Table 1.
Agreement level according to topic areas
| Topic 1: What are diagnostic and distinctive criteria for chronic GVHD? | ||
|---|---|---|
| Agreement level | Agreed answer or controversial question | Category |
| High* (R) | Two or more distinctive manifestations should be considered sufficient to diagnose chronic GVHD. (Q3) | Diagnosis |
| High | Only one site with acute manifestations (skin, liver or GI) is enough to diagnose “overlap” chronic GVHD. (Q5) | Subcategory of GVHD |
| High | Overlap chronic GVHD and progressive onset are NOT interchangeable terms. (Q8) | Subcategory of GVHD |
| High | It is difficult to distinguish deep from superficial sclerosis in the abdominal skin among obese patients. (Q23) | Skin |
| High | By careful history taking and physical examination of fascia and joints, you can distinguish joint problems related to chronic GVHD from other cause of joint impairment. (Q53) | Joint/fascia |
| High | Nephrotic syndrome after allogeneic transplantation should be considered a manifestation of chronic GVHD. (Q72) | Other sites |
| Moderate* (NR) | There should be no distinctive features of chronic GVHD for the GI tract and liver. (Q2) | Diagnosis |
| Moderate* (NR) | There should be no pediatric modifications to the categorizations of diagnostic and distinct manifestations. (Q4) | Diagnosis |
| Moderate* (NR) | It is not necessary to revise the terms “acute” and “chronic” GVHD to something else. (Q6) | Subcategory of GVHD |
| Moderate | There are no imaging methods that can help to distinguish deep from superficial sclerosis. (Q24) | Skin |
| Moderate | Neither acute nor chronic GVHD should be diagnosed for a patient who had ocular dryness very early after transplantation (for example, 30 days after transplantation), with no other manifestations of chronic GVHD. (Q26) | Eye |
| Moderate | Isolated early fasciitis manifested by edema is diagnostic for chronic GVHD. (Q52) | Joint/fascia |
| Moderate* (R) | Clinical bronchiolitis obliterans syndrome should be considered a diagnostic manifestation (sufficient to make the diagnosis of chronic GVHD). (Q56) | Lung |
| Controversial* | Currently, there are no diagnostic features of chronic GVHD for the eyes, liver and GI tract except esophagus. Should there be? (Q1) | Diagnosis |
| Controversial | Do you categorize the following patient as late acute GVHD or overlap chronic GVHD? The patient had overlap chronic GVHD (oral lichenoid changes and gut GVHD). All manifestations were completely resolved after six months of systemic treatment. Now 2 years after transplantation, the patient has recurrent lower gut GVHD without any other signs of chronic GVHD. (Q7) | Subcategory of GVHD |
| Controversial | If a patient has “new ocular sicca documented by Schirmer test” or “a new onset of keratoconjunctivitis with Schirmer score <10 mm”, is this sufficient to diagnose chronic GVHD? (Q33) | Eye |
| Controversial* | Should gingivitis, oral mucositis and pain continue to be considered “common” signs, even if mouth is not a recognized target organ in acute GVHD? Or should these be considered distinctive signs of chronic GVHD? (Q40) | Mouth |
| Controversial | Do you think joint pain mimicking rheumatoid arthritis after transplant is joint GVHD? (Q54) | Joint |
| Controversial | Is cryptogenic organizing pneumonia a form of lung GVHD? (Q57) | Lung |
| Controversial* | Should cryptogenic organizing pneumonia still be considered a “common” sign, since lung is not a recognized target organ in acute GVHD? (Q58) | Lung |
| Controversial | How do you determine if peripheral neuropathy is due to chronic GVHD in a patient with an established diagnosis of chronic GVHD? (Q71) | Other sites |
| Topic 2: Can pathology discriminate chronic GVHD from other causes? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High | Pathologists can NOT distinguish between acute and chronic GVHD in the liver. (Q10) | Pathology |
| High | Pathologists can NOT confidently diagnose liver chronic GVHD. (Q11) | Pathology |
| Moderate | Pathologists can NOT distinguish in GI tract except for esophagus. (Q10) | Pathology |
| Moderate | Pathologists can distinguish between acute and chronic GVHD in the skin, lung and mouth. (Q10) | Pathology |
| Moderate | If muscle biopsy is positive for myositis but diagnostic or distinctive features of chronic GVHD are absent in other sites, it should be sufficient to diagnose chronic GVHD. (Q55) | Muscle |
