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Haematology (E) > Bone Marrow Transplant > Flashcards

Bone Marrow Transplant Flashcards

1
Q

Describe the principles of cyclical chemotherapy

A

There are always both normal cells and cancer cells present
The chemotherapy will kill both the cancer cells and the normal cells
The normal cells will bounce back quicker and therefore if further chemotherapy is given the cancer cells will be reduced more than the normal body cells

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2
Q

Why do we do transplants?

A

They offer salvage for disease that is not curable by chemotherapy alone

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3
Q

How do we choose a donor?

A

Well matched for tissue type - HLA type

Ideally sibling

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4
Q

Which are the HLA class I molecules?

A

HLA-A, -B and -C

Present peptide to CD8+ (cytotoxic T-cells)

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5
Q

What are HLA class II molecules?

A

HLA-DP, -DQ and -DR

Present peptide to CD4+ (helper T cell)

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6
Q

Where is HLA encoded?

A

Major histocompatibility complex on chromosome 6

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7
Q

What is the function of HLA?

A

Present foreign peptides to T cells

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8
Q

What are the benefits of haematopoietic stem cell transplants?

A

Can use higher dose chemotherapy so haematopoietic stem cells can rescue them afterwards

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9
Q

What are the steps of autologous transplantation?

A

Give growth factor
Collect and freeze stem cells
Thaw and reinfuse following high dose chemotherapy

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10
Q

What is given as the growth factor in autologous transplantation?

A

GCSF

Granulocyte colony stimulating factor

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11
Q

When is autologous transplantation suitable?

A 
Acute leukaemia
Solid tumours
Autoimmune disease
Myeloma
Lymphoma
Chronic lymphocytic leukaemia
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12
Q

What are the steps of allogenic transplantation?

A

High dose chemotherapy +/- radiotherapy to the patient

Bone marrow or peripheral stem cells transplanted from donor

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13
Q

When is allogenic transplantation suitable?

A 
Acute leukaemia
Chronic leukaemia
Myeloma
Lymphoma
BM failure
Congenital immune deficiencies
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14
Q

What are the principles of transplantation?

A

Identify disease unlikely to respond to standard treatment
Treat patient to remission
Identify donor and collect stem cells
Give patient myeloablative therapy
Infuse stem cells
Continue immunosuppression and support patient through period of cytopenia

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15
Q

What are the possible complications of stem cell transplantation?

A

Graft failure
Infections
GVHD
Relapse

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16
Q

What is the aim collection from stem cell sources?

A

2 x 10^6/kg CD34+ cells

17
Q

What is GVHD?

A

Graft versus host disease

An immune response when donor cells recognise the patient as foreign

18
Q

What is affected in acute GvHD?

A

Skin
GI tract
Liver

19
Q

What is affected in chronic GvHD?

A 
Skin 
Mucosal membranes
Lungs
Liver
Eyes
Joints
20
Q

What is time considered acute GvHD?

A

Up to 3months / 100 days

21
Q

What is the basis of staging and grading GvHD for skin, liver and GI?

A

Skin - area covered
Liver - bilirubin
GI - quantity of diarrhoea

22
Q

What are the risk factors for acute GvHD?

A 
Degree of HLA disparity
Recipient age
Conditioning regimen
R/D gender combination
Stem cell source
Disease phase
Viral infections
23
Q

What is the treatment of acute GVHD?

A 
Corticosteroids
Calcineurin inhibitors
Mycophenylate mofetil
Monoclonal antibodies
Photopheresis
Total lymphoid irradiation
Mesenchymal stromal cells
24
Q

What is used for prevention of acute GvHD?

A 
Methotrexate
Corticosteroids
Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
CsA plus MTX
T-cell depletion
Post-transplant cyclophosphamide
25
Q

How is chronic GvHD different?

A

Immune dysregulation
Immune deficiency
Impaired end-organ function
Decreased survival

26
Q

What are the symptoms of chronic GvHD?

A 
Dry eyes
Oral lesions
Nail dystrophy
Skin sclerosis
Deep sclerosis
Bronchiolitis obliterans
Loss of bile ducts
Skin ulcers
27
Q

What are the risk factors for chronic GvHD?

A 
Prior acute GvHD
Increased degree of HLA disparity
Male recipient: female donor
Stem cell source (PB>BM>UCB)
T-cell replete
Older donor age
Use of DLI
28
Q

What are the most frequently isolated organisms in bacterial infections in transplant patients?

A

Gram positive e.g. staph epidermis

29
Q

What organisms cause most deaths from sepsis in transplant patients?

A

Gram negative organisms e.g. E. coli, pseudomonas aeruginosa

30
Q

What are the sources of fungal infection?

A

Yeasts from translocation from the intestinal mucosa or indwelling catheters
Moulds: inhalation, chronic sinusitis, skin, mucosa

31
Q

What virus is of particular concern in transplant patients?

A

CMV

32
Q

Why is CMV relevant in transplant patients?

A

Member of herpes virus family: primary infection usually as a child, remains latent
Can be reactivated if immunosuppressed
Reactivation does not always result in infection

33
Q

How can CMV manifest in transplant patients?

A

Pneumonitis
Retinitis
Gastritis - colitis
Encephalitis

34
Q

How do we prevent CMV in transplant patients?

A

Twice weekly quantitative monitoring of peripheral blood viraemia to day 100
Thresholds for treatment together with evidence of increasing viral load
Ganciclovir/valganciclovir: oral and IV preparations
Minimum of 2/52 treatment with clear evidence of reduction in viral load

35
Q

What are some other viral complications of SCT?

A

EBV: acute infection, PTL
Respiratory: influenza, parainfluenza, respiratoyr syncytial virus, rhino, metapneumovirus, COVID-19
PAPOVA viruses: BK and haemorrhagic cystitis
Adenovirus

36
Q

What affects the outcome of transplants?

A 
Age
Disease phase
Gender of R/D
Time to BMT
Donor
37
Q

What was learnt through trying to remove T cells from the donor product?

A

The donor lymphocytes are essential in achieving remission and curing the patient

Haematology (E) (14 decks)

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