Bone Marrow Transplant Flashcards
Which CD marker is expressed on haematopoietic stem cells?
CD34
Recall the process of autologous transplant
- Give G-CSF: lots of stem cells leak into blood
- Freeze (drop temp + store in liquid N2)
- Pt has chemo/radio to permanently destroy their haematopietic system
- Re-infuse stem cells from freezer
What is autologous stem cell transplant used for?
To allow a higher dose of chemo/ radio to be given
Acute leukaemia, solid tumours, AI disease
Myeloma, Lymphoma + CLL
Describe the process of allogeneic stem cell transplant
- Give G-CSF to donor with normal BM
- Treat pt with high-dose chemo + radio to ablate their BM
- Give patient harvested cells
When should allogenic stem cell transplant be used?
Acute leukaemias
Chronic leukaemia
Myeloma
Lymphoma
BM failure
Congenital immune deficiencies
Thalassaemia
SCD
Recall some principles of donor choice for a bone marrow transplant
- HLA-matched
- Ideally a sibling (1 in 4 chance of matching with each sibling)
How is patient’s room pressure adjusted to prevent infection during BM transplant?
Make it a higher pressure than corridor so that air flows out rather than in
What kind of matching is preferential?
High resolution (DNA) vs low resolution (Serological)
Describe bone marrow sampling from the pelvis
Puncturing bone + getting to medulla damages it
First few ml contains stem cells, the rest is blood flowing into damaged site
Keep re-puncturing, collect small amount each time
Describe peripheral blood sampling
G-CSF used to stimulate granulocyte production
BM releases some white cells + stem cells
Donor connected to centrifuge which spins blood, removes the white cell component + re-infuses the rest
What proportion of CD34 can be harvested from each source?
Pelvis: 1.5L, 1% CD34 = 15ml CD34
Peripheral: 10L, 1%CD34 = 100ml CD34
Umbilical: 0.1L, 1% CD34 = 1ml CD34
Which patients can receive umbilical cord blood cells?
Only babies
As can only harvest a small volume Success depends on number of CD34 cells per kg of weight of recipient
List 4 complications of stem cell transplant
Graft failure
Infections
GVHD (Allografting only)
Relapse
Which 5 factors contribute to the EBMT risk score for the outcomes of transplants?
Age: <20, <40, 40+
Disease phase: Early, Int, Late
Gender of R/D
Time to BMT: <1 / >1
Donor: Sib / VUD
List 4 risk factors for infection post stem cell transplant
Neutropenia
Breakdown of protective barriers
Decreased antibody levels
Depressed T-cell immune responses
Name 2 infections commonly seen in SCT patients
Aspergillosis: high mortality if invasive
CMV: CMV pneumonia high mortality
What is graft versus host disease?
An immune response when the donor cells recognise the patient as foreign
What is the time frame for acute GvHD? What symptoms and signs arise?
<100d
Rash, itchy, red skin
Diarrhoea
Hepatitis + Jaundice
What is the time frame for chronic GvHD? What symptoms and signs arise?
> 100d
Rash
Hepatitis + Jaundice
Dry mucous membranes + mouth ulcers
SOB
Dry eyes
Arthritis
How does GvHD arise?
Damaging the skin, GIT + other tissues by giving chemo causes release of cytokines which activates APCs
These present the antigens to the donor lymphocytes
Immune reaction against host tissue
Give 4 risk factors for GvHD
Degree of HLA disparity
Conditioning regimen
Stem cell source (BM, Periphery, Umbilical)
R/D gender combination
What is the treatment for GvHD?
Corticosteroids
Ciclosporin
Monoclonal antibodies
Photophoresis
Give 3 prophylactic measures for GvHD
Corticosteroids
Ciclosporin
Methotrexate
How does the goal differ in autologous and allogenic BM transplant?
Auto: Kill all leukaemia with radio/ chemo
Allo: Accept cannot kill leukaemia from radio/ chemo, rely on BM from donor
Which cells are thought to cause GvHD? Why can’t this be avoided?
Maturę lymphocytes in donor sample (rather than those produced by donor stem cells)
Impossible to select out specific T cells- some will be mature lymphocytes
But don’t want to isolate as donor lymphocytes are important in prevention of relapse
What is considered to be the future in transplant therapy?
CAR-T cells
Engineer autologous T cells to recognise + destroy cancer cells
Give 3 side effects of CAR-T therapy
Tumour lysis syndrome
Cytokine release syndrome
Neurologic toxicity