| Controversial | Pathologists can distinguish between acute and chronic GVHD in fascia, esophagus, and genital tract. (Q10) | Pathology |
| Topic 3: Is biopsy necessary to diagnose chronic GVHD in certain organs? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High* (NR) | Skin biopsy is NOT mandatory for diagnosis of skin chronic GVHD. (Q16) | Skin |
| High | If a patient with already diagnosed chronic GVHD has LFT abnormalities but no liver biopsy, LFT abnormalities should be considered GVHD. (Q49) | Liver |
| Moderate | We should score diarrhea in the NIH GI scoring section when the patient has chronic GVHD in other sites but biopsy is negative for GI GVHD. (Q42) | GI |
| Moderate | Diarrhea should be scored as GI GVHD if no biopsy is done but a patient has diagnostic chronic GVHD in other sites. (Q43) | GI |
| Controversial | A patient has chronic GVHD in other sites plus nausea and anorexia. Is a biopsy required for the diagnosis of GI involvement? (Q44) | GI |
| Topic 4: How should severity of chronic GVHD be scored? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High | Cardiomyopathy, cardiac conduction defects, and coronary artery involvement should NOT be included in the global scoring system. (Q14) | Global score |
| High* (R) | We should revise the current consensus that recommends rating organ severity without distinguishing between active disease and fixed deficits. (Q15) | Response |
| High | Maclopapular rash, lichen planus-like feature, erythroderma, sclerotic features, erythema, papulosquamous lesions or ichthyosis and poikiloderma should be considered for calculating body surface area (BSA). (Q19) | Skin |
| High | Pruritus should NOT be considered for calculating BSA. (Q19) | Skin |
| High | Just pruritus (without any skin changes) is NOT sufficient for NIH skin score 1 or greater. (Q21) | Skin |
| High | A patient had punctual plugging and had symptomatic relief to such an extent that he requires eye drops only 2 times a day. If you confirm that the punctal plugs fall out, the NIH eye score should be score 1. (Q29) | Eye |
| High | If a patient lost vision in one eye because of chronic GVHD but is completely asymptomatic in the other eye, the NIH eye score is score 3. (Q36) | Eye |
| Moderate | Esophageal stricture or web, thrombocytopenia, pericardial effusion, and pleural effusion should be included in the global scoring system. (Q14) | Global score |
| Moderate* (R) | The rule should be revised in scoring 3 for hidebound changes in only a small area (for example 1% of legs). (Q17) | Skin |
| Moderate | Keratosis pilaris and hair involvement should be considered for calculating BSA. (Q19) | Skin |
| Moderate | Just nail and/or hair involvement is sufficient for NIH skin score 1. (Q20) | Skin |
| Moderate | Just hyperpigmentation and/or hypopigmentation of skin is sufficient for NIH skin score 1 or greater. (Q22) | Skin |
| Moderate | A patient had punctual plugging and had symptomatic relief to such an extent that he requires eye drops only 2 times a day. If you confirm that the punctal plugs are still in the eyes, the NIH eye score should be score 2. (Q28) | Eye |
| Moderate | A patient started special contact lenses for treatment of ocular GVHD and had symptomatic relief to such an extent that he requires eye drops 2 times a day. The NIH eye score should be score 3. (Q30) | Eye |
| Moderate* (R) | If a patient has diagnostic signs such as lichenoid changes but has no oral symptoms, the NIH mouth score should be score 1. (Q37) | Mouth |
| Moderate | We should consider superficial mucoceles that come and go when you determine the NIH mouth score. (Q41) | Mouth |
| Controversial* | Performance status scoring is not incorporated into the NIH global scoring system. Should this be revised? (Q13) | Global score |
| Controversial | Ascites, eosinophilia, polymyositis, nephrotic syndrome, myasthenia gravis should be included in the global scoring system. (Q14) | Global score |
| Controversial | Nail involvement, hypopigmentation and hyperpigmentation should be considered for calculating BSA. (Q19) | Skin |
| Controversial | Should we consider excessive tearing as one form of GVHD in the NIH eye score? (Q34) | Eye |
| Controversial | A female patient is asymptomatic due to sexual inactivity and has moderate signs of genital GVHD. What is the NIH genital score? (Q67) | Genital |
| Controversial | A female patient tells you that she is asymptomatic but uses a dilator for her fixed moderate vaginal stricture. What is the NIH genital score? (Q68) | Genital |
