Hematopoietic stem cell transplantation Flashcards
HSCT allows for reconstitution of hematopoiesis
yep
HSCT in some cases provides a graft vs. ______ effect
malignancy
stem cell sources
- (a) largest reservoir (b) removed by putting a needle in to the iliac crest
- (a) small numbers (b) hematopoietic growth factors are given to release stem cells from bone marrow (c) apheresis: a needle placed in a vein, blood passes through a machine that removes the stem cells from the blood
- (a) rich but limited amount (b) stored in a cord blood blank for future use
- Bone Marrow
- peripheral blood
- umbilical cord blood
many tumors show a steep-dose response curve (hematologic malignancies) and as the dose increased, organ toxicities develop
yep
-multiple myeloma
- non-hodkin lymphoma
- hodkin lymphoma
- AML
amyloidosis
- Germ cell tumors
-peds solid tumors
malignant disorders treated with autologous HSCT
- scleroderma
- SLE
- MS
non-malignant disorders treated with autologous HSCT
what has replaced bone marrow harvest for autologous HSCT recovery phase
peripheral blood stem cell harvest
how are HSCT cells preserved?
they are suspended in DMSO which prevents ice crystals from forming when it is cryopreserved in liquid nitrogen this way of preservation allows cells to remain viable for many years
preparative or conditioning regimen
this is when high dose chemo is given with/without total body irradiation with the purpose to eliminate malignant disease.
how is DMSO eliminated
via the lungs
Side effect of conditioning regimen autologous
eradication of the bone marrow and its function thus the patient’s HSC will be thawed and infused with a rescue after high dose chemo is given. without this rescue the patient would succumb to bone marrow failure
benefits vs downside in autologous HSC
there is rare rejection of the transplant but the anti-tumor effect relies entirely on the conditioning regimen in autologous SCT and thus there is a higher relapse rate
Graft-versus-tumor effect is the
good response that happens when the donor cells attack any of the recipient’s cancer cells that may remain after chemotherapy
Graft-versus-tumor effect occurs in
allogeneic transplantation
curative potential of AlloHSCT relies on 3 concepts
- high dose chemo overcome resistance to standard chemo and eliminate host bone marrow cells
- donor serves as marrow rescue and re-establishes normal hematopoiesis
- graft vs tumor effect
a suitable donor is determined by matching of HLA
Human leukocyte antigens
8/8 match
all 4 pairs of molecules are matched
each sibling has a ___ chance of matching
25%
allogeneic HSCT conditioning phase allows (2)
- cytoreductive to eliminate the malignant disease
2. immunosuppressive to facilitate engraftment
regimen consists of doses of chemo with/without radiation that will irreversibly ablate the bone marrow resulting in permanent bone marrow aplasia. these patients will not recover bone marrow function without donor HSC
myeloablative conditioning in AlloHSCT
regimen have been developed to reduce morbidity and mortality for older and sicker patients by not completely destroying the bone marrow
non-myeloablative conditioning in AlloHSCT
there is a period of marrow aplasia for a few weeks requiring transfusion support
yep
in AlloHSCT along with donor stem cells, the product contains mature donor
T lymphocytes
what is the purpose of the donor T cells in AlloHSCt
- facilitate engraftment - decreases the chances of graft failure
- immune reconstitution- T cells are the last of immune cell to recover thus more prone to infections
- GVT effect - eliminates residual malignant cells
caused by donor derived immune cells, particularly T cells that react against recipient tissues
graft vs host disease
typically affects the epithelial cells of 3 organs like skin, liver and GI tract occurring before day 100 post SCT
Acute GVHD
evolved from acute GVHD or de novo affecting epithelial and mesenchymal cells of skin, eye, GI tracts, lungs, liver and joints
Chronic GVHD
with each increasing grade of GVHD, patient outcomes worsen
yep
all allogeneic recipients receive immunosuppressive agents before the graft is infused
what combination?
yep, a combination of a calcineurin inhibitor and methotrexate
- very immunosuppressive
- block TCR signaling pathways
- nephrotoxic
- given at least 6 months
calcineurin inhibitors like cyclosporine and tacrolimus
- dihydrofolate reductase inhibitor
- inhibits expansion of dividing cells
- slows expansion of donor T cell clones s
- given first week or two post SCT
methotrexate
first line therapy for patients who develop AGVHD
steroids
- phase 1- pre engrafment what type of infection is common
- in phase II - post engrafment what type of infection is common
- in phase III- late phase what type of infection is common
- bacterial
- fungi
- viral
infection control
- hygiene
- environmental
- antimicrobial prophylaxis
- preemptive therapy
- vaccinations
common- especially with TBI conditioning regimen
mucositis
what happens in mucositis and what is an interventions used at tufts
it is the breakdown of mucosal barrier accompanied with pain and infection
- at tufts we use caphosol a calcium phosphate rinse
this SE develops around the time of neutrophil recovery with symptoms related to cytokine (TNF) release from engrafting donor cells
engraftment syndrome
engraftment syndrome is defined by ? what are some of the treatments ?
defined as either Major or minor. Major criteria is increased temp with no fever, rash and hypoxia while minor criteria is both hepatic and renal dysfunction and weight gain
treatments include high dose steroids, oxygen, diuretics and antibiotics
pathogenesis is unknown but there is pulm. infiltrates with hypoxia and persisten hemorrhagic lavage on BAL leading to a high mortality rate
diffuse alveolar hemorrhage
treatments for diffuse alveolar hemorrhage include
- high dose steroids
- RFII
- supplemental oxygen
- optimize fluid balance
manifested by weight gain, hyperbilirubinemia and tender hepatomegaly is due to damage of the hepatic venous endothelium by the conditioning regimen
sinusoidal obstructive syndrome SOS
SOS is increased in patients who have ______.
the treatment include
patients who have liver disease are at increased risk
treatment includes ursodial as both a prevention and treatment
manifests as hemolytic anemia, thrombocytopenia and renal dysfunction and it is due to endothelial cell damage by the conditioning regimen and is also associated with the use of calcineurin inhibitors used to prevent and treat GVHD
thrombotic microangiopathy TMA
TMA is associated with a worse prognosis if
the complement system is activated
late effects of HSCT
- endocrinopathies such as hypothyroidism
- iron overload- especially with leukemia pt.
- secondary malignancies such as in the skin
