HLA Antibody Incompatible Transplantation.

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HLA Antibody Incompatible Transplantation.

• Dave Lowe
• HI Birmingham

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• Centres who have referred patients
• and helped with follow up information
• Centres collaborating in research
• Sheffield, Cambridge
• Coordinators
• Nick West, Pat Hart
• Plasmapheresis nurses
• Kath McSorley, Razia Bibi, Pat Cain
• Histocompatibility lab
• Dave Lowe, David Briggs, Mark Hathaway
• Red cell lab
• Ian Skidmore, Paul Fleetwood
• Surgeons and physicians
• FT Lam, Habib Kashi, Chris Imray
• Peter Roberts, Lam Chin Tan
• Andrew Short, Simon Fletcher, Andy Stein
• Rizwan Hamer, Nithya Krishnan
• Pathology
• Klaus Chen, Alec Howie, Sari Suortami

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Development of Antibody Incompatible
Transplantation

• Success of antibody compatible transplantation
• better use of drugs
• better diagnostics
• Living donors
• control of transplant date
• Better measurement of HLA antibodies
• quantification of donor-specific antibodies
• better definition of non-damaging antibodies

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Are Antibody Barriers to Transplantation Common?

• 25 of patients waiting for deceased donor kidney
  have HLA antibodies
• Many are transplantable with sophisticated
  matching schemes, many are not
• In UK, at least 500 living donor transplants per
  annum complicated by antibody incompatibility
  found during work-up testing
• 5050 ABOi and HLAi

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Coventry Protocol

• Double filtration plasmapheresis
• Glycorex for ABOi
• 3-6 sessions
• tacrolimus, mycophenolate, Simulect, prednisolone
• Daily Luminex monitoring post-op

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150 patients referred to Coventry
Proceeded to antibody incompatible
transplantationDecided not to enter the
programme Antibody levels were to
highReceived antibody compatible transplant Don
or or recipient were not fit enough
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24
9
5
11
November 2008
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Programme 2003-2008

• 69 entered
• 2 not transplanted
• 67 transplanted
• 60 HLAi
• 4 ABO HLA
• 3 ABO
• HLAi transplanted
• 18 CDC ve
• 26 FC ve
• 18 bead ve
• 2 bead ve/FC ve

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Patient and graft survival
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Case Study

• 48 year old lady
• Haemodialysis 3 years
• Previous pregnancies
• No previous transplant
• Diabetic
• coronary artery angiogram normal
• Multiple drug sensitivities

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HLA details

• Recipient
• JH HLA A01 B08, 44 C05, 07
• DRB103,04 DRB301 DRB401 DQQ102, 03
• Antibodies
• A2, A28, B17 (pregnancy/transfusion)
• since Feb 2004
• Donor
• BH HLA A01, 02 B08, 44 C05, 07
• DRB103,04 DRB301 DRB401 DQQ102, 03

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Pre-treatment risk factors

• Comorbidity
• Diabetes drug sensitivities
• Intermediate risk
• Immunology
• First transplant lower risk
• Class 1 lower risk
• CDC ve FC ve
• Intermediate risk

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Pre-transplant

• 5 sessions double filtration plasmapheresis
• Day -10 Mycophenolate
• Day -4 Tacrolimus
• Day 0 Prednisolone
• Basiliximab
• No IVIg

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Early progress

• Urine output 3250 ml in first 13 hours
• Post perfusion biopsy normal
• Hb 9.7 5.3 g/dl
• Urine output falling day 2, 1315 ml
• Oliguria often first sign of rejection
• Creatinine fell to 98 umol/l

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Luminex data over first week
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Day 7

• No evidence rejection
• Urine output 1750ml/24 hr
• Creatinine 87umol/l
• Discharged home

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Day 10

• 350 ml up to 1200, then none
• Had been 1325 ml/24hr on day 9
• Creatinine 158
• Ultrasound scan
• Good flow, resistive index 08-1.0

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Antibody levels
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Choices for management

• Biopsy
• Dialysis
• Plasmapheresis
• Drug therapy
• steroids rituximabOKT3

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Management

• That night-
• Dialysis
• OKT3
• Next 2 days
• Plasmapheresis
• Dialysis
• OKT3

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Progress

• 5 days after onset
• Urine output 2170 ml/24hr
• Creatinine falling off dialysis
• 10 days after onset
• Urine output 2 litres/24hr
• Creatinine 121 umol/l

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Progress
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This case illustrates

• Sometimes easy to remove DSA pre-op
• Rapid onset presumed rejection day 10
• Therapeutic dilemmas
• Not easy to remove DSA post-op
• Recovery of graft with accommodation
• Anti-T cell therapy effectively treats presumed
  humoral rejection

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FIRST INTERNATIONAL WORKSHOP ON
ANTIBOD
INCOMPATIBLE
Focus on kidney transplantation How to
characterise patients B-cells in
transplantation Antibodies and transplantation Tol
erance HLA incompatible transplantation Opportunit
ies for clinical studies
TRANSPLANTATION
Friday 12 December 2008 Clinical Science
Building, University Hospital Clifford Bridge
Road, Coventry CV2 2DX, UK 40 registration fee
by 14 November 2008 For more information and
registration contact the organisers
Dr Rob Higgins Dr David Briggs Dr Daniel
Zehnder robert.higgins_at_uhcw.nhs.uk David.Briggs_at_nb
s.nhs.uk d.zehnder_at_warwick.ac.uk