Bone Marrow Transplantation

Question 1

Determine/ define the 3 types of organ transplant rejection

Answer 1

1. Hyperacute: less than 1% of patients, within 6-8 hours
   - mediated by preexisting humoral immunity (abs)+complement
2. Acute (cell or antibody mediated)
3. Chronic: over 5-10 years

Question 2

Define strategies to prevent rejection

Answer 2

• closely match donor and recipient
• remove preformed antibodies from recipient to prevent hyper acute rejection
• block co stimulatory molecules e.g. CD28
• immunosuppressive medications

Question 3

Define the mechanism of action of commonly used immunsuppression medications

Answer 3

• blocks interaction between APC and T cell at different sites, e.g. Anti-CD25
• inhibits signal transduction in T cell, e.g. complexing and binding calcineurin to prevent entering nucleus and T cell activation
• inhibits nucleotide synthesis

Question 4

Define the complications of over immunosuppression

Answer 4

• infections: viral, fungal, bacterial

- malignancies: EBV, lymphoproliferative disease, kaposi’s sarcoma, squamous cell carcinomas

Question 5

What are indications for allogeneic HSC transplantation?

Answer 5

1. hematologic malignancies
2. bone marrow failure
3. inherited genetic disease
4. immunodeficiency and autoimmune disease

Question 6

How do translated HSC home to host bone marrow?

Answer 6

-CXCR4 and CXCL12 receptor and ligand interactions help home cells to bone marrow

Question 7

What mediates graft versus host reaction?

Answer 7

• CD3 T cells can proliferate and cause run

- all leukocytes in blood are infused, not separated from progenitor cells

Question 8

What are the principles behind graft versus host disease?

Answer 8

• donor T cell recognizes genetically disparate recipient who can’t reject donor cells
• donor T cells recognize host antigens via host antigen presenting cells

Question 9

What are the risk factors for graft v host disease?

Answer 9

-Histoincompatibility
HLA
Non HLA
-Patient age –older patients have greater risks
-Donor-recipient sex mismatch
-Graft source: PBSC  BM  Cord blood
-Allosensitization of donor
-Conditioning intensity

Question 10

What is the clinical presentation of GVHD?

Answer 10

Acute: skin, liver, GI tract 
-maculopapular rash
-cholestasis, elevated transaminases
-nausea, vomiting, diarrhea
Chronic: multi system disease the resembles autoimmune disorders

Question 11

What is the pathogenesis of acute GVHD?

Answer 11

1. priming of immune response: chemotherapy causes host tissue damage–>release of cytokines pro inflammatory and activation of APC
2. induction of T cell activation
3. homing of T cells and other cells to target tissues
4. effector phase: destruction of target tissues via cell surface and soluble immune effector molecules

Question 12

What is the graft versus tumor effect?

Answer 12

• donor cells see tumor tissues as foreign and destroys the tissue
• mediated by expression of tumor antigens, minor or major histocompatibility antigens on malignant cells
• Extent of effect varies depending on disease: CML> AML>ALL

Question 13

How can GVHD be prevented?

Answer 13

-post transplant immunosuppression, e.g. calcineurin inhibitor+methotrexate/other
-in vitro or in vivo T cell depletion of graft
however can increase infection risk

Question 14

What are the complications of allogeneic HSCT?

Answer 14

• Regimen related toxicity
• Engraftment failure-donor cells won’t engraft
• Infections
• Graft-versus-host disease (acute and chronic)
• Late effects-radiation, secondary malignancies

Question 15

What are the risk factors for infection in HSCT?

Answer 15

• Neutropenia
• Venous catheters
• Mucosal damage (conditioning and GVHD)
• Steroid therapy
• Impaired cellular immunity (immunosuppression, acute GVHD)
• Impaired humoral immunity (chronic GVHD)