Stem Cell Transplantation Flashcards
How are donors for stem cell transplantation chosen?
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 are the chances of HLA match within a family?
Each sibling has a 25% 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.
Which patients are autologous stem cell transplants suitable for?
Acute leukaemia
Solid tumours
Autoimmune disease
Myeloma
Lymphoma
Chronic lymphocytic leukaemia
Which patients are allogenic stem cell transplants suitable for?
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 a donor and collect stem cells
Give patient myeloablative therapy
Infuse stem cells
Continue immunosuppression & support patient through period of cytopenia
Where do haemopoeitic stem cells come from?
Umbilical cord
Plasma
Bone marrow
What are complications associated with stem cell transplant?
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.
What are risk factors for GvHD?
Degree of HLA disparity
Recipient age
Conditioning regimen
R/D gender combination
Stem cell source
Disease phase
Viral infections
What is the treatment for acute GvHD?
Corticosteroids
Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
Mycophenylate mofetil
Monoclonal antibodies
Photopheresis
Total lymphoid irradiation
Mesenchymal stromal cells
How can acute GvHD be prevented?
Methotrexate
Corticosteroids
Calcineurin inhibitors: cyclosporin A, tacrolimus, sirolimus
CsA plus MTX
T-cell depletion
Post-transplant cyclophosphamide
What are features 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 risk factors for chronic GvHD?
Affects 50% of patients who survive >1 year from transplant.
- 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 main sources of infection in neutropenic patients?
Gram +ve: Vascular access
Gram -ve: GI tract