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Equine Clinical Immunology > Chapter 32 Haematopoetic Stem Cell Transplantation > Flashcards

Chapter 32 Haematopoetic Stem Cell Transplantation Flashcards

1
Q

What is hematopoietic stem cell transplantation (HSCT)?

A

A procedure that replaces the hematopoietic cells of a patient with stem cells from autologous, allogeneic, or syngeneic sources.

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2
Q

What is the main difference between autologous, allogeneic, and syngeneic HSCT?

A

Autologous uses the patient’s own cells, allogeneic uses cells from an MHC-matched donor, and syngeneic uses cells from an identical twin.

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3
Q

What is non-familial haploidentical HSCT?

A

HSCT using an MHC-matched unrelated donor, often used when a matching sibling is not available.

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4
Q

What clinical conditions indicate the need for HSCT?

A

Myeloid and lymphoid malignancies, acquired or congenital bone marrow failures, primary immunodeficiencies, and autoimmunity.

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5
Q

What factors are associated with successful HSCT?

A

MHC matching, pre-transplantation chemotherapy and/or irradiation conditioning, post-transplantation suppression of GvHD, use of antimicrobials, and supportive care.

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6
Q

What are the mortality rates associated with HSCT?

A

Approximately 22%.

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7
Q

What is graft-versus-host disease (GvHD)?

A

A condition where the donor’s immune cells attack the recipient’s tissues, causing severe transplant reactions.

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8
Q

How can incompatible MHC antigens affect HSCT outcomes?

A

They can induce severe transplant reactions and rejections, increasing the risk of GvHD.

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9
Q

What are minor histocompatibility antigens?

A

Peptides from other cellular proteins that differ between individuals and can cause slower graft rejection.

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10
Q

What is the beneficial effect of tolerance to non-inherited maternal antigens (NIMA) in HSCT?

A

NIMA-mismatched donors can increase graft survival and decrease the risk of GvHD.

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11
Q

What is non-T cell-depleted NIMA-mismatched haploidentical HSCT?

A

A safer transplantation method by evaluating IFN-gamma-producing cells of donors against NIMA using mixed-lymphocyte reactions.

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12
Q

What are some evolving approaches in HSCT for primary immunodeficiency patients?

A

Reduced-intensity and nonmyeloablative conditioning regimens.

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13
Q

What are the possible outcomes of HSCT?

A

Successful engraftment, graft rejection, hematopoietic chimerism, GvHD, engraftment syndrome, thrombotic microangiopathy, and infections.

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14
Q

What is the role of the graft-versus-tumor effect in GvHD?

A

It prevents tumor relapse by allowing the donor’s immune cells to attack residual tumor cells.

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15
Q

What are the sources of hematopoietic stem cells for HSCT?

A

Bone marrow, blood, umbilical cord, and amniotic fluid.

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16
Q

What is the difference between intramarrow and intravenous HSCT?

A

Both have comparable success, but different engraftment profiles may result.

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17
Q

What are the advantages of autologous HSCT?

A

Lower risk of infection and rapid recovery of immune function, though there is a higher risk of cancer relapse.

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18
Q

What are the challenges with allogeneic HSCT using umbilical cord stem cells?

A

Low cellular yield, making them more suitable for children.

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19
Q

What is the importance of MHC matching in allogeneic HSCT?

A

MHC class I mismatch increases the risk of graft rejection, and MHC class II mismatch increases the risk of GvHD.

20
Q

What is myeloablative conditioning in HSCT?

A

A regimen with chemotherapy and total body irradiation to eliminate tumoral cells and suppress rejection of allogeneic stem cells.

21
Q

What is non-myeloablative conditioning?

A

Uses lower doses of chemotherapy and radiation, reducing bone marrow destruction and allowing recipient-donor chimerism.

22
Q

What is the significance of post-transplantation immunosuppression?

A

To prevent GvHD and manage the immune response after transplantation.

23
Q

What percentage of patients undergoing MHC-matched related donor HSCT experience clinically significant GvHD?

A

34-40%.

