Bone Marrow transplantation

Question 1

what is autologous transplantation suitable for

Answer 1

acute leukaemia, solid tumours, autoimmune disease, myeloma, lymphoma, chronic lymphocytic leukaemia

Question 2

how does autologous transplantation work

Answer 2

o GCSF given and obtain a CD34+ population of cells from the bone marrow (the stem cells)
o These are preserved in the freezer
o A high dose of chemotherapy is given to eradicate the bone marrow  reinfuse the stem cells

Question 3

how does allogenic transplant work

Answer 3

o Used when patient’s disease is unlikely to be eradicated from the bone marrow by standard chemotherapy
o Give them high dose chemoradiotherapy to ablate the bone marrow (malignant and normal cells)
o Then give them some bone marrow from a healthy donor
o Issue with BM transplantation is that donor immune cells recognise patient as foreign…

Question 4

what is allogenic transplant used for

Answer 4

 Acute leukaemia Chronic leukaemia Thalassaemia
 Myeloma Lymphoma SCD
 Bone marrow failure Congenital immune deficiencies

Question 5

how does bone marrow sampling work

Answer 5

o Difficult  involves anaesthetising the patient and sampling some bone marrow from their pelvis
o Puncturing the bone and getting into the medulla damages it, meaning that the first few millilitres that you collect will contain stem cells, however, the rest of it will be blood flooding into the damages site
o So, you keep re-puncturing the bone, collecting a small amount at a time until you have a good harvest

Question 6

how does pheripheral blood sampling work

Answer 6

o	Hormones (e.g. G-CSF) can be used to stimulate granulocyte production (given 5 days before) 
o	This leads to the bone marrow releasing some white cells as well as some stem cells 
o	The donor is connected to a centrifuge device which spins the blood, removes the white cell component, reassembles the red cells and plasma and reinfuses it into the patient

Question 7

what factors contribute to the EBMT risk score

Answer 7

= EBMT risk score:
o Age <20=0,20-40=1,>40=2
o Disease phase Early=0, int=1, late=2 Higher score = less chance of successful outcome
o Gender of R/D Female into male = 1 VUD = Volunteer Unrelated Donor
o Time to BMT <1 yr = 0, >1 yr = 1
o Donor Sib = 0, VUD = 1

Question 8

what is acute graft versus host disease

Answer 8

• Acute GvHD (<100 days) effects:
o Skin rash, itchy, red
o GI tract diarrhoea
o Liver hepatitis, jaundice

Question 9

what is chronic graft versus host disease

Answer 9

(>100 days) effects – similar to Sjögren’s; ranked by severity (04): 
o	Skin 			rash	
o	Liver 			hepatitis, jaundice
o	Mucosal membranes 	dry, mouth ulcers
o	Lungs			SoB
o	Eyes 			dry
o	Joints 			arthritis

Question 10

what is the method of CAR-T therapy

Answer 10

o CAR-T therapy overview:
 (1) Leukapheresis (T-cells are collected)
 (2) T-cell activation (engineered chimeric-TCR put into a virus which infects the collected T-cells)
 (3) Modified T-cell expansion (new T cells are expanded)
 (4) Quality and release testing: potency checks and infection checks
 (5) Chemotherapy
 (6) Modified T-cell infusion

Question 11

car-t toxicity side effects

Answer 11

o Tumour lysis syndrome (rarely occurs)
o Cytokine release syndrome (potentially fatal – chimeric T-cells can release massive amounts of cytokines)
o Neurologic toxicity, cytopaenia (macrophage activation syndrome), B-cell aplasia (hypogammaglobulinaemia)
 

Question 12

how does graft vs host disease occur

Answer 12

• Damaging the skin, GI tract and various other tissues by giving chemotherapy will cause the release of cytokines which activates APCs, which then present the antigens to the donor lymphocytes  immune reaction against the host tissue