Haematology part 2 (p22-34- leukaemia, lymphomas, myeloproliferative + transfusions) Flashcards
Clinical features of acute leukaemia?
BM function failure- anaemia, thrombocytopenia (bleeding) + neuropenia (infection)
Organ infiltration- hepatomegaly, splenomegaly, lymphadenopathy, bone pain, CNS, skin, gum hypertrophy
What causes acute leukaemia?
Most of the time unknown Ionising radiation- radiotherapy Cytotoxic drugs- chemo Benzene Pre-leukaemic disorders- MDS, MPD Down's Neonates
How is haematological malignancy diagnosed?
Morphology +/- cytochemistry (stains) Immunophenotyping using flow cytometry (lineage, differentiation) Cytogenetics (chromsomal translocations) Molecular genetics (PCR, point mutations etc)
Epidemiology of ALL?
Children (ALL children get cancer)
Epidemiology of AML?
Adulthood (risk increases with age) and under 2s (infant peak)
Clinical features of ALL?
Anaemia Thromobocytopenia Neutropenia Lymphadenopathy+++ CNS involvement+++ Testicular enlargement Thymic enlargement
Clinical features of AML?
Anaemia
Thrombocytopenia
Neutropenia
Investigation findings for ALL?
High WCC (blasts) Lymphocytes+++
Flow cytometry:
CD34- Precursor/stem cells
CD3- T lymphocytes
CD19- B lymphocytes
Investigation findings for AML?
High WCC (blasts) Auer rods and granules
Flow cytometry:
CD34: precursor/stem cells
MPO: myeloid cells
What is the treatment for ALL?
Chemotherapy:
Remission induction- chemo agents with steroids
Consolidation- high dose multi drug chemo
CNS treatment
Maintenance- 2y in girls and adults, 3y in boys
Supportive:
Blood products, abx, allopurinol, fluid, electrolytes
What is the treatment for AML?
Chemo:
Similar to ALL but no CNS prophylaxis/maintenance therapy
(ATRA for M3 subtype)
Supportive:
Blood products, abx, allopurinol, fluid, electrolytes
Epidemiology of CML?
Middle aged typically 40-60
Investigation findings for CML?
Ph +ve (philadelphia chromosome) in 80%
PCR for BCR-ABL (philadelphia ch) fusion gene
WBC, Neutrophils 50-5000
Hypercellular BM with spectrum of immature and mature granulocytic cells in the blood
On examination- massive splenomegaly
Three different phases of CML?
Chronic phase
Accelerated phase
Blast phase
How is chronic phase CML treated?
Imatinib (BCR-ABL tyrosine kinase inhibitor)
Highly effective
Epidemiology of CLL?
M>F, elderly
Clinical features of CLL?
Asymptomatic and diagnosed on bloods in 80% of cases
Symmetrical painless lymphadenopathy
BM failure- anaemia, thrombocytopenia, neutropenia
Weight loss, fever, night sweats
Hepatomegaly and splenomegaly
Investigation findings for CLL?
High WBC with lymphocytosis >5
Low serum Ig
Smear cells (SMEAR CLLs)- blood film
What is the staging for CLL?
Binet:
Stage A- High WBC, <3 groups of enlarged lymph nodes and no treatment required
Stage B- >3 groups of enlarged lymph nodes
Stage C- Anaemia or thrombocytopenia
Treatment for CLL?
Many benefit from watchful waiting
Supportive treatment with transfusions, infection prophylaxis
1st line- if p53 deletion = alemtuzumab otherwise chlorambucil
What is a lymphoma?
Neoplastic tumour of lymphoid tissue (lymph nodes, spleen, MALT etc)
Epidemiology of Hodgkin’s lymphoma?
20% of lymphoma
M>F
Bimodal age incidence- 20-29 and >60
EBV associated
Clinical presentation of Hodgkin’s lymphoma?
Asymmetrical painless lymphadenopathy +/- obstructive/mass effect symptoms
B-symptoms (fever >38, drenching night sweats + weight loss >10% in 6m)
Pain in affected nodes after ALCOHOL
Investigations + findings for Hodgkin’s lymphoma?
CT/PET
Tissue diagnosis- LN or BM biopsy- cells stain with CD15+CD30
REED-STERNBERG cells- binucleate (owl eyed) cell
Staging of Hodgkin’s lymphoma?
