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BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Graft versus Host Disease in HSCT
Anthony Oyekunle FMCPath.
Senior Lecturer & Consultant Haematologist
Obafemi Awolowo University, Ile-Ife
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
What is GvHD? A cell-mediated reaction of donor origin
against recipient tissues It requires:
immunologically competent or T-cell replete donor graft tissue
immunologically incompetent or immuno-ablated recipient
recipient expressing tissue (MHC or mHC) antigens that are absent in the donor.
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Basic Immunology Auditors - responsible for sifting through all
available info to find evidence of intrusion. Present data to Regulators and Enforcers.
Regulators - Reviews data presented by Auditors and contacts Enforcers. (includes prosecutors and defenders)
Enforcers - Kill things.
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Auditors Dendritic cells B cells Macrophages Endothelial
cells Kupffer cells
Sample Outside Sample Inside Process
Specimen Present Data
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Communicating Trouble
HLA Class I - i.e. HLA-A, B, C
HLA Class II - i.e. HLA - DR, DQ, DP
CD4
CD8
“Regulator”
“Enforcer”
Dendritic cellB cellMacrophage
“Meaning of Life”
“Trouble” signal
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Pathogenesis of Acute GvHD
Culled from Hematopoietic Stem Cell Transplantation; ESH-EBMT (2008).
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Clinical Features of Acute GvHD Risk Factors
HLA compatibility Gender mismatch: female
male Alloimmunization:
multiparity, transfusions SC source: PB>BM>CB Recipient age Conditioning GvH prophylaxis CMV positive Tissue injury
Signs/Symptoms Skin
Inflammatory rash
Gut Secretory diarrhea
Liver Cholestasis
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Severity and Grading system (Glucksberg)
Culled from Hematopoietic Stem Cell Transplantation; ESH-EBMT (2008).
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Why do HLA matching?
BMT = immune system transplant HLA molecules act as T cell
“superantigens” All somatic tissues express HLA class I Transferred T cell could “over-react” Transferred T cells won’t work if they
can’t bind their own HLA molecule
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
If there is a “match”, then why GvHD?
MHC antigens are the ones typically “matched”
There are several other “minor” tissue antigens other than the MHC e.g. H-Y
GvHD results from T cell reactivity toward polymorphisms between donor and hostThis can be good e.g. GvL, GvT
OR
This can be bad e.g. GvHD
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Polymorphisms can help rid disease or cause GVHD H -Y
antigen from Y chromosome
expressed ubiquitously target for CTL
responses CTL response leads to
less relapse, more GVHD
HA-1 polymorphic unknown function expressed only on
hematopoietic cells target for CTL
responses CTL response leads to
less relapse, no GVHD Others: KIR antigens in multiple myeloma
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Myeloablative SCTMyeloablative SCT
High dose High dose radiationradiation
High doseHigh dose chemochemo
Stem cellsStem cells
Watch and waitWatch and wait
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Non-myeloablative SCT
ImmunoImmunosuppressionsuppression
Stem cellsStem cells
Manipulate the immune response Manipulate the immune response to maximize G vs. diseaseto maximize G vs. disease
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Preventing GVHD• HLA matching• Best donor-recipient pair: age, CMV, gender,
parity, etc.• Rigorous infection screening and prophylaxis• Minimize tissue injury during conditioning• Specific GvH prophylaxis
• MRD myeloabl. SCT: Mtx + calcineurin inhibitor (CsA or tacrolimus)
• Others: T-cell depletion (in vitro, ex vivo, in vivo)• ATG, MMF, sirolimus, etc
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
GVHD Prophylaxis - How much?
Aggressive ProphylaxisAggressive Prophylaxis•LESS GVHDLESS GVHD•MORE infectionMORE infection•MORE relapseMORE relapse
Minimal ProphylaxisMinimal Prophylaxis•MORE GVHDMORE GVHD•LESS infectionLESS infection•LESS relapseLESS relapse
SURVIVALSURVIVAL
Graft versus Host Disease in HSCT BENIN BLOOD & MARROW TRANSPLANT SOCIETY OF NIGERIA
15-27 JULY 2013. STEM CELL TRANSPLANT CENTRE, BENIN
Dr A A Oyekunle
Treating GVHD
• 1st Line: Methylprednisolone alone
• MMF, tacrolimus, sirolimus• ATG• Oral non-absorbable steroids• Monoclonal antibodies• Pentostatin• Extracorporeal photopheresis• Mesenchymal stem cells