Therapeutics & Investigations 2 (Part 3) Flashcards
What is transplantation? + issues that this has with the immune system?
- The introduction of biological material, e.g. organs, tissue and cells, into another organism
- The immune system is evolved to remove anything that it regards as non self.
• Can transplant the cornea, kidney, liver, heart, and even full face
• Some of these had to wait until the development of immunotherapy
Describe donor/recipient relationships in transplants
- The importance of MHC matching
- There are rejection mechanisms
- Immune cells are also transplanted
- Immunosuppression occurs in transplant medicine
Describe donor/ recipient relationships and how they can be autologous and synergic
- Donors and recipients = genetically identical
- Do not usually generate any immunological problems
Mice = autologous transplant is when it is taken from one part to another part of the mice synergic is using genetically identical clones
Describe the autologous transplant in humans
Autologous = when it is all on the SAME person - section of one persons body being transferred to another section, like a skin graft auto = automatic… can be done automatically because it is all from the same person.
Describe the syngeneic transplant in humans
- Transplantation with genetically identical twins = syngeneic (“same-geneic”)
Describe the donor/recipient relationships - allogenic
- Donors and recipients are from the same species but are genetically different
- Tissues / organs from one mouse to anther mouse
Donor/recipient relationships = xenogenic
- This is when the donor and the recipient are different species
- X in Xenogenic = shows the cross between species that occurs
- Best transplant animal = pig, also baboons can be used
Describe the process of Xenogeneic transplantation in humans
- E.g. pigs heart can be put into humans (xenogeneic)
- Mismatch in the MHC between the animal and the donor
The importance of MHC matching :
Major histocompatability antigens
- MHC = most important component of transplants
- Histocompatability = tissue compatability
- Immune responses to the transplant are caused by genetic differences between the donor and the recipient
- The most important = differences between the major histocompatabiity antigens
- Human transplants = largely unsuccessful until there is identification of human MHC
- Human MHC proteins are named HLA (Human Leukocyte Antigen)
Ø HLA = immune system can discriminate between self and non self
Describe the HLA class 1 frequency of expression
- This is showing the mean HLA frequency from the 5 major world populations
- There is a large amount of variation within HLA alleles
- Frequency of alleles is not the same which is a good thing
- This makes it easier to match donors
Action of T cells and their recognition abilities
- T cells need to be able to recognise foreign peptides that are bound to self MHC
- CD8 and CD4 immunity = T cell immunity is MHC restricted
- This refers to the need of MHC to present the antigen to T cells
- Antibody on B cell can usually bind the antigen irrespective of proteins
- Peptide can only bind to TCR as part of the MHC complex
• This is termed T cell immunity - This is the MHC peptide complex (PMHC)
- Identifies residues on the peptide and also on the HLA molecule
- This is important for transplantation
- This is also important for CD4 - detection of peptides in the context of MHC class 2 & the peptides can alter the properties of the MHC
- Class 2 = 2 binding requirements are more promiscuous. Amino acid can be between 9-20 amino acids long
- Diversity of the HLA - favourite peptide image - there is a complex that is formed and immunity in bacteria
Relationship between T Cells and MHC class 1
- The T cells will recognise short peptide fragments that are presented to them by major histocompatibility (MHC) proteins
- Important difference = all of our somatic cells have HLA class 1
- Proteins that are degraded are loaded onto MHC and then go on the surface
