Stem cell Transplantation Flashcards
How do we choose a donor?
- Well matched for tissue type - also known as HLA type
- Ideally a sibling (one in four chance of matching with each sib)
- If not, a volunteer unrelated donor or minimally mismatched family member
- More recently, increased use of haploidentical family member – almost every patient has a donor
What is the HLA system?
A person’s tissue type comprises a set of distinct proteins called Human Leukocyte Antigens (HLA), found on the surface of most nucleated cells.
What HLA molecules are relevant in transplantation?
•HLA-A, -B, -C, (class I), present peptide to CD8+ (cytotoxic T-cells)•HLA-DP,-DQ and -DR (class II), present peptide to CD4+ (helper T-cells)
Where is HLA encoded?
HLA encoded by the Major Histocompatibility Complex, MHC, on chromosome 6
What is the function of HLA?
•Function – present foreign peptides to T cells
What HLA do we type in transplantation?
•Routinely, HLA-A, -B and DR are typed for compatibility purposes.
What is the chance of an HLA match within siblings?
Each sibling has a 35% chance of being HLA identical with the patient
Given n siblings the probability that at least one with be HLA0identical is given by the formula 1 – 3n/4n
What is autologous transplantation?
- Stimulate with GCF by SC injection
- Collect stem cells and freeze
- Thaw and rein fuse after chemotherapy
Good use: Multiple Sclerosis
What is allogeneic transplantation?
What are the principles of transplantation?
Where do we get stem cells from?
- Bone marrow
- Peripheral blood - done more now
- Umbilical cord
We need 2 million/kg CD34+ cells - easier to get this for BM and PB
What are the complications of SCT?
- Graft Failure
- Infections
- Graft-versus-host disease (GVHD):allografting only
- Relapse
What is GvHD?
- An immune response when donor cells recognise the patient as ‘foreign’•
- Acute GvHD affects skin, gastrointestinal tract and liver•
- Chronic GvHD affects skin, mucosal membranes, lungs, liver, eyes, joints - very like an AI disease like scleroderma
What has happened?
GvHD
What is the pathophysiology of GvHD?
What are the risk factors for acute GvHD?
- Degree of HLA disparity
- Recipient age
- Conditioning regimen
- R/D gender combination (male patients with female donors)
- Stem cell source
- Disease phase
- Viral infections
What is the treatment of acute GvHD?
- Corticosteroids
- Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
- Mycophenylate mofetil
- Monoclonal antibodies
- Photopheresis
- Total lymphoid irradiation
- Mesenchymal stromal cells
How do we prevent acute GvHD?
- Methotrexate
- Corticosteroids
- Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
- CsA plus MTX
- T-cell depletion•Post-transplant cyclophosphamide
What are the consequences of chronic GvHD?
- Immune dysregulation
- Immune deficiency,
- Impaired end-organ function
- Decreased survival.
What is the prognosis of chronic GvHD?
- Diagnosis within 6 months of transplant, lasts 2-5 years
- 85% of survivors can discontinue treatment at that time
- 5-year survival is 70–80%, in persons with low risk cGVHD and those responding to corticosteroids.
- Five-year survival is 30–40% for those with high-risk disease +/- failure of steroids
What are the signs of chronic GvHD?
What are the RFs 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
When do patients tend to get the infections?
Bacterial - early when pt is neutropenic
Viruses - much later - more to do with macrophages
Fungi - some very early like candida but aspergillus develops a little later
Pneumocystis - any time in the first couple of years
What are the main sources of infection in neutropenic patients?
