Day 18, Lecture 1: Transplant Medicine Flashcards
1
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2
Q
Hematopoetic Stem Cells are capable of
A
- Capable of reconstituting the ability to make blood
- Can be translplanted from one individual to another
- Can be used to create a new immune system in the recipient
- In other words, the cellular components of blood and everything derived from them can be produced from hematopoietic stem cells
3
Q
General indications for hematopoietic stem cell transplantation
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- To treat a hematologic (blood derived) malignancy (cancer) that is unlikely to be cured using a standard chemotherapy regimen
- To replace defective bone marrow and/or as pre-emptive treatment to prevent the development of hematologic malignancy
- As a rescue after treatment of a non-hematologic malignancy kills the normal bone marrow
- To treat an immunodeficiency
- To suppress or eliminate an auto-immune disease
4
Q
Autologous
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- Harvested from patient and stored in freezer in cryopreservative
- Typically used in treating malignancies not involving the marrow such as neuroblastoma, infant brain tumors, and lymphoma in first remission
5
Q
Syngeneic
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- genetically identical donor (twin)
- very unusual
- useful in treating malignancies but not for gene defects
6
Q
Allogeneic
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- Partly or fully HLA-matched donor
- Used in hematologic malignancies and broad variety of gene defects including things like sickle cell disease, Hurler syndrome, and SCID
7
Q
Allogeneic donors by order of preference
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- HLA-matched sibling
- Matched unrelated donor (MUD)
- Partially matched unrelated donor (8/10 or better)
- Umbilical cord blood stem cells (4/6 or better)
- Haploidentical
8
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A
9
Q
Unrelated donors are typed at ____ loci allowing mismatches at numerous ___ loci
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- Unrelated donors are typed at five loci allowing mismatches at numerous minor loci
10
Q
Sources of Stem Cells
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- Bone Marrow
- Umbilical cord blood stem cells
- Peripheral blood stem cells
- Someday:
- iPSC differentiated into HSCT
11
Q
Bone marrow harvest
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12
Q
Peripheral blood stem cell harvest
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13
Q
Umbilical cord blood stem cells
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14
Q
Treatments of patient prior to stem cell infusion
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- Patients must be treated prior to the stem cell infusion to allow the new stem cells to grow
- Treatments:
- Chemotherapy:
- +/- radiation accomplishes several things
- suppression of the donor’s immune system
- Creates space for the new stem cells to grow
- Treatment of the malignancy
- +/- radiation accomplishes several things
- Many different preparative regimens are used and have a range of intensities
- Myeloablative
- Full dose that ablates the marrow
- Reduced intensity
- Lower doses but ablative
- Non-myeloablative
- marrow may recover with mixed chimerism
- Myeloablative
- Chemotherapy:
15
Q
Graft versus host disease (GVHD)
A
- Occurs in allogenic transplants when the new immune system derived from the donor attacks the recipient (the patient)
- GVHD prophylaxis is almost always essential in allogeneic transplants. Different combination of medications are used including durgs like:
- A calcineurin inhibitor (cyclosporine or tacrolimus)
- Antibodies that kill off lymphocytes (ATG or Alemtuzumab)
- Post-Transplant methotrexate or cyclophosphamide
- Mycophenolate
- Rapamycin (Sirolimus)
- Glucocorticoids (Prednisone or Prednisolone)
- Dr. Craword’s usual regiment:
- Tacrolimus + Methotrexate +/- ATG
16
Q
Infectious disease prophylaxis in transplant
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- Amoxicillin
- for Gram-positive organisms
- Fluconazole for fungi
- Acyclovir for HSV
17
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A
18
Q
Unavoidable Transplant Complications
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- Nausea and Vomiting
- Diarrhea
- Anorexia
- Febrile neutropenia +/- overt infection
- Painful mucositis
- Platelet and PRBC transfusions
- Alopecia
- Sterility (often)
19
Q
Severe Common Complications of HSCT
A
-
Serious Bacterial or fungal infection
- empiric treatment for bacteria and fungi
-
Graft-versus-host disease
- Prophylaxis
- Sinusoidal Obstruction syndrome (SOS)/veno-occlusive disease (VOD)
- Severe liver damage caused by chemotherapy often accompanied by multi-organ failure
- Diffuse Alveolar hemorrhage
- Bleeding in the lungs
- Viral reactivation
- CMV, HSV, VZV, and adenovirus
- Post-transplant lymphoproliferative disease
- Usually driven by EBV
- Renal Failure
- Highly associated with poor outcome
- Acute cardiac toxicity
- Rare complication but very bad
20
Q
Acute graft versus host disease (GVHD)
A
- usually occurs within the firs 100 days after transplant
- Skin GVHD
- Erythematous maculopapular (flat and raised) rash
- Liver GVHD
- Elevations in bilirub (hyperbilirubinemia)
- Gut GVHD
- Diarrhea (sometimes bloody) and/or persistant nausea and vomiting
- more than one organ is frequently affected
- A scoring system defines severity
21
Q
Chronic Graft vs. Host disease (GVHD)
A
- Occurs after day +100
- more likely in patients that had severe acute GVHD
- Clinical features
- Dermal
- Lesions like lichen planus and scleroderma
- Hepatic
- Cholestatic jaundice
- Ocular
- Dry eyes with buring, irritation, and pain
- Oral
- Dryness and sensitivity
- Pulmonary
- Obstructive lung disease
- GI
- Dysphagia
- Genitourinary
- Vaginitis and Vaginal Strictures
- Dermal
22
Q
Sinusoidal obstruction syndrome (SOS) or hepatic veno-occlusive disease (VOD)
A
- Hepatic sinusoid injury characterized by:
- Painful hepatomegaly
- Fluid retention with weight gain
- Jaundice
- Severity
- Mild
- Resolves spontaneously without treatment
- Moderate
- Requires treatment with analgesics and diuretics but resolves
- Severe
- Multi-organ failure or fails to resolve with treatment by day 100
- Mild
23
Q
Diffuse Alveolar Hemorrhage
A
- Characterized by diffuse infiltrates, cough, dyspnea, and hemoptysis
- Diagnosed by bronchoscopy
- Toxic damage to lung by chemo and XRT
- Older age is a risk factor
- Usually occurs in first 30 days
- Mortality is high
- Treatment with high dose steroids and recombinant factor VIIa (rFVIIa)
24
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