NIH Consensus Development Project on Criteria for
Clinical Trials in Chronic GVHD (June 6, 2005)
• Clinical features emphasized rather than time of onset

Clinical features for each organ

Features grouped as Diagnostic, Distinctive, Other,
Common .

More specific diagnostic criteria

Scoring criteria for each organ, taking function taken into account

Global Score - mild, moderate or severe
The NIH Consensus System is provisional, awaiting validation of its value for prognosis, correlation with quality of life, and value for therapeutic trials (sensitivity of scoring to change).

Is there anyone out here who can tell us the true meaning of the NIH consensus guidelines?

ACUTE
CHRONIC
Day 100
NIH Classification
CLASSIC ACUTE
LATE
ACUTE
OVERLAP
CHRONIC
CLASSIC

Diagnostic Sufficient to make a diagnosis of chronic GVHD
Distinctive
Not seen in acute GVHD but insufficient alone for diagnosis of cGVHD. Need biopsy, test, or other organ with Distinctive feature.
Other
Common
Rare, controversial, or nonspecific features (but may be used for scoring once diagnosis has been established)
Found in both chronic and acute GVHD (but may be used for scoring once diagnosis has been established)

1. Consider causes other than cGVHD
2. Minimal Criteria for diagnosis

Diagnostic features in at least one organ OR

Distinctive feature plus additional test, biopsy or distinctive feature in another organ OR other organ specific criteria
3. Organ scoring (0-3)
4. Global scoring (mild, moderate, severe)

Areas in which there is an enlargement or overgrowth the cells
Hyperkeratosis of the tongue

Diagnostic
Lichen Planus

Diagnostic
Deep Sclerosis

Diagnostic
Morphea – think
“localized scleroderma”

Diagnostic
Lichen Sclerosus
“Patchy white thin skin”
“Cigarette-paper wrinkling”

Distinctive
Papulo-squamous chronic GVHD – Papules and small scaly plaques

"Papulosquamous hyperkeratotic cutaneous conditions” – DISTINCTIVE not DIAGNOSTIC
Papulosquamous hyperkeratotic cutaneous conditions are those that present with papules and scales
Cowen, Edward (NIH/NCI):
Pap-Sq is a wastebasket term for psoriasis-looking and other eruptions with scale that do not appear like the classic
"lichen-planus-like" cGVHD [62 entities].

“Chicken Skin”

Distinctive features
Dystrophy, Onycholysis, Pterygium unguis
Dystrophy: Longitudinal ridging, splitting or brittle features
Onycholysis: Loosening or separation of a fingernail or toenail from its nail bed
Pterygium unguis: Forward growth of the cuticle over the nail bed
Nail Loss: Usually symetric, affects most nails

Diagnostic
Deep Sclerosis - Hidebound

Note:
1. Elevated ggt not included because it is too non-specific and variable
2. If one or more of LFTs listed is > 2x ULN, then the box can be checked

ORGAN
Skin, includes hair & nails
Mouth
Genitalia
Muscles, fascia, joints
Eyes
GI
Liver
Lungs
DIAGNOSTIC
CRITERIA
Yes
Yes
Yes
Yes
No
Yes
No
Yes
DISTINCTIVE
CRITERIA?
Yes
Yes
Yes
Yes
DIAGNOSIS OF CHRONIC GVHD BY ORGAN
A diagnosis of chronic GVHD can be made if one or more of the following situations below are present
Cause due to infection/drug reaction/or other must be ruled out
1. A diagnostic skin feature
2. Distinctive feature with biopsy confirming GVHD
3. A diagnostic mouth feature
4. A distinctive feature with biopsy confirming GVHD
5. A diagnostic feature
6. A distinctive feature with biopsy confirming GVHD
15. A diagnostic feature
16. Myositis or polymyositis confirmed as GVHD on biopsy
Yes
No
No
Yes
7. New ocular sicca with Schirmer < 5 mm (both eyes) at 5 min
PLUS a distinctive feature in another organ
8. New onset of keratoconjunctivitis sicca by slit-lamp exam
PLUS Schirmer 6 to 10 mm at 5 min PLUS a distinctive feature in another organ
9. A diagnostic feature
10. A common feature PLUS a biopsy/endoscopy confirming
GVHD PLUS a distinctive feature in another organ
11. Exocrine pancreatic insufficiency PLUS a biopsy/endoscopy confirming GVHD PLUS a distinctive feature in another organ
12. Abnormal LFTs (common feature) confirmed as GVHD by biopsy PLUS a distinctive feature in another organ
13. BO confirmed by lung biopsy
14. BO confirmed by PFT and radiology (see specific criteria)
PLUS a distinctive feature in another organ

What happens next?

• Mild chronic GVHD
Only 1 or 2 organs or sites (except the lung: see below), with no clinically significant functional impairment (maximum of score 1 in all affected organs or sites).
• Moderate chronic GVHD
(1) at least 1 organ or site with clinically significant but no major disability (maximum score of 2 in any affected organ or site) OR
(2) 3 or more organs or sites with no clinically significant functional impairment (maximum score of 1 in all affected organs or sites). A lung score of 1 will also be considered moderate chronic GVHD.
• Severe chronic GVHD
Major disability caused by chronic GVHD (score of 3 in any organ or site). A lung score of 2 or greater will also be considered severe chronic GVHD.

• Scoring categories are a mix of functional aspects, clinical features and diagnostic tests
• Score all symptoms/features related to GVHD
(or if cause unknown); include symptoms/features from all clinical feature categories*
• Do not score symptoms/features known to have a cause other than GVHD
• Include symptoms of chronic and acute (i.e. the common symptoms) when scoring (this is overlap syndrome and falls under the chronic GVHD umbrella)
*Clinical feature categories are: Diagnostic, distinctive, common, other

• If there is a diagnosis of chronic GVHD in an organ other than the liver AND there are abnormal LFTs (> 2 x ULN) that are thought to be related to GVHD (even if not biopsy proven) then the liver should be scored and included when determining the GLOBAL SCORE
• Once the initial diagnosis of chronic GVHD has been confirmed – All GVHD symptoms that occur later are scored using the chronic GVHD scoring scheme – See next slide for example

• Month 6: First onset of chronic GVHD is confirmed
• Month 12: Mild Diarrhea present, <5% weight loss
Alk phos > 2 X ULN
(causes other than GVHD ruled out for both)
• Both organs (GI and liver) should be scored for chronic
GVHD (due to previous diagnosis of chronic GVHD)
• GI score = 1; Liver score =1
• Global Score = mild

Teamwork!
• In-person assessment at visit time points
• Use Worksheet Part A & B at the visit
• Worksheet = Source Document
• Use the table to confirm or exclude cGVHD
• Keep in regular communication to capture onset of cGVHD in real time