Pre-transplant screening

• 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

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

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