GVHD… The Saga Continues…

1. GVHD… The Saga Continues…

3. 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 • Featuresgrouped 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).

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

5. Classification of cGVHD • ACUTE • CHRONIC Day 100 NIH Classification • CLASSIC ACUTE LATE ACUTE • CLASSIC CHRONIC OVERLAP

6. Classification of Features of cGVHD

8. NIH Criteria: Steps in applying • Consider causes other than cGVHD • 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 • Organ scoring (0-3) • Global scoring (mild, moderate, severe)

9. Mouth

10. DiagnosticLichen-type features (mouth)

11. Diagnostic Hyperkeratotic plaques (mouth) Areas in which there is an enlargement or overgrowth the cells Hyperkeratosis of the tongue

12. DistinctiveUlcer

13. DistinctiveMucocele

14. Skin

15. DiagnosticPoikiloderma

16. DiagnosticLichen Planus

17. Diagnostic Lichen Planus

18. Diagnostic Deep Sclerosis

19. Diagnostic Morphea – think “localized scleroderma”

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

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

22. "Papulosquamous hyperkeratotic cutaneous conditions” – DISTINCTIVEnot 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].

23. “Other” feature Keratosis Pilaris “Chicken Skin”

24. Nails

25. Distinctive featuresDystrophy, 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

26. Scalp

27. Muscle, Fascia, Joints

28. Diagnostic Deep Sclerosis - Hidebound

29. Eyes

30. Genitalia

31. Lungs

32. GI Tract

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

34. The Tools

38. What happens next?

39. Scoring happens after a diagnosis of chronic GVHD is confirmed

40. 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.

42. 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

43. 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

44. 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

45. 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

46. Questions?