Transplantation Flashcards
When/what was the first successful human organ transplant?
Kidney in 1954 (identical twin donor, Joseph Murray was the transplant doctor and recently passed in 2012)
What is the most common organ transplanted?
Kidney
Can a living donor donate a kidney?
Yes!
Can a living donor donate the following? Liver? Lung? Pancreas? Intestine? Heart?
Liver? Yes Lung? Yes Pancreas? Not as common, but yes Intestine? Not as common, but yes Heart? Yes, but it’s a living donor swap out (perhaps during heart lung transplant)
Define Allograft
Transplanted between same species
Define Autografts
Transplanted in the same individual
Define Isografts
Transplanted between genetically identical individuals.
While anatomically identical to allografts, they are closer to autografts in terms of the recipient’s immune response
Define Xenografts
Grafts transplanted between different species
Define split transplants
Graft divided between two recipients (e.g., split-liver transplant)
Define “en bloc” transplants
Example: kidney transplant –> Both pediatric donor kidneys into single adult recipient
What are the two types of deceased-donors?
Donation after brain death (DBD)
Donation after circulatory death (DCD)
The length of time that donated organs can be kept outside the body varies:
Heart/lung: ____ hours
Liver: ____ hours
Kidney: ____ hours
Heart/lung: 4-6 hours
Liver: 12-24 hours
Kidney: 48-72 hours
Is UNOS the only organization to operate the Organ Procurement and Transplant Network (OPTN)?
Yes
CDC “high-risk” donors are patients with what condition(s)?
Hepatitis B and C and HIV
What is the HOPE Act in regards to transplantation/donors?
Signed by US President into law November 21, 2013
Stipulates that the OPTN may develop standards for use of organs from HIV–positive donors for transplant in individuals who were already infected with HIV
A pt is on the transplant waiting list. Their location on the list is dependent on what factors? (~6)
ABO/HLA type Candidate height/weight Medical urgency Time on list Center, state and regional characteristics Specific organ required
What are some options to consider for recipients with extended wait times on the transplant list?
Multiple listings
Living donors
Paired and list donation
As part of the pre-transplant evaluation, what factors should be taken into consideration? (~7)
Indication(s) appropriate No contraindications present Adequate organ function Blood type and sensitization risks Psychological barriers Adequate social/caregiver support Adequate financial support
You should refer a pt for kidney transplant when the pt has:
Irreversible advanced _____
Initiate referral for CKD stage ___ or glomerular filtration rate (GFR) ____ mL/min
UNOS policy mandates listing only once GFR ____ ml/min
CKD
4
(GFR) < 30 mL/min
< 20 mL/min
As part of a patient’s pre-transplant evaluation, what other tests, studies, etc should be done? (A LOT, this is more of a reference card)
Complete physical exam
Blood type and baseline laboratory evaluation/urinalysis
Specific infectious disease testing/screening
HLA typing and a panel reactive antibody assay to detect previous sensitization
Chest x-ray and electrocardiogram +/- further diagnostics dependent on age/comorbidities
Gender specific, age appropriate screening
Testicular and digital rectal exam in men
Breast exam, mammography, pregnancy test and Pap smear in women
Screening colonoscopy in all patients >50 years of age [+/- esophagogastroduodenoscopy (EGD)]
Other relevant radiographic imaging (e.g., abdominal and pelvic ultrasounds in renal transplant, CT chest in lung transplant)
Immunizations and PPD or IGRA testing
Multidisciplinary consultation (including social work/psychiatry)
What are the different types of pancreas transplant? What percentage of total pancreas transplants does each type comprise?
SPK: simultaneous kidney-pancreas (75%)
PAK: pancreas after kidney transplant (15%)
PTA: pancreas transplant alone (10%)
**Islet cell transplantation
What are the indications for a pt to have a pancreas transplant?
