HSCT and GvHD

Question 1

What are the four purposes of SCT?

Answer 1

1. Replacement therapy
2. Ablative therapy
3. Immunotherapy
4. Gene therapy

Question 2

What is replacement therapy?

Answer 2

Pts BM is damaged or doesnt exist so it does not make enough SCs, only treatment is to get someone elses SCs.

example is in aplastic anemia

Question 3

What is ablative therapy?

Answer 3

Pt has normal stem cells, but we use chemo to kill there stem cells.

• do this by first taking stem cells from the patient out, then you give them high dose chemo to kill everything in their body like a tumor, then you reinject the SCs back into the patient and allow them to repopulate the BM.
• imporant is the disease can not be of the stem cells otherwise wont work

Question 4

What is immunotherapy?

Answer 4

This is graft vs. tumor effect, which is desired

• you give the patient a slightly allogenic BM transplant in hope that the graft will kill the tumor
• you are using GvHD to your advantage to kill the tumor, basically giving the patient a new immune system

Question 5

What are the four type of SCT? examples of each?

Answer 5

autologous from self to self

synergenic from genetically indentical twin

allogeneic from matched sibling, or matched donor, also haploidentical donor which would be a parent, or cord blood

xenogeneic from another species

Question 6

What is the stem cell marker?

Answer 6

They are CD34 positive, and lineage negative

Question 7

Why would you use a slight HLA mistmatch

Answer 7

This is to use acute GvHD to your advantage to seek out a tumor

Question 8

What is most common cause of death in patients with chronic GvHD?

Answer 8

Infection

Question 9

What are the two most common fungal infections in pateitns following transplantation?

Answer 9

Candida Albicans and Aspergillus Niger

Question 10

•3 year old boy was brought to the pediatrician with a history of failure to thrive, fever and h/o recurrent diarrhea that now has become chronic. On examination, the boy appears malnourished, small for age, mild pallor, slightly distended abdomen, and mild hepatomegaly. Temperature was 100.8 degrees F. CBC showed Hemoglobin 9.6 g/dl (low); WBC 2200/μl (low); Platelet 240,000/μl (normal). Liver function test showed slightly elevated alkaline phosphatase and normal AST and ALT. Stool test was positive for cryptosporidium. CD4; CD19; CD20 counts were normal. Immunoglobulin panel showed low IgG, low IgA and low IgE level and very high IgM level. HIV test was negative in mother and the child. A congenital immunodeficiency disorder was suspected.

Based on the clinical presentation what kind of inheritance pattern would be suspected?

A)Autosomal recessive

B)Autosomal dominant

C)X linked recessive

D)Y linked

Answer 10

X-linked Recessive

Question 11

Antigen presenting cells of recipient origin present minor histocompatibility antigen disparity to donor derived T lymphocytes that leads to activation of TCR/CD3 receptor activation followed by secondary signaling through CD28/CD80/CD86 (co-stimulatory molecules) interaction resulting in cytokine secretion, recruitment of macrophages, B and cytotoxic T cells activation, eventually leading to tissue damage and the picture of acute graft versus host disease. Which of the counter-regulatory pathways in the T-cell repertoires actually is helpful in preventing this cascade and ameliorate signs and symptoms of acute GVHD?

A) Activation of NFAT pathway in activated TH1 cells

B) Activation of phospholipase C and cyclo-oxygenase pathway in CD4 cells

C) B cell Immunoglobulin class switching by CD 40-CD40 Ligand interaction

D) Activation of FOXP3 in CD25+ T-regulatory cells

Answer 11

D) Activation of FOXP3 in CD25+ T-regulatory cells