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Pre and posttransplant vaccination of transplant recipients

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Pre-transplant vaccinations -SCT ... Higher levels of antibodies if vaccination are started 3-6 months after SCT than ... between donor or no donor vaccination ... – PowerPoint PPT presentation

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Title: Pre and posttransplant vaccination of transplant recipients


1
Pre- and posttransplant vaccination of
transplant recipients
Per Ljungman, Stockholm
2
Why should we immunize?
  • The patients point of view
  • Risk for infection
  • Risk of severe disease
  • Risk for side-effects
  • The societys point of view
  • Risk for epidemics
  • Cost

3
Pre-transplant vaccinations - SOT
  • Timing is usually not a problem
  • The results are variable and not as strong as in
    healthy individuals.
  • However, the results are usually better before
    than after SOT and to complete a primary schedule
    before SOT is generally recommended
  • Pre-transplant immunity might disappear more
    quickly than in normal controls.
  • Post-transplant boosters might be needed

4
Pre-transplant vaccinations -SCT
  • Usually undergo cytotoxic chemotherapy limiting
    the possibilities to perform pre tx vaccinations.
  • Efficacy during chemotherapy usually poor
  • Pre-transplant immunity is frequently lost
  • However in patients not on chemotherapy,
    pre-transplant vaccination can be considered for
    example against varicella.

5
Why is the immunity lost?
  • No. of antigen specific cells before SCT in the
    recipient
  • Eradication of recipient memory B-cells
  • Graft-vs-host (lymphocyte) reaction?
  • Cytotoxic chemo-radiotherapy?
  • No. of antigen specific cells in the donor graft

6
Measles, influence of previous antigen challenge
1
0,8
0,6
0,4
Natural disease
0,2
Immunized
0
0
12
24
36
48
60
72
84
96
108
120
132
144
156
Ljungman et al Blood 1994
7
Donor vaccination
  • It has been shown to improve recipient immunity
    for
  • Haemophilus influenzae (Molrine et al 1996)
  • Tetanus toxoid (Wimperis et al 1986 Molrine et
    al 1996)
  • Hepatitis B (Wimperis et al 1986 Ilan et al
    1993, 1994)
  • Conjugate pneumococcal vaccine (Molrine et al
    2003)
  • Donor vaccination should be combined with early
    posttransplant patient vaccination

8
Donor vaccination
  • Key questions
  • When will patients be at risk for infection?
  • Against which agents will transfer of donor
    immunity be protective?
  • How do you get to the donors?
  • Ethics - unrelated donors / children
  • Time frame - the window of opportunity is narrow.

9
Post-transplant vaccinations factors to consider
  • Risk - benefit
  • Cost - benefit

10
Infections against which vaccines exist
  • Important and common
  • Influenza
  • Pneumococci
  • HIB
  • Varicella
  • HBV
  • HAV
  • Probably important and might become (more) common
  • Measles
  • Tuberculosis
  • Important but rare
  • Diphtheria
  • Tetanus
  • Polio

11
When should vaccinations be given?
  • Inactivated poliovirus vaccine
  • Immunizations initiated 6 months after BMT
  • are effective (Parkkali et al)
  • are frequently not effective (Engelhard et al)
  • Hemophilus influenzae type B
  • Higher levels of antibodies if vaccination are
    started 3-6 months after SCT than at 12 months
    (Vance et al 1998)
  • Tetanus toxoid
  • Vaccination is effective at 6 months after SCT
    (Parkkali et al 1996)

12
Schedules in SCT patients
  • Repeated doses are necessary in patients who have
    undergone myeloablative SCT
  • Shown for tetanus, diphtheria, inactivated
    poliovirus, Haemophilus influenzae.

13
Influenza
  • Important pathogen in transplant patients
  • Several vaccination studies looking at
    serological responses
  • What about the clinical efficacy?

14
Efficacy of influenza vaccination SOT
  • Serological response to vaccination are decreased
    in
  • Adult renal tx patients
  • Adult liver tx patients
  • Adult heart and/or lung tx patients
  • but are normal in
  • Pediatric renal tx patients
  • No increased risk for rejection

15
Clinical efficacy of vaccination SCT recipients
  • Risk factors for influenza during an epidemic in
    Brazil
  • 177 patients were analyzed
  • Vaccination recommended at 6 months
  • Compliance 44
  • Among vaccinated patients, the protection rate
    was 80
  • Machado et al 2005

16
Pneumococcal vaccination - polysaccaride vaccine
  • No effect of early vaccination (before 12
    months) (Parkkali et al 1996)
  • No effect of repeated doses (Guinan et al
    1994)
  • No effect of vaccinating donors (Molrine
    et al 1996)

17
Conjugate vaccine
  • 96 patients and there donors were included
  • Randomized between donor or no donor vaccination
  • Three doses with conjugated pneumococcal vaccine
    were given at 3,6 and 12 months after SCT
  • 67 vs 36 of patients in the vaccinated / not
    vaccianated donor groups had protective
    antibodies to all 7 serotypes following the first
    dose (p.05)
  • No difference after the third dose.
  • Molrine et al 2003

18
Live vaccines
  • Varicella
  • Measles
  • Rubella
  • Mumps
  • Yellow fever
  • BCG

19
Risks
  • What is the possibilty for vaccine induced side
    effects
  • Early
  • Late
  • Can they be treated?

20
Measles
  • Safe if given 2 years after SCT (no chronic GVHD,
    no ongoing immunosuppression) Ljungman
    et al 1990 King et al 1996
  • Effective in adults if given 2 years after SCT
    Ljungman et al 1990
  • Effective if given at 2 years after SCT in
    children
  • King et al 1996
  • High failure rate if given at 2 years after SCT
    in children
  • Spolou et al 2004
  • Safe if given at 1 year after SCT
    Machado et al unpublished data

21
A common practical question
  • What do I do with a transplant patient travelling
    to .. ?

22
What vaccines might come up?
  • HBV No risk / data exist
  • HAV No risk / limited data
  • Polio (inactivated) No risk / data exist
  • Measles Some risks? / some data exist
  • BCG Poor risk / benefit ratio?
  • Typhoid No data / should be no risk
  • Japanese B encephalitis No data / should be no
    risk
  • Yellow fever Limited data / risk?

23
Thank you for your attention!
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