(See animation on the actual slides to see the order in which this progresses)
MHC class 2 loading
- MHC loading is similar. Class 2 = only on
surface of WBCs like dendritic cells etc. - Not present on other somatic cells
- MHC 2 gets its peptides to present to T cells in different way
Ø Engulfs dying red cell
Ø Processes the peptide in that cell and presents them an HLA to the CD40 cell
Key points about MHC (Major Histocompatability Complex) CLASS 1
IT BINDS - Fragments of intracellular proteins
- All somatic cells
• Presents them as peptide MHC complex
IT IS SEEN BY
- T cell receptor, on cytotoxic T cells
- With assistance from CD8
Key points about MHC (Major Histocompatability Complex) CLASS 2
IT BINDS - Fragments of proteins which have been taken up by endocytosis
• This is only on the professional immune cells
• Can internalise exogenous dying cells and break up these proteins
IT IS SEEN BY -T cell receptor on helper T cells
- With assistance from CD4
Characteristics of helper T cells
- Information + support for other immune cells, via cytokine production
- Helper T cells are required to produce antibody + cytotoxic T cell responses
- Interferon gamma = interact with class 1 and these cells can lyse the infected cells, or cells that they regard as foreign
Characteristics of cytotoxic T cells
- They are highly specific killer cells
MHC protein in transplants
- In transplants both the MHC protein AND the peptide in its binding groove may be foreign
Describe HLA mismatch and graft survival
- In transplants both the MHC protein AND the peptide in its binding groove may be foreign
Describe HLA mismatch and graft survival
- Usually try to match 4/6 MHC class 2 loci
- Reduces the likelihood of future transplants and problems with future transplants
- Decreasing amount oof time of acceptance by host
Comparison between live vs. dead donors
- Recipients will have a history of disease, which will have resulted in a degree of inflammation
- Organs from deceased donors are also likely to be inflammed condition due to ischaemia
- Transplant success is less sensitive to MHC mismatch for live donors
Rejection mechanisms
Ø Types of graft rejection
- Hyperacute rejection
- Acute rejection
- Chronic rejection
Characteristics of hyperacute rejection
- This is within a few hours of the transplant
- Due to a strong antibody response - this is usually because the reciepients of the transplant has seen the antigen = even from pregnancy.
- Most commonly seen for highly vascularised organs, e.g. kidney
- Requires pre existing antibodies
Ø Usually to ABO blood group antigens or MHC-1 proteins - ABO antigens are expressed on endothelial cells of blood vessels
- Antibodies to MHC can arise from pregnancy, blood transfusion or previous transplant
How can antibodies cause damage to transplanted tissue
- There is recognition of Fc region.
Ø Has a FAB hypervariable region which is responsible for binding the antibodies - This leads to
Ø Complement activation
Ø Antibody dependent cellular cytotoxicity (Fc receptors on NK cells)
Ø Phagocytosis (FC receptors on macrophages)
Describe Hyperacute rejection
- The antibodies will bind to endotheial cells
- Complement fixarion
• Promotes the transfer of cells
• Internalise damaged cells - Accumulation of innate immune cells
- Endothelial damage, platelets accumulate and then thrombi will develop
Describe what occurs in acute rejection
- Inflammation results in activation of organs resident dendritic cels
- T cell response will develop as a result of MHC mismatch
- Based on the immune cells in the donor transplant - inflammed kidney
- Immune cells in the kidney have been activated
MHC protein
- In transplants, both the MHC protein and the peptide in its binding groove might be foreign
Describe the direct allorecognition of foreign MHC
- In transplant, both the MHC and the peptide can be foregin
- Recipients immune system can detect that MHC
