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8. CP - Core Haematology > (41) Lymphoma and myeloma > Flashcards

(41) Lymphoma and myeloma Flashcards

1
Q

What stages of B cell differentiation occur in the bone marrow?

A

Pro-B cells become pre-B cells which become immature B cells

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2
Q

What is the pathway of plasma cell differentiation called?

A

NF-kB pathway

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3
Q

What does an error in the NF-kB pathway lead to?

A

Plasma cell dysplasia

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4
Q

What are immunoglobulins?

A

Glycoprotein molecules produced by plasma cells in response to an immunogen

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5
Q

Describe the structure of an immunoglobulin

A

Composed of 4 polypeptide chains - 2 light chains and 2 heavy chains which are held together by covalent disulphide bridges

Each chain has one variable and one constant region

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6
Q

How are immunoglobulins classified?

A

According to the amino acid sequences in the constant region of the:

  • heavy chains (IgG, IgM, IgA, IgD, IgE)
  • light chains (kappa or lambda)
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7
Q

What is protein electrophoresis?

A

Lab technique whereby serum is placed in a gel and exposed to an electric current

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8
Q

In protein electrophoresis, 5 major fractions are normally identified. What are they?

A
  • serum albumin
  • alpha-1 globulins
  • alpha-2 globulins
  • beta globulins
  • gamma globulins
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9
Q

What is immunofixation?

A

Enables the detection and identification of monoclonal immunoglobulins - performed when “M-spike” seen on electrophoresis

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10
Q

How is immunofixation done?

A
  • serum or urine is placed on a gel and electric current is applied to separate the proteins
  • anti-immunoglobulin antisera is added to each migration lane
  • if the immunoglobulin is present, a complex is precipitated
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11
Q

What is myeloma?

A

An incurable malignant disorder of clonal plasma cells

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12
Q

What is the incidence of myeloma?

A

Annual incidence = 60-70 millions in the UK

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13
Q

What is the median age at presentation of myeloma?

A

70 years

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14
Q

Which ethnicity has a higher incidence of myeloma?

A

Afro-Carribean ethnic groups have a higher incidence compared with Caucasians

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15
Q

Myeloma is preceded by what?

A

Asymptomatic MGUS

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16
Q

Myeloma is one of a spectrum of plasma cell dyscrasias. What is at the bottom and top end?

A

Bottom end = MGUS

Top end = myeloma and then plasma cell leukaemia (PCL)

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17
Q

What else is on the spectrum of plasma cells dyscrasias?

A
  • MGRS
  • high-risk MGUS (almost certainly will progress to myeloma)
  • asymptomatic myeloma
  • amyloidosis
  • solitary plasmacytoma (with or without minimal bone marrow involvement)
  • systemic AL amyloidosis
  • POEMS syndrome
  • myeloma with adverse cellular features
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18
Q

How is myeloma diagnosed? (using IMWG diagnostic criteria)

A

Clonal bone marrow plasma cells more than 10% or biopsy-proven bony or extra medullary plasmacytoma AND any one of the - CRAB features - MDEs

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19
Q

In myeloma, more than 10% of the plasma cells in the bone marrow are what?

A

Noeplastic / clonal

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20
Q

What is a plasmacytoma?

A

Discrete, solitary mass of neoplastic monoclonal plasma cells in either bone or soft tissue (extra medullary) eg. lump of plasma cells on femur

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21
Q

What are the CRAB features? (used in diagnosis of myeloma)

A

C = hypercalcaemia (more than 2.75mmol/L)

R = renal insufficiency (creat clearance less than 40ml/min or serum creat more than 177mmol/L)

A = anaemia (Hb less than 100g/L)

B = bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET/CT)

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22
Q

What is the ‘C’ of the myeloma CRAB features?

A

Hypercalcaemia (more than 2.75mmol/L)

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23
Q

What is the ‘R’ of the myeloma CRAB features?

A

Renal insufficiency (creatinine clearance of less than 40ml/min OR serum creatinine of more than 177mmol/L)

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24
Q

What is the ‘A’ of the myeloma CRAB features?