Patients with ESRD who have had or plan to have a kidney transplant
Patients without ESRD candidates for PTA if
History of frequent, acute, severe metabolic complications (hypoglycemia, marked hyperglycemia, ketoacidosis)
Incapacitating clinical and emotional problems with exogenous insulin therapy
Consistent failure of insulin-based management to prevent acute complications
Primary underlying dx is diabetes mellitus (type 1>2)
Also done for chronic pancreatitis, CF, pancreatic/bile duct cancers
T/F Lung transplant patients are at high risk for infections
True; breath in dust and other things, boom! infection.
The most common pancreas transplant procedure includes (part of the/the whole) pancreas + attached portion of the ______ containing the _____
whole; duodenum; ampulla of Vater
Indications for liver transplant include…..
Acute liver failure
Cirrhosis with complications
Other disease specific problems affecting survival and quality of life
What does MELD stand for? What is it, what is it used for, and what is it based on?
Model for end-stage liver disease
Score range 6-40
Predicts 3-month mortality
Calculation based upon total bilirubin, INR, serum sodium, and creatinine
Liver transplant waitlist pts are no longer mostly comprised of pts with hepatitis c, why? What population now comprises the majority of liver transplant waiting list patients, why?
In large part likely due to hep c medications
Cirrhosis (?) due to an increase in obesity
Arterial anastomosis iliac artery and venous anastomosis iliac vein –> pancreatic [exocrine/endocrine] drainage
Duodenal segment connected to the urinary bladder or to a loop of bowel –> pancreatic [exocrine/endocrine] drainage)
endocrine
exocrine
During pancreas transplant surgery, where is the pancreas placed?
laterally into the pelvis
Describe a couple details regarding the liver transplant surgical procedure
Deceased donor procedure
Total native hepatectomy
Venous followed by arterial re-anastomosis
Bile duct reconstruction
Primary duct-to-duct (choledochocholedochostomy)
Alt: Roux-en-Y choledochojejunostomy
Split liver procedure
Liver split along falciform ligament
Left lateral typically transplanted into child
Remaining transplanted into an adult
Living donor procedure
Heart transplant transplantation indications include…
Hemodynamic compromise due to heart failure
Severe symptoms of ischemia
Limit routine activity
Not amenable to coronary artery bypass surgery or percutaneous coronary intervention
Recurrent instability of fluid balance/renal function
What are the different types of heart transplant procedures?
Typically orthotopic transplantation in adults
Standard (biatrial)
Bicaval
Total
Lung transplant indications include….
Failing maximal medical and/or surgical therapy
Limited life expectancy
Acceptable nutritional status
Satisfactory psychosocial and financial structure
Lung Allocation Score (LAS) has a range of ___-___ and incorporates projected survival in the next ____ yrs w/o a transplant and survival post-transplant
Range 0-100
Incorporates projected survival in next 1 yr without a transplant and survival post-transplant
Different types of lung transplant procedures include…. (x4)
Single Lung Transplant (SOLT)
Bilateral Lung Transplant (BOLT)
Transplantation of lobes from living related donors
Heart-Lung Transplant (HLT)
How many sets of antigens are involved in graft rejection?
3
How many sets of antigens are involved in graft rejection? What are they?
3
Major histocompatibility complex (MHC)
Minor histocompatibility complex (mHC)
Blood group antigens
Immune response mechanisms to transplant are either cellular (_______-mediated) or humoral (_______-mediated)
Cellular (lymphocyte-mediated)
Humoral (antibody-mediated)
What are human leukocyte antigens (HLAs)? What type of expression do they have?
Primary antigens associated with graft rejection
Co-dominant expression
Immune response mechanisms to transplant are either cellular (_______ -mediated) or humoral (_______ -mediated)
Cellular (lymphocyte-mediated)
Humoral (antibody-mediated)
What does sensitization to HLA antigens occur due to? (x4)
Pregnancies
Blood transfusions
Prior transplant(s)
Prior viral/bacterial infections
______ antibodies against donor HLA antigens result in hyperacute or accelerated acute antibody-mediated rejection
Preformed antibodies
High level panel reactive antibodies (PRA) is defined as ____ %
> 80%
What type of transplant rejection is described below?