- Eg. With the kidney = dendritic cells which are tissue white blood cells, transplanted kidney ==> all of the cells become weary
- DCs are pro-bound to migrate to the lymph nodes where the lymph nodes reside
• In order to trigger T cell immunity - T cells will identify these DCs - binding of the MHC molecule
Describe the process of chronic rejection
- Alloantibodies recruit inflammatory cells to the blood vessel walls of the transplanted organ - bind to the endothelial cells
○ Causes them to be internalised by the recipient APC
○ Start to process the donor MHC molecules - Increasing damage will enable the immune effectors to enter the tissue of the blood vessel wall, and to inflict increasing damage
MHC protein and peptide
- In transplants, both the MHC protein and the peptide in its binding groove may be foreign
Chronic rejection results from indirect allorecognition of foreign MHC
- The donor derived cells will die
- Membrane fragments containing donor MHC are taken up by host DC
- Donor MHC is presented into peptides which are presented by host MHC
- T cell response is generated
Transplantation of immune cells
Ø Haematopoietic Stem Cell Transfer
- This was previously called bone marrow transplant - has now been renamed because the source is often peripheral blood; rather than bone marrow
- Often autologous
• To transfer biological material from one part of one person to another part of that same person
• Irradiate the immune system = put the stem cells back in and migrate to the bone marrow - Until 1980 only HLA identical siblings could be used as donors due to the risk of rejection or graft vs. host disease
HSCs finding their way to bone marrow
- HSCs can find their way to bone marrow, after infusion and regenerate there
- They can be cryopreserved with little damage
- Become a large number of different cell types = ALL start from pluripotent hematopoitic stem cells
Describe graft vs. host disease
- Having a replacement immune system being transplanted into you altogether - When transplanted tissue is immune cells themselves
- Have the risk of the donor immune cells attacking the host = GVHD (graft vs. host disease)
- This can be lethal = best approach is prevention
- Removing the T cells from the transplant reduces GVHD
- Remove immune cells from the recipient so they won’t be attacked or the HSTs transplanted so that they won’t be attacked
- Prevent GVHD using immunotherapy
Graft versus leukaemia
- Patient could have residual chemotherapy - the new immune system will think that things that are self are actually not theirs.
- Sometimes mismatch + donor leukocytes can be beneficial - removing original leukaemia
- Graft versus leukaemia response
- Development of GVL may prevent disease relapsing (might think self cancer cells are foreign and therefore kill them - which is the sort of outcome that we want )
Immunosuppression in transplant medicine
Characteristics of immunosuppression
- Essential, to maintain non autologous transplant
- Immunosuppressants for transplant can be:
Ø General immune inhibitors (e.g. corticosteroids)
Ø Cytotoxic
○ Kill proliferating lymphocytes, e.g. mycophenolic acid, cyclophosphamide, methotrexate
Ø Inhibit T cell activation
○ Cyclosporin, tacrolimus, rapamycin - Immunosuppressives might need to be maintained indefinitely
- Creating a more toloregenic system - cytogenic which will kill lymphocytes and there are other agents which inhibit T cell activation
Characteristics of cyclosporin
- Breakthrough transplant drug
• Essential for the maintenance and the differentiation of t cells - Blocks T cell proliferation and differentiation
- Next generation therapies less toxic and effective at lower doses
Combination immunosuppressive regime characteristics
- Steroids (prednislone)
- Cytotoxic (mycophenolate motefil)
- Immunosuppressive specific for T cells (e.g. cyclosporin A, FK506)
Describe immunsuppressive therapy monitoring
- Our immune systems are not meant to be inhibited indefinitely. People on immunosuppressive therapy = greater risk of cancer.
