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
  • 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
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