A

Anaemia (Hb of less than 100g/L)

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25
Q

What is the ‘B’ of the myeloma CRAB features?

A

Bone lesions (one or more osteolytic lesions on skeletal radiography, CT, or PET/CT)

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26
Q

What are the myeloma-defining events (MDEs) using in diagnosing myeloma?

A
  • over 60% clonal plasma cells on bone marrow biopsy
  • SFLC ratio of more than 100mg/L provided the absolute level of the involved LC is more than 100mg/L
  • more than 1 focal lesion on MRI measuring more than 5mm
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27
Q

What does SFLC stand for?

A

Serum free light chains

28
Q

How does myeloma affect the kidney?

A
  • 20-25% will have renal insufficiency at diagnosis
  • 50% will have renal sufficiency at some point during disease course
  • 50% will have persistent renal impairment despite therapy
  • 2-12% will require RRT
29
Q

Name 9 external factors that can affect the kidney, other than myeloma

A
  • renal vein thrombosis
  • bisphosphonates
  • hypercalcaemia
  • ACE inhibitors
  • dehydration
  • NSAIDs
  • CT contrast
  • hyperviscosity
  • type 1 cryoglobulinaemia
30
Q

Acute kidney injury with suspected myeloma is a medical injury. What drug should you give before test results even come back?

A

Steroids

31
Q

Acute kidney injury with suspected myeloma is a medical emergency. What tests should be done? (within 24 hrs)

A
  • blood film
  • electrophoreses
  • immunofixation
  • bone marrow biopsy with flow cytometry
32
Q

Describe the process of intensive therapy in myeloma

A
  • chemotherapy is given (VCD)
  • G-CSF is given and stem cells are harvested
  • chemotherapy (melphalan if given)
  • stem cells are given back

This allows bone marrow to recover

33
Q

What is G-CSF?

A

Granulocyte-colony stimulating factor

34
Q

What are some newer agents in myeloma intensive therapy?

A
  • daratumumab (antiCD138)
  • carfilzomib (proteosome inhibitor)
  • ixazomib (proteosome inhibitor)
  • various combinations of the above
35
Q

Allogenic hematopoietic stem cell transplantation (HSCT) is sometimes used in second remission but it is controversial, why?

A
  • high transplant-related mortality

- high relapse rate

36
Q

What does the future involve for myeloma treatment?

A
  • individualised therapy (particularly for those with high risk disease)
  • monoclonal antibodies
  • targeted therapies
  • maintenance therapy
37
Q

What are the basics in management of myeloma?

A
  • early diagnosis and intervention - STEROIDS!

- simple measures like hydration, avoid nephrotoxics, and appropriate chemotherapy (attenuated dosing)

38
Q

What is the MGUS diagnostic criteria?

A
  • serum M-protein (paraprotein) less than 30g/L
  • less than 10% clonal plasma cells in bone marrow
  • absence of end-organ damage (CRAB)
39
Q

What is MGUS?

A

Monoclonal gammopathy of undetermined significance (MGUS) is a condition in which an abnormal protein (monoclonal protein, or M protein) is in the blood. M protein is produced by plasma cells, a type of white blood cell. Monoclonal gammopathy of undetermined significance usually causes no problems

40
Q

Who gets MGUS?

A
  1. 2% = less than 50 years
  2. 3% = less than 70 years
  3. 9% = less than 80 years

affects more men than women

41
Q

What is the risk of progression of MGUS?

A

Approx 1% per year

42
Q

What does MGUS progress to?

A

Majority progress to myeloma (27%)

Others progress to:

  • Waldenstrom’s macroglobulinaemia
  • primary AL amyloidosis
  • lymphoproliferative disorders
43
Q

What makes MGUS more likely to progress?

A

If there is high M-protein (more than 15g/L), IgA/IgM rather than IgG paraprotein, abnormal SFLC ratio

44
Q

Congo red stain preparates is indicative for what?

