W17 - Intro to SCT

Question 1

why do we do cyclical chemotherapy in terms of normal cell vs cancer cell count?

Answer 1

b/s with each cycle of chemo round, the number of cancer cells falls a bit more because the normal cells have a better ability to recover than the cancer cells. so with many cycles, cancer cells will deplete

Question 2

Each organ has a diff tolerance to irradiation - T or F?

Answer 2

True

Question 3

Name 3 HLA molecules of class I and 3 for class II

Answer 3

Class I - HLA-A, HLA-B, HLA-C
Class II - HLA-DP, HLA-DQ, HLA-DR

Question 4

Which 3 HLA are commonly used for compatibility purposes?

Answer 4

HLA-A, HLA-B, HLA-DR

Question 5

The probability that each sibling is HLA-identical with patient is….

Answer 5

25% (1/4)

Question 6

Describe 4 step process of autologous transplantation?

Answer 6

1. Give GFs
2. BM will release more stem cells + WBCs => collect SCs and freeze
3. high dose chemo
4. Thaw and re-infuse HSCs

Question 7

Which conditions (6) can autologous transplantation treatment be used for?

Answer 7

1. Acute leukaemia
2. Solid tumours
3. Autoimmune disease
4. Myeloma
5. Lymphoma
6. Chronic lymphocytic leukaemia

*technically shouldn’t work well for 4, 5, 6 where BM is affected but it does!!

Question 8

Which conditions (6) can allogeneic BM/peripheral blood SC transplantation treatment be used for?

Answer 8

1. Acute leukaemia
2. Chronic leukaemia
3. Myeloma
4. Lymphoma
5. BM failure
6. Congenital immune
   deficiencies

Question 9

Name 3 sources of HSCs

Answer 9

1. BM
2. PB
3. UC

Question 10

Name 4 big complications of SCT

Answer 10

1. Graft failure
2. Infections
3. GVHD (allografting only)
4. Relapse

Question 11

Which organs does acute GvHD affect?
Which organs does chronic GvHD affect?

Answer 11

Acute GvHD = skin, GI tract, liver
Chronic GvHD = skin, mucosal membranes, lungs, liver, eyes, joints

Question 12

In GvHD, the response from the donor to host tissue is a _____ response

Answer 12

cellular (T cell) usually

Question 13

The rash described in GvHD is a _______ rash

Answer 13

maculopapular

Question 14

The advancement of GvHD is based on 3 factors - name them

Answer 14

1. Skin damage (measured by % SA)
2. Liver damage (measured by bilirubin)
3. GI damage (measured by quantity of diarrhoea)

Question 15

Name 7 risk factors for acute GvHD

Answer 15

1. High degree of HLA mismatch
2. Older age
3. Radiation in the conditioning regimen
4. Male with female donors (many female donors may have had children, incl. male children, and are likely to have seen Y antigens)
5. PB as stem cell source (less GVHD with BM)
6. More advanced disease
7. Viral infections (presumably if you have a viral infection, your T cells may be excited with that)

Question 16

2 treatments of acute GvHD

Answer 16

1. Corticosteroids
2. Calcineurin inhibitors (cyclosporin A, tacrolimus)
   - these 2 are usually background drugs)
   then we can add:
3. monoclonal abs
4. photophoresis
5. total lymphoid irradiation
6. mesenchymal stromal cells (can have anti-inflammatory effects)

*dont really need to know

Question 17

3 main steps to prevent acute GvHD

Answer 17

1. methotrexate
2. Corticosteroids
3. Calcineurin inhibitors (cyclosporin A, tacrolimus)

• can do T cell depletion from donor
• can do post-transplant cyclophosphamide (dampen cytokine storm)

Question 18

Describe what immune abnormalities chronic GvHD involves? What is the prognosis?

Answer 18

It involves immune dysregulation (involves auto-abs) and immune deficiency, leading to impaired end-organ function. There is decreased survival with relatively poor 5 year survival.

Question 19

When is chronic GvHD usually diagnosed?

Answer 19

within 6 months of transplant

Question 20

Describe 9 clinical features of chronic GvHD?

