W17 - Intro to SCT Flashcards
why do we do cyclical chemotherapy in terms of normal cell vs cancer cell count?
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
Each organ has a diff tolerance to irradiation - T or F?
True
Name 3 HLA molecules of class I and 3 for class II
Class I - HLA-A, HLA-B, HLA-C
Class II - HLA-DP, HLA-DQ, HLA-DR
Which 3 HLA are commonly used for compatibility purposes?
HLA-A, HLA-B, HLA-DR
The probability that each sibling is HLA-identical with patient is….
25% (1/4)
Describe 4 step process of autologous transplantation?
- Give GFs
- BM will release more stem cells + WBCs => collect SCs and freeze
- high dose chemo
- Thaw and re-infuse HSCs
Which conditions (6) can autologous transplantation treatment be used for?
- Acute leukaemia
- Solid tumours
- Autoimmune disease
- Myeloma
- Lymphoma
- Chronic lymphocytic leukaemia
*technically shouldn’t work well for 4, 5, 6 where BM is affected but it does!!
Which conditions (6) can allogeneic BM/peripheral blood SC transplantation treatment be used for?
- Acute leukaemia
- Chronic leukaemia
- Myeloma
- Lymphoma
- BM failure
- Congenital immune
deficiencies
Name 3 sources of HSCs
- BM
- PB
- UC
Name 4 big complications of SCT
- Graft failure
- Infections
- GVHD (allografting only)
- Relapse
Which organs does acute GvHD affect?
Which organs does chronic GvHD affect?
Acute GvHD = skin, GI tract, liver
Chronic GvHD = skin, mucosal membranes, lungs, liver, eyes, joints
In GvHD, the response from the donor to host tissue is a _____ response
cellular (T cell) usually
The rash described in GvHD is a _______ rash
maculopapular
The advancement of GvHD is based on 3 factors - name them
- Skin damage (measured by % SA)
- Liver damage (measured by bilirubin)
- GI damage (measured by quantity of diarrhoea)
Name 7 risk factors for acute GvHD
- High degree of HLA mismatch
- Older age
- Radiation in the conditioning regimen
- Male with female donors (many female donors may have had children, incl. male children, and are likely to have seen Y antigens)
- PB as stem cell source (less GVHD with BM)
- More advanced disease
- Viral infections (presumably if you have a viral infection, your T cells may be excited with that)
2 treatments of acute GvHD
- Corticosteroids
- Calcineurin inhibitors (cyclosporin A, tacrolimus)
- these 2 are usually background drugs)
then we can add: - monoclonal abs
- photophoresis
- total lymphoid irradiation
- mesenchymal stromal cells (can have anti-inflammatory effects)
*dont really need to know
3 main steps to prevent acute GvHD
- methotrexate
- Corticosteroids
- Calcineurin inhibitors (cyclosporin A, tacrolimus)
- can do T cell depletion from donor
- can do post-transplant cyclophosphamide (dampen cytokine storm)
Describe what immune abnormalities chronic GvHD involves? What is the prognosis?
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.
When is chronic GvHD usually diagnosed?
within 6 months of transplant
Describe 9 clinical features of chronic GvHD?
- dry eyes
- oral lesions
- nail dystrophy
- skin sclerosis
- deep sclerosis (of organs)
- bronchiolitis obliterans
- loss of bile ducts
- fasciitis
- skin ulcers
Name 7 risk factors for chronic GvHD
- Prior acute GvHD
- High degree of HLA mismatch
- Male with female donors
- PB as stem cell source (PB>BM>UCB)
- T cell depletion
- Older donor age
- Use of donor lymphocyte infusion (DLI)
At what phase are transplant patients susceptible to bacterial infections? Name the types of bacteria that are common.
Phase I (pre-engraftment):
- Gram negative bacilli
- Gram positive organisms
- GI streptococci species
Phase III (late phase): encapsulated bacteria
At what phase are transplant patients susceptible to viral infections? Name the types of viruses that are common.
Phase I (pre-engraftment) Phase II (post-engraftment) Phase III (late phase)
- Herpes simplex virus => Phase I to III
- Cytomegalovirus => Phase II to III
- Resp and enteric viruses (seasonal) => Phase I to III
- EBV, etc => Phase II to III
(viral later phases b/c dependent on total recovery of lymphocytes/macrophages) - Varicella zoster => phase III
At what phase are transplant patients susceptible to fungal infections? Name the types of fungi that are common.
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.
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
Vascular access = G+
GI tract = G-
Neutropenic sepsis - what is it?
Defined as temperature >38 sustained for one hour, or single fever >39, in a patient with neutrophils <1.0 x 109/L
How is neutropenic sepsis managed (5 things)?
- Assess patient (temp; pulse; O2 sat; BP; evidence of source of infection)
- Blood cultures
- MSU
- CXR
- Initiate empirical broad spectrum abx + supportive care
CMV - primary infection usually as a child, remains latent and can be reactivated if immunosuppressed - T or F
True
What 4 things does CMV disease include?
- Pneumonitis
- Retinitis
- Gastritis - colitis
- Encephalitis
(these are all really bad - you want to notice the reactivation early and treat it before the viruses causes 1 of these)
How do we prevent(4 steps) CMV disease post-transplant?
- 2x weekly pos-ttransplant peripheral blood viraemia to day 100
- Threshold for treatment together with evidence of increasing viral load
- Antiviral regiments
- Minimum 2/52 treatemnts reduces viral load
What 5 factors affect the outcome of HSCT?
- Age (young vs old)
- Disease phase (early vs advanced)
- Gender of R/D (i.e. male to male better)
- Time to BM transplantation (less than 1 year, over 1 year)
- Donor (sibling vs unrelated donor)
When leukaemia patients received SCT that were T cell depleted, they got no GvHD, but had early disease relapse! How was this resolved?
Infusing patient with more donor lymphocytes restores remission!!
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
2) Transplant related mortality after allografting in unacceptably high in most patients with myeloma
1) wrong b/c can’t get GVHD from your own transplant
3) wrong because there is also myeloma left behind
What is the strongest prognostic factor in cGvHD?
- Older donor age
- Prior acute GvHD
- Use of peripheral derived stem cells
- Prior acute GvHD
Cytomegalovirus reactivation:
- typically occurs in the first 15 days after transplant
- Can be prevented by giving prophylactic abx
- is more common in CMV seropositive compared to seronegative
- is more common in CMV seropositive compared to seronegative
- wrong = 30 days after transplant onwards
- virus cant be treated with abx
