Blood - Level 2 Flashcards

1
Q

Definitions of anaemia? Men, children, women, pregnant women and postpartum?

A

o In children aged 12–14 years — Hb concentration less than 120 g/L.
o In men (aged over 15 years) — Hb concentration less than 130 g/L.
o In women (aged over 15 years) — Hb concentration less than 120 g/L.
o In women who are pregnant — Hb concentration less than 110 g/L.
 An Hb level of 110 g/L or more appears adequate in the first trimester, a level of 105 g/L appears adequate in the second and third trimesters.
o Postpartum — Hb concentration less than 100 g/L.

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2
Q

Definition of macrocytosis?

A
  • Macrocytosis (MCV >100)

o Usually occurs due to problems with synthesis of RBCs

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3
Q

Physiology, absorption of folate?

Deficiency due to?

A

o Found in green vegetables and offal
o Absorbed in SI and stores last 4 months
o Deficiency by Diet, malabsorption, Leukaemia, heart failure, hepatitis, dialysis, drugs (alcohol, anticonvulsants, methotrexate, sulfasalazine, trimethoprim)

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4
Q

Physiology, absorption of vitamin B12?

Deficiency of B12 due to?

A

o Animal products provide only dietary source
o B12 binds to intrinsic factor secreted by gastric parietal cells and absorbed in terminal ileum
o Transported as transcobalamin and stored in liver with around 2-5 years supply
o Deficiency due to pernicious anaemia, surgery (ileal resection, gastrectomy), HIV, vegans, metformin, PPI, H2RA

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5
Q

Definition of pernicious anaemia?

Epidemiology?

Associated with?

A

o Autoimmune atrophic gastritis leading to achlorhydria and lack of gastric IF
o Usually >40 and women
o Associated with – myxoedema, thyrotoxicosis, Hashimoto’s, Addison’s, vitiligo
o Risk of gastric cancer

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6
Q

Causes of megaloblastic macrocytosis?

A

 B12 deficiency
 Folate deficiency
 Cytotoxic drugs

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7
Q

Causes of non-megaloblastic macrocytosis?

A
	Alcohol
	Reticulocytosis 
	Liver disease
	Hypothyroidism
	Pregnancy
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8
Q

Other causes of megaloblastic macrocytosis?

A

Myelodysplasia, myeloma, aplastic anaemia

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9
Q

Symptoms of anaemia?

A

o Asymptomatic
o Symptoms - SOBOE, fatigue, palpitations, exacerbation of angina, pale
o Signs – pallor, bounding pulse, systolic pulmonary flow murmur

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10
Q

Symptoms of vitamin B12 and folate deficiency?

A
o	Cognitive changes
o	SOB
o	Headache
o	Anorexia
o	Palpitations
o	Tachypnoea
o	Visual disturbance
o	Weakness, lethargy
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11
Q

Signs of B12 and folate deficiency?

A
o	Anorexia
o	Angina
o	Angular stomatitis
o	Glossitis
o	Liver enlargement
o	Mild jaundice
o	Tachycardia
o	Weight loss
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12
Q

Bloods done in macrocytic anaemia?

A

o FBC (Low Hb, high MCV (>100))

o Serum B12 (<200ng/L) - If cobalamin levels low – check serum anti-IF antibodies

o Serum Folate (<3mcg/L) - If folate levels low & malabsorption history – Check anti-endomysial & anti-transglutaminase antibodies

o Other investigations to identify cause:
 LFTs, GGT, TFTs

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13
Q

Blood film findings in macrocytic anaemia?

A

B12 and folate deficiency
• Hypersegmented polymorphs (neutrophil)
o >5% of neutrophils with 5 or more lobes, or 1 or more neutrophils with 6 or more lobes
• Oval macrocytes

Target cells if liver disease

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14
Q

What tests to perform to find cause of macrocytic anaemia?

A

o If low folate – assess dietary folic acid and check antiendomysial or anti-TTG antibodies for coeliac

o If low cobalamin – anti-IF antibodies for pernicious anaemia

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15
Q

When to refer to haematologist in macrocytic anaemia?

A

o Urgent – neurological symptoms, pregnant, malignancy suspected

o Routine – cause of B12 or folate deficiency uncertain following investigations

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16
Q

When to refer to gastroenterologist in macrocytic anaemia?

