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Flashcards in Bone Marrow Transplantation Deck (15):

Determine/ define the 3 types of organ transplant rejection

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


Define strategies to prevent rejection

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


Define the mechanism of action of commonly used immunsuppression medications

-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


Define the complications of over immunosuppression

-infections: viral, fungal, bacterial
-malignancies: EBV, lymphoproliferative disease, kaposi's sarcoma, squamous cell carcinomas


What are indications for allogeneic HSC transplantation?

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


How do translated HSC home to host bone marrow?

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


What mediates graft versus host reaction?

-CD3 T cells can proliferate and cause run
-all leukocytes in blood are infused, not separated from progenitor cells


What are the principles behind graft versus host disease?

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


What are the risk factors for graft v host disease?

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


What is the clinical presentation of GVHD?

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


What is the pathogenesis of acute GVHD?

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


What is the graft versus tumor effect?

-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


How can GVHD be prevented?

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


What are the complications of allogeneic HSCT?

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


What are the risk factors for infection in HSCT?

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