Haematology II: Leukaemias and Lymphomas Flashcards
What are leukaemias?
Malignant neoplasms of haemopoietic stem cells which result in diffuse replacement of bone marrow and normal blood precursor cells by neoplastic cells.
What does this bone marrow failure lead to?
Anaemia
neutropenia - low number of white blood cells called neutrophils in your blood.
thrombocytopenia - deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury.
Leukaemic cells can then spill over into blood & may infiltrate organs
How are leukaemias classified?
They’re classified on basis of cell type involved and its maturity i.e. for cell type:
-Myeloid cell line
-Lymphoid cell line
And for maturity:
-Acute leukaemia (>50% of cells present are myeloblasts or lymphoblasts in bone marrow at clinical presentation)
-Chronic leukaemia (cells are more differentiated)
What is the diagnosis of leukaemias based on?
Blood film
Diagnosis suggested due to abnormal WCC, as well as presence of immature blast cells which are not normally present in the peripheral blood,
How is a leukaemia diagnosis confirmed?
Bone marrow aspirate (if it’s hypercellular and there are numerous blast cells, this is considered an indicator)
What important prognostic indicators can be ascertained from doing a blood film and bone marrow biopsy?
Leukaemia type
Cell phenotype
Chromosomal abnormalities
What are the possible causes of leukaemia?
Ionising 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 does the neoplastic cell infiltration in the bone marrow result in?
Anaemia
pallor
malaise - a general feeling of discomfort, illness, or unease whose exact cause is difficult to identify.
fever & infections
bleeding
bruising/petechiae
What can tissue infiltration of the neoplastic cells look like?
slide 13
Who does acute lymphoblastic leukaemias (ALL) typically affect?
Children: peak incidence of 4-5 years old
How is ALL managed?
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
Who is typically affected by acute myeloid leukaemia (AML)?
It’s the most common leukaemia in adults but the incidence increases with age
There are also genetic factors at play: children with Down’s syndrome are 400x more likely to develop AML than the general population
How is AML managed?
> 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
How common is chronic lymphocytic leukaemia (CLL) and who is typically affected?
Accounts for 25% of all leukaemias and typically more prevalent in elderly population (>60yrs) and tends to be more common in men than women, with a 2:1 ratio.
What are the clinical features of CLL?
-Constitutional symptoms
-Lymphadenopathy
-Splenomegaly
-Recurrent infections
-Abnormal FBC (anaemia, thrombocytopenia)
-Hypogammaglobinaemia
How is CLL treated?
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
How prevalent is chronic myeloid leukaemia (CML) and who is typically affected by it?
Accounts for <20% of all leukaemias
Median age of onset is 40-50yrs & there is a slight male predominance.
How is CML treated?
The initial chronic phase may last for years and needs no treatment and simple monitoring
It may develop into an accelerated phase before developing a blast crisis at which point treatment is initiated
What are the clinical features of CML?
-Bone marrow failure (anaemia, thrombocytopenia)
-Hypermetabolism (anorexia, weight loss, night sweats)
-Splenomegaly
-Leucostasis (visual disturbances, priapism)
-Hyperuricaemia (gout, renal failure)
What is the Philadelphia chromosome and how many people have it?
Over 90% of CML patients have the Philadelphia chromosome and it is a ‘balanced translocation between chromosome 9 and 22.
What is the importance of the Philadelphia chromosome?
The importance of it is the resultant oncogene which is associated with tyrosine kinase activity (an important enzyme within cellular activity)
The identification of this chromosome led to the first targeted therapy for leukaemia- imatinib (tyrosine kinase inhibitor)
How are lymphomas classified?
- Hodgkin’s disease:
-Nodal - cancer cells may spread to lymph nodes near the primarytumour.
-Contiguous - Lymphomas in which the lymph nodes with cancer are next to each other.
-Good outcome
-Not associated with immunodeficiency - Non-Hodgkin’s disease:
-Extranodal - lymphomatous infiltration of anatomic sites other than the lymph nodes
-Non-contiguous
-Variable outcome
-Associated with immunodeficiency
Describe the incidence of Hodgkin’s disease.
Peak incidence in the third decade
Annual incidence varies depending on gender: male- 3 per 100,000 whereas female was 1.8 per 100,000
There is a possible bimodal age with a second peak potentially developing in adults >60yrs
What is the aetiology of Hodgkin’s disease?
