Myeloma and lymphoma Flashcards
where does the first stage of B cell differentiation take place
bone marrow.
what happens to B cells in the first stage of differentiation.
pro B cells form naïve B cells.
gain surface immunoglobulins
each B cell is committed to a single light chain (kappa or lambda)
what are 2 light chains in B cell called
kappa and lambda.
the first stage of B cell differentiation is also known as
antigen independent stage.
where does the second stage of B cell differentiation take place.
inside the lymph organs- lymph nodes
what is the second stage of B cell differentiation also known as
antigen dependent stage.
what happens in the second stage of cell differentiation
Mature naïve B cells develop into proliferating blast cells after encountering an antigen or T cell activation, and here they apoptose, become short-lived plasma cells or enter the germinal centre.
where does somatic hypermutation and heavy class switching occur
germinal centre in response to antigen presentation.
The process by which naïve B-cell blasts become either plasma or memory B-cells involve four steps which are
proliferation immunoglobulin somatic hypermutation and class switching, selection and differentiation.
what protein is needed to form plasma blasts
NF-kB
what B cells which undergo somatic hypermutations are known as
centrocytes/ centroblasts.
define somatic hypermutation
A process by which the Mature B cells undergo mutation making them more or less specific to the antigen which they were presented with.
If the mutation is not favourable the cell will undergo apoptosis.
what molecule are immunoglobulins made up of
glycoprotein.
immunoglobulins are composed of how many polypeptide chains
two “light chains” and two “heavy chains”
what tip of bond holds the light and heavy chains of an immunoglobulin together
covalent disulphide bonds
what are the 5 main types of heavy chains
IgG, IgM, IgA, IgD, IgE-
define protein electrophoresis
laboratory technique whereby serum is placed in a gel and exposed to an electric current
what 5 major fractions are shown on a normal antibody electrophorus
Serum albumin Alpha-1 globulins Alpha-2 globulins Beta glogulins Gamma globulins- flat hump, with no peaks as all the immunoglobulin’s are produced in equal amounts.
When is immunofixation used
after the protein electrophoresis comes back with a M peak.
what does a immunofixation show
Enables the detection and identification of monoclonal immunoglobulins
define myeloma
incurable malignancy of plasma cells.
what form do all myelomas originate at
MGUS- monoclonal gammopathy of uncertain significance- abnormal spike on protein electrophoresis up asymptomatic.
what organ is commonly affected in myeloma
kidney
MGRS- monoclonal gammopathy of renal significance- so has renal dysfunction
define solitary plasmacytoma
group of plasma cells deposit e.g. in femur., not much myeloma in the bone marrow.
what is the name given to the worst form of myeloma
plasma cell leukaemia- full-blown myeloma with severe symptoms
what is the diagnostic criteria for myeloma.
Clonal BM plasma cells >10%( more than 10% neoplastic plasma cells in bone marrow) or biopsy-proven bony or extramedullary plasmacytoma AND any one or more of:
CRAB features
MDEs
what are CRAB features
– C- hypercalcemia (177 micrimol/L.
– A- anaemia Hb
what are the myeloma defining events.
– > 60% clonal plasma cells on BM biopsy
– SFLC (serum free light chain) ratio >100mg/L provided the absolute level of the involved LC is >100mg/L
– Light chains clog up the kidney.
– >1 focal lesion on MRI measuring >5mm
how is initial management of acute kidney injury with suspected myeloma carried out.
(what investigations need to be carried out)
- Blood film
- Electrophoresis
- Immunofixation
- Bone marrow biopsy with
- flow cytometry
- start on steroids- even before diagnosis.
what intensive therapy is provided for patients with myeloma
VCD-chemotherpay (given in 4 cyclic whilst you harvest patient stem cell)
GCSF- injections which helps spill stem cells form the bone marrow in t peripheral blood.
Melphalan-big chemotherapy dose resulting in neutropenia, reduced RBC and platelets and then they patient is regiven their stem cells to help them recover.
what is the function of treatment with GCSF
spill stem cells form the bone marrow in t peripheral blood.
what are the negative consequences of melphalan chemotherapy
neutropenia, reduced RBC and platelets
newer drugs from the treatment of myeoma
Daratumumab (antiCD138)
Carfilzomib (proteosome inhibitor)
Ixazomib (proteosome inhibitor)
what is the non-intensive therapy that is used to treat myeloma
- CDTa- given initially (a= attenuated)= attenuated chemotherapy.
- VCD- given next in small dose= aim of treatment is to prevent complications such as bone injury not cure.
- RD (oral chemotherapy)= given after CDTa and VCD until disease progression.
In what groups of people are non-invasive treatment for myeloma typically provided
elderly, immunocompromised.
what is the initial treatment given all all patients who have suspected myeloma even if it hasn’t yet been confirmed
steroids
what are patients in remission treated with
oral chemotherapy- RD
what is the future of treatment of monoclonal antibodies
Targeted therapies
Individualised therapy
monoclonal antibodies
what condition is commonly associated with myeloma
AL amyloidosis
define AL amyloidosis
Amyloid light chain amyloidosis.
Neoplastic plasma cells secrete abnormal proteins which misfold and then accumulate in organs causing them to enlarge.
Light chain fragments misfold and self-aggregate to form beta-pleated fibrils
what are the complications of AL amyloidosis
Nephrotic-range proteinuria: Mainly albumin Small monoclonal light chain component Cardiac and liver involvement in 30% Peripheral neuropathy in 10% end stage renal failure
how does follicular lymphoma commonly present
painful lump in eck
define follicular lymphoma
neoplastic disorder of lymphoid tissue.
how do you acquire follicular lymphoma
chromosomal translocation – t(14;18) – which brings the bcl2 protooncogene under the influence of the immunoglobulin heavy-chain gene leading to over-expression of the bcl-2 protein.
if follicular lymphoma equally present in both genders
yes
Follicular International Prognostic Index (FLIPI) can be used to prognosticate lymphoma:
- age >60 years
- LDH above the limit of normal at diagnosis.
- Hb
is follicular lymphoma a hodgkin or non hodgkin lymphoma
non- hodgkin lymphoma
In AL amyloidosis the light chains misfiled into what.
Light chain fragments misfold and self-aggregate to form beta-pleated fibrils
