Bone Marrow Transplant Flashcards
Describe the principles of cyclical chemotherapy
There are always both normal cells and cancer cells present
The chemotherapy will kill both the cancer cells and the normal cells
The normal cells will bounce back quicker and therefore if further chemotherapy is given the cancer cells will be reduced more than the normal body cells
Why do we do transplants?
They offer salvage for disease that is not curable by chemotherapy alone
How do we choose a donor?
Well matched for tissue type - HLA type
Ideally sibling
Which are the HLA class I molecules?
HLA-A, -B and -C
Present peptide to CD8+ (cytotoxic T-cells)
What are HLA class II molecules?
HLA-DP, -DQ and -DR
Present peptide to CD4+ (helper T cell)
Where is HLA encoded?
Major histocompatibility complex on chromosome 6
What is the function of HLA?
Present foreign peptides to T cells
What are the benefits of haematopoietic stem cell transplants?
Can use higher dose chemotherapy so haematopoietic stem cells can rescue them afterwards
What are the steps of autologous transplantation?
Give growth factor
Collect and freeze stem cells
Thaw and reinfuse following high dose chemotherapy
What is given as the growth factor in autologous transplantation?
GCSF
Granulocyte colony stimulating factor
When is autologous transplantation suitable?
Acute leukaemia Solid tumours Autoimmune disease Myeloma Lymphoma Chronic lymphocytic leukaemia
What are the steps of allogenic transplantation?
High dose chemotherapy +/- radiotherapy to the patient
Bone marrow or peripheral stem cells transplanted from donor
When is allogenic transplantation suitable?
Acute leukaemia Chronic leukaemia Myeloma Lymphoma BM failure Congenital immune deficiencies
What are the principles of transplantation?
Identify disease unlikely to respond to standard treatment
Treat patient to remission
Identify donor and collect stem cells
Give patient myeloablative therapy
Infuse stem cells
Continue immunosuppression and support patient through period of cytopenia
What are the possible complications of stem cell transplantation?
Graft failure
Infections
GVHD
Relapse
What is the aim collection from stem cell sources?
2 x 10^6/kg CD34+ cells
What is GVHD?
Graft versus host disease
An immune response when donor cells recognise the patient as foreign
What is affected in acute GvHD?
Skin
GI tract
Liver
What is affected in chronic GvHD?
Skin Mucosal membranes Lungs Liver Eyes Joints
What is time considered acute GvHD?
Up to 3months / 100 days
What is the basis of staging and grading GvHD for skin, liver and GI?
Skin - area covered
Liver - bilirubin
GI - quantity of diarrhoea
What are the risk factors for acute GvHD?
Degree of HLA disparity Recipient age Conditioning regimen R/D gender combination Stem cell source Disease phase Viral infections
What is the treatment of acute GVHD?
Corticosteroids Calcineurin inhibitors Mycophenylate mofetil Monoclonal antibodies Photopheresis Total lymphoid irradiation Mesenchymal stromal cells
What is used for prevention of acute GvHD?
Methotrexate Corticosteroids Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus CsA plus MTX T-cell depletion Post-transplant cyclophosphamide
How is chronic GvHD different?
Immune dysregulation
Immune deficiency
Impaired end-organ function
Decreased survival
What are the symptoms of chronic GvHD?
Dry eyes Oral lesions Nail dystrophy Skin sclerosis Deep sclerosis Bronchiolitis obliterans Loss of bile ducts Skin ulcers
What are the risk factors for chronic GvHD?
Prior acute GvHD Increased degree of HLA disparity Male recipient: female donor Stem cell source (PB>BM>UCB) T-cell replete Older donor age Use of DLI
What are the most frequently isolated organisms in bacterial infections in transplant patients?
Gram positive e.g. staph epidermis
What organisms cause most deaths from sepsis in transplant patients?
Gram negative organisms e.g. E. coli, pseudomonas aeruginosa
What are the sources of fungal infection?
Yeasts from translocation from the intestinal mucosa or indwelling catheters
Moulds: inhalation, chronic sinusitis, skin, mucosa
What virus is of particular concern in transplant patients?
CMV
Why is CMV relevant in transplant patients?
Member of herpes virus family: primary infection usually as a child, remains latent
Can be reactivated if immunosuppressed
Reactivation does not always result in infection
How can CMV manifest in transplant patients?
Pneumonitis
Retinitis
Gastritis - colitis
Encephalitis
How do we prevent CMV in transplant patients?
Twice weekly quantitative monitoring of peripheral blood viraemia to day 100
Thresholds for treatment together with evidence of increasing viral load
Ganciclovir/valganciclovir: oral and IV preparations
Minimum of 2/52 treatment with clear evidence of reduction in viral load
What are some other viral complications of SCT?
EBV: acute infection, PTL
Respiratory: influenza, parainfluenza, respiratoyr syncytial virus, rhino, metapneumovirus, COVID-19
PAPOVA viruses: BK and haemorrhagic cystitis
Adenovirus
What affects the outcome of transplants?
Age Disease phase Gender of R/D Time to BMT Donor
What was learnt through trying to remove T cells from the donor product?
The donor lymphocytes are essential in achieving remission and curing the patient
