267. Stem Cell Transplant Flashcards
What is a Stem Cell Tx (2 functions)
The use of HSC to:
- restore quantitative or qualitative bone marrow function (bone marrow rescue)
- create long-term alloreactivity against a malignancy (graft vs. tumor effect = intentional)
What are the 2 categories of HSC Tx and two subtypes of one of them?
- Cellular Therapy/Transplant (unmanipulated)
- Autologous: pt receive own cells (usually after high dose chemo that would destroy specific blood cancers - reimplant after chemo suppresses/clears everything)
- Allogenic: pt receive stem cells from someone other than self - Manipulated Cellular Therapy
- selection/engineering of specific types of HSC (removed T Cells, only CD34+ cells, etc)
- Chimeric Antigen Receptor (CAR) T Cells
What are the uses of HSCT?
- Non-Malignant Conditions
- Reconstitue pt’s hematopoietic tissue (aplastic anemia, thalassemia, sickle cell, severe combined immunodeficiency, enzymatic diseases- Gaucher’s) - Malignant Conditions
- permit tx with high dose chemo/radiotherapy (myeloablative) - prevent immunosuppression
- graft vs. tumor (implant healthy blood cells to fight cancer)
For HSC Donors, what is the priority of donor?
How is matching done?
- Fully Matched Sibling Donor
- Fully Matched Unrelated Donor
- Alternative Donor - Umbilical Cord Blood, Haploidentical (Half Match) Related Donor (sibling, parent, child), Mismatched unrelated Donor (last resort)
Young M donors are preferred to older and f (pregnant = foreign antigen exposure)
IHC antigens
HLA: Class I (A, B, C - activate CD8 T Cells), Class II (DR, DQ, DP - activate CD4 T Cells) inherited co-dominantly from parents
- fully matched = 10/10 (self, 25% siblings)
- half match = 5/10 (parent, child, 50% siblings)
- unmatched = 0/10 (25% siblings)
- Umbilical cord blood - less match required due to naive HSC
- mismatched donors - 8/10 or 9/10 okay (but more risk), haploidentical not impossible
How does the conditioning regimen intensity correlate with toxicity and GvT effect?
Increasing conditioning regimen intensity increases toxicity - use when you want myeloablative tx pre-transplant (destroy cancer in pt: ex. young AML pts)
Less intensity of conditioning regimen = less toxic, and more requirement of GvT effect - use when you want graft to fight tumor (or tumor is highly sensitive to graft)
What are the 3 phases of SCT and what happens at each?
- Pre-engraftment: cytopenic with no evidence of graft differentiation (0 - 11/12)
- Engraftment - graft cells differentiate Day 11-12 - Early Post-engraftment: emergence of end cell products (platelets, neutrophils) (10-40 til 100)
- Late Post-engraftment: most cell counts normalize (Day 100+)
What are some acute and chronic complications to SCT?
Acute
- disease relapse
- infection/sepsis
- toxicity from chemo or meds
- acute GvHD (cutaneous, hepatic, GI) - donor T-cells get INFLAMED, tx with steroids
- Sinusoidal Obstructive Sydrome (SOS) of liver
- Engraftment Syndrome (fever rash = tx with steroids)
Chronic
- relapse, infections, chronic GvHD (multiorgan disorder, high morbidity, worse survival, but sign of GvT effect), secondary malignancy, psychological disorders
- in peds: growth retardation, learning disabilities
Describe CAR T Cell Therapy
Remove HSC, leukopheresis (isolate T Cells), retroviral transduction with anti-CD19 chimeric antigen receptor (helps prime T Cells to recognize CD19+ cancer) - reinfuse transduced T Cells
- tx for ALL, large B Cell Lymphoma,
- SE: insertional mutagenesis (interrupt gene may cause cancer), myelosuppression (cytopenia), cytokine release syndrome (due to more T cell activity - fevers, flu-like sx, hypotension)