Leukaemia & Lymphoma Flashcards
what 2 groups do blood stem cell differentiate into?
- myeloid
- lymphoid
when can a haematological cell line turn neoplastic?
at a number of stages
earlier in the cell line this occurs the more potentially aggressive the malignancy
DNA mutation - translocation
Part of DNA strand artificially added on to the wrong DNA chain
what can be the result of incorrect protein synthesis?
- clonal proliferation
- cancer cells (Uncontrolled proliferation; Loss of apoptosis; Loss of normal functions/products)
what is a subsequent issue of harder to kill off cell lines?
tumours reappearing later
acute occurs….
rapid, now
symptoms in 6 months
chronic occurs…
slow onset
can take 5, 10, 20 years to show
name for acute lymphoid disease
acute lymphoblastic leukaemia
- severe illness right now
chronic lymphocytic leukaemia
chronic lymphoid disease
- Chronic white cell enlargement -; no symptoms
- Will switch to acute - will kill - all bone marrow does is make cancer cells not any other vital blood cells
multiple myeloma
chronic lymphoid disease
- chronic malignancy of plasma cells - dissolve bones, sits in them and hollows them out
name for acute myeloid disease
acute myeloid lymphoma
chronic myeloid leukaemia
chronic myeloid disease
Myeloproliferative disorders
Thromobocythemia
- Over producing not quite normal platelets
- Lead to change
- Grumbling along and change in mutation in cell to show change
what does Lymphocytic, lymphoblastic or myeloid describe
the point in the cell lines or cell type at fault
- when the mutation occurs
what does acute and chronic denote
clinical behaviour
what is a blast
immature cell
lymphocytic
looks like cell line they will be
lymphoblastic
differentiation so far up cell line can’t tell what final cell will
leukaemia describes
a group of cancers of the bone marrow which prevent normal manufacture of the blood and therefore result in:
- anaemia (RBC)
- infection/neutropenia (WBC)
- bleeding/thrombocytopenia (platelets)
why is limited bone marrow space a factor o remember?
Can only produce so many cells per day, If 90% leukemic - not enough left over for healthy cells
- Symptoms relate to shortages of normal cell types
- Not making as so busy making these cells
pathogenesis of leukaemia and lymphoma
- Clonal proliferation
- Replacement of marrow
- Increasing marginalisation of productive normal marrow (not enough bone marrow to make marrow needed to survive)
Marrow failure
Organ infiltration
6 ways to clinically present with leukaemia or lymphoma
Anaemia
- Carry O2
Neutropenia
- infection
Thrombocytopenia
- Problem with bleeding
Lymphadenopathy - neck lumps
- Migration of extra WCC into tissues
- Too many rapidly occupy bone marrow - spill out into outside world
Splenomegaly/Hepatomegaly - swollen abdomen
- Accumulating cells so increase in size
Bone pain - especially in children
- Marrow is trying to expand in closed cavity itself
symptoms of anaemia
- breathlessness
- tiredness
- easily fatigued
- chest pain/angina
signs of anaemia
- pallor
- signs of cardiac failure (ankle swelling, breathlessness)
- nail changes e.g. brittle nails, koilonychia
what are potential portals of entry for infections>
- Mouth
- Throat - tonsillitis, pharyngitis
- Chest - bronchitis, pneumonia
- Skin - impetigo, cellulitis
- Perianal - thrush, abscesses
what can occur after an infection seems to to be resolved?
reactivation of latent infection
i. e. TB never really get rid off
- Infections stay in the body and wait for chance to become active again
what can happen to a leukaemia patient with an infection?
