boot camp: transplant Flashcards
what is considered immunosupressed
Active treatment for solid tumor and hematologic malignancies
* Receipt of solid‐organ transplant and taking immunosuppressive therapy
* Receipt of CAR‐T‐cell or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
* Moderate or severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott‐Aldrich syndrome)
* Advanced or untreated HIV infection
* Active treatment with:
* high‐dose corticosteroids (i.e., ≥20mg prednisone or equivalent per day)
* alkylating agents, antimetabolites
* transplant‐related immunosuppressive drugs
* cancer chemotherapeutic agents classified as severely immunosuppressive
* tumor‐necrosis (TNF) blockers and other biologic agents that are immunosuppressive or immunomodulatory.
Define autologous vs allogenic stem cell transplant?
Autologous stem cell transplant (lower infection risk)
* The patient’s own stem cells are collected before high‐dose chemotherapy
and then reintroduced after treatment. This allows for high doses of
chemotherapy that would otherwise kill the patient’s normal blood cells.
Allogeneic stem cell transplant (higher infection risk)
* Stem cells from a donor, who can be a blood relative or someone who is not related but is a close genetic match
* Haploidentical: stem cells from a “half‐matched” donor
* Cord blood: stem cell found via an umbilical cord blood bank
* Reduced‐intensity allogeneic stem cell transplantation (also called mini‐ transplant or nonmyeloablative transplant): conditioning treatment contains lower, less toxic doses of chemotherapy and radiation
what is the 2 step common immunosupression after organ transplant?
(1) Induction (T-cell depleting(antithymocyte globulin, alemtuzumab (campth); Il2 antagnoist (basiliximab) or high dose steroids. (2) tacrolimus/cyclosporin + MMF (cellcept) +/- prednisone
timeline of organ infection after transplant
what is the common immunosupression after allogneic stem cell transplant?
- Chemotherapy
- Anti‐graft versus host disease prophylaxis
- Tacrolimus, cyclosporin
- Methotrexate
- Mycophenolate mofetil
- Antithymocyte globulin (rabbit)
- Anti‐graft versus host disease treatment
- The first‐line treatment of acute GVHD is methylprednisolone
draw timeline of infection after HSCT
what is the pre-immunosuppression evaluation
what is the pre-solid organ transplant evaluation
who should get tested for TB?
contacts with TB, HIV/immunouspressed, endemic country, illegal dugs, live or work somehre in the US where TB disease is more common.
what does the Tspot or quantiferon gold test?
- Enumerates effector T‐cell response to stimulation with a combination of
peptides simulating ESAT‐6 and CFP10 (+ TB7.7 for QFN) antigens - Detects prior exposure to:
- M. tuberculosis complex organisms (M. tuberculosis, M. bovis, M. africanum, M. microti, M. canetti)
- M. kansasii, M. szulgai, and M. marinum
- Not + with prior BCG vaccine (bacille Calmette–Guérin)
- Interpret test correctly:
- If either test or PPD positive, take as positive
- Borderline results = partway b/w + and negative
- Indeterminate results = assay did not work
what is the most common infection after SOT/SCT?
CMV
what is the antiviral prophylaxis options for CMV?
give example of prophylaxis regimen after SOT
what is the antiviral prophylaxis for SCT?
Acyclovir/valacyclovir/famvir for everyone
* Prevents herpes, varicella/zoster
* Duration varies a lot across programs, 6‐12+ months is common
* Letermovir x 100 days if higher CMV risk
* if recipient is CMV positive – opposite of solid organ (D‐R+ is high risk after HSCT)
* Prevents CMV, NOT herpes, varicella/zoster
* Decreased mortality
* If small viral load “blips”, carry on and retest a week later – only stop therapy if high blips (>1,000 IU/ml)
* Main side effect is cost
what is the pneumocystits/toxoplasmosis prophylaxis tx?
- First line:
- Bactrim SS daily or DS three times a week
- Second line (only if real Bactrim allergy or intolerance) alternatives:
- Atovaquone (Mepron) 1500 mg QD
- Dapsone 100 mg QD
- Check G6PD
- watch for methemoglobinemia, low white blood cell count
- Pentamidine IV q month (does not cover Toxoplasmosis) - add pyrimethamine/sufadiazine/folinic acid.
- Duration variable, usually until end of PPx
what is the SOT antifungal prophyalxis?
what are the big side effect profile for voriconazole?
osteitis, mucoromycosis, augmented risk of skin cancer
CMV treatment algorithim(MGH)
what kind of fungal infections seen in SCT/SOT?
- Post‐solid organ transplant: Incidence of invasive fungal infections in the first year has been reported to
be 3%1 - Candidiasis (sterile space), esp liver transplant*surgery
- Cryptococcal disease
- Among most common causes of meningitis
- Invasive aspergillosis in 1‐15%2
- Accounts for significant % of deaths in first year
- Mortality dropping in recent times, however
- Mucormycosis less common, higher mortality
- Stem cell transplant: similar, longer risk if graft‐vs‐host disease
- Non‐transplant immunocompromised hosts: less frequent/”net state of immunosuppression”
name a septate vs non-septtate hyphae invovled in fungal infections ?
septate (aspergillus) vs non-septate (mucor/zygomycetes) hyphae
what are the diagnostic fungal markers wiht respect to sensitivity/specificity?
what are some key drug interactions with transplant medications and antimicrobials (aoles/Rifamycins)
