Term
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Definition
blood making organ
bone marrow produces stem cells |
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Term
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Definition
immature cell
parent cells to other blood cell lines: WBC, RBC, platelets |
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Term
| 2 main reasons for transplant |
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Definition
1
to CURE the patient by REPLACING defective bone marrow with a healthy marrow
"marrow is bad"
2
to RESCUE the patient by RESTORING their bone marrow after high dose chemotherapy
"treatment is bad" |
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Term
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Definition
person receiving the stem cells
undergoing transplant |
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Term
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Definition
person providing hematopoietic stem cells
provides the "graft" |
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Term
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Definition
newly transplanted cells begin to function and produce new blood cells within the host
defined as ANC > 500 for 3 consecutive days
can usually take 10-16 days |
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Term
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Definition
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Term
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Definition
(<1%)
host immune system does not tolerate foreign cells
transplant fails
very small chance of rejection |
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Term
| graft versus host disease |
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Definition
graft mounts an immune response against the host (donor rejecting recipient)
liver, skin, gut |
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Term
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Definition
graft mounts an immune response against the disease
helpful in preventing relapse
"graft vs. leukemia" or "graft vs. tumor"
having graft vs. disease lessens the chance that the patient will have a relapse |
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Term
| where do you get stem cells? |
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Definition
BONE MARROW
harvested
multiple needle aspirations
requires general anesthesia
PERIPHERAL STEM CELLS
pheresis
colony stimulating factor (mobilization)
stem cells that have been released from the bone marrow
taking just the pluripotent stem cells
UMBILICAL CORD BLOOD
issue is small volume of stem cells (not enough to support an adult sized person) |
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Term
| source of stem cells: time to engraftment, risk of relapse, and risk of GVHD (graft vs. host disease) |
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Definition
BONE MARROW:
time to engraftment: moderate
risk of relapse: lower
risk of GVHD: higher
PERIPHERAL BLOOD:
time to engraftment: fastest
risk of relapse: lower
risk of GVHD: higher
CORD BLOOD:
time to engraftment: slowest
risk of relapse: highest
risk of GVHD: lowest |
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Term
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Definition
allogeneic: family/unrelated donor
autologous: self-donation
syngeneic: identical twin |
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Term
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Definition
cure by replacing
"marrow is bad"
rescue by restoring
"treatment is bad" |
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Term
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Definition
allogeneic = CURE
to replace missing or abnormal component
to rescue from myeloablative treatment regimens
to establish graft vs. disease effect
destruction or inhibition of unwanted host cell
donors:
matched sibling donor
mismatched sibling or related donor
matched unrelated donor
mismatched unrelated donor
disease states:
"marrow is bad"
leukemia (ALL, AML, CML, CLL)
aplastic anemia
myelodysplastic syndrome (MDS)
severe combined immunodeficiency disease (SCID)
severe autoimmune diseases
risk/benefit:
increased risk of graft vs. host disease
decreased risk for disease relapse (graft vs. tumor advantage)
usually more complications |
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Term
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Definition
stem cells from an identical twin
higher risk for disease relapse
decreased risk of GVHD |
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Term
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Definition
autologous = RESCUE
to restore a patients' bone marrow after high dose chemotherapy
patient's OWN stem cells
"self" transplant
disease states:
"treatment is bad"
disease states not involving bone marrow: hodgkin's lymphoma, non-hodgkin's lymphoma, solid tumors (usually relapsed), sarcomas (usually relapsed)
allows use of higher doses of chemotherapy (in order to treat disease or tumor)
stem cells collected before high dose chemo
risk/benefit:
decreased risk of graft versus host disease
decreased risk of rejection
less immunosuppression
increased risk of disease relapse |
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Term
| donor types: relative risk of relapse, GVHD, and other complications |
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Definition
ALLOGENEIC:
relapse +
GVHD +++
other complications +++
SYNGENEIC
relapse ++
GVHD -
other complications +
AUTOLOGOUS
relapse +++
GVHD -
other complications + |
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Term
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Definition
chemotherapy +/- irradiation
given prior to transplant
kill remaining cancerous cells
suppress immune reactions
to facilitate engraftment
create sufficient space needed in the marrow for new cells
provide some mild GVHD/GVD
given over 3-10 days prior to transplant
one or two days of "rest"
DAY 0 = DAY OF TRANSPLANT |
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Term
| goals for hematologic malignancies |
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Definition
ablation of stem cells with chemotherapy
replace the disease free cells to repopulate the marrow |
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Term
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Definition
stem cells are not completely ablated
more potent conditioning/chemotherapy regimens can be given
able to "rescue" patient after treatment
some graft versus tumor effects |
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Term
| goals for non-malignant disease states |
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Definition
powerful immunosuppression
facilitate engraftment
host versus graft tolerance develops
"mixed chimerism"
the host's old cells and the new cells battle with each other for which one will develop
hopefully the donor cells will win and normal cell line will be produced |
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Term
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Definition
more advanced disease or later in course
unrelated donor
increased mismatch between host and donor
increased age
decreased performance status
co-morbid illness or significant organ dysfunction pre-transplant |
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Term
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Definition
suppression of bone marrow activity
pancytopenia = decreased # of cells
produces anti tumor effect
neutropenia, infection, mucositis |
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Term
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Definition
eradication or suppression of immune system