A

o Suspected malabsorption, pernicious anaemia with GI symptoms, gastric cancer suspected, coeliac disease

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17
Q

Management of vitamin B12 deficiency?

A

Treat cause

Dietary Advice - Food rich in B12 – eggs, fortified food (breakfast cereals, breads), meat, milk, dairy, salmon, cod

Hydroxocobalamin (B12) 1mg IM 3x a week for 2 weeks (if neurological symptoms - alternate days until no improvement)
 If not diet related – hydroxocobalamin 1mg IM every 3 months for life
 If diet – either oral cyanocobalamin 50-150mcg daily between meals or twice-yearly IM 1mg injection

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18
Q

Management of folate deficiency?

A

Assess underlying cause – poor diet, malabsorption

Dietary Advice - Foods rich in folate – asparagus, broccoli, brown rice, brussel sprouts, chickpeas, peas

Folic acid 5mg/day PO for 4 months (never without B12 unless known normal – worsens SACDC)

In pregnancy
 Prophylactic 400mcg/day given from conception until 12 weeks recommended to all
 5g/day up to 12 weeks – previous/FHx NTD, anti-epileptic meds, DM, SCC, thalassaemia, BMI>30
• SCC, thalassaemia – take throughout pregnancy

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19
Q

Monitoring in macrocytic anaemia?

A

o Within 7-10 days commencing treatment – FBC, reticulocyte count
o 8 weeks – FBC, reticulocyte count, iron and folate levels
o Completion of folic acid treatment – FBC, reticulocyte count
o Cobalamin levels 1-2 months after treatment if no symptom response

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20
Q

Complications of vitamin B12 deficiency?

A

Paraesthesia, ataxia, progressive symmetrical neuropathy, numbness, memory lapses

Neural tube defects

Sterility

Subacute combined degeneration of the spinal cord
 Insidious onset of peripheral neuropathy – symmetrical posterior dorsal column loss causing vibration and proprioception and LMN signs & symmetrical corticospinal tract loss causing motor and UMN signs
 Triad – extensor plantars, absent knee jerk, absent ankle jerk

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21
Q

Complications of folate deficiency?

A

o Prematurity
o CVD and colorectal cancers
o Neural tube defects
o Sterility

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22
Q

Acquired causes of haemolytic anaemia?

A
Immune-mediated and Coomb’s test positive
	Drug-induced
	Autoimmune haemolytic anaemia
	Paroxysmal cold haemoglobinuria
	Acute transfusion reaction
	Haemolytic disease of newborn
Coombs Negative Autoimmune haemolytic anaemia
Microangiopathic haemolytic anaemia
Infection
Paroxysmal Nocturnal Haemoglobinuria
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23
Q

Hereditary causes of haemolytic anaemia?

A

o Glucose-6-phosphate dehydrogenase (G6PD) deficiency
o Pyruvate kinase deficiency
o Hereditary Spherocytosis
o Hereditary elliptocytosis, ovalocytosis – refer to haematology
o Sickle cell disease
o Thalassaemia

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24
Q

Definition of drug-induced haemolytic anaemia?

A

• Formation of RBC autoantibodies from binding to RBC membranes (penicillin) or production of immune complexes (quinine)

