Hematopoietic stem cell transplantation

Question 1

HSCT allows for reconstitution of hematopoiesis

Answer 1

yep

Question 2

HSCT in some cases provides a graft vs. ______ effect

Answer 2

malignancy

Question 3

stem cell sources

1. (a) largest reservoir (b) removed by putting a needle in to the iliac crest
2. (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
3. (a) rich but limited amount (b) stored in a cord blood blank for future use

Answer 3

1. Bone Marrow
2. peripheral blood
3. umbilical cord blood

Question 4

many tumors show a steep-dose response curve (hematologic malignancies) and as the dose increased, organ toxicities develop

Answer 4

yep

Question 5

-multiple myeloma
- non-hodkin lymphoma
- hodkin lymphoma
- AML
amyloidosis
- Germ cell tumors
-peds solid tumors

Answer 5

malignant disorders treated with autologous HSCT

Question 6

• scleroderma
• SLE
• MS

Answer 6

non-malignant disorders treated with autologous HSCT

Question 7

what has replaced bone marrow harvest for autologous HSCT recovery phase

Answer 7

peripheral blood stem cell harvest

Question 8

how are HSCT cells preserved?

Answer 8

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

Question 9

preparative or conditioning regimen

Answer 9

this is when high dose chemo is given with/without total body irradiation with the purpose to eliminate malignant disease.

Question 10

how is DMSO eliminated

Answer 10

via the lungs

Question 11

Side effect of conditioning regimen autologous

Answer 11

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

Question 12

benefits vs downside in autologous HSC

Answer 12

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

Question 13

Graft-versus-tumor effect is the

Answer 13

good response that happens when the donor cells attack any of the recipient’s cancer cells that may remain after chemotherapy

Question 14

Graft-versus-tumor effect occurs in

Answer 14

allogeneic transplantation

Question 15

curative potential of AlloHSCT relies on 3 concepts

Answer 15

1. high dose chemo overcome resistance to standard chemo and eliminate host bone marrow cells
2. donor serves as marrow rescue and re-establishes normal hematopoiesis
3. graft vs tumor effect

Question 16

a suitable donor is determined by matching of HLA

Answer 16

Human leukocyte antigens

Question 17

8/8 match

Answer 17

all 4 pairs of molecules are matched

Question 18

each sibling has a ___ chance of matching

Answer 18

25%

Question 19

allogeneic HSCT conditioning phase allows (2)

Answer 19

1. cytoreductive to eliminate the malignant disease

2. immunosuppressive to facilitate engraftment

Question 20

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

Answer 20

myeloablative conditioning in AlloHSCT

Question 21

regimen have been developed to reduce morbidity and mortality for older and sicker patients by not completely destroying the bone marrow

Answer 21

non-myeloablative conditioning in AlloHSCT

Question 22

there is a period of marrow aplasia for a few weeks requiring transfusion support

Answer 22

yep

Question 23

in AlloHSCT along with donor stem cells, the product contains mature donor

Answer 23

T lymphocytes

Question 24

what is the purpose of the donor T cells in AlloHSCt

Answer 24

1. facilitate engraftment - decreases the chances of graft failure
2. immune reconstitution- T cells are the last of immune cell to recover thus more prone to infections
3. GVT effect - eliminates residual malignant cells

Question 25

caused by donor derived immune cells, particularly T cells that react against recipient tissues

Answer 25

graft vs host disease

Question 26

typically affects the epithelial cells of 3 organs like skin, liver and GI tract occurring before day 100 post SCT

Answer 26

Acute GVHD

Question 27

evolved from acute GVHD or de novo affecting epithelial and mesenchymal cells of skin, eye, GI tracts, lungs, liver and joints

Answer 27

Chronic GVHD

Question 28

with each increasing grade of GVHD, patient outcomes worsen

Answer 28

yep

Question 29

all allogeneic recipients receive immunosuppressive agents before the graft is infused what combination?

Answer 29

yep, a combination of a calcineurin inhibitor and methotrexate

Question 30

1. very immunosuppressive 2. block TCR signaling pathways 3. nephrotoxic 4. given at least 6 months

Answer 30

calcineurin inhibitors like cyclosporine and tacrolimus

Question 31

1. dihydrofolate reductase inhibitor 2. inhibits expansion of dividing cells 3. slows expansion of donor T cell clones s 4. given first week or two post SCT

Answer 31

methotrexate

Question 32

first line therapy for patients who develop AGVHD

Answer 32

steroids

Question 33

1. phase 1- pre engrafment what type of infection is common 2. in phase II - post engrafment what type of infection is common 3. in phase III- late phase what type of infection is common

Answer 33

1. bacterial 2. fungi 3. viral

Question 34

infection control

Answer 34

1. hygiene 2. environmental 3. antimicrobial prophylaxis 4. preemptive therapy 5. vaccinations

Question 35

common- especially with TBI conditioning regimen

Answer 35

mucositis

Question 36

what happens in mucositis and what is an interventions used at tufts

Answer 36

it is the breakdown of mucosal barrier accompanied with pain and infection - at tufts we use caphosol a calcium phosphate rinse

Question 37

this SE develops around the time of neutrophil recovery with symptoms related to cytokine (TNF) release from engrafting donor cells

Answer 37

engraftment syndrome

Question 38

engraftment syndrome is defined by ? what are some of the treatments ?

Answer 38

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

Question 39

pathogenesis is unknown but there is pulm. infiltrates with hypoxia and persisten hemorrhagic lavage on BAL leading to a high mortality rate

Answer 39

diffuse alveolar hemorrhage

Question 40

treatments for diffuse alveolar hemorrhage include

Answer 40

1. high dose steroids 2. RFII 3. supplemental oxygen 4. optimize fluid balance

Question 41

manifested by weight gain, hyperbilirubinemia and tender hepatomegaly is due to damage of the hepatic venous endothelium by the conditioning regimen

Answer 41

sinusoidal obstructive syndrome SOS

Question 42

SOS is increased in patients who have ______. the treatment include

Answer 42

patients who have liver disease are at increased risk treatment includes ursodial as both a prevention and treatment

Question 43

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

Answer 43

thrombotic microangiopathy TMA

Question 44

TMA is associated with a worse prognosis if

Answer 44

the complement system is activated

Question 45

late effects of HSCT

Answer 45

1. endocrinopathies such as hypothyroidism 2. iron overload- especially with leukemia pt. 3. secondary malignancies such as in the skin