Graft versus host disease Flashcards
Organ systems involved in acute GVHD
- Rash
- GI tract (high concentration of WBCs)
- Liver
- nausea and emesis
RF’s
- High HLA disparity
- Donor and recipient gender disparity
- Unrelated donor
- Intensity of transplant conditioning regimen
- peripheral-blood stem-cell graft
Acute GVHD timing
Can occur at any point but most commonly in early post-transplant period (first couple months)
Description of rash in acute GVHD
Maculopapular
**see photos online
Presentation of GI involvement with GVHD
Diarrhea (can be severe) + abdominal pain
Lab abnormalities of acute GVHD
rising serum bili
Diagnosis
1) Clinical if presentation consistent (classic rash, rising bili)
2) Sometimes, ddx is less clear and you need bx of skin or GI tract
Key concept of treating GVHD
- Treatment requires suppression of donor T cells, but these same cells are responsible for immunologic effect on tumor, so you need to balance benefit of treating GVHD with harming of decreasing GVT effect .
Approach to treatment depends on
Grade of GVHD
Grade I GVHD management
1) Topical steroids
2) Optimize or restart prophylaxis
Grade II or higher GVHD management
Systemic steroids + oral steroids if GI involvement
GVHD prophylaxis for ablative allo HCT
- calcineurin inhibitor (Cyclosporine or tacrolimus) + MTX
Presentation of chronic GVHD
- skin involvement (lichen planus or scleroderma)
- dry oral mucosa
- GI tract (ulceration)
- rising bilirubin
skin findings in acute vs. chronic
acute = maculopapular rash chronic = lichen planus or scleroderma
organ systems involved in chronic GVHD
skin (most common)
liver
GI tract
**lungs
More advanced skin stage of acute GVHD presentation
Blistering and ulceration
GVHD prophylaxis for reduced intensity HCT
Cyclophosphamide
New, evolving approach to GVHD prophylaxis
- post transplant cyclophosphamide
What is Grade I GVHD?
Rash less than 1/4 of BSA + NO liver or GI involvement
Management of steroid refractory acute GVHD?
- No standard therapy (most don’t work and mortality rate is high, bad prognosis)
- ruxolitinib is FDA approved
Standard prednisone dosing for acute GVHD
1 mg/kg
Pathogen patients are at highest risk of early on after transplant
bacteria
Bacterial pathogen patients are at highest risk of later on after transplant
encapsulated bacteria
bacterial prophylactic medicifications
fluoroquinolones (levoquin)
encapsulated bacteria ppx for patients with chronic GVHD
Bactrim
What is pentamidine used for?
PCP ppx
Patients who are at highest risk of CMV reactivation
Seropositive patient, seronegative donor
How to monitor for CMV in seropositive patient
PCR q2 weeks until 1 year post-transplant
When acute GVHD typically occurs
- early transplant period
- within 19 days of HCT
RF’s for acute GVHD
- HLA mismatch or unrelated donor
- gender disparity (female donor to male recipient)
- lack of prophylactic GVHD regimen (MTX, cyclosporine)
Acute vs chronic GVHD in terms of timing
Acute = within 100 days Chronic = any time
RF’s for chronic GVHD
- older age of donor or recipient
- prior acute GVHD
- seropositive CMV in donor or recipient
Description of rash in chronic GVHD
- resembling lichen planus or scleroderma + areas of hypo or hyperpigmentation
other clinical features of chronic GVHD
- dry oral mucosa with ulcerations
- dry eyes
- esophageal webs or strictures
- fasciitis or joint strictures
incidence of chronic GVHD in post-transplant patients
- very high (around 50%)
acute GVHD timeframe
Less than 100 days
acute GVHD clinical features
rash + diarrhea and nausea + LFT abnormalities
Other common prophylaxis regimens
- cyclosporine
- methotrexate
Grade II or higher generally speaking
- liver or GI tract involvement or skin involvement that is greater than 50% of body surface area
Clinical features of gastrointestinal tract involvement in GVHD
- usually presents with lower tract symptoms (diarrhea and abdominal pain), but may also present with nausea, vomiting, and anorexia
Stage 3 means
- rash greater than 50% BSA
- bili 6.1-15
- Stool greater than 7 episodes per day
Stage 4 means
- bili greater than 15
- severe abdominal pain with or without ileus or bloody stool
- rash: bullous formation or desquamation
stem cell graft type that is a risk factor for chronic GVHD + why
- peripheral stem cell graft (higher number of T cells in peripheral blood compared to a bone marrow graft)
pulmonary manifestation of chronic GVHD
bronchiolitis obliterans
RF’s for development of chronic GVHD
- high degree of HLA mismatching
- Older age of donor and/or recipient
- donor and recipient gender disparity
- alloimmunization of donor (history of pregnancy, transfusions)
- peripheral blood as stem cell source
- previous splenectomy
- CMV seropositivity (donor or recipient)
- donor EBV virus seropositivity
HCT donors for which acute GVHD is more common
- matched unrelated donors
- female donors (more often alloimmunized due to pregnancy)
- haploidentical donors
MDS pathophys
- blood cells remain in an immature stage within the bone marrow, never developing into mature cells.
- eventually, marrow may be filled with blast cells suppressing normal cell development
Second line for chronic GVHD
ibrutinib
Second line for acute GVHD
jakafi
