Stem Cell Transplant

Question 1

What are the main indications for autologous SCT?
What about allogenic SCT?

Answer 1

Autologous - MM, Hodgkins and NHL
Allogenic SCT - Myeloid disorders (AML, MDS, pyeloproliferative neoplasma) + ALL

Question 2

How are haematopoetic stem cells obtained?

Answer 2

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

Question 3

Is the risk of GVH disease higher with peripheral blood or bone marrow used to obtain the Haem SCs?

Answer 3

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

Question 4

What are the subdivisions of HLA that are compared in the process of doner and host matching?

Answer 4

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

Question 5

Explain the different doner possibilities for allogenic SCT?

Answer 5

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

Question 6

What is the role of conditioning in autologous SCT? What about allogenic SCT?

Answer 6

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

Question 7

What are teh two types of allogenic conditioning regimes?

Answer 7

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

Question 8

What is the main risk in autologous stem cell transplant?

Answer 8

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

Question 9

What is the main risk in allogenic stem cell transplant?

Answer 9

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

Question 10

Explain the various infections and the time course of these infections post allogenic SCT?

Answer 10

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

Question 11

Who typicality gets fungal diseases post allogenic stem cell transplant?

Answer 11

People with GVHD because duration of immunosupression is much longer (ie indefinite)

Question 12

Explained prophylaxis strategies post SCT?

Answer 12

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

Question 13

Why is porphylaxis with acyclovir or valacylovir prefered over valgan or gan in SCT pts?

Answer 13

Because valgan and gan are meylosupressive (we want the graft to grow)

Question 14

What is the biggest risk factors for post transplant lymphoproliferative disease?

Answer 14

EBV infection (DNA virus that incorperates into DNA therefore is oncogenic)

Question 15

Pt has high levels of EBV viraemia post SCT. What are they most at risk of?

Answer 15

Post transplant lymphoproliferative disease

Question 16

How is high levels of EBV treated post transplant?

Answer 16

Rituxumab
- EBV needs the B cell to replicate, therefore kill B cell kills EBV

Question 17

Which antiviral agents are effective against CMV?

Answer 17

Valganciclovir
Gancyclovir
Letermovir

(Acyclovir and valacyclovir are not)

Question 18

What is letermovir? what is the indication for use?

Answer 18

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

Question 19

What is GVHD in SCT? (basically)

Answer 19

Immune system, usually T cells initially but can include B cell chronically , of the graft attacking the host immune system

Question 20

Where is acute GVHD usually seen?

Where can chronic GVHD occur?

Answer 20

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

Question 21

There are many regimes for GVHD proph. What is one of the main ones and what is the regime?

Answer 21

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

Question 22

IF you have a haploidentical doner, what is the preferred Post transpolant GVHD prophylaxis?

Answer 22

Post transplant cyclophosphamide given day 3

Question 23

WHen does acute GVHD classically occur?

Answer 23

<100 days post transplant

Question 24

What is the most severe / worst prog maniferstation of chronic GVHD? How does this manifest?

Answer 24

Lung involvement
Manifests as bronchiolitis obliterans
- Obstructive picture on PFTs, minimal CT change until advanced

Question 25

Mainline therapy for GVHD?

Answer 25

Steroids, usually systemic if moderate or survival

Other medications include
- Ruxolitinib (JAK 1 and 2 inh)

Question 26

What would be the best agent for steroid refractory acute graft vs host disease? What about chronic?

Answer 26

Ruxolitinib

Also ruxolitinib in chronic

Question 27

What is sinusoidal obstructive syndrome?

Answer 27

due to conditioning regime and immune mediated injury following allogenic stem cell transplant, the liver sinusoidal cells are damaged and slough off and then obstruct the sinusoids leading to reduced hepatic outflow and liver damage

THe hallmark is increasing bilirubin and weight gain (fluid retention)

Question 28

When would you suspect sinusoidal obstructive disease vs acute GVHF involving the liver?

Answer 28

Bili rises early ie in first fe weeks (first 21 days), with associated weight gain then suspect sinusoidal obstructive disease

Need to do liver Bx to confirm

Question 29

What is the prophylaxis agent used to prevent sinusoidal obstructive disease?

Answer 29

urodeoxycholic acid to day 90

Question 30

What is a low doner CD34 count indicative off at time of grafting?

Answer 30

Higher rates of graft failure
- CD34 is basically a marker of number of lymphoctyes in the graft. More lymphocytes = more chance of engraftment