Introduction to Haematology lecture Block Myeloma

Question 1

what is the classification of haematological malignancies based on?

Answer 1

disease behaviour & lineage

Question 2

what are the 4 classes of haematological malignancies?

Answer 2

acute, chronic, myeloid, lymphoid

Question 3

what is multiple myeloma?

Answer 3

Neoplastic proliferation of bone marrow plasma cells
( bone marrow cancer)

Question 4

what does multiple myeloma feature?

Answer 4

-The accumulation of malignant plasma cells in the bone marrow leading to progressive bone marrow failure
-The production of a characteristic paraprotein
-Kidney failure
-Destructive bone disease and hypercalcaemia

Question 5

what is multiple myeloma characterised by?

Answer 5

-Monoclonal protein in serum/urine
-Lytic bone lesions/ CRAB end organ damage
-Excess plasma cells in bone marrow

Question 6

why is multiple myeloma difficult to diagnose?

Answer 6

difficult to diagnose as it has non-specific symptoms

Question 7

what criteria do you need for diagnosis?

Answer 7

-Protein in blood
-Bone marrow plasma cells in excess of 10%
-CRAB (cancer renal anaemia bone)

Question 8

describe CRAB

Answer 8

C - ad Ca>0.25mmol/l above upper limit of normal or >2.75mmol/l
R – renal impairment, creatinine>173mmol/l (40% pts at Δ have some degree of RF; 10% req dialysis Dimopolous et al, 2008, Leukaemia, 22, 1485-1493 Pathogenesis and treatment of renal failiure in multiple myeloma)
A – anaemia 2g <NR or <10g/dl (75% at diagnosis; normochromic, normocytic, Kyle et al 2003)
B – lytic lesions, osteoporosis c compression #, spinal cord compression

Question 9

what are the chromosomal abnormalities associated with multiple myeloma?

Answer 9

-T(11;14) most common
-13q- associated with treatment resistance and poorer prognosis

Question 10

what are the common presenting features of multiple myeloma?

Answer 10

-Tiredness and malaise
-Bone/back pain +/- fractures
-Infections
-Non-specific
-Laboratory – anaemia, abnormal FBC, renal failure, hypercalcaemia, raised globulins, raised ESR, serum/urine paraprotein

Question 11

what is plasma cell dycrasias?

Answer 11

an abnormal state of a body part

Question 12

what does MGUS stand for?

Answer 12

monoclonal gammopathy of undetermined significance

Question 13

smouldering myeloma

Answer 13

when you’ve surpassed certain thresholds
paraprotein is larger than 30g/l or larger than 10% plasma cells in bm

Question 14

symptomatic myeloma

Answer 14

evidence of end organ damage- but must ensure that its not driven by anaemia, renal or any other reasons and must be due to the myeloma

Question 15

what is MGUS?

Answer 15

mainly stable
very little risk for it to progress into myeloma

Question 16

which type of myeloma do you treat?

Answer 16

only treat symptomatic myeloma
for MGUS and smouldering myeloma you just watch and wait

Question 17

name 4 examples of plasma cell dyscrasias

Answer 17

-Myeloma
-Solitary plasmacytomas
-Multiple solitary plasmacytoma
-Extramedullary plasmacytoma

Question 18

what is the main cause of death in myeloma ?

Answer 18

infection- but if caught early it can be manageable

Question 19

what is amyloidosis?

Answer 19

a group of rare, serious conditions caused by a build-up of an abnormal protein called amyloid in organs and tissues throughout the body

Question 20

describe the response rates of multiple myeloma

Answer 20

-Many respond to treatment, but all will eventually relapse
-Can we prolong survival by keeping the disease in plateau phase rather than try and cure it
-Both disease and treatment have morbidity – sickness and mortality – death

Question 21

what are the aims of treatment?

Answer 21

Reduce number of myeloma cells
Reduce symptoms and complications ie protect body organs and tissues
Improve quality and length of life

Question 22

what are the 5 types of anti- myeloma chemotherapies?

Answer 22

1. Monoclonal antibodies – daratumumab (anti CD38)
2. Proteasome inhibitors – bortezomib (sc), carfilzomib (iv), ixazomib (po)
3. Immunomodulatory drugs – thalidomide and analogues lenalidomide (Revlimid) and pomalidomide
4. Corticosteroids – dexamethasone, prednisolone
5. Alkylating agents – cyclophosphamide, melphalan