GVHD Flashcards
Settings that GVHD can occur in
- Most commonly due to transfer of foreign donor haematopoietic stem cells into a host recipient via an allogeneic haematopoietic stem cell transplant
- Other settings it can occur in:
- Non-irradiated blood products to immuocompromised host
- Maternal-foetal transmission
- Solid organ transplantation
Most important predictor of GVHD
HLA compatability between donor and recipient
40% HLA-identical develop, and 60-70% of mismatched develop
What does using umbilical cord blood or peripheral blood do for risk of GVHD
Increasing use of umbilical cord blood and peripheral blood due to lower rates of GVHD, but has higher rates of non-engraftment
Which is the preferred stem cell source
Peripheral blood
Peripheral blood has more rapid engraftment, but has increased risk of GVHD
How does stem cell transplant work?
Donor: gets treated with GCSF, which mobilizes donor stem cells from the marrow into circulation –> then collected and infused into recipient
What things affect natural history of GVHD
- T-cell depletion
- Total body irradiation for conditioning
- Donor lymphocyte infusions –> administered after to augment the graft versus tumour effect –> altered traditional acute and chronic, so it can induce acute after 100 days
Risk factors for developing GVHD
- Donor
- HLA incompatibility with recipient
- Unrelated to recipient
- Female with male recipient (especially multiparous)
- Recipient
- Older aged
- Stem cell source
- Peripheral blood > bone marrow > cord blood
- T cell replete
- Other
- Myeloablative conditioning regimen
Pathogenesis of GVHD
- Host APC activation from HSCT conditioning and consequent damage to host tissues
- Donor T cells proliferate once come into contact with APC
- Destruction of target tissues: occurs via cytotoxic T lymphocytes, NK cells and soluble factors (TNF, IFN-gamma, IL-1, nitric oxide)
- However, cGVHD often resembles autoimmune, suggesting B cell process, and rituximab helps –> ?B cells prime T cells to MHC antigens
- B cell activating factor of the TNF family (BAFF) correlate with cGVHD –> ANA, anti-dsDNA, anti-smooth muscle antibodies
- Early-onset cGVHD: 3-9 months: IFN-gamma, increased Tregs, and T cell cytokine response
- Late cGVHD: >9 months, lack of Th2 shift, BAFF, TLR9 induction, and also mixed Th1/Th17 signature with IFN-gamma and IL-17
Clinical - Acute GVHD
- Usually 4-6 weeks post HSCT
- Morbilliform exanthem, with predilection for acral areas - dorsal hands and feet, palms, soles, forearms, ears, upper trunk
- Pruritus is variable
- Folliculocentric pattern may be seen
- Thrombocytopaenia –> looks haemorrhagic
- GIT:
- Nausea
- Voluminous diarrhoea
- Abdominal pain
- Liver: transaminitis, cholestasis, bilirubin elevation
- Stage 4 can look like SJS
What is measured in the clinical staging of AGVHD
Skin
Liver - bilirubin
Gut - diarrhoea
Histology
CGVHD cutaneous
- Stage 1 <25% BSA, 2 25-50%, 3 >50%, 4 generalized erythroderma
- skin and mucosa very common
- Most characteristic: reticulate pink to violet papules and plaques with overlying scale
- Often involve the dorsal aspects of the hands and feet, forearms, trunk but then can become widespread
- not associated with sclerodactyly, pinched facies or Raynauds like you see in systemic sclerosis
- deep-seated fibrosis of the subcutaneous fascia may present with insidious loss of joint range of motion or as nonspecific myalgias and cramping
- subtle rippling of the overlying skin may be present with a form, nodular texture noted with deep palpation
All the findings:
- LP like
- morphoea like
- scleroderma like
- fasciitis –> subcutaneous rippling of skin with joint contractures, Groove sign - path of vascular structures of fascial bundles
- other: psoriasiform, eczematous, dyshidrotic, SCLE, pit rosea, eczema craquelee, ichthyosis like, KP like, dyspigmetation, vitiligo
- angiomatous nodules - rare
- ulcerations: from long standing fibrosis
- patterned hyperpigmentation
CGVHD mucous findings
LP like
Mucocele like
Oral mucosa: keratotic plaques, LP like, restriction of oral opening due from sclerosis, gingivitis, mucositis, pseudomembranes, ulcers, xerostomia, mucosal atrophy, mucocele
Genital: 50% female patients - burning, pruritus, dyspareunia
Erythema, fissuring to labial resorption and fusion
Vaginal scarring, shortening, narrow of vaginal canal
LP like
Risk of hematocolpos
Male genital less common - balanoposthitis, LP like, phimosis
CGVHD nails and hair
ridging, thinning, splitting, brittleness, onycholysis, dorsal pterygium, anonychia
new onset alopecia, alopecia areata, premature greying
What’s the difference between AGVHD and CGVHD
traditionally used to be acute <100 days, chronic >100 days but now changing regimens means you can get both at the same time
AGVHD histology
- widespread keratinocyte necrosis
- Basal layer hydropic degeneration
- Band like lymphohistiocytic infiltrate in the upper dermis
- however can just be confined to the hair follicle
- Features overlap with viral and drug, which makes diagnosis more tricky
