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

Day 100

CHRONIC

ACUTE

CLASSIC CHRONIC

CLASSIC ACUTELATE

ACUTE

OVERLAP

NIH Classification

Classification of Features of cGVHD

Diagnostic Sufficient to make a diagnosis of chronic GVHD

DistinctiveNot 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

DiagnosticLichen-type features (mouth)

Diagnostic Hyperkeratotic plaques (mouth)

Areas in which there is an enlargement or overgrowth the cells

Hyperkeratosis of thetongue

DistinctiveUlcer

DistinctiveMucocele

Skin

DiagnosticPoikiloderma

DiagnosticLichen Planus

DiagnosticLichen Planus

DiagnosticDeep Sclerosis

DiagnosticMorphea – think“localized scleroderma”

DiagnosticLichen Sclerosus“Patchy white thin skin”

“Cigarette-paper wrinkling”

DistinctivePapulo-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” featureKeratosis Pilaris

“Chicken Skin”

Nails

Distinctive featuresDystrophy, Onycholysis, Pterygium unguis

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

Scalp

Muscle, Fascia, Joints

DiagnosticDeep Sclerosis - Hidebound

Eyes

Genitalia

Lungs

GI Tract

Liver

Note: 1. Elevated ggt not included because it is too non-specific and variable2. If one or more of LFTs listed is > 2x ULN, then the box can be checked

The Tools

ORGAN DIAGNOSTIC

CRITERIA

DISTINCTIVE

CRITERIA?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

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

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

• 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

Teamwork!

Questions?