Increased severity, frequency and can rapidly lead to systemic infection
- E.g. May present with oral candida; Then progress to pneumonia; Then septicaemia
- As immune system is decreasing
symptoms of neutropenia
- recurrent infection
- unusual severity of infection e.g. no immune response to contain it
signs of neutropenia
- Unusual patterns of infection and rapid spread (Typically wouldn’t cause healthy people an issue usually)
- Will respond to treatment but recur
- Signs of systemic involvement - fever, rigors, chills
symptoms of bleeding (thrombocytopenia)
- Bruises easily or spontaneously
- Minor cuts fail to clot
- Gingival bleeding or nose bleeds
- Menorrhagia
signs of bleeding (thrombocytopenia)
- Bruising
- Petechiae
- BOP
- Bleeding/bruising following procedures (E.g. after tooth brushing)
Petechiae
small red or purple spot caused by bleeding into the skin.
when does acute lymphoblastic leukaemia occur?
peak at 4, but does occur in adults
cases of acute lymphoblastic leukaemia
25 per 1,000,000 per year
time scale and clinical process of acute lymphoblastic leukaemia
- develops over days or weeks
- catabolic state leads to fever, sweats, malaise (non-specific collection of symptoms)
what are common clinical signs of acute lymphoblastic leukaemia?
- lymphadenopathy
- tissue infiltration
who has the best prognosis for acute lymphoblastic leukaemia?
younger patients and females
- Girls 2-12 years do best
- expectation you will survive initial treatment for ALL
>80% of children are cured
cases of acute myeloid leukaemia
25 cases per million per year
age affected by acute myeloid leukaemia
more common in elderly, but can affect any age
clinical presentation of acute myeloid leukaemia
similar clinical signs as ALL
catabolic state leads to fever, sweats, malaise (non-specific collection of symptoms)
- lymphadenopathy
- tissue infiltration
prognosis of acute myeloid leukaemia
- 30-40% of <60 years
- 10% cure for >70 years but improving
what type of disease is chronic lymphocytic (lymphoid) leukaemia?
B-cell clonal lymphoproliferative disease
who are more effected by chronic lymphocytic (lymphoid) leukaemia?
older adults, peak age >70 years
males 2:1 females
an issue in detecting chronic lymphocytic (lymphoid) leukaemia?
mostly asymptomatic and only discovered in blood tests by coincidence
slow progression, may not require treatment before person dies of another cause
Occasional blast transformation makes it aggressive
- Based on monoclonal antibodies
what occurs in chronic myeloid leukaemia?
Increase in neutrophils and their precursors
who is affected by chronic myeloid leukaemia?
- Peak 50-70 years but can occur at any age
- Slight male preponderance
15 cases per 1,000,000 per year
- 95% of patients have “Philadelphia” chromosome
(Presents in fairly unspecific way)
clinical presentation of chronic myeloid leukaemia
- Fatigue, weight loss, sweating
- Anaemia, bleeding, splenomegaly
translocation gone wrong so faulty gene products
difference between leukaemia and lymphoma
Leukaemia has 3-4 times normal WCC
Lymphoma – have solid lumps (WCC normal; abnormal collections)
lymphoma
Clonal proliferation of lymphocytes arising in a lymph node or associated tissue
- solid tumour but some cell in blood
2 types of lymphoma
- Hodgkin lymphoma
- Non-hodgkin lymphoma
behaviour and clinical features are different
NHL more common 6:1
what does staging require?
imaging - CT, PET/CT or MRI
need to be aware they have a lymphoma lesion
- not obvious as no blood changes, need to spot lump or pick up by accident
what 3 things does staging assess?
- No. of nodes involved and site
- Extra-nodal involvement
- Systemic symptoms
Based on: - How far down progression line
- Where lumps are
why is staging important?
predicting prognosis and deciding treatment
stage I
single lymph node region or single extralymphatic site
stage II
2 or more sites, same side of diaphragm or contiguous extralymphatic site
stage III
both side of diaphragm or spleen or contguous extralympatic site
stage IV
diffuse involvement of extralymphatic sites and nodal disease
who is effected by Hodgkin lymphoma more?