Occurs w/in min-hrs post-transplant
Humorally-mediated
Pre-existing recipient antibodies against the graft (ABOI, HLA-antibodies)
Antigen-antibody complexes activate complement system massive thrombosis
Kidney most susceptible, liver least
Hyperacute rejection
What type of transplant rejection is described below?
Occurs mos-yrs after acute rejection episodes have subsided
Both antibody- and cell-mediated
Appears as fibrosis and scarring in all transplanted organs but specific histopathological picture depending on SOT group
Chronic rejection
What type of transplant rejection is described below?
Most common during first 6-mos post-transplant
May be primary acute cellular rejection and/or acute humoral rejection
Acute rejection
What are different classes of immunosuppressive medications?
Coritcosteroids Antiproliferative/antimetabolites Calcineurin inhibitors (CNIs) mTOR inhibitors Depleting antibodies (aka anti-lymphocyte antibodies, ALA)
What are some examples of corticosteroids used for immunosuppression in transplant pts?
Prednisone, methylprednisolone
What are some examples of Antiprolifreatice/antimetabolites used for immunosuppression in transplant pts?
Azathioprine, mycophenolate
What are some examples of Calcineurin inhibitors (CNIs) used for immunosuppression in transplant pts?
Cyclosporine, tacrolimus
What are some examples of mTOR inhibitors used for immunosuppression in transplant pts?
Sirolimus
What are some examples of depleting antibodies (aka anti-lymphocyte antibodies, ALA) used for immunosuppression in transplant pts?
Monoclonal AB (OKT-3, basiliximab, alemtuzumab_) Polyclonal Ab (ATG - rabbit, ATGAM - horse)
What is the activity of an immunosuppressive corticosteroid in the treatment of a transplant patient?
Inhibit inflammatory response and cytokine expression (and thus T-cell activation) by several mechanisms
What is the activity of an immunosuppressive Antiproliferative (aka antimetabolites) in the treatment of a transplant patient?
Inhibit purine/DNA synthesis and prevent differentiation/proliferation of B and T-lymphocytes
What is the activity of an immunosuppressive Calcineurin inhibitors (CNIs) in the treatment of a transplant patient?
Inhibit calcineurin phosphatase and prevent interleukin-2 (IL-2) mediated T-cell activation and lymphocyte proliferation
What is the activity of an immunosuppressive mTOR inhibitors in the treatment of a transplant patient?
Inhibit IL-2 mediated T-cell activation and lymphocyte proliferation
What is the activity of an immunosuppressive Depleting antibodies (aka anti-lymphocyte antibodies, ALA) in the treatment of a transplant patient?
Deplete T-cells (and B cells)
What are three induction agents used for transplant immunosuppressive therapy?
Polyclonal antibodies
Monoclonal antibodies
Corticosteroids
What are three maintenance agents used for transplant immunosuppressive therapy?
Corticosteroids
Antiproliferative agents
Calcineurin inhibitors or mTOR inhibitors
What are two agents used for reversal of an established rejection in transplant immunosuppressive therapy?
High dose corticosteroids (i.e. “pulse” steroids) and polyclonal/monoclonal antibodies
What does HCT stand for?
Hematopoietic Cell
Transplantation
What are malignant hematologic indications for HCT?
Acute leukemias, chronic leukemias, myelodysplastic syndromes, myeloproliferative syndromes, hodgkin/non-hodgkin lymphoma, plasma cell dyscrasias
What are malignant selected solid tumor indications for HCT?
Renal cell carcinoma, ewing sarcoma, neuroblastoma, breast/colon/ovarian/pancreatic
What are non malignant acquired indications for HCT?
Aplastic anemia and red cell aplasias, paroxysmal nocturnal hemaglobinuria, Autoimmune disorders (i.e. SLE, systemic sclerosis)
What are non malignant congenital indications for HCT?
Immunodeficiency syndrome, hemoglobinopathies, congenital anemias (i.e. Fanconi), storage diseases, bone marrow failure syndromes, osteopetrosis
Describe an autologous HCT transplant
Donor source: patients’ own cells
Cells are extracted (apheresis) and stored
Patients treated with high dose chemotherapy +/- radiotherapy (conditioning regimen)
Stem cells then transfused
Describe an allogenic HCT transplant type
Donor source: identical twin (syngeneic), related donor (sibling or parent), unrelated donor, umbilical cord transplant
Cells are harvested from the donor
Patients treated with conditioning regimen
Stem cells then transfused
What are potential complications of stem cell transplantation?