- There is currently no immunosuppressive that is able to prevent transplant rejection whilst maintaining other immune responses
- Transplant patients are more susceptible to infection + malignancy
• Immediate risk, e.g. CMV - Immunosuppressive drug toxicity can lead to organ failure - either of the transplanted organ, or healthy organs
- Vital for a patients outcomes after transplanation
• e.g. cyclosporin nephrotoxicity in kidney transplant
Summary of transplant rejection
- Transplant rejection results from genetic differences between the donor and the recipient
- Variability between MHC proteins is the major genetic difference in transplant rejection
- Host attacks transplant - rejection (hyperacute, acute, chronic)
- Transplant attacks the host - GVHD (Graft vs. Host Disease)
- Immunosuppression can prolong the survival of transplanted organs
Lymphoid malignancies
- They correspond to the normal stages of lymphoid development
- The state or presence of a malignant tumour, cancer
Malignancy types:
Acute lymphoblastic leukaemia (ALL)
- This is characterised by infiltration of blood and bone marrow
Ø Corresponding normal cell =
Ø B cell precursors in the bone marrow
Malignancy types:
Acute lymphoblastic leukaemia (CLL)
- This is characterised by infiltration of blood and bone marrow
Malignancy types:
Lymphomas
- Tumours of lymph nodes and other secondary lymphoid organs
Ø Corresponding normal cell =
Ø B-cells in the secondary lymphoid organs
Malignancy types:
Myeloma
- Foci of malignant cells in bone marrow
The corresponding normal cell In 1. Acute Lymphoblastic Leukaemia (ALL) Malignancy
Ø B cell precursors
Ø That are in the bone marrow
The corresponding normal cell In T-ALL malignancy
Ø T cell precursors
Ø In the bone marrow
Ø OR in the thymus
The corresponding normal cell In 3. Lymphoma
Ø From B cells in the secondary lymphoid organs
The corresponding normal cell IN 4. Chronic Lymphocytic Leukaemia (CLL) malignancy
Ø This corresponds to the mature circulating B cells
The corresponding normal cell In 5. Myeloma
Ø Immunoglobulin secreting plasma cells
Ø That are in the bone marrow
Describe lymphocyte development in the bone marrow
HSC: haematopoietic stem cell [START point]
CMP: common myeloid progenitor,
Ø These go on to produce
- Neutrophils
- Red cells
- Platelets
CLP-:common lymphoid progenitor
Ø Go on to produce Pre T, and Pre B cells
Pre-T: T-cell precursors
Pre-B: B-cell precursors
Imm-B: immature B-cell [end product] - which is produced when there is immunoglobulin gene rearrangemen
What are the characteristics of the primary and secondary lymphoid organs
- The secondary lymphoid organs are lymph nodes, spleen, peyers patches etc.
- Stem cells in the bone marrow give rise to pre B and Pre T
- Pre T = migrate to the thymus where they do their PCR gene rearrangement
- B cells do all of this in the bone marrow before they then go to the secondary lymphoid organs
- Immature lymphocytes will wait, looking for an antigen and looking for a reason to do something
Light chain restrictions
- Immunoglobulins will make 2 x heavy chain and 2x light chains
- Light chains can either be kappa or lambda = EITHER , not both.
- Series of cells in normal person, will be light
- Mutations happen in one cell (shown by the circled cell) = then all of the malignant cells descend from this one abnormal chain
Ø E.g. if it is making one type of light chain, you will see so many in this type - See cells that are all making one light chain = clear sign of clonal disease and malignancy
Presentation of ALL
- Usually non specific symptoms of bone marrow suppression
- Symptoms of organ infiltration, more often in advanced disease
Epidemiology of ALL
- Commonest leukaemia in children that are less than 10 years old - generally no longer a cause of death
- But majority of patients are over 40 years old, overall.
What investigations would you carry out and how would you come to a diagnosis of ALL
- Bone marrow morphology
• Infiltration by undifferentiated blast cells - Immunophenotyping
Ø B cell surface markers (or T markers for T-ALL)
○ See that there are too many white cells, or too many of the same type of cell.
Ø Look for Light chain restriction
Ø TdT positive
○ Tdt = enzyme
○ Made in early pre B cells at the stage when they are messing around with Ig genes to make a new antibody
○ Marker for early lymphoblasts
○ If you see a lot of them = they are leukaemic cells. - Cytogenetics
Treatment - what are the characteristics of chemotherapy
- Induction
- Intensification, adding an extra stage
- CNS directed chemotherapy
• Cells can lurk behind the blood brain barrier
• Do a direct injection behind the spinal cord - (can kill the patient if the dosage is too high.)
