Haem: Bone Marrow Transplantation Flashcards
Which organ in the body is most resistant to radiation?
CNS
NOTE: bone marrow is very vulnerable to radiation
What is the main cellular marker of stem cells?
CD34
What is the risk of dying from bone marrow transplant?
More than 50%
It is the most expensive and risky elective procedure
Outline the process of autologous stem cell transplantation.
- 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
What are the most common reasons for autologous stem cell transplantation?
- Myeloma
- Lymphoma
- CLL
When is allogeneic bone marrow transplantation used?
- When it is very unlikely that the patient’s disease will be eratdiacted from the bone marrow by standard chemotherapy
NOTE: suitable for acute leukaemia, chronic leukaemia, myeloma, lymphoma, bone marrow failure, congenital immune deficiencies
List some parameters used to gauge outcome of transplantation techniques.
- Overall survival
- Disease-free survival
- Transplant-related mortality
- Relapse incidence
State an equation that relates the probability of having a sibling with a matching tissue type to the number of siblings a patient has.
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
What are the main classes of HLA based on?
- Serological reactions (e.g. HLA-A)
- It can be increasingly specified by DNA sequencing
Name three ways of harvesting stem cells.
- Bone marrow sampling
- Peripheral blood sampling
- Umbilical cord stem cells
Why is bone marrow sampling a difficult process?
- 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
Outline the process of peripheral blood sampling for stem cells.
- 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
- 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
What proportion of a sample taken during stem cell sampling actually contains stem cells?
1%
What factor (related to stem cell harvesting) does the success of a bone marrow transplant depend on?
Number of CD34 cells per kg of weight of the recipient
List some complications of stem cell transplantation.
- Graft failure
- Infections
- GvHD
- Relapse
Listsome other factors affecting the outcome of a bone marrow transplant.
- Age
- Disease phase (early or late)
- Gender of recipient and donor
- Time to BMT
- Donor (sibling or not)
NOTE: this is used to calculate the EBMT risk score
List some risk factors for infection that are related to bone marrow transplantation.
- Neutropaenia
- Breakdwon of protective barriers
- Decreased antibody levels
- Depressed T cell responses
What are the risk factors for CMV infection following bone marrow transplantation?
- Patient and donor serological status
- Type of stem cells
- Type of transplant
- CMV viral load
Which parts of the body are affected in acute graft-versus-host disease?
- Skin
- GI tract
- Liver
Which parts of the body are affected in chronic graft-versus-host disease?
- Skin
- Mucosal membranes
- Lungs
- Liver
- Eyes
- Joints
Why must patients receiving chemotherapy or radiotherapy have a treatment-free interval before stem cell transplantation?
Chemotherapy and radiotherapy can damage tissues leading to the release of loads of cytokines which activate antigen-presenting cells which present antigens to donor lymphocytes.
List some risk factors for acute graft-versus-host disease.
- Degree of HLA disparity
- Recipient age
- Conditioning regimen
- Recipient and donor gender combination (male donors with female patients have worse GvHD)
- Stem cell source
- Disease phase
- Viral infections
List some treatment options for GvHD.
- Corticosteroids
- Ciclosporin A
- FK506
- Mycophenolate mofetil
- Monoclonal antibodies
- Photophoresis
- Total lymphoid irradiation
List some drugs used to prevent GvHD.
- Methotrexate
- Corticosteroids
- Ciclosporin A
- FK506
- T cell depletion
- Post-transplant cyclophosphamide
Which component of the transplanted cells is responsible for GvHD?
- It is the mature lymphocytes within the cell population (i.e. not the stem cells) that are responsible for GvHD
- You cannot, however, remove these mature lymphocytes from the sample because they are important in preventing relapse