Ann-Arbor Staging
Stage 1- one LN region
Stage 2- Two or more LN regions on same side of diaphragm
Stage 3- Two or more regions on opposite side of diaphragm
Stage 4- Extranodal sites (Liver, BM)
A: No constitutional symptoms
B: Constitutional symptoms
Hodgkin’s lymphoma treatment?
Excellent prognosis but intensive treatment-
1. Combo chemo (ABVD)
Adriamycin, bleomycin, vinblastine and dacarbazine
2. Radiotherapy (high risk of breast Ca)
3. Intensive chemo and autologous SCT (Relapsed pts)
What similar symptoms are there between the various subtypes of Non-Hodgkin’s lymphoma?
Painless lymphadenopathy
Constitutional symptoms
No pain after alcohol
What B cell subtypes of NHL are there?
Burkitt's Diffuse large B-cell Mantle cell lymphoma Follicular Mucosal associated lymphoid tissue (MALT)
What T cell subtypes of NHL are there?
Anaplastic large cell Peripheral Adult T cell leukaemia/lymphoma Enteropathy associated T cell lymphoma Cutaneous T cell lymphoma
What are the three types of Burkitt’s lymphoma?
Endemic- Most common malignancy in equatorial africa, EBV associated, jaw involvement and abdo masses
Sporadic- Found outside africa, EBV associated
Immuno-deficiency- Non-EBV, HIV/post transplant patients
What is the histology of Burkitt’s described as?
Starry sky appearance
Treatment for Burkitt’s?
Chemotherapy (rituximab (anti-CD20 on B cells) + leukaemia protocol) or SCT
How does Diffuse Large B-Cell (DLBC) present?
Middle aged and elderly
Aggressive
Richter’s transformation
Other lymphomas occur secondary
Histology of DLBC?
Sheets of large lymphoid cells
Treatment for DLBC and Mantle cell lymphoma?
Rituximab-CHOP
Auto-SCT for relapse
How does Mantle cell lymphoma present?
Middle aged, M>F
Aggressive
Disseminated at presentation
Survival 3-5yrs
Histology of mantle cell lymphoma?
Angular nuclei
How does follicular B cell lymphoma present?
Indolent
Mostly incurable
12-15y survival
Treatment for follicular B cell lymphoma?
Watch and wait
Rituximab CVP
How does Mucosal associated lymphoid tissue present?
Marginal zone NHL Middle-aged Chronic antigen stimulation: H pylori -> gastric MALT lymphoma Sjogren's -> parotid lymphoma
Treatment for MALT?
Remove antigenic stimulus e.g. H pylori triple therapy
Chemotherapy
How are T cell lymphomas treated?
Alemtuzumab (anti-CD52) can be used
How does anaplastic large cell lymphoma present?
Children and young adults
Aggressive
Large epithelioid lymphocytes
How does peripheral T-cell lymphoma present?
Middle aged and elderly
Aggressive
Large T cells
When you hear adult T-cell leukaemia/lymphoma, what should you think?
Caribbean and Japanese
HTLV-1 infection, aggressive
What is multiple myeloma?
Neoplasia of plasma cells of BM leading to production of monoclonal immunoglobulin
Epidemiology of multiple myeloma?
Middle-Aged to Elderly
Increased incidence in Afro-Caribbeans
Clinical features of MM?
CRAB
Calcium high- thirst, moans, grones, stones, bones
Renal failure (plus amyloidosis and nephrotic syndrome)
Anaemia (+ pancytopenia)
Bones- pain, osteoporosis, osteolytic lesions, fractures
Investigation findings in MM?
Dense narrow band on serum electrophoresis Rouleaux on blood film Bence Jones proteins in urine ESR very high >10% plasma cells in BM
Staging of MM?
Durie-Salmon staging
Treatment of MM?
Supportive for CRAB symptoms e.g. bisphosphonates
Aim- Induce remission for consideration of autologous SCT
First line- Bortezomib +/- dexamethasone, cyclophosphamide, lenalidomide
Auto-SCT- curative
How does Waldenstrom’s Macroglobinaemia present?
Elderly men
Low grade NHL
Weight loss, fatigue, hyperviscosity syndrome (visual problems, confusion, CCF, muscle weakness)
Treatment for Waldenstrom’s Macroglobinaemia?
Plasmapheresis for hyperviscosity, chlorambucil, cyclophosphamide
How is amyloidosis diagnosed?
Congo-Red stain -> apple-green birefringence
How is amyloidosis treated?
Velcade/chemo/auto-SCT
What are myelodysplastic syndromes?