24
Q

What immunosuppressive drugs are used in post-transplantation therapy?

A

Glucocorticoids, tacrolimus, methotrexate, and cyclophosphamide.

25
Q

What is the role of antimicrobial therapy in HSCT?

A

Broad-spectrum antibiotics, anti-herpes virus, and antifungal medications are essential for preventing infections.

26
Q

What are the components of post-HSCT care?

A

Immunosuppression, antimicrobial therapy, supportive care, and vaccination protocols.

27
Q

What was the outcome of fetal liver cell transplantation in SCID foals?

A

No functional engraftment, with some foals developing mild GvHD and hepatic necrosis.

28
Q

What is common variable immunodeficiency (CVID) in horses?

A

A condition characterized by late-onset recurrent bacterial infections due to failure of B cell development.

29
Q

What was the result of HSCT in a Thoroughbred mare with CVID?

A

Partial chimerism with no improvement in serum IgG and IgM concentrations, leading to euthanasia due to persistent symptoms.

30
Q

What is the process of collecting bone marrow for HSCT in horses?

A

Bone marrow is collected from the sternebrum using a Jamshidi needle and heparinized syringe.

31
Q

What are the post-transplantation care steps for horses undergoing HSCT?

A

Immunosuppressive therapy, antimicrobial therapy, anti-ulcer medication, daily physical examination, and regular blood tests.

32
Q

What is the significance of chimerism in HSCT?

A

The presence of donor genomic DNA in the recipient’s blood or tissues, indicating partial or complete engraftment.

33
Q

What are the potential side effects of long-term dexamethasone therapy in horses?

A

Increased appetite, muscle waste, polyuria, polydipsia, and abnormal blood parameters.

34
Q

What is the role of peripheral blood immunophenotyping in post-HSCT monitoring?

A

To assess the distribution of immune cell populations such as CD4+ T cells, CD8+ T cells, and B cells.

35
Q

What are the challenges in maintaining critical equine patients long-term after HSCT?

A

The complexity and cost-prohibitive nature of long-term care and therapy.

36
Q

What are the potential applications of HSCT in equine medicine?

A

Treatment of primary immunodeficiencies, bone marrow failures, and certain malignancies.

37
Q

What is the importance of supportive therapy in HSCT?

A

To manage complications such as infections, GvHD, and engraftment syndrome.

38
Q

What are the risks associated with non-myeloablative HSCT regimens?

A

Lower risks of lethal infections but increased risks of cancer relapse and GvHD.

39
Q

What is the role of T cell allodepletion in HSCT?

A

To decrease early transplant-related mortality and GvHD while enabling robust engraftment.

40
Q

What is the significance of CD34+ marker in HSC enrichment?

A

CD34+ is a marker used to identify and enrich hematopoietic stem cells for transplantation.

41
Q

What is the potential benefit of reduced-intensity conditioning regimens in HSCT?

A

Increased eligibility for elderly and comorbid patients with reduced risks of severe complications.

42
Q

What are the potential complications of GvHD in HSCT?

A

High morbidity and mortality, requiring effective prophylactic and therapeutic strategies.

43
Q

What is the role of mixed-lymphocyte reactions in NIMA-mismatched HSCT?

A

To evaluate the reaction of IFN-gamma-producing cells of donors against NIMA before transplantation.

44
Q

What are the clinical features of GvHD in HSCT patients?

A

Skin rashes, liver dysfunction, gastrointestinal symptoms, and increased susceptibility to infections.

45
Q

What is the role of vaccination protocols post-HSCT?

A

To develop adaptive immunity against relevant pathogens once engraftment is confirmed.

46
Q

What are the potential challenges in developing HSCT protocols for horses?

A

Cost, lack of species-specific reagents, and limited availability of MHC typing assays.

47
Q

What are some measures to reduce early transplant-related mortality in HSCT?

A

Depletion of T cells from donor HSC, transplantation of mega amounts of stem cells, and appropriate antimicrobial therapy.

Equine Clinical Immunology (32 decks)

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