- Maintenance, continuation of low level chemotherapy
- Radiotherapy to CNS
Prognosis of chemotherapy
- Children = >90% cure
- Adults have much lower survival rate, due to
Ø Differentiated cell of origin
Ø Different oncogene mutations
Ø Older patients = do not tolerate intensive treatment, it also depends on how fit they are
○ Adults biologically do not have the same disease for the reasons above
Hodgkins lymphoma
- Presentation = with enlarged lymph node(s)
- Epidemiology =
Ø Peak incidence is in young adults
○ There is a second smaller peak in older people
Ø Possible associations with Epstein Barr Virus (EBV) aka Human Herpes Virus 4 (HHV4)
○ HHV4 =
What is the histopathology of Hodgkins lymphoma
- Presence of large Reed-Sternberg cells = pathognomonic
• IF there is this cell present, there is DEFINITELY Hodgkins Lymphoma - These are malignant B cells
- But typically 99% of cells are reactive to non-malignant cells
- Multinuclear
What is the pathognomonic sign of Hodgkins lymphoma
- Presence of large Reed-Sternberg cells
Ø Giant cells that are found in those with Hodgkins lymphoma
Treatment of Hodgkins lymphoma
- Chemotherapy, +/- radiotherapy
- Prognosis = 5 year survival
• About 50-90% depending on age, stage and histology
• Especially good results in young adults
Characteristics of Non-Hodgkins lymphomas
- These are all of the remaining lymphomas
- Can be characterised into Low grade, High grade
- T cell lymphomas
- EBV (HHV4) - driven lymphomas in immunosuppressed patients
Chromosome translocations and lymphoma
- Many lymphomas carry chromosome translocations, involving the Ig heavy chain or light chain loci
- Ig genes are highly expressed in B cells
Ø Each Ig gene has a powerful tissue specific enhancer, near to the constant “C” segment - OMA = lump in the lymph nodes. Tumour in the lymph nodes.
Chromosome translocations and lymphoma - Follicular lymphoma
- Most cases of follicular lymphoma will carry t(14;18) (q32;q31)
- This juxtaposes the BCL-2 gene on chromosome 18, with the IgH locus on chromosome 14 -
- Causes overexpression of BCL-2 protein
- BCL-2 is an apoptosis inhibitor - the cells do not die when they are suppsoed to.
What does BCL-2 gene do
- B cell lymphoma 2 is encoded in humans by the BCL2 gene
- BCL2 = apoptosis inhibitor; inhibits the process of programmed cell death
Ø Regulator proteins, which regulate apoptosis
Ø By either inducing pro apoptotic, or inhibiting anti-apopotic apoptosis
○ BCL-2 = oncogene (therefore cancer causing)
Chromosome translocations and lymphoma - High grade lymphoma
- Some cases of high grade lymphoma carry t(8;14) (q24;q32)
- This juxtaposes the MYC gene on chromosome 18, with the IgH locus on chromosome 14
- MYC = powerful oncogene
• Once overexpressed it drives the cells into the cell cycle..
• Slow growing lymphoma they are not cycling faster, but are just failing to die. - Can also get MYC, or BCL-2 translocations to one of the Ig light chain loci
Characteristics of low grade NHL
- Presentation = enlarged lymph nodes
- Histology
Ø Normal tissue architecture partially preserved = in cancer terms low grade is that the cells and tissues are not THAT changed from normal
○ High grade = the cells are VERY changed from the norm.
Ø Normal cell of origin recognisable
○ Used to name lymphoma - follicular lymphoma, mantle cell lymphoma etc.
○ Named by comparing it to the normal tissues
Diagnosis of low grade NHL
- Histology
- Immunocytochemistry
- Cytogenetics
- Light chain restriction
- PCR
• For looking for the clonal Ig gene rearrangement
• For chromosome translocations - e.g. (t(14;18) Ig Bcl-2)
○ For these, look directly at the DNA
Ig gene PCR
- Look at PCR + amplify the DNA = there are lots of differently sized band
- The bands that you get = single size
- Get single monoclonal band
- These are polyclonal therefore they are not malignant.
