Pre-transplant screening: Difference between revisions

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*Screen for latent infections that may reactivate, and for risk for future infections
= Pre-tranplant screening =


=Approach=
* Screen for latent infections that may reactivate, and for risk for future infections


== Approach ==
==History==


*Look for primary infections, based on epidemiology
=== History ===
**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==
* 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


*Signs of active infections
=== Physical Exam ===


==Investigations==
* Signs of active infections


*Chest and abdomeinal CT for staging and signs of active infection
=== Investigations ===
*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=
* 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


==CMV==
== Specific Diseases ==


*Donor and recipient are both screened with serology
=== CMV ===
*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


{| class="wikitable"
* Donor and recipient are both screened with serology
!Transplantation
* Preventing CMV infection prevents end-organ damage
!Donor
* Approaches
!Recipient
** Prophylaxis: in SOT for 90 days, unless D-/R- (lowest risk)
!Risk category
*** Avoided in HSCT, because would like to avoid bone marrow suppression from valgan/etc.
!Approach
** 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
| rowspan="4" |SOT
| +
| +
|
|–
| highest risk
|highest risk
| prophylaxis
|prophylaxis
|-
|-
| SOT
| +
| +
| +
| +
|moderate risk
|
| prophylaxis
|prophylaxis
|-
|-
|–
| SOT
| –
| +
| +
|moderate risk
|
| prophylaxis
|prophylaxis
|-
|-
|–
| SOT
|
|–
|lowest risk
| –
|no treatment
| lowest risk
| no treatment
|-
|-
| allo-HSCT
|allo-HSCT
| +/–
| +/–
| +
| +
| high risk
|high risk
| pre-emptive
|pre-emptive
|-
|
|
|
|
|
|-
| Use of AMT
|
|
| higher risk
|
|}
|}


==== Treatment ====
==Treatment==

*Start treatment, repeat the viral load at 2 weeks
*Monitor for failure with a 1-log decrease at 2 weeks


==EBV==
* Start treatment, repeat the viral load at 2 weeks
* Monitor for failure with a 1-log decrease at 2 weeks


*90% of adults are IgG positive
=== EBV ===
*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==
* 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


*Can cause morbidity
=== HSV/VZV ===
*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==
* 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


*Risk factors for reactivation
=== Hepatitis B ===
**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==
* 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


*If serology positive, get HCV-RNA
=== Hepatitis C ===
*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==
* 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


*Testing is for both, does not distinguish
=== HTLV-I/II ===
*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==
* 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


*VDRL, ideally treat before transplantation
=== Other Routine ===
*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==
* 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==
=== Other Optional ===


*Consider it in undocooked meat, especially game animals, or lots of cats
==== Toxoplasmosis ====
*Concern is for reactivation in alloHSCT


==HPV==
* Consider it in undocooked meat, especially game animals, or lots of cats
* Concern is for reactivation in alloHSCT


*Talk to the women about it
==== HPV ====
*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==
* 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==
=== Travel-specific Screening ===


*Screen high-risk populations with Trypanosoma cruzi antibody
==== Trypansoma cruzi ====
*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==
* 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


*Present in southern US and eastern Europe
==== Strongyloides ====
*Low threshold for screening and treating


==Malaria==
* Present in southern US and eastern Europe
* Low threshold for screening and treating


*Can be transmited via graft in alloHSCT
==== Malaria ====
*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==
* 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


*Coccidioides in recipient does have a higher risk of reactivation
==== Endemic fungi ====
**Maybe fluconazole prophylaxis
*No information on Paracoccidoides
*Histoplasmosis in recipient does not tend to reactivate
*Many recipients get prophylaxis for other fungi anyway


=Contraindications=
* 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


*HIV infection
== Contraindications ==
*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=
* 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


==Pre-transplantation==
== Vaccination ==


*Can give inactivated, non-live vaccines
=== Pre-transplantation ===
**Give them their flu shot
*Will need to be repeated post-engraftment


==Post-transplantation==
* Can give inactivated, non-live vaccines
** Give them their flu shot
* Will need to be repeated post-engraftment


*Need to be reviewed as
=== Post-transplantation ===


[[Category:Transplant patients]]
* Need to be reviewed as

Latest revision as of 21:13, 19 September 2020

  • 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