Solid Organ Transplant - Induction Immunosuppression Flashcards
What are the classes of induction agents?
polyclonal antibodies
monoclonal antibodies
IL-2alpha receptor antagonists
What are polyclonal antibodies?
Rabbit antithymocyte globulin (ThymoglobulinTM)
Horse antithymocyte globulin (ATGAMTM)
What are monoclonal antibodies?
Alemtuzumab (Campath-1HTM)
What are IL-2alpha receptor antagonists?
Basiliximab (SimulectTM)
Where do the induction immunosuppression agents target?
signal 1: anti-CD3 mAb
signal 3: anti-CD25 mAb
anti-CD52 mAb - CD52 depletion
What is the indication for Rabbit Antithymocyte Globulin?
induction and/or rejection therapy
What is the MOA of Rabbit Antithymocyte Globulin?
- Composed of polyclonal IgG against human T-lymphocytes derived from horses
(ATGAMTM) or rabbits (ThymoglobulinTM) - Reduces the number of circulating T-lymphocytes, which alters T-cell activation, homing, cytotoxic function
- Ultimately affects cell-mediated & humoral immunity
- lymphocyte depletion persisting for ~3months
What are the AEs of rabbit antithymocyte globulin?
- Leukopenia, thrombocytopenia
- Dose limiting
- Fever,chills
- Pre-medication with diphenhydramine & acetaminophen
What to monitor with rabbit antithymocyte globulin?
- White blood cells(WBC), absolute
lymphocyte count (ALC), platelets - Vital signs
What is the indication of alemtuzumab?
off-label use in SOT as induction
What is the MOA of alemtuzumab?
- Humanized anti-CD52 monoclonal antibody
- CD52 cell surface glycoprotein located on T & B lymphocytes, NK cells, and less densely on monocytes & macrophages
- Antibody-dependent cellular cytotoxicity
- Profound depletion of T cells
What are the AEs of alemtuzumab?
- Infusion-related: chills, rigors, fever
- Pre-medication with diphenhydramine and acetaminophen
What to monitor with alemtuzumab?
- WBC, Platelets, ALC
- Vital signs
What is the indication of basiliximab?
induction only
What is the MOA of basiliximab?
- Recombinant, chimeric (murine/human) monoclonal antibody against CD25
- Bind to the α subunit of the IL-2R
- Competitively inhibits IL-2-mediated activation of lymphocytes
- NON-lymphodepleting
What are the AEs of basiliximab?
minimal, well tolerated
What is basiliximab reserved for?
patient specific factors:
- History of malignancy
- High infection risk, immunocompromised
- HIV, untreated HCV
- Advanced age (>65)
Choosing an induction agent
- Lymphocyte depleting therapy is more commonly used
- Especially for patients with high immunologic risk
monoclonal depleting: alemtuzumab
monoclonal non-depleting: basiliximab
polyclonal depleting: thymoglobulin