Treatment of low grade NHL (non hodgkins lymphoma)
Ø Chemotherapy
Ø Glucocorticoids (like prednisolone)
• Because they cause cell death in lymphocytes
Ø Radiotherapy
• Targeting particular lymph nodes
Ø Monoclonal Ab therapy (mouse)
• Rituximab against human CD20 (anti CD20)- this is a B cell marker
• This antibody will attack B cells = this is effective treatment
Prognosis of low grade NHL (non hodgkins lymphoma)
Ø Chemotherapy
Ø Glucocorticoids (like prednisolone)
• Because they cause cell death in lymphocytes
Ø Radiotherapy
• Targeting particular lymph nodes
Ø Monoclonal Ab therapy (mouse)
• Rituximab against human CD20 (anti CD20)- this is a B cell marker
• This antibody will attack B cells = this is effective treatment
Prognosis of low grade NHL (non hodgkins lymphoma)
- Creation of human antibodies against the mouse immunoglobulin
- Relatively indolent (lazy and does not grow particularly fast)
- Responds well to therapy ; But is hard to cure - patients can be managed, but are never actually cured. If the disease starts to come back then you could re treat it.
High grade non hodgkins lymphoma
- Presentation = enlarged lymph nodes
- Histology shows:
Ø Loss of normal tissue architecture
Ø Normal cell of origin hard to determine
○ Cells have changed a LOT from normal
Diagnosis of high grade NHL
- Histology
- Immunocytochemistry
- Cytogenetics
- Light chain restriction
- PCR
Ø For clonal Ig gene rearrangement
Ø For chromosome translocations
Treatment of high grade NHL
- Chemotherapy
- Glucocorticoids
- Radiotherapy
- Monoclonal Ab therapy
Ø Rituximab - anti CD20
High Grade NHL prognosis
- Prognosis
• This is variable depending on type, stage and other factors e.g. health of patient
• Overall long term survival is about 65%
T -cell lymphomas
- These are rare (Most lymphomas are B cell)
- Usually CD4 cells
- Often present with skin infiltration, - it is not that clear why e.g.
Ø Sezary syndrome
Ø Mycosis fungoides
Mycosis Fungoides Characteristics
- Starts off looking like a fungal infection of the skin
- But may be a T cell lymphoma
Acute T cell leukaemia / lymphoma
- Found in Japan, Caribbean, UK citizens of Caribbean origin = this is where the disease is found
- Associated with retrovirus HTLV-1 human T cell leukaemia/lymphoma virus 1 infection
• Predisposes you do developing this but is not a guarantee
Epstein Barr Virus (EBV) driven lymphocytes characteristics
- EBV, or Human Herpes Virus 4 (HHV4)
Ø Will directly transform B lymphocytes in culture
Ø Cells transform & start growing. - This is due to viral oncogene LMP1
- Over half of all normal individuals carry latent EBV infection
• Experience in early childhood
• If you are exposed when you are older; get glandular fever (infectious mononucleosis) - develop cytotoxic T cells and immunity - Do not develop lymphomas, due to effective immune surveillance by cytotoxic T cells
- Do not eliminate virus from the body - lurking somewhere but is not actually a problem.
What happens in highly immunosuppressed individuals
- The endogenous latent EBV might transform B cells
- No longer eliminated by cytotoxic T cells
- Develop high grade lymphoma
• Situations when people are immunosuppressed
• Infection with HIV aids
• Giving transplant = immunosuppression so that they do not reject the graft.
What happens to transplant patients on cyclosporine
- Lymphoma usually regressed on withdrawal of immunosuppression - t cells come back
- But the patient might lose the graft; therefore this is a difficult clinical balance
AIDs patients treatments
- Lymphoma might regress on successful HAART (HIGHLY active anti retroviral therapy)
- Not successful in eliminating virus
- But good at stopping it progressing into AIDS
CLL presentation
- Most often as incidental finding on FBC
- Persistent infections
• Due to immunosuppression - suppression of the bone marrow and low neutrophil count. Large number of malignant B cell but not normal B cells.