Answer 20

• dry eyes
• oral lesions
• nail dystrophy
• skin sclerosis
• deep sclerosis (of organs)
• bronchiolitis obliterans
• loss of bile ducts
• fasciitis
• skin ulcers

Question 21

Name 7 risk factors for chronic GvHD

Answer 21

1. Prior acute GvHD
2. High degree of HLA mismatch
3. Male with female donors
4. PB as stem cell source (PB>BM>UCB)
5. T cell depletion
6. Older donor age
7. Use of donor lymphocyte infusion (DLI)

Question 22

At what phase are transplant patients susceptible to bacterial infections? Name the types of bacteria that are common.

Answer 22

Phase I (pre-engraftment):

1. Gram negative bacilli
2. Gram positive organisms
3. GI streptococci species

Phase III (late phase): 
encapsulated bacteria

Question 23

At what phase are transplant patients susceptible to viral infections? Name the types of viruses that are common.

Answer 23

Phase I (pre-engraftment) 
Phase II (post-engraftment) 
Phase III (late phase) 

1. Herpes simplex virus => Phase I to III
2. Cytomegalovirus => Phase II to III
3. Resp and enteric viruses (seasonal) => Phase I to III
4. EBV, etc => Phase II to III
   (viral later phases b/c dependent on total recovery of lymphocytes/macrophages)
5. Varicella zoster => phase III

Question 24

At what phase are transplant patients susceptible to fungal infections? Name the types of fungi that are common.

Answer 24

Phase I (pre-engraftment) 
Phase II (post-engraftment) 
Phase III (late phase) 

Aspergillus => Phase I to III
Candida => Phase I to II
Pneumocystis => Phase II to III

*most of us have aspergillus spores in our sinuses waiting for us to become immunosuppressed.

Question 25

In transplanted patients, patients become susceptible to bacterial infections if neutropenic. Name 2 common sources and the Gram status of the bacteria associated with each

Answer 25

Vascular access = G+ GI tract = G-

Question 30

Neutropenic sepsis - what is it?

Answer 30

Defined as temperature \>38 sustained for one hour, or single fever \>39, in a patient with neutrophils \<1.0 x 109/L

Question 31

How is neutropenic sepsis managed (5 things)?

Answer 31

1. Assess patient (temp; pulse; O2 sat; BP; evidence of source of infection) 2. Blood cultures 3. MSU 4. CXR 5. Initiate empirical broad spectrum abx + supportive care

Question 32

CMV - primary infection usually as a child, remains latent and can be reactivated if immunosuppressed - T or F

Answer 32

True

Question 33

What 4 things does CMV disease include?

Answer 33

1. Pneumonitis 2. Retinitis 3. Gastritis - colitis 4. Encephalitis (these are all really bad - you want to notice the reactivation early and treat it before the viruses causes 1 of these)

Question 34

How do we prevent(4 steps) CMV disease post-transplant?

Answer 34

1. 2x weekly pos-ttransplant peripheral blood viraemia to day 100 2. Threshold for treatment together with evidence of increasing viral load 3. Antiviral regiments 4. Minimum 2/52 treatemnts reduces viral load

Question 35

What 5 factors affect the outcome of HSCT?

Answer 35

1. **Age** (young vs old) 2. **Disease phase** (early vs advanced) 3. **Gender of R/D** (i.e. male to male better) 4. **Time to BM transplantation** (less than 1 year, over 1 year) 5. **Donor** (sibling vs unrelated donor)

Question 36

When leukaemia patients received SCT that were T cell depleted, they got no GvHD, but had early disease relapse! How was this resolved?

Answer 36

Infusing patient with more donor lymphocytes restores remission!!

Question 37

Autografting, rather than allografting, is the preferred option for treating myeloma because: 1) There is a stronger graft versus myeloma effect from autografting than allografting 2) Transplant related mortality after allografting in unacceptably high in most patients with myeloma 3) Myeloma cells can be efficiently removed from an autologous stem cell product

Answer 37

2) Transplant related mortality after allografting in unacceptably high in most patients with myeloma ## Footnote 1) wrong b/c can't get GVHD from your own transplant 3) wrong because there is also myeloma left behind

Question 38

What is the strongest prognostic factor in cGvHD? 1. Older donor age 2. Prior acute GvHD 3. Use of peripheral derived stem cells

Answer 38

2. Prior acute GvHD

Question 39

Cytomegalovirus reactivation: 1. typically occurs in the first 15 days after transplant 2. Can be prevented by giving prophylactic abx 3. is more common in CMV seropositive compared to seronegative

Answer 39

3. is more common in CMV seropositive compared to seronegative ## Footnote 1. wrong = 30 days after transplant onwards 2. virus cant be treated with abx