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25
Description, classification and management of autoimmune haemolytic anaemia?
• Autoantibodies causing extravascular haemolysis and spherocytosis • Classified: • Warm – IgG-mediated, bind at body temperature, Rx = steroids/immunosuppressants • Cold – IgM-mediated, bind at low temperature (<4o), often with Raynaud’s or acrocyanosis, o Rx = keep warm o May be caused by CLL, lymphoma, drugs, SLE, infection (EBV, mycoplasma)
26
Description of paroxysmal cold haemoglobulinuria?
* With viruses/syphilis, caused by Donath-Landsteiner antibodies sticking to RBCs in cold * Self-limiting complement-mediated haemolysis on rewarming
27
Description of Rhesus haemolytic disorder?
o Usually identified antenatally when woman Rh negative and baby Rh positive o Presents with anaemia, hydrops, hepatosplenomegaly with rapidly developing jaundice o Usually anti-D blood group
28
Description of ABO incompatibility haemolytic disorder?
o Now more common than Rhesus incompatibility o Most ABO antibodies are IgM and do not cross placenta, but some blood group O women have IgG anti-A-haemolysin which haemolyses red blood cells of a group A infant o Occasionally group B infants affected by anti-B haemolysins o Can cause jaundice – peaks 12-72 hours o Anaemia is less severe and no hepatosplenomegaly o Coombs test positive
29
Causes of Coombs negative autoimmune haemolytic anaemia?
 Autoimmune hepatitis, hepatitis B&C, post vaccinations, drugs (piperacillin, rituximab)
30
Description of microangiopathic haemolytic anaemia?
 Disruption in RBC circulation, causing intravascular haemolysis and schistocytes  Causes include HUS, TTP, DIC, pre-eclampsia, eclampsia  Treat underlying disease, transfusion or plasma exchange may be needed
31
Description of paroxysmal nocturnal haemoglobinuria?
 Stem cell disorder with haemolysis (especially at night – haemoglobinuria), marrow failure + thrombophilia  Diagnosed – urinary haemosiderin, Harris test positive  Management – anticoagulation, eculizumab
32
Description, symptoms and management of glucose-6-phosphate dehydrogenase (G6PD) deficiency?
```  From Mediterranean, Middle-East and Far East  Males mostly, develop severe jaundice  Symptoms • Most asymptomatic, but get oxidative crisis due to low glutathione production precipitated by drugs (primaquine, sulphonamides, aspirin) or broad beans • In crisis – rapid anaemia and jaundice  Film – bite and blister cells  Diagnosis – Enzyme assay  Management – Avoid precipitants, transfuse if severe  Drugs need to be avoided • Henna • Sulfonamides • Aspirin • Primaquine • Broad beans ```
33
Description of pyruvate kinase deficiency?
 Autosomal recessive low ATP production causes lower RBC survival  Homozygotes – neonatal jaundice, haemolysis and splenomegaly  Diagnosis – enzyme assay  Management – Often none, splenectomy may help
34
Description of hereditary spherocytosis?
 Autosomal dominant inheritance with FHx in 75%  Early, severe jaundice in newborn infants  May cause anaemia, jaundice, splenomegaly, aplastic crisis and gallstones  Diagnosed on blood film  Treatment with folic acid, splenectomy if symptomatic
35
Symptoms and signs of haemolytic anaemia?
``` Anaemia – if longstanding may be asymptomatic but acute crisis causes: o Pallor o Tachycardia o SOB o Dizziness o Angina o Weakness Jaundice Gallstones Dark urine (haemoglobinuria) Splenomegaly ```
36
Investigations to perform in haemolytic anaemia? What are the findings?
1. Bloods - FBC (Low Hb, platelets normal usually), reticulocytes, LFTs (bilirubin), LDH, Haptoglobin 2. Coombs Test - Detects immune-mediated haemolytic anaemia 3. Urinary urobilinogen 4. Thick and thin blood films  Hypochromic microcytic cells (thalassaemia)  Sickle cells (SCD)  Schistocytes (microangiopathic haemolytic anaemia)  Abnormal cells in blood cancers  Spherocytes (hereditary spherocytosis or autoimmune haemolytic anaemia)  Heinz bodies, bite cells (glucose-6-phosphate dehydrogenase deficiency)
37
Further tests to perform in haemolytic anaemia?
o Direct antiglobulin test (Coomb’s test) – identifies autoimmune cause as red cells coated with antibody or complement o RBC lifespan – chromium labelling o Hb electrophoresis o Enzyme assays
