W04 - HAEM: Haematological Malig.; Myeloid Malig.; Lymphoid Malig.; Flashcards
Understand the principles of leukaemogenesis.
Proliferation of a mutant clone dt advantagenous acquired mut., mutation accum. over time, resulting in domination of tissue eg. BM or LN.
(HStemCell)
=> myeloid malignancies
= chronic phase => accelerated => blast crisis
*AMLeukemia = myeloid progenitor => downstream cells
=> lymphoid malignancies
= chronic phase => accelerated => leukemic transformation
Understand the presentations of leukaemias
M>F
- AML = more common in adults
*ALLeukemia = more common in children
- contained in BM
CLL – chronic lymphocytic leukaemia – this is mainly a disease of the elderly, often incidentally
- often contained in nodes
CML – chronic myeloid leukaemia; often present in chronic phase
Discuss the principles of chemotherapy and bone marrow transplantation.
a
MPN
Myeloproliferative neoplasms (MPNs) are types of blood cancer that begin with an abnormal mutation (change) in a stem cell in the bone marrow. The change leads to an overproduction of any combination of white cells, red cells and platelets.
LN Structure and associated cell pops.
- B cells in follicles
- T cells in paracortex
- Plasma cells in medulla
- B cell differentiation and expnsion in germinal centres = become memory or plasma cells and exit GC
- naive cells = mantle zone
Lymphoma presentation and dx modes
= nodal disease = lymphadenopathy
= extranodal disease (40% of NHLymph)
= systemic symptoms = fever, sweats, wt loss, pruritis, fatigue
*BIOPSY Dx
* Staging: imaging etc.
Significance of lymphadenopathy
1) LOCALISED
+pain
INFECTION
-pain
INFECTION, HARD METS., RUBBERY LYMPHOMA, REACTIVE
2) GENERALISED
+pain
VIRAL INFECTIONS
-pain
LYMPHOMA, LEUKEMIA, CONNECTIVE TISS. DISEASE, SARCOIDOSIS, REACTIVE, DRUGS
Outline the symptoms, diagnostic tests and treatment of:
Chronic myeloid leukaemia
- cells differentiate and proliferate w/o BM failure thus survival for a few years
anemia, splenomegaly, wt loss, gout, hyperleukostasis in fundus and venous congestion
+ ⇪⇪WCC, platelet
+ philadelhpia chromosome
(1)
> TKInhibitors: imatinib, daatibin (-ib endings)
(2)
> allogenic transplantation - when TKIs fail
Outline the symptoms, diagnostic tests and treatment of:
AML
- nil differentiation thus BM failure, fatal
anemia, thrombocytopenic bleeding (petechiae), infection (dt neutropenia) - blood count, blood film, BM aspirate = 20%+ blasts makeup
- cytogenetics, immunophenotyping, CSF
- gene panels
AUER RODS
> supportive
anti-leukemic ChTx = remission
- DAUNORUBICIN & CYTOSINE ARABINOSIDE
- GEMTUZUMAB OZOGAMICIN = targetted abs
- CPX-351
> allogenic SCell transplant
> Acute Promyelocytic Leukemia = ALL-TRANS RETINOIC ACID
Outline the symptoms, diagnostic tests and treatment of:
Myelodysplastic syndromes
MDS are generally considered precursors to leukaemia. 30% of all individuals suffering with MDS will go on to develop acute myoblastic leukaemia (AML).
acquired, and generally occur in the elderly.
pancytopaenia (nil rbc, wbc, plt.): anaemia, infection, and/or bleeding
*⇪blast cells in BM
> low dose ChemoT: azacytidine / High dose
> BM transplant
> conservative
Red cell infusions
Platelet infusions
Antibiotics for infection
Hemopoietic growth factors
Outline the symptoms, diagnostic tests and treatment of:
CHRONIC Myeloproliferative disorders/neoplasms
POLCYTHEMIA VERA: JAK2 V617F muts
* headaches, vac. occ, itch, TIA stroke, thrombosis, splenomegaly
+⇪Hb, haematocrit, ⇪WCC, platelet, ⇪ uric acid
> Venesection
Aspirin
Hydroxcarbamide / alpha interferon
JAK2 inhibitor
=> !thrombotic compl., BM failure, transformation to AML
ESSENTIAL THROMBOCYTHAEMIA: JAK2 V617F muts, CALR muts.
* significantly raised platelet count, thrombotic pres., gout, splenomeg.
> aspirin, hydroxycarb. or anagrelide
! progression to AML or myelofibrosis
IDIOPATHIC MYELOFIBROSIS
Marrow fibrosis and splenomegaly, de novo or following transformation of PV or ET
Usually >50 years old
Signs of BM Failure
anemia, thrombocytopenic bleeding (petechiae), infection: bacterial fungal (dt neutropenia)
Lymphoma Classification
HODGKIN LYMPHOMA
Vs
NH-LYMHPOMA: more common than H-Lymphoma
=> HIGH-GRADE
-diffuse large B cell lymphoma
=> LOW-GRADE
- follicular, marginal zone
Outline the symptoms, diagnostic tests and treatment of:
Acute lymphocytic leukaemia
nil differentiation, uncontrolled accum. often in BM
-children, B cell lineage
presents: BM failure (2/3w) or bone/joint pain + WCC increase
* 17yo male, 1mos impaired vision, 1/2stone wt loss, breathless on minimal exertion
- large immature B cells with CD19
> ChemoT aim remission
Consolidation therapy
CNS tx
Maintenance tx for 18mos
> SC transplantation high risk
(newer)
> Blinatumumab = T cell engagers
> CAR-t Tx = Chimeric antigen receptor T cells
! cytokine release syndrome = fever, hypoT, dyspnoea
! neurotox.
