Transcript CBMTG 0801 GVHD… The Saga Continues…

GVHD… The Saga Continues…
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?
Classification of cGVHD
ACUTE
CHRONIC
Day 100
NIH Classification
CLASSIC ACUTE
LATE
ACUTE
OVERLAP
CHRONIC
CLASSIC
Classification of Features of cGVHD
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
Rare, controversial, or nonspecific features (but may
be used for scoring once diagnosis has been
established)
Common
Found in both chronic and acute GVHD (but may be
used for scoring once diagnosis has been
established)
NIH Criteria: Steps in applying
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)
Mouth
Diagnostic
Lichen-type features (mouth)
Diagnostic
Hyperkeratotic plaques (mouth)
Areas in which there is an enlargement or
overgrowth the cells
Hyperkeratosis of the
tongue
Distinctive
Ulcer
Distinctive
Mucocele
Skin
Diagnostic
Poikiloderma
Diagnostic
Lichen Planus
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].
“Other” feature
Keratosis Pilaris
“Chicken Skin”
Nails
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
Scalp
Muscle, Fascia, Joints
Diagnostic
Deep Sclerosis - Hidebound
Eyes
Genitalia
Lungs
GI Tract
Liver
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
The Tools
ORGAN
DIAGNOSTIC
CRITERIA
DISTINCTIVE
CRITERIA?
Skin, includes
hair & nails
Yes
Yes
1. A diagnostic skin feature
2. Distinctive feature with biopsy confirming GVHD
Mouth
Yes
Yes
3. A diagnostic mouth feature
4. A distinctive feature with biopsy confirming GVHD
Genitalia
Yes
Yes
5. A diagnostic feature
6. A distinctive feature with biopsy confirming GVHD
Muscles,
fascia, joints
Yes
Yes
15. A diagnostic feature
16. Myositis or polymyositis confirmed as GVHD on biopsy
Eyes
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
GI
Yes
No
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
Liver
No
No
12. Abnormal LFTs (common feature) confirmed as GVHD by
biopsy PLUS a distinctive feature in another organ
Lungs
Yes
Yes
13. BO confirmed by lung biopsy
14. BO confirmed by PFT and radiology (see specific criteria)
PLUS a distinctive feature in another organ
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
What
happens next?
Scoring happens after
a diagnosis of chronic GVHD
is confirmed
Global Score
• 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.
Key Points Re Scoring
• 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
Key Points Re Scoring (continued)
• 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
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
Questions?