• Low IgG, suppression of normal B cells - Lymph node enlargement
- Symptoms of bone marrow suppression
Epidemiology = 85% of cases are over 50 years old
CLL diagnosis
- FBC : lymphocytosis
- Immunophenotyping
Ø Cell surface markers
Ø Light chain restriction - Cytogenetics, chromosome translocations
CLL film appearance
Ø Huge amount of mature lymphocytes seen in CLL
Paraproteinaemia
- This is the presence of a single, monoclonal Ig in the serum / plasma
Proteins & disease - benign
Ø Monoclonal gammopathy of undetermined significance (MGUS)
• Low levels of paraprotein
• Low levels of paraprotein occasionally seen in lymphoma, or chronic lymphocytic leukaemia
Ø IgM paraprotein seen in Waldenstroms macroglobulinaemia
Characteristics of myeloma
- There are THREE aspects of myeloma that all give rise to different clinical features
1. Suppression of the normal bone marrow, blood cell and immune cell function
2. Bone resorption, and release of calcium
Ø Stimulate bone resorption
Ø Pushing out lots of immunoglobin = there is so much of it that it causes problems
3. Pathological effects of the paraprotein
What happens in the blood cell / immune suppression of myeloma
- Anaemia
- Recurrent infections
- Bleeding tendency
What happens when there is bone resorption in myeloma
- Myeloma cells produce cytokines (especially IL-6)
• Which stimulate bone marrows stromal cells, to release the cytokine RANKL
• This will activate osteoclasts which will produce
1. Lytic lesions of bone
2. Bone pain
3. Fractures - Presentation of this = unexpected fractures.
- Calcium released from the bone causes hypercalcaemia
- Multiple symptoms including mental disturbance = therefore need for psychiatry in high blood calcium
Skull X ray; of somebody with myeloma
- There are holes / areas of thinning in the skull.
- This is very typical of multiple myeloma = malignant B cells
Effects of paraprotein on myeloma
- Plasma cytes = factories of producing Ig. They are making too much = is too much protein going out into the circulation.
- Precipitates in kidney tubules, cause renal failure
- Deposited as amyloid in many tissues - amyloid. This can be damaging to tissues.
- 2% cases develop hyper viscosity syndrome = blood gets TOO thick
• Increased viscosity of blood, which leads to stroke and heart failure
Treatment of myeloma
- Chemotherapy; not curative Ø Cytotoxic drugs Ø Glucocorticoids Ø Thalidomide analouges Ø Bortezomib - Allogeneic bone marrow transplant Ø Only is available for a small number of younger patients (less than 45 years old, not too ill) Ø Need to find an HLA (MHC) matched donor Ø But potentially curative
Definition of the leukaemia’s
- Group of diseases
- That are characterised by malignant overproduction of white blood cells; or their immature precursors- (there are too many white blood cells and not enough room for other things like RBCs, platelets.)
- (Or their immature precursors)
General presentation of leukaemia
- Varies between the type of leukaemia
- There is suppression of normal haemopoiesis
- But typically first presents with symptoms, due to the loss of normal blood cell production
Ø Most common presentation = abnormal bruising
Ø Or repeated, abnormal infection
Ø Sometimes just anaemia
These things are all affected by the overproduction of White blood cells
○ Less neutrophils = infection
○ Less RBCs= anaemia
○ Less platelets = abnormal brusing
What is the most common presentation of leukaemia
- Abnormal bruising
- Or repeated, abnormal infection
Classification - describe what lymphoid leukaemias are
- Involving cells of the lymphocyte lineages
Ø Commonly B cell
Ø And more rarely T cell
Classification - describe what myeloid leukaemias are
- Involving any of the non-lymphocyte blood cell lineages
- Commonly neutrophils, or their precursors
- But can be erythroid, platelet, basophil lineages etc.
What are acute leukaemias defined as
- Undifferentiated leukaemia’s
- Characterised by immature white cells (known as blast cells)