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Hematology > Bone Marrow Transplantation > Flashcards

Flashcards in Bone Marrow Transplantation Deck (15):
1

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

2

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

3

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

4

Define the complications of over immunosuppression

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

5

What are indications for allogeneic HSC transplantation?

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

6

How do translated HSC home to host bone marrow?

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

7

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

8

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

9

What are the risk factors for graft v host disease?

-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

10

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

11

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

12

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

13

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

14

What are the complications of allogeneic HSCT?

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

15

What are the risk factors for infection in HSCT?

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