Mucositis, hemorrhage cystitis, infections, graft-vs-host disease (GVHD), transplantation-associated thrombotic microangiopathy (TA-TMA), hepatic veno-occlusive dz, pulmonary complications
In graft-versus-host dz (GHVD), donor ______ recognize foreign ______, which leads to a destruction of_______ cells and therefore causes abnormalities in the recipient’s ____, ___, and _____.
T-lymphocytes
HLA antigens
lymphopoietic
skin, liver, and GI tract
T/F GVHD continues to be major causes of morbidity and mortality in allogeneic HCT recipients
True
Can GVHD be acute or chronic or both?
Both, GHVD can be acute or chronic
What are some sx of Acute GVHD that present on the skin? The liver? GI tract?
Skin: Maculopapular rash, may progress to diffuse erythema or bullae formation
Liver: Elevated LFTs
GI Tract: Loss of appetite, dyspepsia, large volume crampy secretory diarrhea, N/V
What is the overall incidence of an HLA identical donor?
40-50%
What is the Graft versus Leukemic (GVL) Effect?
Alloreactive T-lymphocytes from the donor immune system recognizing antigenic differences expressed on residual leukemic cells
What can be done to eliminate the GVL effect?
Remove the t-cells (i.e. a t-cell depleted graft
What are first line agents used in the prevention and treatment of GVHD?
Methotrexate, cyclosporine, tacrolimus, mycophenolate, sirolimus, prednisone, in-vivo t-cell depletion w/ alemtuzumab (Anti-CD 52)
What are second line agents used in the prevention and treatment of GVHD?
Anti-thymocyte globulin (ATG), t-cell depletion w/ photo activation (photopheresis, PUVA), Anti-TNF inhibitors (Etanercept, inflixumab), Anti-CD 25 (Rituximab)
Immunosuppressive therapy is utilized to prevent and/or treat allograft rejection and GVHD but often carries significant adverse effects including _____ and ______
increased risk of infection and drug interactions
Peripheral blood progenitor cells (PBPCs)
More widely used due to _____
Neutropenic phase _____ days
Contains more T-cells, thus has an increased risk for ______
ease of collection
~ 14 days
graft versus host disease (GVHD)
Bone marrow (BM) is no longer the favored source and has a Neutropenic phase of ____ days
~ 21
Umbilical cord blood (UCB) Limited quantity of collection overcome by \_\_\_\_\_\_\_\_ Neutropenic phase \_\_\_\_\_ days Delayed acquired immune reconstitution Less \_\_\_\_\_\_ More infections but not \_\_\_\_\_\_
dual cord transplantations
~ 30 days
GVHD
infection-related death
What are two allogeneic considerations?
Myeloablative (MA)
Non-myeloablative (NMA)
______ is major cause of morbidity/mortality in Solid Organ Transplant (SOT)
CMV
Define CMV Infection:
CMV replication regardless of symptoms
Define CMV Disease:
CMV infection + symptoms
Describe CMV syndrome:
Fever and/or malaise, thrombocytopenia, leukopenia
CMV has a predilection to invade an ______
allograft
T/F Receipt of anti-lymphocyte antibodies (ALA) for rejection also increases risk for CMV
True
What does CMV universal prophylaxis entail?
All at-risk recipients receive therapy (options: oral/IV ganciclovir, oral valganciclovir)
What does CMV pre-emptive screening entail?
Serial monitoring for viremia and prompt treatment with detection
If the donor serostatus is positive for CMV and the recipient’s serostatus is negative for CMV, what is the risk level (High/Intermediate/Low)?
High
If the donor serostatus is negative for CMV and the recipient’s serostatus is negative for CMV, what is the risk level (High/Intermediate/Low)?
Low
If the donor serostatus is positive for CMV and the recipient’s serostatus is positive for CMV, what is the risk level (High/Intermediate/Low)?
