Haematology 15 - Bone Marrow Transplant Flashcards
(23 cards)
Which CD marker is expressed on haematopoietic stem cells?
CD34
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
Which patients can receive umbilical cord blood cells?
Only children - as you can only harvest a small volume so patient needs to be of a low weight
What are bone marrow transplant donors matched on?
tissue type (HLA type) HLA-A/B/C (class I) - present peptides to CD8+
HLA-DP/DQ/DR (class II) - present peptides to CD4+
What is the probability of having an HLA match with a sibling?
1 in 4 chance of matching with each sibling
1-(3/4) number of siblings
Serological vs dna HLA testing
- serology = low resolution matching (broad group)
- DNA = high resolution matching
Recall the process of autologous transplant
- GCSF given (stimulates stem cell release into bloods)
- obtain a CD34+ cells from BM (stem cells) → preserve and freeze
- high dose chemo → eradicate BM
- reinfuse stem cells
What is autologous stem cell transplant used for?
- Acute leukaemia
- Solid tumours
- Autoimmune disease
also , as allogeneic dangerous for following pop (high transplant related mortality)
Myeloma/ lymphoma/ CLL
Describe the process of allogeneic stem cell transplant
- high dose chemoradiotherapy to ablate BM (malignant and normal cells)
- then give BM from healthy donor
When should allogenic stem cell transplant be used?
Bone marrow failure
when patient’s disease unlikely to be eradicated from BM by standard chemotherapy
- Acute leukaemia
- Chronic leukaemia
- Thalassaemia
- Myeloma
- Lymphoma
- SCD
- Bone marrow failure
- Congenital immune deficiencies
Main difference between autologous and allogenic SCT
Autologous HSCT → goal to kill all leukaemia with radio/chemo
Allogenic HSCT → accepted you cannot kill leukaemia from radio/chemo → rely on BM from donor
What type of infections can you get with BM transplantation?
organism depends on time after transplant
- bacterial - when pt neutropenic (<30 days)
- viral - dependent on total recovery of lymphocytes and macrophages (up to 1 yr)
- fungus - candida early
What are some common causes of bacterial infection after BM transplant?
most common - gram positive (skin - e.g. staph epidermis)
but most deaths from sepsis gram neg (gut - e coli, pseudomonas, aeruginosa)
What are some common causes of viral infection after BM transplant?
CMV (pneumonitis/retinitis/gastritis/colitis/encephalitis)
ABV, resp. PAPOVA, adenovirus
What is graft vs host disease?
immune response when donor cells recognise patient as foreign
Pathophysiology of GvHD
- high dose chemo → cell damage → cytokine storm
- cytokines activate APCs → present Ag to donor lymphocytes
- → immune reaction against host tissue
- could wait for longer after chemo for effects to die down before giving stem cell transplant - but increases time susceptible to infection
NB - GvHD happens v soon after transplant - so likely due to mature lymphocytes in donor sample rather than lymphocytes produced from stem cells
S/S of acute GvHD
<100days
Skin rash, itchy, red
GI tract diarrhoea
Liver hepatitis, jaundice
S/S of chronic GvHD
>100 days – similar to Sjögren’s
- Skin rash
- Liver hepatitis, jaundice
- Mucosal membranes dry, mouth ulcers
- Lungs SoB
- Eyes dry
- Joints arthritis
treatment for GvHD
Corticosteroids
Calcineurin inhibitors (tacrolimus, cyclosporin A, sirolimus)
Mycophenolate mofetil
Monoclonal antibodies
Photopheresis
Total lymphoid irradiation
Mesenchumal stromal cells
prevention of GvHD
immunosuppressing patients
- methotrexate
- corticosteroids
- Cs A + MTX
- Calcineurin inhibitors (tacrolimus, cyclosporin A, sirolimus)
- T cell depletion
- Post-transplant cyclophosphamide
Describe T cell depletion
remove T cells from stem cell product before giving to pt
ex-vivo: monocloncal Ab aginst T cells → kills lymphocytes
but pts with TCD relapsed → but more donor lymphocytes restores remission → graft vs leukaemia effect
With lymphocytes = infection control, no leukaemia relapse, GvHD
Removing lymphocytes = infection (CMV), leukaemia relapse, no GvHD
Transplant outcome is measured using this risk score
EBMT risk score:
What is the strongest prognostic factor for cGvHD?
prior acute GvHD
