Bone Marrow Transplant

Question 1

Describe the principles of cyclical chemotherapy

Answer 1

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

Question 2

Why do we do transplants?

Answer 2

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

Question 3

How do we choose a donor?

Answer 3

Well matched for tissue type - HLA type

Ideally sibling

Question 4

Which are the HLA class I molecules?

Answer 4

HLA-A, -B and -C

Present peptide to CD8+ (cytotoxic T-cells)

Question 5

What are HLA class II molecules?

Answer 5

HLA-DP, -DQ and -DR

Present peptide to CD4+ (helper T cell)

Question 6

Where is HLA encoded?

Answer 6

Major histocompatibility complex on chromosome 6

Question 7

What is the function of HLA?

Answer 7

Present foreign peptides to T cells

Question 8

What are the benefits of haematopoietic stem cell transplants?

Answer 8

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

Question 9

What are the steps of autologous transplantation?

Answer 9

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

Question 10

What is given as the growth factor in autologous transplantation?

Answer 10

GCSF

Granulocyte colony stimulating factor

Question 11

When is autologous transplantation suitable?

Answer 11

Acute leukaemia
Solid tumours
Autoimmune disease
Myeloma
Lymphoma
Chronic lymphocytic leukaemia

Question 12

What are the steps of allogenic transplantation?

Answer 12

High dose chemotherapy +/- radiotherapy to the patient

Bone marrow or peripheral stem cells transplanted from donor

Question 13

When is allogenic transplantation suitable?

Answer 13

Acute leukaemia
Chronic leukaemia
Myeloma
Lymphoma
BM failure
Congenital immune deficiencies

Question 14

What are the principles of transplantation?

Answer 14

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

Question 15

What are the possible complications of stem cell transplantation?

Answer 15

Graft failure
Infections
GVHD
Relapse

Question 16

What is the aim collection from stem cell sources?

Answer 16

2 x 10^6/kg CD34+ cells

Question 17

What is GVHD?

Answer 17

Graft versus host disease

An immune response when donor cells recognise the patient as foreign

Question 18

What is affected in acute GvHD?

Answer 18

Skin
GI tract
Liver

Question 19

What is affected in chronic GvHD?

Answer 19

Skin 
Mucosal membranes
Lungs
Liver
Eyes
Joints

Question 20

What is time considered acute GvHD?

Answer 20

Up to 3months / 100 days

Question 21

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

Answer 21

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

Question 22

What are the risk factors for acute GvHD?

Answer 22

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

Question 23

What is the treatment of acute GVHD?

Answer 23

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

Question 24

What is used for prevention of acute GvHD?

Answer 24

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

Question 25

How is chronic GvHD different?

Answer 25

Immune dysregulation Immune deficiency Impaired end-organ function Decreased survival

Question 26

What are the symptoms of chronic GvHD?

Answer 26

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

Question 27

What are the risk factors for chronic GvHD?

Answer 27

``` 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 ```

Question 28

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

Answer 28

Gram positive e.g. staph epidermis

Question 29

What organisms cause most deaths from sepsis in transplant patients?

Answer 29

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

Question 30

What are the sources of fungal infection?

Answer 30

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

Question 31

What virus is of particular concern in transplant patients?

Answer 31

CMV

Question 32

Why is CMV relevant in transplant patients?

Answer 32

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

Question 33

How can CMV manifest in transplant patients?

Answer 33

Pneumonitis Retinitis Gastritis - colitis Encephalitis

Question 34

How do we prevent CMV in transplant patients?

Answer 34

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

Question 35

What are some other viral complications of SCT?

Answer 35

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

Question 36

What affects the outcome of transplants?

Answer 36

``` Age Disease phase Gender of R/D Time to BMT Donor ```

Question 37

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

Answer 37

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