A

The presence of amyloid fibrils

45
Q

What is AL amyloidosis?

A

Amyloid light chain (AL) amyloidosis

- light chain fragments misfold and self-aggregate to form beta-pleated fibrils

46
Q

How common is AL amyloidosis?

A

600 new cases in the UK per year

47
Q

Describe the proteinuria in AL amyloidosis?

A

Nephrotic-range proteinuria:

  • mainly albumin
  • small monoclonal light chain component
48
Q

What are the other systemic components of AL amyloidosis?

A
  • cardiac and liver involvement in 30%
  • peripheral neuropathy in 10%
  • end stage renal failure in 40%
49
Q

What are the possible malignant causes of a neck mass?

A
  • lymphoma
  • chronic lymphocytic leukaemia
  • metastatic cancer of the lung/breast/cervix
50
Q

What are the possible non-metastatic causes of a neck mass?

A
  • infective (bacterial, viral, mycobacterial)
  • inflammatory (sarcoidosis)
  • lipoma
  • fibroma
  • haemangioma
51
Q

What would you see on a lymph node biopsy in a follicular lymphoma?

A

Lots of large pale follicles in the lymph nodes (follicles normal but increase in number)

Lymphoma - B cells form giant follicles

52
Q

What is follicular lymphoma?

A

Neoplastic disorder of lymphoid tissue - type of non-Hodgkin lymphoma characterised by slowly enlarging lymph nodes

53
Q

Follicular lymphoma is a type of what?

A

Non-Hodgkin lymphoma - accounts for 15% of all non-Hodgkin lymphoma diagnoses

54
Q

Incidence of follicular lymphoma rises with what?

A

With age

M=F

55
Q

What is the chromosomal abnormality in follicular lymphoma?

A

t(14;18)

Translocation between chromosomes 14 and 18 - over expression of bcl-2 protein = gives survival advantage to neoplastic lymphoid cells by inhibiting apoptosis

56
Q

What is the prognosis for follicular lymphoma?

A

Median survival = 8-10 years

Five year overall survival = 72-77%

57
Q

What is used to prognosticate in follicular lymphoma?

A

The Follicular Lymphoma International Prognostic Index (FLIPI)

58
Q

What factors does the FLIPI include?

A
  • age over 60 years
  • Ann Arbor stage III or IV
  • LDH above limit of normal at diagnosis
  • Hb less than 120g/L
  • presence of more than 4 nodal sites of disease

4 or more prognostic factor, 10 year survival = 36% rather than 71%

59
Q

What is the incidence of Hodgkin lymphoma?

A

2.7 per 100,000 per year

60
Q

Hodgkin lymphoma is characterised by…

A
  • presence of Hodgkin Reed-Sternberg (HRS) cells within a cellular infiltrate of non-malignant inflammatory cells eg. eosinophils
61
Q

How do HRS cells (in Hodgkin lymphoma) evade apoptosis?

A

HRS fails to express surface immunoglobin and evade apoptosis through several mechanisms eg.

  • activation of NFkB
  • incorporation of EBV and latent membrane proteins (LMP1 and LMP2)
62
Q

What are different classifications of Hodgkin lymphoma?

A
  • nodular lymphocyte predominant
  • classical:
  • nodular sclerosis
  • mixed cellularity
  • mixed lymphocyte-rich
  • lymphocyte depleted
63
Q

How is Hodgkin lymphoma treated?

A
  • chemotherapy eg. ABVD

- radiotherapy

64
Q

What signs are favourable in Hodgkin lymphoma?

A
  • ESR less than 50 and no B syx
  • ESR less than 30 and B six
  • no large mediastinal LN
  • age les than 50
  • 1-3 LN sites involved
65
Q

What is the prognosis for Hodgkin lymphoma?

A
  • high proportion are cured (86% 5 year survival)
  • long term effects of therapy are important:
  • increased mortality still see over 20 years post-therapy
  • pulmonary toxicity
  • cardiovascular disease
  • secondary malignancies

8. CP - Core Haematology (11 decks)

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