Graft versus host disease

Question 1

Organ systems involved in acute GVHD

Answer 1

• Rash
• GI tract (high concentration of WBCs)
• Liver
• nausea and emesis

Question 2

RF’s

Answer 2

• High HLA disparity
• Donor and recipient gender disparity
• Unrelated donor
• Intensity of transplant conditioning regimen
• peripheral-blood stem-cell graft

Question 3

Acute GVHD timing

Answer 3

Can occur at any point but most commonly in early post-transplant period (first couple months)

Question 4

Description of rash in acute GVHD

Answer 4

Maculopapular

**see photos online

Question 5

Presentation of GI involvement with GVHD

Answer 5

Diarrhea (can be severe) + abdominal pain

Question 6

Lab abnormalities of acute GVHD

Answer 6

rising serum bili

Question 7

Diagnosis

Answer 7

1) Clinical if presentation consistent (classic rash, rising bili)
2) Sometimes, ddx is less clear and you need bx of skin or GI tract

Question 8

Key concept of treating GVHD

Answer 8

• 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 .

Question 9

Approach to treatment depends on

Answer 9

Grade of GVHD

Question 10

Grade I GVHD management

Answer 10

1) Topical steroids

2) Optimize or restart prophylaxis

Question 11

Grade II or higher GVHD management

Answer 11

Systemic steroids + oral steroids if GI involvement

Question 12

GVHD prophylaxis for ablative allo HCT

Answer 12

• calcineurin inhibitor (Cyclosporine or tacrolimus) + MTX

Question 13

Presentation of chronic GVHD

Answer 13

• skin involvement (lichen planus or scleroderma)
• dry oral mucosa
• GI tract (ulceration)
• rising bilirubin

Question 14

skin findings in acute vs. chronic

Answer 14

acute = maculopapular rash
chronic = lichen planus or scleroderma

Question 15

organ systems involved in chronic GVHD

Answer 15

skin (most common)
liver
GI tract
**lungs

Question 16

More advanced skin stage of acute GVHD presentation

Answer 16

Blistering and ulceration

Question 17

GVHD prophylaxis for reduced intensity HCT

Answer 17

Cyclophosphamide

Question 18

New, evolving approach to GVHD prophylaxis

Answer 18

• post transplant cyclophosphamide

Question 19

What is Grade I GVHD?

Answer 19

Rash less than 1/4 of BSA + NO liver or GI involvement

Question 20

Management of steroid refractory acute GVHD?

Answer 20

• No standard therapy (most don’t work and mortality rate is high, bad prognosis)
• ruxolitinib is FDA approved

Question 21

Standard prednisone dosing for acute GVHD

Answer 21

1 mg/kg

Question 22

Pathogen patients are at highest risk of early on after transplant

Answer 22

bacteria

Question 23

Bacterial pathogen patients are at highest risk of later on after transplant

Answer 23

encapsulated bacteria

Question 24

bacterial prophylactic medicifications

Answer 24

fluoroquinolones (levoquin)

Question 25

encapsulated bacteria ppx for patients with chronic GVHD

Answer 25

Bactrim

Question 26

What is pentamidine used for?

Answer 26

PCP ppx

Question 27

Patients who are at highest risk of CMV reactivation

Answer 27

Seropositive patient, seronegative donor

Question 28

How to monitor for CMV in seropositive patient

Answer 28

PCR q2 weeks until 1 year post-transplant

Question 29

When acute GVHD typically occurs

Answer 29

- early transplant period | - within 19 days of HCT

Question 30

RF's for acute GVHD

Answer 30

- HLA mismatch or unrelated donor - gender disparity (female donor to male recipient) - lack of prophylactic GVHD regimen (MTX, cyclosporine)

Question 31

Acute vs chronic GVHD in terms of timing

Answer 31

``` Acute = within 100 days Chronic = any time ```

Question 32

RF's for chronic GVHD

Answer 32

- older age of donor or recipient - prior acute GVHD - seropositive CMV in donor or recipient

Question 33

Description of rash in chronic GVHD

Answer 33

- resembling lichen planus or scleroderma + areas of hypo or hyperpigmentation

Question 34

other clinical features of chronic GVHD

Answer 34

- dry oral mucosa with ulcerations - dry eyes - esophageal webs or strictures - fasciitis or joint strictures

Question 35

incidence of chronic GVHD in post-transplant patients

Answer 35

- very high (around 50%)

Question 36

acute GVHD timeframe

Answer 36

Less than 100 days

Question 37

acute GVHD clinical features

Answer 37

rash + diarrhea and nausea + LFT abnormalities

Question 38

Other common prophylaxis regimens

Answer 38

- cyclosporine | - methotrexate

Question 39

Grade II or higher generally speaking

Answer 39

- liver or GI tract involvement or skin involvement that is greater than 50% of body surface area

Question 40

Clinical features of gastrointestinal tract involvement in GVHD

Answer 40

- usually presents with lower tract symptoms (diarrhea and abdominal pain), but may also present with nausea, vomiting, and anorexia

Question 41

Stage 3 means

Answer 41

- rash greater than 50% BSA - bili 6.1-15 - Stool greater than 7 episodes per day

Question 42

Stage 4 means

Answer 42

- bili greater than 15 - severe abdominal pain with or without ileus or bloody stool - rash: bullous formation or desquamation

Question 43

stem cell graft type that is a risk factor for chronic GVHD + why

Answer 43

- peripheral stem cell graft (higher number of T cells in peripheral blood compared to a bone marrow graft)

Question 44

pulmonary manifestation of chronic GVHD

Answer 44

bronchiolitis obliterans

Question 45

RF's for development of chronic GVHD

Answer 45

- 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

Question 46

HCT donors for which acute GVHD is more common

Answer 46

- matched unrelated donors - female donors (more often alloimmunized due to pregnancy) | - haploidentical donors

Question 47

MDS pathophys

Answer 47

- 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

Question 48

Second line for chronic GVHD

Answer 48

ibrutinib

Question 49

Second line for acute GVHD

Answer 49

jakafi