Chapter 32 Haematopoetic Stem Cell Transplantation Flashcards
What is hematopoietic stem cell transplantation (HSCT)?
A procedure that replaces the hematopoietic cells of a patient with stem cells from autologous, allogeneic, or syngeneic sources.
What is the main difference between autologous, allogeneic, and syngeneic HSCT?
Autologous uses the patient’s own cells, allogeneic uses cells from an MHC-matched donor, and syngeneic uses cells from an identical twin.
What is non-familial haploidentical HSCT?
HSCT using an MHC-matched unrelated donor, often used when a matching sibling is not available.
What clinical conditions indicate the need for HSCT?
Myeloid and lymphoid malignancies, acquired or congenital bone marrow failures, primary immunodeficiencies, and autoimmunity.
What factors are associated with successful HSCT?
MHC matching, pre-transplantation chemotherapy and/or irradiation conditioning, post-transplantation suppression of GvHD, use of antimicrobials, and supportive care.
What are the mortality rates associated with HSCT?
Approximately 22%.
What is graft-versus-host disease (GvHD)?
A condition where the donor’s immune cells attack the recipient’s tissues, causing severe transplant reactions.
How can incompatible MHC antigens affect HSCT outcomes?
They can induce severe transplant reactions and rejections, increasing the risk of GvHD.
What are minor histocompatibility antigens?
Peptides from other cellular proteins that differ between individuals and can cause slower graft rejection.
What is the beneficial effect of tolerance to non-inherited maternal antigens (NIMA) in HSCT?
NIMA-mismatched donors can increase graft survival and decrease the risk of GvHD.
What is non-T cell-depleted NIMA-mismatched haploidentical HSCT?
A safer transplantation method by evaluating IFN-gamma-producing cells of donors against NIMA using mixed-lymphocyte reactions.
What are some evolving approaches in HSCT for primary immunodeficiency patients?
Reduced-intensity and nonmyeloablative conditioning regimens.
What are the possible outcomes of HSCT?
Successful engraftment, graft rejection, hematopoietic chimerism, GvHD, engraftment syndrome, thrombotic microangiopathy, and infections.
What is the role of the graft-versus-tumor effect in GvHD?
It prevents tumor relapse by allowing the donor’s immune cells to attack residual tumor cells.
What are the sources of hematopoietic stem cells for HSCT?
Bone marrow, blood, umbilical cord, and amniotic fluid.
What is the difference between intramarrow and intravenous HSCT?
Both have comparable success, but different engraftment profiles may result.
What are the advantages of autologous HSCT?
Lower risk of infection and rapid recovery of immune function, though there is a higher risk of cancer relapse.
What are the challenges with allogeneic HSCT using umbilical cord stem cells?
Low cellular yield, making them more suitable for children.
What is the importance of MHC matching in allogeneic HSCT?
MHC class I mismatch increases the risk of graft rejection, and MHC class II mismatch increases the risk of GvHD.
What is myeloablative conditioning in HSCT?
A regimen with chemotherapy and total body irradiation to eliminate tumoral cells and suppress rejection of allogeneic stem cells.
What is non-myeloablative conditioning?
Uses lower doses of chemotherapy and radiation, reducing bone marrow destruction and allowing recipient-donor chimerism.
What is the significance of post-transplantation immunosuppression?
To prevent GvHD and manage the immune response after transplantation.
What percentage of patients undergoing MHC-matched related donor HSCT experience clinically significant GvHD?
34-40%.
What immunosuppressive drugs are used in post-transplantation therapy?
Glucocorticoids, tacrolimus, methotrexate, and cyclophosphamide.
What is the role of antimicrobial therapy in HSCT?
Broad-spectrum antibiotics, anti-herpes virus, and antifungal medications are essential for preventing infections.
What are the components of post-HSCT care?
Immunosuppression, antimicrobial therapy, supportive care, and vaccination protocols.
What was the outcome of fetal liver cell transplantation in SCID foals?
No functional engraftment, with some foals developing mild GvHD and hepatic necrosis.
What is common variable immunodeficiency (CVID) in horses?
A condition characterized by late-onset recurrent bacterial infections due to failure of B cell development.
What was the result of HSCT in a Thoroughbred mare with CVID?
Partial chimerism with no improvement in serum IgG and IgM concentrations, leading to euthanasia due to persistent symptoms.
What is the process of collecting bone marrow for HSCT in horses?
Bone marrow is collected from the sternebrum using a Jamshidi needle and heparinized syringe.
What are the post-transplantation care steps for horses undergoing HSCT?
Immunosuppressive therapy, antimicrobial therapy, anti-ulcer medication, daily physical examination, and regular blood tests.
What is the significance of chimerism in HSCT?
The presence of donor genomic DNA in the recipient’s blood or tissues, indicating partial or complete engraftment.
What are the potential side effects of long-term dexamethasone therapy in horses?
Increased appetite, muscle waste, polyuria, polydipsia, and abnormal blood parameters.
What is the role of peripheral blood immunophenotyping in post-HSCT monitoring?
To assess the distribution of immune cell populations such as CD4+ T cells, CD8+ T cells, and B cells.
What are the challenges in maintaining critical equine patients long-term after HSCT?
The complexity and cost-prohibitive nature of long-term care and therapy.
What are the potential applications of HSCT in equine medicine?
Treatment of primary immunodeficiencies, bone marrow failures, and certain malignancies.
What is the importance of supportive therapy in HSCT?
To manage complications such as infections, GvHD, and engraftment syndrome.
What are the risks associated with non-myeloablative HSCT regimens?
Lower risks of lethal infections but increased risks of cancer relapse and GvHD.
What is the role of T cell allodepletion in HSCT?
To decrease early transplant-related mortality and GvHD while enabling robust engraftment.
What is the significance of CD34+ marker in HSC enrichment?
CD34+ is a marker used to identify and enrich hematopoietic stem cells for transplantation.
What is the potential benefit of reduced-intensity conditioning regimens in HSCT?
Increased eligibility for elderly and comorbid patients with reduced risks of severe complications.
What are the potential complications of GvHD in HSCT?
High morbidity and mortality, requiring effective prophylactic and therapeutic strategies.
What is the role of mixed-lymphocyte reactions in NIMA-mismatched HSCT?
To evaluate the reaction of IFN-gamma-producing cells of donors against NIMA before transplantation.
What are the clinical features of GvHD in HSCT patients?
Skin rashes, liver dysfunction, gastrointestinal symptoms, and increased susceptibility to infections.
What is the role of vaccination protocols post-HSCT?
To develop adaptive immunity against relevant pathogens once engraftment is confirmed.
What are the potential challenges in developing HSCT protocols for horses?
Cost, lack of species-specific reagents, and limited availability of MHC typing assays.
What are some measures to reduce early transplant-related mortality in HSCT?
Depletion of T cells from donor HSC, transplantation of mega amounts of stem cells, and appropriate antimicrobial therapy.
