Haem: Bone Marrow Transplantation Pt.1

Question 1

Which organ in the body is most resistant to radiation?

Answer 1

CNS

NOTE: bone marrow is very vulnerable to radiation

Question 2

What is the main cellular marker of stem cells?

Answer 2

CD34

Question 3

What is the risk of dying from bone marrow transplant?

Answer 3

More than 50%

It is the most expensive and risky elective procedure

Question 4

Outline the process of autologous stem cell transplantation.

Answer 4

• Growht factor is given to the patient to stimulate the production of cells from the bone marrow
• Cells are sampled from the patient’s bone marrow (some of them will be CD34+ stem cells)
• These are preserved in a freezer
• High-dose chemotherapy is given to the patient to eradicate their bone marrow
• Stem cells are re-infused

Question 5

What are the most common reasons for autologous stem cell transplantation?

Answer 5

• Myeloma
• Lymphoma
• CLL

Question 6

When is allogeneic bone marrow transplantation used?

Answer 6

Acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune or haematological conditions

Question 7

What are some advantages of allogenic vs autologous HSCT

Answer 7

Autologous
* No GvHD
* No need to wait for match
* No risk of rejection

Allogenic
* Graft vs tumour effect (graft immune cells kill residual cancer cells)
* Reduced risk of disease recurrence (which can happen in autologous HSCT)

Question 8

List some parameters used to gauge outcome of transplantation techniques.

Answer 8

• Overall survival
• Disease-free survival
• Transplant-related mortality
• Relapse incidence

Question 9

State an equation that relates the probability of having a sibling with a matching tissue type to the number of siblings a patient has.

Answer 9

Probability of match = 1 — (3/4)^{number of siblings}

NOTE: there is a 25% chance that your sibling has the same tissue type as you

Question 10

What are the main classes of HLA based on?

Answer 10

• Serological reactions (e.g. HLA-A)
• It can be increasingly specified by DNA sequencing

Question 11

HLA molecules relevent for transplantation

Answer 11

HLA-A, B, C : Class I - Present to CD8+ (cytotoxic T cells)

HLA-DP, DQ, DR: Class II - Present peptide to CD4+ (Helper T cells)

6 HLAs, 2x Parents = Match rated /12

Question 12

Name three ways of harvesting stem cells.

Answer 12

• Bone marrow sampling
• Peripheral blood sampling
• Umbilical cord stem cells

Question 13

Why is bone marrow sampling a difficult process?

Answer 13

• It involves anaesthetising the patient and sampling bone marrow from the pelvis
• Puncturing the bone causes damage and only sampling a small number of stem cells means that re-puncturing of the bone is necessary

Question 14

Outline the process of peripheral blood sampling for stem cells.

Answer 14

• Hormones (e.g. G-CSF) is given to stimulate granulocyte production
• This leads to the bone marrow producing some stem cells along with the granulocytes
• G-CSF is given for 5 days and stem cells are harvested on the 5th day
• Apheresis - the donor is connected to a centrifuge which spins the blood, removes the white cell component, reassembles the red cells and plama and reinfuses it into the patient

Question 15

When are autologous stem cell transplants suitable

Answer 15

In Myeloma - Elderly - cant handle GvHD

Acute Leukaemia

Solid tumours

Germ cell tumours

Lymphoma

CLL

Question 16

List some other factors affecting the outcome of a bone marrow transplant.

Answer 16

• Age
• Disease phase (early or late)
• Sex of recipient and donor
• Time to BMT
• Donor (sibling or not)

NOTE: this is used to calculate the EBMT risk score

Question 17

Describe Allogenic Transplantation

Answer 17

1. Identify disease unlikely to respond to standard treatment
2. Treat patient into remission
3. Identify donor and collect stem cells
4. Give patient myeloablative therapy
5. Infuse stem cells
6. Continue immunosuppression and support patient through period of cytopenia