38
How to approach haemolytic anaemia?
``` Increased red cell breakdown?:  Anaemia with normal or high MCV  High bilirubin (unconjugated from haem breakdown – pre-hepatic jaundice)  High urinary urobilinogen  High serum LDH (released from RBCs) ``` Increased red cell production?:  High reticulocytes causing high MCV (large immature RBCs)  Polychromasia Extra or intra-vascular?  Extravascular – splenomegaly  Intravascular • Raised free plasma haemoglobin • Methaemalbuminaemia (haem combines with albumin) • Low plasma haptoglobin • Haemoglobinuria – red-brown urine with no RBCs • Haemosiderinuria – free Hb filtered by glomeruli (sloughed tubular cells by Prussian staining) What is the cause?
39
Management of haemolytic anaemias?
- General Measures o Folic Acid – if folate deficiency o Stop precipitating medications - Transfusion o Only when necessary o Use most compatible blood if transfusions - Iron o For severe intravascular haemolysis and iron deficient - Splenectomy o Recommended in hereditary spherocytosis and when other measures failed
40
Definition of lymphoma?
- Malignancy of lymphocytes which can be divided into Hodgkin and non-Hodgkin lymphoma
41
Definition of Non-Hodgkin's lymphoma?
o Group of lymphoproliferative malignancies | o A much greater predilection to disseminate to extranodal sites than in Hodgkin's lymphoma
42
Definition of Hodgkin's lymphoma?
o Malignant tumour of the lymphatic system that is characterised histologically by the presence of multinucleated giant cells (Reed-Sternberg cells) o Mirror image nuclei in Reed-Sternburg cells
43
Epidemiology of lymphoma?
NHL more common HL - peak around adolescence NHL - peak around 50-70
44
Aetiology and risk factors of Hodgkin's Lymphoma?
o Aetiology  Classical HL (95%) – nodular sclerosis, mixed cellularity, lymphocyte rich/depleted  Nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL) o Risk Factors  EBV, HIV, immunosuppression, cigarette smoking
45
Aetiology of Non-Hodgkin's Lymphoma?
``` Mature (peripheral) B-cell neoplasms • Diffuse large B-cell lymphoma (30-60%) • Mediastinal large B cell • Burkitt’s lymphoma • Follicular lymphoma (20-25%) • MALT lymphoma ``` Precursor T-cell neoplasms Mature (peripheral) T-cell neoplasms • Enteropathy-type T-cell lymphoma • Peripheral T-cell lymphoma
46
Risk factors of Non-Hodgkin's Lymphoma?
```  Chromosomal translocations  EBV, HepC, Kaposi’s sarcoma  Pesticides, herbicides, hair dye, chemo  Hashimoto’s thyroiditis  H.pylori ```
47
Symptoms and signs of Hodgkin's lymphoma?
o Painless, large, firm lymphadenopathy o May cause airway obstruction, SVC obstruction o Several months o Systemic B-symptoms  Sweating, pruritus, night sweats, weight loss, fever
48
Symptoms and signs of Non-Hodgkin's lymphoma?
o Lymphadenopathy o Skin - Sezary syndrome o Other sites  Gastric  Small Bowel – diarrhoea, vomiting, abdominal pain, weight loss  Bone  CNS  Lung o Mediastinal mass with bone marrow infiltration o Superior vena cava obstruction o Systemic symptoms (less common than in Hodgkin’s lymphoma)  Sweating, pruritus, night sweats, weight loss, fever o Pancytopenia
49
When to refer lymphoma in primary care?
- Hodgkin’s Lymphoma referral in primary care: o 2-week cancer referral in adults with unexplained lymphadenopathy or splenomegaly - Non-Hodgkin’s Lymphoma referral from primary care: o 2-week cancer referral in adults with unexplained lymphadenopathy or splenomegaly o Specialist assessment within 48 hours for children if unexplained lymphadenopathy or splenomegaly
50
Testing in lymphoma?
``` o Bloods  FBC, film, ESR, LFT, LDH, urate, Ca o Lymph node excision biopsy o FISH gene testing if histological high-grade lymphoma o CT scan, CXR o PET scan staging if:  Stage 1 diffuse large B-cell lymphoma  Stage 1/2 follicular lymphoma  Stage 1/2 Burkitt lymphoma ```
51
Staging system in Hodgkin's Lymphoma?
``` o Ann Arbor system  Stage 1: single site  Stage 2: >1 site and on 1 side  Stage 3: on both sides of diaphragm  Stage 4: disseminated disease  Each stage either A (no systemic symptoms other than pruritus) or B (weight loss >10% in 6m, fever >38, night sweats) ```