Unknown, although EBV (infectious mononucleosis) has been suggested.
What are the clinical features of Hodgkin’s disease?
slide 24
How is Hodgkin’s disease staged?
Ann Arbor system
How is Hodgkin’s disease managed?
Investigations:
-FBC (normochromic normocytic anaemia)
-Elevated ESR
-LFTs / U&Es / bone profile / LDH
-CXR / CT
-Lymph node biopsy (Reed-Sternberg cells)
-Rarely bone marrow examination
Treatment (curative)
-Early stage disease (IA/IIA) can be treated with 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 worse prognosis
Describe the presentation and incidence of non-Hodgkin’s disease.
Varied presentation because it’s essentially a heterogeneous group of disorders
Annual incidence of 11 per 100,000
Slightly male preponderance
Increases with age, it’s rare under the age of 40
Describe the aetiology of non-Hodgkin’s disease.
-Immunodeficiency
-Infections
-Ionising radiation
-Carcinogenic chemicals
-Inherited disorders affecting DNA damage and repair
What are the clinical features of non-Hodgkin’s disease?
-Generalised lymphadenopathy
-Oropharyngeal involvement (Waldeyer’s ring)
-Bone marrow infiltration
-Anaemia
-Recurrent infections
-Haemorrhage
How is non-Hodgkin’s disease managed?
Management is based on the grade of the disease:
Low grade disease- may be asymptomatic requiring no treatment or potentially intermittent oral chemotherapy only
High grade disease- requires combination chemotherapy with only 30% cure on average
How does a multiple myeloma arise?
From malignant transformation of terminally differentiated B cell (plasma cell) and this monoclonal expansion results in secretion of monoclonal Ig or light chains (paraproteins)
There is typically a long asymptomatic phase that can last for many years (MGUS- monoclonal gammopathy of undetermined significance)
What age group is typically affected by multiple myelomas?
40-80yr olds
What are the clinical features of multiple myeloma?
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
How is multiple myeloma managed?
Investigations
-FBC = bone marrow failure
-Raised ESR and Ca2+
-U&Es demonstrate renal damage
-Protein electrophoresis demonstrates monoclonal paraprotein
-Bence-Jones proteins in urine
Management
-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
What is the dental relevance of all of this?
Oral manifestations may result as secondary to the underlying process, including anaemias; haemorrhagic tendency; increased susceptibility to infection; as well as neutropenic ulceration.
How can leukaemic infiltration orally manifest?
-Typically gingival however also bone infiltration
-3.6% of dentate patients
-18.5% in AML
-Friable and haemorrhagic
-Increased tooth mobility
Can lymphomas develop intra-orally?
Yes, these are typically non-Hodgkin’s lymphomas associated with HIV and the most commonly affected sites are the fauces and gingivae
They typically present as rapidly enlarging masses with bone destruction
Managed with chemotherapy and radiotherapy
What kinds of oral complications can the treatments of these conditions result in?
Commonest complications
-Mucositis - sore and inflamed
-Infection including candidosis and viral (HSV, VZV)
-Mucosal bleeding
-Xerostomia
What is mucositis associated with?
A number of chemotherapy agents and radiotherapy:
-5-fluorouracil
-Methotrexate
-Bleomycin
-Daunorubicin
-Doxorubicin
Does mucositis go away quickly?
It has a rapid onset but good recovery following cessation of chemotherapy
The severity of it is related to white cell depletion
(It does increase the risk of infection and may limit chemotherapy)
What are the common oral complications of radiotherapy?
-Mucositis
-Xerostomia
-Caries
-Candidosis
-Loss of taste
-Trismus - spasm of the jaw muscles, causing the mouth to remain tightly closed, typically as a symptom of tetanus.
-Osteoradionecrosis and osteomyelitis
How should you consider the oral care of a patient before and after radiotherapy?
Before radiotherapy:
-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)
Following radiotherapy:
-Reinforcement of oral hygiene and preventive dental care
-Palliation for dry mouth
-Dental extractions
-Minimal trauma with careful suturing
-Prophylactic antibiotics
What is graft vs host disease (GvHD)?
Serious complication of allogenic haematopoietic stem cell transplant (can be divided into acute and chronic GvHD depending on findings).
What is the most common presentation of GvHD and how is it managed?
Oral chronic GvHD, 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
