Pre-transplant screening
From IDWiki
- Screen for latent infections that may reactivate, and for risk for future infections
Approach
History
- Look for primary infections, based on epidemiology
- e.g. Chagas in higher risk people from South America
- What is the planned transplantation, and for stem cell transplants, what is the planned conditioning regimen?
- e.g. ATG prolongs T-cell dysfunction
- Prolonged neutropenia
- Recent live vaccines within 4 weeks of transplantation
- Travel or exposure history
- Tuberculosis
- Strongyloidiasis
- Malaria
- Sexual history
- Many patients have unknown STIs
- Dental assessment
Physical Exam
- Signs of active infections
Investigations
- Chest and abdomeinal CT for staging and signs of active infection
- Routine
- HIV serology & p24 antigen, followed by NAT if positive
- Donor may be screened with NAT/PCR depending on the centre
- Positive donor precludes transplant
- Positive recipients have higher risk of HCV reactivation, but otherwise seem to do okay
- Should get control of HIV before transplant if possible
- CMV, EBV, HSV, VZV, HBV, HCV, HTLV 1&2, syphilis serologies
- HIV serology & p24 antigen, followed by NAT if positive
- Targetted
- Toxoplasmosis serology
- Stronyloides serology
- Malaria
- Endemic fungi in high-risk patients
- Histoplasmosis only rarely reactivates post-transplant
- Tuberculosis, thought TST may be negative depending on their immunosuppression and IGRA is unstudied
Specific Diseases
CMV
- Donor and recipient are both screened with serology
- Preventing CMV infection prevents end-organ damage
- Approaches
- Prophylaxis: in SOT for 90 days, unless D-/R- (lowest risk)
- Avoided in HSCT, because would like to avoid bone marrow suppression from valgan/etc.
- Pre-emptive: done in HSCT
- PCR is positive 1+ week before end-organ damage, so screening and treatment is useful
- CMV reactivation extremely rare in first 30 days
- PCR weekly starting at day 21; if above threshold, treat
- Threshold is 1451 copies/mL
- Screen until day 100, or longer if persistently immunocompromised as in GVHD
- Prophylaxis: in SOT for 90 days, unless D-/R- (lowest risk)
Transplantation | Donor | Recipient | Risk category | Approach |
---|---|---|---|---|
SOT | + | – | highest risk | prophylaxis |
+ | + | moderate risk | prophylaxis | |
– | + | moderate risk | prophylaxis | |
– | – | lowest risk | no treatment | |
allo-HSCT | +/– | + | high risk | pre-emptive |
Treatment
- Start treatment, repeat the viral load at 2 weeks
- Monitor for failure with a 1-log decrease at 2 weeks
EBV
- 90% of adults are IgG positive
- High risk populations for developing PTLD
- Highest risk are children who acquire primary EBV after transplantation
- Others: mismatched BMT, T-cell depleted BMT, ATG, splenectomy
- Monitor these patients weekly for 3 months post-transplant
- Treatment
- No antivirals that are helpful
- Decrease immunosuppression
- Rituximab is a treatment option
HSV/VZV
- Can cause morbidity
- Usually reacivates pre-engraftment
- All HSV-positive patients get acyclovir until day 30 or discharge
- All VZV-positive get prophylaxis for one year post-alloHSCT
- Acyclovir may prevent VZV reactivation
- Acyclovir 800 mg bid or valacyclovir 500 mg bid
- Extend duration if T-cell suppression or ongoing GVHD
- In SOT, depends on centre and specific organ, but likely prophylaxed with acyclovir at least until off prednisone
Hepatitis B
- Risk factors for reactivation
- Alemtuzumab, bortezomib, fludarabine/rituximab
- High-dose glucocorticoids
- Screen for HBsAg, HBsAb, and HBcAb, but ignore the HBsAb
- If positive, do HBV-DNA
- If sAg negative but cAb positive, prophylax with lamivudine until 6 months after stopping immunosuppression
- If sAg positive, needs treatment with two drugs
- If donor is positive, recipient should be given HBIg immediately and at 1 months, then reimmunized as well as the routine prophylaxis
Hepatitis C
- If serology positive, get HCV-RNA
- If HCV-RNA negative, not at risk for reactivation
- May be able to donate HCV-positive donor organs, though still early developments
HTLV-I/II
- Testing is for both, does not distinguish
- HTLV-I endemic in SW Japan and Caribbean, and causes clinical disease
- HTLV-II associated with IVDU in US/Europe, but does not appear to cause clinical disease
- If donor is positive, may have increased risk of progression to T-cell lymphoma
- Send testing to public health for HTLV-I, and if positive, precludes donation
Other Routine
- VDRL, ideally treat before transplantation
- Can do TBST for latent TB in the recipient, depending on the clinical context
- May benefit from LTBI treatment with isoniazid
- WNV NAT/PCR in donor only, and precludes HSCT
Other Optional
Toxoplasmosis
- Consider it in undocooked meat, especially game animals, or lots of cats
- Concern is for reactivation in alloHSCT
HPV
- Talk to the women about it
- Up to 40% of positive women can develop high-grade genital tract lesions, usually years after HSCT
- Ensure they get Pap smears routinely, and likely more frequently than normal-risk populations
Travel-specific Screening
Trypansoma cruzi
- Screen high-risk populations with Trypanosoma cruzi antibody
- Lived in endemic countries (Mexico, Central America, South America) x6+ months
- Either donor or recipient's mother was born in an endemic area
- Maternal history of unexplained cardiac disease
- High-risk living conditions in an endemic country even if less than 6 months
- Reduviid bug exposure
- Mud wall dwellings
- Unmilled logs or sicks
- Thatched roof
Strongyloides
- Present in southern US and eastern Europe
- Low threshold for screening and treating
Malaria
- Can be transmited via graft in alloHSCT
- Diagnostic tests of the donor may be negative but still transmit infection, so don't bother
- Ideally defer if donor traveled within 1 to 3 years
- If donor has infection, treat them first
Endemic fungi
- Coccidioides in recipient does have a higher risk of reactivation
- Maybe fluconazole prophylaxis
- No information on Paracoccidoides
- Histoplasmosis in recipient does not tend to reactivate
- Many recipients get prophylaxis for other fungi anyway
Contraindications
- HIV infection
- HTLV-1 infection
- ACUTE CMV or EBV infection
- Acute hepatitis A infection (ie, Hepatitis A IgM+)
- Acute toxoplasmosis
- Active TB (ie, until it is well controlled)
- An acute tickborne infection, such as Rocky Mountain spotted fever, babesiosis, anaplasmosis, ehrlichiosis, Q fever, or Colorado tick fever
- Active or past history of Chagas disease
- Acute or recent West Nile Virus infection
- Chronic, active hepatitis B or C is relative contraindication
Vaccination
Pre-transplantation
- Can give inactivated, non-live vaccines
- Give them their flu shot
- Will need to be repeated post-engraftment
Post-transplantation
- Need to be reviewed as