Chronic Graft versus host disease Tamás Masszi Dept of Haematology and SCT St István & St László Hospital of Budapest
Outline ●
Definition & Pathology
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Diagnosis & Clinical Manifestations
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Epidemiology
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Grading & Prognosis
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Treatment
Definition ●
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cGVHD is an immunoregulatory disorder occurs after allogeneic hematopoetic cell transplantation and shares features of autoimmunitiy and immunodeficiency cGVHD is the major cause of late non-relapse mortality and morbidity after allogeneic hematopoetic cell transplantation Mortality and morbidity is due to cGVHD and it’s treatment as well
Pathology of cGVHD ●
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Chronic GVHD is also thought to be induced by donor T-cells but the pathophysiology is not well defined. Features of cGVHD resemble other autoimmune diseases like –
Sjogren syndrome,
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scledroderma and
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primary biliary cirrhosis
Major risk factors for the development of chronic GVHD 1.
Higher degree of HLA mismatch
2.
Older age (donor/recipient)
3.
Prior acute GVHD
4.
Previous splenectomy
5.
CMV seropositivity (donor/recipient)
6.
TBI
7.
Female donor to male recipient
8.
PBSCT Carlens et al Bone Marrow Transplant 1998 Oct;22(8):755-61.
Diagnosis
Jan Steen: Doctor and His Patient
Diagnosis – Distinction between acute and chronic GVHD Old definiton: SCT time Day 100 Acute GVHD
Chronic GVHD
Diagnosis – Distinction between acute and chronic GVHD Old definiton: SCT time Day 100 Acute GVHD
Chronic GVHD Onset Progressive Quiescent De novo
Diagnosis – Distinction between acute and chronic GVHD Old definiton:
3 years
SCT time Day 100 Acute GVHD
Chronic GVHD Onset Progressive Quiescent De novo
Diagnosis – Distinction between acute and chronic GVHD New definition
Filipovich et al Biol Blood Marrow Transplant. 2005;11:945–956.
Clinical manifestations of chronic GVHD ● Skin ●
Mouth
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Eyes
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Gastrointestinal tract
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Liver
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Lung
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Joints, fascia and muscles
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Other manifestations
Other clinical and laboratory manifestations ●
Exocrine pancreatic insuffiency
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Ascites, pericaridal or pleural effusions
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Thrombocytopenia, eosinopihlia, lymphopenia Autoantibodies, IgA deficiency
NIH consensus criteria for diagnosis of chronic GVHD ●
Other possible diagnosis must be excluded
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No time limit is set for the diagnosis
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Presence of –
at least 1 diagnostic clinical sign
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Or at least 1 distinctive sign confirmed by pertinent biopsy or other relevant test ( eg Schirmer)
