Vascularized Composite Allografts (VCA) Banff

Linda C. Cendales, M.D.Assistant Professor of Surgery

Division of Plastic Surgery and Division of TransplantationDirector, Vascularized Composite Allotransplantation and

the Laboratory of Microsurgery

EMORY TRANSPLANT

CENTER

VCA Banff 2007

• Reported VCA at the time of the meeting– Hand Transplants: n=22– Other VCA:

• Skin containing : 13• Non- skin containing : 26

International Registry on Hand and Composite Tissue Transplantation

VCA Banff 2011 World Experience

• Reported VCA < 100 patients• Hand transplant patients

– N= 51

• Other VCA: face, laryngx, abdominal wall, knee– N= 43

International Registry on Hand and Composite Tissue Transplantation, accessed June 9, 2011

Michael MengelUniversity of Alberta, Edmonton, Canada

Laboratory Medicine and PathologyAlberta Transplant Applied Genomics Centre and Transcriptome Sciences Inc

Chronic immune injury in solid organ transplantation

• Dr. Mengel presented an excellent overview of chronic changes in solid organs

• The topics discussed included:– the deterioration of allografts, particularly in kidneys– Antibody-mediated causes are a major problem– Failure also due to other causes (e.g. recurrent disease,

calcineurin inhibitor toxicity)– C4d deposition pattern in VCAs is not clear and

probably cannot be currently relied upon

Chronic Changes in Non-Human Primates

Gerhard S. Mundinger, M.D.

University of Maryland Medical Center,Baltimore, MD

11th Banff Conference on Allograft PathologyEnghien-les-Bains, France

June 8th, 2011

• Dr Mundinger presented the group’s experience in nonhuman primate models of face and vascularized fibula

• Studies attempt to induce tolerance in VCAs• The group’s observations included lymphoid

aggregates, which the investigators relate to as tertiary lymphoid organs (TLOs)– The data presented included CD3, CD4, & CD20 stains

• Findings showed evidence for a notch/jagged pathway activation

• Findings showed chronic rejection and transplant arteriopathy

• Results demonstrated superficial vs deep histologic discrepancy

Histologic findings in late vascularized

composite allotransplantation

Jean Kanitakis

Depts. of Dermatology/Dermatopathology Ed. Herriot Hospital

Lyon, France

10th Banff Meeting - Paris, June 8, 2011

Presented an overview of the spectrum of histologic changes observed in patients grafted and/or followed in

Lyon

• 1st hand alloTx Sept 1998 2.5 yrs (amputation after IST

discontinuation)

• 1st 2e hand alloTx - Jan 2000 11 yrs

• 2e hand alloTx Apr 2003 8 yrs

• 2e hand alloTx Feb 2007 4 yrs

• 2e hand alloTx Jul 2008 2 yrs

• 2e hand alloTx Jul 2009 1.5 yrs

• 1st face alloTx Nov 2005 5 yrs

• Face alloTx Nov 2009 1.5 yrs

•Presented a variety of ancillary stains, including

– CD3, CD4, CD8, TIA-1, FOXP3, and C4d– C4d pattern is still not clear

•Differential diagnosis is broad

Polish Experience Polish Experience in Hand Transplantationin Hand Transplantation

Departament of General SurgeryDepartament of General Surgery Trzebnica , PolandTrzebnica , Poland

Adam Chełmoński, Adam Chełmoński, Jerzy Jabłecki, Agnieszka Hałoń, Aleksandra KlimczakJerzy Jabłecki, Agnieszka Hałoń, Aleksandra Klimczak

Presented the Polish ExperiencePresented the Polish Experience

Total of 6 Hand Transplant Patients Total of 6 Hand Transplant Patients

-5 unilateral-5 unilateral

-1 bilateral hand transplant-1 bilateral hand transplant

wrist level wrist level – – 2 unilat2 unilat (2008,201(2008,2011)1),1 bilateral ,1 bilateral ((20102010))

mid - forearm – mid - forearm – 1 unilat1 unilat ( 200 ( 20066) )

mid – armmid – arm – – 2 unilat 2 unilat ( 2009,2010 )( 2009,2010 )

The last case required two partial finger The last case required two partial finger amputations: the cause is being studiedamputations: the cause is being studied

Louisville VCA Program

Christina Kaufman PhD

Vasculopathy in Vascularized Composite Allotransplantation (VCA)

• Data demonstrated chronic changes in hand allografts as delineated in the 2007 VCA Banff consensus discussions manuscript– Vascular intimal thickening– Nail changes– Loss of hair follicles

• Observations showed skin with a VCA Banff Grade 0 and marked concentric intimal and medial hypertrophy at the same time point in the same patient

• Development of HLA alloantibodies in two patients• The Louisville group is using ultrasound BioMicroscopy

Technology to follow vascular changes

VCA Banff Working Group Pre-meeting survey

• University of Maryland• Johns Hopkins University School of Medicine

• Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

• University of Pittsburgh Medical Center• Cleveland Clinic

• Christine M. Kleinert Institute• University Paris

• United States Department of Defense• Innsbruck Medical University

• St. Hedwig's Hospital , Trzebnica• St Vincent's Hospital• Ed. Herriot hospital

• Bridgman Woman’s Hospital• University of Oxford/NDS

• Emory University

• New pathological findings from the last Banff meeting– Neointimal proliferation– Arteritis– Vasculopathy– Increasing C4d deposits– Expression of adhesion molecules– Capillary thromboses– Tertiary lymphoid organ development

Topics to Discuss

• Chronic changes• Inflammation vs rejection• Antibody Mediated Rejection

– DSA - / +C4d /intimal hyperplasia

• Myointimal proliferation• Markers of chronic skin rejection• Pathological changes of sentinel flap vs

functional transplant

VCA Banff Working Group Post-meeting survey

Thank you