Lymphoid Malignancy Flashcards
what can cancers of lymphoid origin present with?
enlarged lymph nodes or extranodal involvelment or bone marrow involvement
systemic symptoms of lymphoid cancers
weight loss > 10% in 6 months swinging fever drenching night sweats pruritis fatigue
what is the only way to classify lymphomas and leukaemias?
bone marrow of lymph node biopsy
list the lymphoproliferative disorders from most to least common
Non-hodgkin lymphoma high grade Non-hodgkin lymphoma low grade chronic lymphocytic leukaemia hodgkin lymphoma acute lymphoblastic leukemia
what cells are affected in ALL?
lymphoblasts
what percentage of lymphoblasts must be present in bone marrow to make a diagnosis of ALL?
> 20%
75% of cases of ALL occur in at what age?
<6
75-90% of cases of ALL are of what lineage?
b cell
presentation of ALL
2-3 week Hx of bone marrow failure or bone/joint pain
sometimes infection
survival rate for <10s in ALL without bone marrow transplant?
90%
standard treatment of ALL
induction combination chemo
consolidation therapy
CNS directed treatment
maintenance for 18 months
what is the purpose of induction treatment in ALL?
to achieve remission
if high risk of recurrence what can you give to ALL patients?
stem cell transplantation
are adults or children more likely to relapse with ALL?
adults
name the newer treatments for ALL
Bispecific T cell engagers (BiTe molecules) - blinatumumab
CAR (chimeric antigen receptor T cells)
describe treatment with CAR for ALL
§ Patient/healthy 3rd party T cells harvested
§ Transfected to express a specific T cell receptor expressed on leukaemia cells
(CD19)
§ Expanded in vitro
§ Re-infused into patient
§ Long term survival
what can T-cell immunotherapy reult in?
cytokine release syndrome
neurotoxicity
what is cytokine release syndrome?
fever
hypotension
dyspneoa
CAR T cell effect correlated to presence of CRS
symptoms of neurotoxicity as a result of T cell immunotherapy in ALL
confusion with normal conscious level
sizure, headache, focal neurology, coma
poor prognostic factors for ALL
• Increasing age • Increased white cell count • Immunophenotyped (more primitive forms) • Cytogenetics/molecular genetics o T(9,22); t(4,11) • Slow/poor response to treatment
adult outcome of ALL
Complete remission rate 78-91%
o Leukaemia free survival at 5 yr. 30-35%
child outcome of ALL
o 5 yr. overall survival 90%
o Poor risk patients (slow response to induction or Philadelphia +ve) 5 yr. OS 45%
CLL lymphocytes in blood
> 5x10^9/l
CLL lymphocytes in bone marrow
> 30%
characteristic immunophenotyping b cell markers in CLL
CD19,20,23
CD5+
M:F CLL
2:1
presentation of CLL
often asymptomatic
frequent findings in CLL
bone marrow failure (anaemia, thrombocytopenia)
lymphadenopathy
splenomegaly
fever and sweats
less common findngs in CLL
hepatomegaly
infections
weight loss
associated findings in CLL
immune paresis
haemolytic anaemia
describe stage A of CLL
<3 lymph node areas
same survival as age matched controls
describe stage B of CLL
> = 3 lymph node areas
8 years survival
describe stage C of CLL
stage B + anaemia or thrombocytopenia
6 years survival
what is the name of the classification system used for CLL?
Binet
indications for treatment in CLL
- Progressive bone marrow failure
- Massive lymphadenopathy
- Progressive splenomegaly
- Lymphocyte doubling time < 6 months or >50% increase over 2 months
- Systemic symptoms
- Autoimmune cytopenias
treatment of CLL
• Cytotoxic chemotherapy e.g. fludarabine, bendamustine
• Monoclonal antibodies e.g. rituximab, obinutuzamab
• Novel agents
o Bruton tyrosine kinase inhibitor e.g. ibrutinib – well tolerated and effective
o PI3K inhibitors e.g. idelalisib
o BCL-2 inhibitor e.g. venetoclax
poor prognostic factors of CLL
• Advanced disease (Binet stage B or C)
• Atypical lymphocyte morphology
• Rapid lymphocyte doubling time (< 12 months)
• CD 38+ expression
• Loss/mutation p53; del 11q23 (ATM gene)
o P53 is poor prognostic factor in almost every cancer cell, it is a tumour suppressor
gene
• Unmutated IgBH gene status
presentation of lymphoma
lymphadenopathy/hepatosplenomegaly
extranodal disease
B symptoms
bone marrow involvement
how is non-hodgkin lymphoma classified?
Lineage (B/T cell)
grade of disease
histological features
what lineafe are the majority of non-hodgkins lymphomas?
B cell
describe low grade non-hodgkin lymphoma
indolent, often asymptomatic
responds to chemo but incurable
describe high grade non-hodgkin lymphoma
aggressive, fast growing
require combination chemotherapy
can be cured
what is the commonest subtype of lymphoma?
diffuse large B-cell lymphoma
is diffuse large B-cell lymphoma high or low grade?
high
what is the 2nd commonest subtype of lymphoma?
follicular lymphoma
is follicular lymphomahigh or low grade?
low grade
treatment of diffuse large B cell lymphoma and follicular lymphoma
combination chemo - typically anti CD20 monoclonal antibody (rituximab) and chemo
what does a biopsy in hodgkin lymphoma show?
normal cells with a hodgkin cell in the middle
what percentage of lymphomas are hodgkin lymphoma ?
30%
describe the age distribution of hodgkin lymphoma
bimodal
15-35 and later in life
M:F hodgkin lymphoma
1.9:1
what is hodgkin lymphoma associated with?
EBV
familial
geographical clustering
treatment of hodgkin lymphoma
o Combination chemotherapy (ABVD)
o +/- radiotherapy
o Use of PET scan to assess response to treatment and to limit use of radiotherapy