- Peak incidence age 15-40years
- Male > Female 2:1
clinical presentation of Hodgkin Lymphoma
- Painless lymphadenopathy – typically cervical, fluctuate in size
- Fever, night sweats, weight loss, itching
- Infection
Stage I and II Hodgkin Lymphoma cure prognosis
> 90%
older people do less well
stage III and IV Hodgkin Lymphoma cure prognosis
50-70%
older people do less well
Hodgkin lymphoma often seen as
lumps in head and neck
aetiology of non-Hodgkin lymphoma
Microbial factors strongly implicated - EBV, HTLV-1, H.pylori Autoimmune disease - Sjögren's Syndrome, Rheumatoid Arthritis Immunosuppression - AIDS, post-transplant
types of Non-hodgkin lymphoma
B-cell (85%) or T-cell (15%) types
effects any age (more laid-back in elderly)
triggers of non-hodgkin lymphoma
Viral and bacterial triggers
- H pylori in stomach - causes ulcers, can lead to gastric lymphoma
If caught early and remove lymphoma will shrink away
External cause often - remove the cause and take away risk disease will spread
presentation of non-hodgkin disease
Lymphadenopathy – often widely disseminated, may be “invisible”
- Unable to see or fell sometimes – incidental finding on scan
Extra-nodal disease more common
- Oropharyngeal involvement
- Waldeyer’s ring (noisy breathing and sore throat)
Symptoms of marrow failure
Constitutional symptoms less commo
If can identify the cause/trigger and remove it, then cancer can go away
prognosis of non-hodgkin disease
- > 50% will relapse after treatment
- Aggressive disease poor prognosis untreated but notably often responds better to treatment
- Indolent disease hard to cure
Standard medical therapy not very effective – finding trigger is best route
what is multiple myeloma
malignant proliferation of plasma cells
incidence of multiple myeloma
50 per million per year
features of malignant myeloma
Monoclonal paraprotein in blood and urine
- Plasma cells - make antibodies. Malignant plasma - lots of antibodies, based on light and heavy chains they normally make - same as from single group clone of cells
- Can clog kidneys as high blood level passes into urine
Lytic bone lesions can lead to pain and fracture
Excess plasma cells in bone marrow can lead to marrow failure
who is more likely to get multiple myeloma
Mean age at diagnosis 70 years,
Males > Females,
blacks>whites
process of bone failure
Infection, bone pain, renal failure and amyloidosis
amyloidosis
- Antibodies in excess amount
- Accumulate tissues e.g. heart, lungs
- And cause them to enlarge
Like rheumatoid arthritis
treatment of haematological malignancies (4)
Chemotherapy
Radiotherapy
Monoclonal antibodies
- Drug ends in MAB; Genetically manufactured to target specific features in specific cell types
Haemopoietic stem cell transplantation
- Can replace the bone marrow. New bone marrow doesn’t believe you should be there as not matching its old host - attacks the new host from inside. Multi system problem)
- Can take out own stem cells - clean them so only good functioning ones - And place back into host (Much less risky - less likely to reject)
4 concepts to know about for the process of leukaemia and lymphoma treatment
- induction
- remission
- maintenance & consolidation
- relapse
induction concept of leukaemia and lymphoma treatment
- Intense chemotherapy
- Blast all bad cells (cancer) out of body
remission concept of leukaemia treatment
- none left (no more acute issues)
maintenance & remission of leukaemia and lymphoma treatment
- Haven’t managed to remove all the cancer cells in first places - drug doesn’t reach all leukemic cells
- Depends if can make treatment work in certain way to reach all cells - reduce chance of relapse
relapse concept of leukaemia and lymphoma treatment
- Can have multiple relapses but then still improve
what is supportive therapy for leukaemia and lymphoma treatment?
- Nutrition
- Psychological and social support
- Prevention and treatment of infection
- Managing symptoms of therapy side effects (e.g.anti-emetics)
- correcting marked blood component deficits
- pain control
why is supportive therapy very important for leukaemia and lymphoma treatment?
as treatments are very unpleasant