Heterogeneous group of progressive disorders featuring ineffective proliferation and differentiation of abnormally maturing myeloid stem cells
Characterised by:
Peripheral cytopenia
Qualitative abnormalities of cell maturation
Risk of AML transformation
How do you differentiate myelodysplastic syndromes from acute leukaemia?
MDS <20% blasts
Acute leukaemia >20% blasts
How do you treat MDS?
Supportive- transfusions, EPO, G-CSF + Abx
Biological modifiers- immunosuppressive drugs, lenalidomide, azacytidine
Chemotherapy
Allogenic SCT
What is the prognosis of MDS like?
Depends on International Prognostic Scoring System (IPSS)- BM blast %, karyotype There is a mortality rule of 1/3: 1/3 die from infection 1/3 from bleeding 1/3 from acute leukaemia
What is aplastic anaemia?
Inability of BM to produce adequate blood cells
What is the management of aplastic anaemia?
Supportive- transfusions, Abx, iron chelation
Drugs- to promote marrow recovery- growth factors and oxymetholone (androgen)
Immunosuppressants- idiopathic AA
SCT
What is Fanconi Anaemia?
Autosomal recessive pancytopenia
Presents at 5-10y
Skeletal abnormalities, renal malformations, microopthalmia, short stature, skin pigmentation
What is dyskeratosis congenita?
X-linked with triad of skin pigmentation, nail dystrophy + oral leukoplakia
BM failure
What are myeloproliferative disorders?
A group of conditions characterised by clonal proliferation of one or more haemopoietic component
Which MPD is philadelphia chromosome positive?
CML
What are Ph -ve MPDs associated with?
JAK2 mutations, especially polycythaemia vera
What are the primary and secondary causes of polycythaemia?
Primary: Polycythaemia vera Familial polycythaemia Secondary (raised EPO): Disease states, high altitude, chronic hypoxia e.g. COPD
What causes relative polycythaemia?
Normal red cell mass but plasma volume reduced e.g. dehydration, burns, vomiting, diarrhoea, cigarette smoking
What is polycythaemia rubra vera?
An MPD where erythroid precursors dominate the BM caused by JAK2 point mutations
What are the clinical features of polycythaemia rubra vera?
Hyperviscosity
Blurred vision, headache
Plethoric, gout, thrombosis and stroke, retinal vein engorgement
Splenomegaly
Histamine release -> aquagenic pruritus (contact with water) and peptic ulcers
Investigation findings in polycythaemia rubra vera?
Raised Hb, HCT, platelets + WCC
Low serum EPO
How is polycythaemia rubra vera treated?
Venesection
Hydroxycarbamide + aspirin
What is myelofibrosis?
A MPD where myeloproliferation leads to fibrosis of BM or replacement with collagenous tissue
What are the clinical features of myelofibrosis?
Elderly
Pancytopenia symptoms
Extramedullary haematopoesis- hepatomegaly, massive splenomegaly, WL, fever
Can present with Budd-Chiari syndrome
Investigation findings for myelofibrosis?
Blood film- tear drop poikilocytes, leukoerythroblasts
BM- fibrosis, ‘dry tap’
How do you treat myelofibrosis?
Support with blood products, in some cases- splenectomy
Hydroxycarbamide, thalidomide, steroids and SCT
What is essential thrombocythaemia?
An MPD where megakaryocytes dominate the BM
What are the clinical features of essential thrombocythaemia?
Incidental finding in 50%
Venous and arterial thrombosis, gangrene and haemorrhage
Erythromelalgia
Splenomegaly, dizziness, headaches, visual disturbances
Investigation findings in essential thrombocythaemia?
Platelet count >600x10^9
Blood film- large platelets and megakaryocyte fragments
Increased BM megakaryocytes
Treatment for essential thrombocythaemia?
Aspirin
Anagrelide- reduces formation of plts from megakaryocytes
Hydroxycarbamide
What causes haemolytic disease of the newborn?
Person may form red cell Ab through blood transfusion or if fetal cells enter woman’s circulation during pregnancy or delivery. If maternal Ab level is high, it can destroy fetal red cells if they have corresponding red cell Ag -> fetal anaemia + jaundice (HDN)
How do you prevent anti-D formation in RhD negative women?
Give intramuscular anti-D Ig when she is at high risk of feto-maternal haemorrhage
Routine antenatal prophylaxis at 28 + 34w
Also give at delivery if baby is RhD positive
Learn Transfusion flow chart on p34
Good job!