*90% remission in adults and children 5y survival
Outline the symptoms, diagnostic tests and treatment of:
Chronic lymphocytic leukaemia
CLL commonest, M>F, familial
* matured cells, low grade condition, B cells with normal markers
* >5 lympjocyte count: doubling lymphocyte time = poor prog.
BM failure, lymphadenopathy, splenomeg., fever+sweats
+immune paresis
+ haemolytic anemia
> watch and wait
Cytotox ChemoT: fludarabine, bendamustine
monoAb: Rituximab, obinatuzumab
TK inhibitor
Outline the symptoms, diagnostic tests and treatment of:
Hodgkin lymphoma
30% of al lymphomas, bimodal age curve
1st pak: 15-35y
2nd peak: later in life
M>F, EBV, familial and geog clustering
*PET scanning for assessment to response to Tx
> Combination chemotherapy (ABVD)
+/- radiotherapy
Monoclonal antibodies (anti-CD30)
Immunotherapy (checkpoint inhibitors)
Outline the symptoms, diagnostic tests and treatment of:
Non-Hodgkin lymphoma HIGH GRADE
Diffuse large B-cell lymphoma, commonest lymphoma
agressive, fast
* combo. chemoT
* curable
> anti-CD20 monoclonal antibody + chemo
Outline the symptoms, diagnostic tests and treatment of:
Non-Hodgkin lymphoma LOW GRADE
Follicular lymphoma (watch and wait if nil symptoms), 2nd commonest lymphoma subtype
- indolent, often asymptomatic, responsive to tx but incurable
> anti-CD20 monoclonal antibody + chemo
Outline the symptoms, diagnostic tests and treatment of:
Myeloma
CRAB
Hypercalcaemia
Anaemia
Renal impairment
Bone pain
MONOCLONAL BANDS dt overprod of antibodies dt malignant proliferation of plasma cells in BM
* Bence-Jones proteins.
- elderly
Ab = hyperviscotic pic
hyperviscosity, amyloidosis and renal failure.
> autologous sc transplant
! neutropenic sepsis
> . induction rx: CHEMOT, STEROIDS, THALIDOMIDE
> supportive
CLL Staging
BINET: based off of LN and clinical features
A - <3 LN
B - 3+ LN, ~8y survival
C - +Anemia or thrombocytopenia, ~6y survival
Staging of Lymphoma
I to IV => I & II (contained in diaphgramic border) vs III vs IV (organ involvement)
A = absence of B symptoms
B = fever, night sweats, wt loss
*biopsy, CT scan, BM aspirate, trephine
Understand what is meant by the term paraprotein
Monoclonal Ig present in blood or urine, indicating monoclonal proliferation of a B lymphocyte/plasma cell somewhere in the body.
- useful for serum protein electropheresis
= separating proteins based on size and chage = Ab diversity
Know what diseases paraproteins are associated with
IgM paraproteins = lymphoma association
maturing b-lymph make IgM @ start of immune response
IgG, IgA = myeloma association
matured cells generate Ig after isotype switching
*amyloidosis
* renal failure
* hyperviscosity
* hypogammaglobulinemia
IgM myelomas dont exist but associated with low-grade lymphomas
- BM failure, lymphadenopathy, hepatosplenomeg., B symptoms
Understand how myeloma commonly presents
Plasma cells: excessive prod of Ig. (BM)
*commoner in black population than white, 7th decade
- bone disease: lytic lesions, fractures, cord compr., hypercalc.
- BM failure
- infections
CRAB
calcium (hyper.)
renal failure: dt cast nephropathyy
anemia
bone disease
+bleeding dt hyperviscocity, also causes cardiac failure, pulmonary congestion, confusion, renal failure
+ HYPOGAMMAGLOBULINEMIA
Understand principles of diagnosis and treatment of myeloma
Paraproteins: monoclonal gammopathy pf uncertain icance (MGUS)
- myeloma dx via excess plasma cells in BM
= >10% of total BM cell pop. - IgG predominates, with IgA, light chain only, then other.
- staging based on ALBUMIN & BETA-2 microglobulin
> chemoT:
carfilzomib, bortezomib (proteasome inhibitors)
lenalidomide, pomalidomide
monoclonal ab.
> BISPHOSPHONATE THERAPY: zoledronic acid
> RT
> Steroids
> Sx: long bone pinning, SC decompression
> autologous SC transplant
Primary role of Ig
Recognise and bind pathogens, impeding processes or direct other components via tagging the antigen
*2 Heavy Chains
Fc = constant
- IgG, IgA, IgM, IgD, IgE
*2 Light Chains
kappa or lambda
=> variable domains on both chains
Role of IgM
Initial phase of Ab prod.
Pentamer
0.5-2.0g/l
Role of IgG
Most prevalent Ab subclass
6-15g/l
IgA
Mucous membrane immunity
1-4.5g/l
IgE
Parasite immune response, hypersens
Other immunological tests
Total Ig levels = measure of Ig subclass by heavy chain
Immunofixation = identifies paraproteins present
Light chains = assess imbalance/excess ofd light chains in urine/serum
