Stem Cell Transplant Flashcards
(30 cards)
What are the main indications for autologous SCT?
What about allogenic SCT?
Autologous - MM, Hodgkins and NHL
Allogenic SCT - Myeloid disorders (AML, MDS, pyeloproliferative neoplasma) + ALL
How are haematopoetic stem cells obtained?
donar given GCSF to stimulate haem stem cell to come out of bone marrow into peripheral blood
Then collect peripheral blood and use leukophoresis to separate the stem cells
Is the risk of GVH disease higher with peripheral blood or bone marrow used to obtain the Haem SCs?
peripheral blood
- this is because peripheral blood usually has more mature / activated T cells in it compared to bone marrow so can mount an attack
What are the subdivisions of HLA that are compared in the process of doner and host matching?
Major HLA
- Chrom 6
- CLass 1 (HLA A, B, C), class 2 (HLA DR, DQ, DP)
- Matched is associated with less GVH. Unmatched is associated with more GVH however an umatched doner is associated with less replase
Minor HLA
- Small peptide on cell surface that are in associated with class 1 or 2 HLA molecules
- Located throughout the genome
Explain the different doner possibilities for allogenic SCT?
Matched sibling
- Matched major HLAs
- statistically 50% matched minor HLAs on average
Matched unrelated
- Matched major HLAs
- Often unmatched minor HLAs
- High risk of GVH compared to matched sibling
Mismatched unrelated doner
- High rates of GVH. Low relapse rate
Haploidentical DOner
- Matched at half the HLAs
What is the role of conditioning in autologous SCT? What about allogenic SCT?
Basically autologous SCT allows you to give very strong chem agents whilt protecting stem and progenitior cells
- ie take out stem and progenitor cells
- Nuke the system with Chemo
- put back in the healthy cells to reform your bone marrow
Conditioning in allogenic SCT has several roles:
- Depletes the host stem cells and progenitor cells thereby clearing out the anatomical space required for engraftment
- It dampens down the host immune system to prevent rejection of the injected cells (ie gives them time to engraft)
- Chemo also depletes any malignant cells
What are teh two types of allogenic conditioning regimes?
Myeloablative conditioning
- this just kills the host bone marrow for good
- nil chance of host bone marrow recovery following this. therefore they are going to be entirely dependant on the graft, or if the graft fails the dependant on transfusions
- Also associated with a lot of inflammation therfore higher rates of GVHD
- Only offered to younger pts
- Associated with lower relapse rates
Reduced intensity conditioning
- Autologous recovery is possible
- Higher rates of relapse but lower rates of GVHD
- Can be given to much older pts
What is the main risk in autologous stem cell transplant?
Treatment related risks are usually quite low, main risk is relapse of initial condition or development of new haem malignancy
- mainly used as a way of prolonging remission (doesnt often cure the condition)
- Often increased rates of new malaignancies due to residual bone marrow exposure to conditioning chemo
What is the main risk in allogenic stem cell transplant?
Relapse overall is still the highest risk, but treatment related mortality is MUCH higher. The main causes for treatment related mortality are:
- Infection, organ failure (renal failure, liver failure), Graft vs host disease
Explain the various infections and the time course of these infections post allogenic SCT?
Early infections:
- very neuitropenic early, so get typical bacterial infections such as staph, strep, gram negative
- Especially line infection as these pts often have lines in
Late:
- due to the degree and length of immunosupression, fungal infection with candida and aspergilosis are important to consider
- CMV and EBV usually for pts on ongoing immunosupression
Viral infections can occur at any time. The most concerning one is CMV
Who typicality gets fungal diseases post allogenic stem cell transplant?
People with GVHD because duration of immunosupression is much longer (ie indefinite)
Explained prophylaxis strategies post SCT?
PJP - Bactrim (usually 1 year post)
FUngal - Prophylxis (1-3 months post)
HSV/.VZV - acyclovir/valacyclovir (often up to 2 years post)
CMV - survailence/prophylaxis
EBV - survailence
Why is porphylaxis with acyclovir or valacylovir prefered over valgan or gan in SCT pts?
Because valgan and gan are meylosupressive (we want the graft to grow)
What is the biggest risk factors for post transplant lymphoproliferative disease?
EBV infection (DNA virus that incorperates into DNA therefore is oncogenic)
Pt has high levels of EBV viraemia post SCT. What are they most at risk of?
Post transplant lymphoproliferative disease
How is high levels of EBV treated post transplant?
Rituxumab
- EBV needs the B cell to replicate, therefore kill B cell kills EBV
Which antiviral agents are effective against CMV?
Valganciclovir
Gancyclovir
Letermovir
(Acyclovir and valacyclovir are not)
What is letermovir? what is the indication for use?
Letermovir is a CMV active antiviral agent like valgan or gan
However it is not myelosupressive like these drugs, therefopre can be used post SCT
It is not very good against CMV disease, however is good for CMV prophylaxis
Used as CMV prophylaxis for CMV negative recipients of CMV positive doners
What is GVHD in SCT? (basically)
Immune system, usually T cells initially but can include B cell chronically , of the graft attacking the host immune system
Where is acute GVHD usually seen?
Where can chronic GVHD occur?
Skin, GIT, Liver
- not seen elsewhere, therefore if get question about lung GVHD then this is not acute
Chronic:
- skin, mouth, eyes, lungs
- ANy organ really
There are many regimes for GVHD proph. What is one of the main ones and what is the regime?
Post transplant cyclophosphamide
- commenced 3 days post transplant
- THis delay gives the graft immune cells time to recognisem and become activated against the host
- then when cyclophosphamide is given it targets the replicating active cells most, allowing the quiecent ones to survive more
IF you have a haploidentical doner, what is the preferred Post transpolant GVHD prophylaxis?
Post transplant cyclophosphamide given day 3
WHen does acute GVHD classically occur?
<100 days post transplant
What is the most severe / worst prog maniferstation of chronic GVHD? How does this manifest?
Lung involvement
Manifests as bronchiolitis obliterans
- Obstructive picture on PFTs, minimal CT change until advanced
