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
What are the most common causative organisms of bacterial infections in neutropaenic patients?
In neutropenic patients, the causative organism is identified in approximately one third of patients.
The most frequently isolated organisms are gram positive eg, staph epidermidis.
Most deaths from sepsis are due to gram negative organisms eg e.coli, pseudomonas aeruginosa.
Reduced incidence of infection using isolation measures and broad spectrum oral antibiotics.
How is neutropaenic sepsis managed?
Emergency situation
Defined as temperature >38 sustained for one hour, or single fever >39, in a patient with neutrophils <1.0 x 109/L.
Assess patient: Temperature, pulse, oxygen saturation and blood pressure. History and examination for evidence of source.
Blood cultures, MSU, CXR.
Initiate empirical broad spectrum antibiotics and supportive care.
Which fungal infections are common in neutropaenic patients?
Yeasts from translocation from the intestinal mucosa, or indwelling catheters.
Moulds: Inhalation, chronic sinusitis, skin, mucosa.
What is the association between CMV and neutropaenia?
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.
What are manifestations for CMV?
Pneumonitis
Retinitis
Gastritis – colitis
Encephalitis
How is CMV prevented?
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.
Which other viruses can cause complications in stem cell transplants?
EBV: Acute infection, PTLD
Respiratory viruses: Influenza, parainfluenza, respiratory syncytial virus, rhino, metapneumovirus, COVID-19
PAPOVA viruses: BK and haemorrhagic cystitis.
Adenovirus
What affects the outcome of a transplant?
Age: <20=0, 20-40=1, >40=2
Disease phase: Early=0, Int=1, Late=2
Gender of R/D: Female into male = 1
Time to BMT: <1yr=0, >1yr=1
Donor: Sib=0, VUD=1