Intermediate
If the donor serostatus is negative for CMV and the recipient’s serostatus is positive for CMV, what is the risk level (High/Intermediate/Low)?
Intermediate
If the donor’s serostatus is positive for CMV and the recipients serostatus is negative for CMV, how long should universal prophylaxis be administered post-transplant?
How long should prophylaxis be administered post ALA for rejection?
Universal prophylaxis for 6 months post-transplant
Prophylaxis at least 1-month post ALA for rejection
If the donor’s serostatus is negative for CMV and the recipients serostatus is positive for CMV, how long should universal prophylaxis be administered post-transplant?
How long should prophylaxis be administered post ALA for rejection?
Universal or pre-emptive strategies for at least 3 months post-transplant
Prophylaxis for at least 1-month post ALA for rejection
If the donor’s serostatus is negative for CMV and the recipients serostatus is negative for CMV, how long should universal prophylaxis be administered post-transplant?
How long should prophylaxis be administered post ALA for rejection?
No universal CMV prophylaxis applied
If the donor’s serostatus is positive for CMV and the recipients serostatus is positive for CMV, how long should universal prophylaxis be administered post-transplant?
How long should prophylaxis be administered post ALA for rejection?
Universal or pre-emptive strategies for at least 3 months post-transplant
Prophylaxis for at least 1-month post ALA for rejection
Describe the shape/form of Apophysomyces elegans
Broad, irregularly branching hyphae with few septations (“aseptate”)
How does a Apophysomyces elegans infection take hold? Where can the infections take place?
Apophysomyces elegans gains access via inhalation or direct skin penetration
Infection types include skin and soft tissue, rhino-orbital-cerebral, gastrointestinal, pulmonary and disseminated infection
Do viruses, bacteria, fungi, mycobacteria, or parasites comprise the largest number of donor-derived infections? Donor derived deaths?
Viruses
Viruses
How does a Nocardia infection take hold?
Gain access via inhalation or direct inoculation of skin/soft tissues
Readily disseminates in immunocompromised host
What is Nocardia?
Ubiquitous gram-positive, strictly aerobic, filamentous, branching, weakly acid-fast bacilli
How can you prevent a Nocardia infection from taking hold? (think: what activities should an immunosuppressed pt avoid?)
Avoid gardening, soil, plants while on significant immunosuppressive therapy
T/F SMX-TMP prophylaxis affords complete protection against Nocardia infection
False; SMX-TMP prophylaxis affords some but not complete protection
Following a solid organ transplant, what types of infections would be expected at 0-1 month?
Nosocomial: PNA, Catheter related
Post-surgical: Wound/abscess, Anastomotic leaks
Donor-derived
Following a solid organ transplant, what types of infections would be expected at 1-6 months?
Opportunistic
Reactivation of latent recipient and donor infections
Following a solid organ transplant, what types of infections would be expected at >6 months?
Community-acquired
Reactivation of latent infections
What is the “troll of transplant infections”?
CMV, hehe ;)
GVH dz is commonly expressed as a _____ presentation
skin
What does a Halo sign (Ground glass opacities surrounding nodule) indicate on CT Chest?
alveolar hemorrhage around infarcted lung
What is the most common fungal pathogen in HCT?
Invasive Aspergillosis
What organ does invasive aspergillosis most commonly infect?
Lungs
What is the most common species of invasive aspergillosis?
A. fumigatus
Aspergillosis is described as a hyaline hyphomycete with septate, narrow (3-6µm) hyphae with acute angle ____° branching when visualized in respiratory secretions and tissue specimens
45
How do you treat an invasive aspergillosis infection?
Voriconazole, isavuconazole or other extended spectrum azole
What infections are most common pre-engraftment in bone marrow transplant pts?
Chemotherapy related
Nosocomial
What infections are most common post-engraftment in bone marrow transplant pts?
Opportunistic
What infections are most common during the late phase in bone marrow transplant pts?
Opportunistic
Community-acquired
T/F Immunosuppression essential to prevent rejection but increases risk for infection
True!