T cells are suppressed in order to prevent rejection
decreased ability to fight infection
viral and fungal infections, EBV associated, lymphoproliferation |
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Term
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Definition
suppress host immune system
to facilitate engraftment
provide long term stable engraftment
minimize regimen related toxicity
utilize best stem cell source available
provide lower, milder rates of GVHD
some graft versus leukemia/disease
eliminate risk of graft rejection
facilitate early immune reconstitution
ALLOGENEIC MALIGNANT DISEASE
immunosuppressive (anti graft rejection): yes
make space (ablate): yes
eradicate malignancy (anti tumor): yes
avoid overlapping toxicities: yes
ALLOGENEIC NON-MALIGNANT DISEASE
immunosuppressive (anti graft rejection): yes
make space (ablate): yes
eradicate malignancy (anti tumor): no
avoid overlapping toxicities: yes
AUTOLOGOUS MALIGNANT DISEASE
immunosuppressive (anti graft rejection): no
make space (ablate): yes
eradicate malignancy (anti tumor): yes
avoid overlapping toxicities: yes |
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Term
| conditioning regimens: myeloablative, reduced intensity (if a person couldn't tolerate a very aggressive preparative regimen), non-myeloablative |
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Definition
MYELOABLATIVE relative risk of:
rejection +
immunosuppression +++
myelosuppression +++
toxicity +++
GVHD +++
REDUCED INTENSITY relative risk of:
rejection ++
immunosuppression +++
myelosuppression ++
toxicity +
GVHD ++
NON MYELOABLATIVE relative risk of:
rejection +++
immunosuppression ++
myelosuppression +
toxicity +
GVHD + |
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Term
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Definition
alemtuzumab
busulfan
carboplatin
carmustine
cyclophosphamide
cytarabine
etoposide
fludarabine
melphalan
thiotepa |
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Term
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Definition
immunosuppressive
infusion reaction
GI effects |
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Term
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Definition
seizures - have to provide seizure prophylaxis
pulmonary fibrosis
VOD (veno-occlusive disease)
BMS (bone marrow suppression) |
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Term
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Definition
N/V
nephrotoxicity
ototoxicity
BMS |
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Term
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Definition
BMS
VOD
pulmonary toxicity
N/V |
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Term
| cyclophosphamide toxicities |
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Definition
hemorrhagic cystitis
SIADH
VOD
nephrotoxicity
leukopenia
cardiac toxicity |
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Term
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Definition
ara-C syndrome
conjunctivitis
BMS |
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Term
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Definition
N/V
mucositis
secondary malignancy
BMS |
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Term
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Definition
neurotoxicity
BMS
pulmonary toxicity |
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Term
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Definition
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Term
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Definition
adverse skin effects
partially eliminated through the sweat glands
BMS
mucositis
neurotoxicity |
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Term
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Definition
infection (40-60%)
fluid overload
graft vs. host disease (GVHD)
acute GVHD
chronic GVHD
veno occlusive disease of the liver (VOD)
GI complications (mucositis) |
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Term
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Definition
Phase I: pre engraftment <30 days
respiratory and enteric viruses
herpes simplex virus
gram negative bacilli
staphylococci epidermidis
GI tract (Streptococci species)
all Candida species
Aspergillus species
Phase II: post engraftment 30-100 days
respiratory and enteric viruses
cytomegalovirus
protozoal infection
Staphylococci epidermidis
GI tract (Streptococci species0
all Candida species
Aspergillus species
Phase III: late phase > 100 days
respiratory and enteric viruses
cytomegalovirus
varicella-zoster virus
protozoal infections
encapsulated bacteria
Aspergillus species
[image] |
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Term
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Definition
viral:
human herpes virus (HSV)
other community acquired viruses
bacterial:
Staphylococcus sp.
Streptococcus sp.
gram negative bacilli
Candida species
community respiratory viruses:
respriatory syncytial virus (RSV)
influenza A and B
parainfluenza type 1,2,+3
adenovirus
rhinovirus |
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Term
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Definition
fungal infections:
Candida species
Aspergillus species
encapsulated bacteria
varicella zoster virus (VZV)
cytomegalovirus (CMV)
epstein barr virus (EBV)
pneumocystis jiroveci pneumonia (PCP) |
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Term
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Definition
acyclovir, valacyclovir
fluconazole
prophylaxis for Candida species
sulfamethoxazole/trimethoprim
pentamidine
dapsone
atovaquone
ampicillin
gram positives
IVIG
viral infections
immunizations |
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Term
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Definition
complication of allogeneic transplant
host appears foreign to the graft
graft with immunocompetent cells
host incapable of mounting an effective immunological reaction to the graft
ACUTE GVHD: day 30 through day 100
CHRONIC GVHD: beyond day 100
developed after day 100 or lasts past day 100 |
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Term
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Definition
skin: maculopapular, erythematous rash
gut: secretory, watery diarrhea; cramping
liver: hyperbilirubinemia; hepatotoxicity
prevention: methotrexate, cyclosporine, tacrolimus, cyclophosphamide, steroids, sirolimus
treatment: maximize cyclosporine treatment then first line is STEROIDS, monoclonal antibodies, MMF (mycophenalate) |
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Term
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Definition
not necessarily related to presence of acute GVHD
40% with identical sib
> 50% with mismatched related sib
70% unrelated mismatched
skin (dark pigmentation)
nails/scalp/hair
mouth
eyes
genitalia
GI tract
liver
lung (difficulty breathing)
muscle/joint (stiffening)
hamatopoietic/immune
supportive care and steroids
remain on cyclosporine for a prolonged period of time |
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Term
| veno occlusive disease (VOD) |
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Definition
obliteration of small intrahepatic central venules
liver's ability to remove waste is impaired
veins and liver become blocked
increased bilirubin
weight gain
ascites
hepatomegaly
supportive care
fluid restriction |
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Term
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Definition
mucositis: increased risk with myeloablative regimens; irradiation; etoposide; melphalan
inadequate nutrition, pain, or infection
oral hygiene and oral care products
skin breakdown associated with thiotepa |
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