
~ Chemotherapy + radiotherapy - Advanced stage disease
~ Combination chemotherapy
~ Complete remission 60-90% - Prognosis is relative to stage of disease
- 90% Stage I (5 year survival)
- B symptoms presence worsens prognosis
Non-Hodgkin’s disease lymphomas
1
presentation?
2
incidence in pop?
3
age?
4
male or female more common?
1
- Varied presentation
- Heterogeneous group of disorders
2
Annual incidence 11 per 100,000
3
Slight male preponderance
4
Increases with age - rare < 40 years
aetiology of Non-Hodgkin’s disease lymphomas
- Immunodeficiency (acquired + congenital)
- Infections
- Ionizing radiation
- Carcinogenic chemicals
- Inherited disorders affecting DNA damage and repair
Non-Hodgkin’s disease lymphomas
clinical features
- Generalised lymphadenopathy
- Oropharyngeal involvement (Waldeyer’s ring)
- Bone marrow infiltration
~ Anaemia
~ Recurrent infections
~ Haemorrhage
Non-Hodgkin’s disease lymphomas
management?
- based on grade of disease
- LOW GRADE DISEASE
~ May be asymptomatic requiring no treatment
~ Intermittent oral chemotherapy - HIGH GRADE DISEASE
~ Combination chemotherapy ~ 30% cure
Multiple myeloma
1
what/ cause?
2
age range?
1
- Arises from malignant transformation of terminally differentiated B cell (plasma cell)
- Monoclonal expansion results in secretion monoclonal Ig or light chains (paraproteins)
- Typically long asymptomatic phase that can last for many years (MGUS – monoclonal gammopathy of undetermined significance)
2
- Most patients are between 40-80yrs old
Multiple myeloma
clinical features?
- Bone destruction
~ Myeloma cells stimulate osteoclasts causing
bone destruction and classic well-defined
osteolytic lesions and raised serum Ca2+ - Bone marrow failure
~ Marrow infiltration leads to anaemia,
thrombocytopenia and neutropenia and
recurrent infections - Renal failure
~ Due to deposition and accumulation of
paraproteins - Hyperviscosity syndrome
~ Headache and dizziness - Amyloidosis (development of abnormal protein cells - deposit in various tissues + infiltrate organs around body)
Multiple myeloma
1
investigations?
2
Management?
1
- FBC = bone marrow failure
- Raised ESR and Ca2+
- U&Es demonstrate renal damage
- Protein electrophoresis demonstrates monoclonal paraprotein
- Bence-Jones proteins in urine
2
- Only if evidence of organ damage
- Chemotherapy if evidence bone marrow failure or bone lesions
- Most patients respond however relapse if common
- Radiotherapy useful if bone pain
DENTAL RELEVANCE OF LEUKAEMIAS + LYMPHOMAS
- oral manifestations may result as secondary to the underlying process
- Secondary
~ Manifestations anaemia
~ Haemorrhagic tendency
~ Increased susceptibility to infection
~ Neutropenic ulceration
DENTAL RELEVANCE OF LEUKAEMIAS + LYMPHOMAS
Leukaemic infiltration?
- in some patients leukaemic cells spill out of bone marrow and deposit in various tissues
- this can include gingiva + bone
- Typically gingival however also bone infiltration
- 3.6% of dentate patients
-c18.5% in AML
- Friable and haemorrhagic
- Increased tooth mobility
DENTAL RELEVANCE OF LEUKAEMIAS + LYMPHOMAS
1
Intraoral lymphomas
2
management
- can develop intraorally
- Typically non-Hodgkin lymphomas (NHL) associated with HIV
- Most commonly affected sites are the fauces and gingivae
- Typically present as rapidly enlarging masses with bone destruction
2
- Chemotherapy
- Radiotherapy
DENTAL RELEVANCE OF LEUKAEMIAS + LYMPHOMAS
treatment of conditions can lead to oral complications
- Mouth care can be overlooked
- Oral complications
~ 90% of children
~ 50% of adults - Mucositis (damage to lining of mouth)
- Infection including candidosis and viral (HSV, VZV)
- Mucosal bleeding
- Xerostomia
DENTAL RELEVANCE OF LEUKAEMIAS + LYMPHOMAS
Mucositis
1
associated with what radiotherapy + chemotherapy agents
2
- onset/ how to stope?
- what is severity of mucositis related to?
1
- Associated with number of chemotherapy agents and radiotherapy
- 5-fluorouracil
- Methotrexate
- Bleomycin
- Daunorubicin
- Doxorubicin
2-
- Rapid onset and good recovery following cessation of chemotherapy
- Severity related to white cell depletion
- Increases risk of infection and may limit chemotherapy
DENTAL RELEVANCE
Radiotherapy common complications
- Mucositis
- Xerostomia
- Caries
- Candidosis
- Loss of taste
- Trismus
- Osteoradionecrosis and osteomyelitis
DENTAL RELEVANCE
1
oral care before radiotherapy
2
oral care following radiotherapy
1
- Assessment and treatment dental disease
- Meticulous oral hygiene and preventative care
- Minimum 2 week interval between extracting and commencing radiotherapy (no bone should be left exposed)
2
- Reinforcement of oral hygiene and preventive dental care
- Palliation for dry mouth
- Dental extractions
~ Minimal trauma with careful suturing
~ Prophylactic antibiotics
Haematopoietic stem cell transplant (HSCT)
Graft vs host disease
- Serious complication of allogenic HSCT
- Divided into acute and chronic GvHD based on clinical findings
- Oral cGvHD most of most common presentations
- Characterised by lichenoid inflammation - particularly on the tongue and buccal mucosa
- Salivary glands may also be involved with hypofunction (major glands) and recurrent mucoceles (minor glands)
MANAGEMENT
- Lichenoid treated with topical steroids
- Xerostomia treated in same way as any other cause
