Pre and posttransplant vaccination of transplant recipients

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Pre- and posttransplant vaccination of
transplant recipients
Per Ljungman, Stockholm
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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

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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

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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.

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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

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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
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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

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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.

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Post-transplant vaccinations factors to consider

• Risk - benefit
• Cost - benefit

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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

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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)

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Schedules in SCT patients

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

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Influenza

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

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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

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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

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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)

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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

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Live vaccines

• Varicella
• Measles
• Rubella
• Mumps
• Yellow fever
• BCG

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Risks

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

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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

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A common practical question

• What do I do with a transplant patient travelling
  to .. ?

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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?

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Thank you for your attention!