52
Staging system in Non-Hodgkin's Lymphoma?
o St. Jude System  Stage 1: single site or nodal area (not abdomen or mediastinum)  Stage 2: regional nodes, abdominal  Stage 3: disease on both sides of diaphragm  Stage 4: bone marrow or CNS disease
53
Management in Hodgkin's Lymphoma?
o Chemotherapy (ABVD) with radiotherapy (if high risk)  Adriamycin, bleomycin, vinblastine, dacarbazine o PET scans monitor disease progression o Pnuemococcal and influenza vaccine o MenC and Hib vaccine o Relapsed disease – high-dose chemo and stem cell transplantation
54
Management in Non-Hodgkin's Lymphoma?
o MDT management o Low Grade  Follicular, marginal zone, lymphocytic  If symptomless – watch and wait  Radiotherapy in local disease o High grade  Burkitt’s (characteristic jaw lymphadenopathy), lymphoblastic, diffuse large B-cell  Chemotherapy (R-CHOP regimen) with radiotherapy  Rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine (oncovin) and prednisolone  G-CSF helps neutropenia (filgrastim, lenograstim) o Pnuemococcal and influenza vaccine o MenC and Hib vaccine
55
Survival rate of lymphoma?
- 5-year survival rate >90% (NHL 70%)
56
Definitions of myeloma?
Progressive malignant disease of plasma cells that normally produce immunoglobulin o Proliferation of abnormal monoclonal immunoglobulins (M proteins) in the blood, referred to as paraproteinaemia  Genetic changes in terminal differentiation of B lymphocytes into plasma cells (1/2 translocation of oncogene onto heavy chain of chromosome 14) o Affects multiple organs and systems including bones, kidneys, blood and immune systems
57
What does myeloma evolve from? What is smouldering myeloma?
- Almost all patients evolve from asymptomatic pre-malignant stage called – monoclonal gammopathy of undetermined significance (MGUS) - Smouldering myeloma – asymptomatic myeloma with no evidence of myeloma-related organ or tissue injury or event
58
Epidemiology of myeloma?
- Second most common haematological malignancy - 2% of cancer related deaths - Prevalence increasing - Classified according to which immunoglobulin produced - Most commonly IgG (other IgA, IgD, IgM)
59
Risk factors of myeloma?
o Men o Black people, Pacific islanders and Maori o Increasing age o FHx
60
Incidental findings seen in myeloma?
o Normochromic, normocytic anaemia o Renal Impairment o Hypercalcaemia o Raised ESR, plasma viscosity, serum protein or globulin
61
Suspect multiple myeloma in adults>60 if symptoms?
o Unexplained bone pain (often lower back or thoracic)  Osteolytic bone lesions o Fatigue o Hypercalcaemia (bone pain, abdominal pain, depression, confusion, muscle weakness, thirst, polyuria) o Weight loss o Hyperviscosity symptoms (headache, visual disturbances, cognitive impairment) o SCC o Fever o Recurrent infections
62
Signs of myeloma?
o Hepatomegaly o Splenomegaly o Lymphadenopathy
63
When to perform tests in primary care when suspecting myeloma?
>60 with persistent bone pain (particularly back) or unexplained fracture:  FBC, Ca, ESR and plasma viscosity If possible myeloma & >60 with hypercalcaemia or leukopenia/raised plasma viscosity and ESR  Very urgent protein electrophoresis and Bence-Jones protein urine test (within 48 hours)  Consider – peripheral blood film, U&E, X-rays of bone pain If results of protein electrophoresis or urinary Bence Jones protein suggest myeloma - refer for 2 week appointment - Blood film Appearance (plasma cells and rouleux formation seen)
64
Laboratory, diagnostic tests in secondary care of myeloma?
Serum protein electrophoresis and serum-free light-chain assay If serum electrophoresis abnormal – use serum immunofixation Bone marrow aspirate and trephine biopsy confirms diagnosis of myeloma Morphology and flow cytometry determine plasma cell percentage and phenotype
65
Diagnosis of myeloma, smouldering myeloma and monoclonal gammopathy of undetermined significance (MGUS)?
