3.5.1 HSCT and GvHD Flashcards
What are the four purposes of SCT?
- Replacement Therapy
- Ablative Therapy
- Immunotherapy
- Gene Therapy
What is replacement therapy?
Pt’s BM doesn’t have enough SCs, so BM transplant is necessary (e.g. Aplastic anemia)
What is ablative therapy?
Pt has a dz in which the SCs are unaffected. The process of ablative therapy is as follows: harvest SCs from patients (typically via peripheral blood stem cells following growth factor injection) and freeze them, give patient maximum dosage of chemo/radiation, then reinject the SCs to allow them to repopulate the BM
What is immunotherapy?
Giving the patient a slightly allogenic BM tranplant in hopes that the graft will fight off the host’s tumor (new immune system).
What are the four types of SCT? What is each?
Autologous (Self)
Syngeneic (Exact match - genetically identical twin)
Allogeneic (matched sibling, unrelated matched donor, haploidentical donor, cord blood)
Xenogeneic (Diff species)
What are the three sources of stem cells?
BM
Peripheral Blood Stem Cells
Cord Blood
What do they use as a biomarker to identify peripheral blood stem cells?
CD34
Why in some cases does Dr. Ganguly prefer to have slight HLA mismatch?
In some cases, Dr. Ganguly is using the slight HLA mismatch to cause mild forms acute GvHD which will help the patient fight off the tumor.
What is the mainstay in the treatment of acute GvHD? Second line?
Mainstay: Glucocorticoids
Second line: MABs, TNFalpha receptor blocker, extra corporeal photophoresis (Remove T cells from patient, numb T cells, and upregulate Treg to reduce cytokine storm)
What is used in the treatment of chronic GvHD?
mainstay glucocorticoids and steroid-sparing agents (MABs, calcineurin inhibitors, extracorporeal photophoresis)
What is the most common cause of death in patients with chronic GvHD?
Infection
What are the two most common fungal infections in patients following transplantation?
Candidasis and Aspergillus Niger
•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
C) X linked recessive
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
D) Activation of FOXP3 in CD25+ T-regulatory cells
