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heme/onc > Hematopoietic stem cell transplantation > Flashcards

Hematopoietic stem cell transplantation Flashcards

1
Q

HSCT allows for reconstitution of hematopoiesis

A

yep

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2
Q

HSCT in some cases provides a graft vs. ______ effect

A

malignancy

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3
Q

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
A
  1. Bone Marrow
  2. peripheral blood
  3. umbilical cord blood
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4
Q

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

A

yep

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5
Q

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

A

malignant disorders treated with autologous HSCT

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6
Q
  • scleroderma
  • SLE
  • MS
A

non-malignant disorders treated with autologous HSCT

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7
Q

what has replaced bone marrow harvest for autologous HSCT recovery phase

A

peripheral blood stem cell harvest

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8
Q

how are HSCT cells preserved?

A

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

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9
Q

preparative or conditioning regimen

A

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

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10
Q

how is DMSO eliminated

A

via the lungs

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11
Q

Side effect of conditioning regimen autologous

A

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

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12
Q

benefits vs downside in autologous HSC

A

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

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13
Q

Graft-versus-tumor effect is the

A

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

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14
Q

Graft-versus-tumor effect occurs in

A

allogeneic transplantation

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15
Q

curative potential of AlloHSCT relies on 3 concepts

A
  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
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16
Q

a suitable donor is determined by matching of HLA

A

Human leukocyte antigens

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17
Q

8/8 match

A

all 4 pairs of molecules are matched

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18
Q

each sibling has a ___ chance of matching

A

25%

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19
Q

allogeneic HSCT conditioning phase allows (2)

A
  1. cytoreductive to eliminate the malignant disease

2. immunosuppressive to facilitate engraftment

20
Q

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

A

myeloablative conditioning in AlloHSCT

21
Q

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

A

non-myeloablative conditioning in AlloHSCT

22
Q

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

A

yep

23
Q

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

A

T lymphocytes

24
Q

what is the purpose of the donor T cells in AlloHSCt

A
  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
25
Q

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

A

graft vs host disease

26
Q

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

A

Acute GVHD

27
Q

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

A

Chronic GVHD

28
Q

with each increasing grade of GVHD, patient outcomes worsen

A

yep

29
Q

all allogeneic recipients receive immunosuppressive agents before the graft is infused

what combination?

A

yep, a combination of a calcineurin inhibitor and methotrexate

30
Q
  1. very immunosuppressive
  2. block TCR signaling pathways
  3. nephrotoxic
  4. given at least 6 months
A

calcineurin inhibitors like cyclosporine and tacrolimus

31
Q
  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
A

methotrexate

32
Q

first line therapy for patients who develop AGVHD

A

steroids

33
Q
  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
A
  1. bacterial
  2. fungi
  3. viral
34
Q

infection control

A
  1. hygiene
  2. environmental
  3. antimicrobial prophylaxis
  4. preemptive therapy
  5. vaccinations
35
Q

common- especially with TBI conditioning regimen

A

mucositis

36
Q

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

A

it is the breakdown of mucosal barrier accompanied with pain and infection

  • at tufts we use caphosol a calcium phosphate rinse
37
Q

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

A

engraftment syndrome

38
Q

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

A

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

39
Q

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

A

diffuse alveolar hemorrhage

40
Q

treatments for diffuse alveolar hemorrhage include

A
  1. high dose steroids
  2. RFII
  3. supplemental oxygen
  4. optimize fluid balance
41
Q

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

A

sinusoidal obstructive syndrome SOS

42
Q

SOS is increased in patients who have ______.

the treatment include

A

patients who have liver disease are at increased risk

treatment includes ursodial as both a prevention and treatment

43
Q

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

A

thrombotic microangiopathy TMA

44
Q

TMA is associated with a worse prognosis if

A

the complement system is activated

45
Q

late effects of HSCT

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

heme/onc (30 decks)

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