 Symptomatic myeloma • Clonal plasma cells >10% on bone marrow biopsy, monoclonal protein in either serum or urine, end-organ damage (CRAB)  Asymptomatic myeloma (smouldering) • Serum paraprotein >30g/L, +/- clonal plasma cells >10% on bone marrow biopsy, no organ damage  Monoclonal gammopathy of undetermined significance (MGUS) • Serum paraprotein <30g/L, clonal plasma cell <10% on bone marrow biopsy and no organ damage
66
Prognostic testing in myeloma?
Same sample for diagnostic and prognostic tests on bone marrow FISH on CD-138-selected bone marrow plasma cells • Identify t(4:14), t(14:16), 1q gain, del(1p) and del (17p)(TP53 deletion) – adverse risk abnormalities • Consider t(14:20) and t(11:14) and hyperdiploidy Immunophenotyping & immunohistochemistry on trephine biopsy • Plasma cell phenotype
67
Imaging tests in myeloma?
o Offer to all people with plasma cell disorder suspected of myeloma o Whole-body MRI (whole-body CT is MRI unsuitable, skeletal survey third-line) Multiple well-defined lytic lesions – raindrop appearance
68
General management of myeloma?
o Prompt psychological assessment and support when needed – Refer if needed o Lifestyle measures to optimise bone and renal function o How to identify MSCC o Patient support groups
69
Management of transplant eligible patients in myeloma?
 First line • Induction – bortezomib +/- dexamethasone and thalidomide • Stem Cell Transplant – First autologous SCT or Allogenic SCT (Letermovir if CMV positive)  Second Line • Daratumumab + Bortezomib + Dexamethasone (used for treating relapsed patients after 1 previous treatment)  Subsequent Treatment (treating relapsed and refractory multiple myeloma) • Daratumumab • Ixazomib + lenalidomide + dexamethasone • Pomalidomide + dexamethasone • Lenalidomide + Dexamethasone  Relapse • Medical 2nd line treatment OR 2nd autologous stem cell transplantation
70
Management of transplant ineligible patients in myeloma?
 First Line • Induction – bortezomib +/- dexamethasone and thalidomide (OR lenalidomide + dexamethasone)  Second Line (used for treating relapsed patients after 1 previous treatment) • Lenalidomide + Dexamethasone • Daratumumab + Bortezomib + Dexamethasone • Carfilzomib + Dexamethasone  Subsequent Treatments (treating relapsed and refractory multiple myeloma) • Daratumumab • Ixazomib + lenalidomide + dexamethasone • Pomalidomide + dexamethasone • Panobinostat + Bortezomib + Dexamethasone • Lenalidomide + Dexamethasone
71
Prevention of bone disease and infection in myeloma?
Bone Disease  Zoledronic Acid (OR Disodium pamidronate OR Sodium Clodronate)  Dental Assessment ``` Infection  Seasonal Influenza Vaccine  Consider: • Pneumococcal vaccine (<65) • IVIG if hypogammaglobulinemia and recurrent infections • Aciclovir • Screen for HepB, HepC, HIV ```
72
Monitoring in smouldering myeloma, treated myeloma and disease progression?
o Smouldering Myeloma – every 3 months for 1st 5 years then decide o Treated myeloma – at least every 3 months  Includes: FBC, U&E, bone profile, serum Ig and protein electrophoresis, serum-free light chain assay o Disease progression – Whole-body MRI (Spinal MRI)
73
Complications of myeloma?
o Pathological bone fractures (osteolysis from proliferation of abnormal plasma cells) o Spinal Cord Compression o Renal Damage (obstruction of renal tubules by excess light chains) o Impaired resistance to infection (leukopenia and abnormal immunoglobulins) o Anaemia o Bleeding disorders o Hyperviscosity of blood
74
Management of acute renal disease in myeloma?
 Start borezomib + dexamethasone immediately
75
Management of fatigue in myeloma?
 Erythropoietin analogues if anaemic
76
Management of non-spinal bone disease in myeloma?
 Zoledronic Acid (OR Disodium pamidronate OR Sodium Clodronate)  Consider surgical stabilisation, radiotherapy
77
Management of peripheral neuropathy in myeloma?
 If on bortezomib – switch to SC, reduce dose or move to weekly
78
Management of spinal bone disease in myeloma?
 Zoledronic Acid (OR Disodium pamidronate OR Sodium Clodronate)  Adjuncts – interventional pain management, bracing. Surgery, radiotherapy
79
Prognosis of myeloma?
- Usually incurable disease - Survival ranges from weeks to years - Most people respond to initial treatment and enter period of stability however, relapse is inevitable and usually occurs after 2-5 years