| Controversial | Is vaginal dryness sufficient for NIH genital score 1 or greater? (Q69) | Genital |
| Topic 5: Should manifestations not due to GVHD be included in the scoring? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High* (R) | We should revise the current consensus that recommends rating all symptoms even if you do not think the symptoms are due to GVHD. (Q12) | Overall |
| High | A patient has just been diagnosed with chronic GVHD in the mouth. If the patient has been using eye drops 3 times a day due to dry eye starting before transplant, the patient should NOT be scored for ocular chronic GVHD. (Q27) | Eye |
| High | Joint tightness due to prior injury or avascular necrosis should be scored as 0 in the NIH joint score. (Q51) | Joint/fascia |
| High | If a patient has chronic obstructive pulmonary disease (COPD) before transplant, we should determine the NIH PFT score according to post-transplant PFTs only if they worsen from pre-transplant PFTs. (Q62) | Lung |
| Moderate | A patient has mild loose stool and the colon biopsy is positive for GVHD. The patient also had 10% weight loss as compared to one month ago, but you attribute the weight loss to poorly controlled steroid-induced diabetes. The NIH GI score should be score 2. (Q46) | GI |
| Moderate | Dyspnea that you believe is due to steroid myopathy should be scored as 0. (Q59) | Lung |
| Controversy | A patient uses eye drops 2 times a day due to dry eye prior to transplant. After transplant, he is diagnosed with chronic GVHD and increases the frequency of eye drops to 4 times a day due to worsening eye dryness. How do you rate the NIH eye score? (Q31) | Eye |
| Controversial | If other etiologies are confirmed for liver abnormalities (for example, hemochromatosis, viral hepatitis, leukemia invasion, drug side effect, or alcohol consumption), how do you rate the NIH liver score for patients with chronic GVHD? (Q50) | Liver |
| Topic 6: How should discrepancies between different evaluations be handled? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High | When you see hyperpigmentation and lichenoid in the same area, the Total Skin Score (Vienna score) is score 2. (Q25) | Skin |
| High | If eye symptoms differ between left and right eyes, I use the worse eye for rating the NIH eye score. (Q35) | Eye |
| Moderate | When lung symptom scores differ from PFT scores, higher values are used for final lung scores. We should continue to use PFT scores to determine the lung score whenever PFT results are available even if the patient has no pulmonary symptoms. (Q60) | Lung |
| Moderate | If a patient has pulmonary symptoms with normal PFT, we should score 0 for the NIH lung score, since you are not sure whether the symptoms are due to GVHD. (Q61) | Lung |
| Moderate | The NIH genital score is score 3 for a female who has mild dyspareunia and severe signs on gynecological exam. (Q70) | Genital tract |
| Controversial | If the patient has extensive oral lichenoid changes but has only mild symptoms, how should we rate the NIH mouth score? (Q39) | Mouth |
| Controversial | How should we rate the NIH mouth score for moderate oral sensitivities without lichenoid changes or other signs of chronic GVHD? (Q38) | Mouth |
| Controversial | A patient has normal AST, ALT and bilirubin, but has elevated alkaline phosphatase (AP). You do not have isozyme information for AP. How do you rate the NIH liver score? (Q48) | Liver |
| Topic 7: When the current NIH recommendations lack clarity or are silent about particularly clinical situations, how should they be scored? | ||
| Agreement level | Agreed answer or controversial question | Category |
| High | Erectile dysfunction is NOT a symptom of genital GVHD. (Q64) | Genital |
| Moderate | All types of eye drops should NOT be included when counting the frequency of eye drops for rating the NIH eye score (i.e., also include cyclosporine eye drop, steroid eye drop, antibiotic eye drops)? (Q32) | Eye |
| Moderate | The same laboratory tests for NIH chronic GVHD (ie, ALT, AST, bilirubin and alkaline phosphatase) should be applied to staging of late acute GVHD in the liver. (Q47) | Liver |
| Moderate | We should score the genitals for men. (Q65) | Genital tract |
| Controversial | When you diagnose recurrent late acute GVHD or quiescent chronic GVHD, how many days of acute GVHD resolution are required before symptoms start again? (Q9) | Subcategory of GVHD |
| Controversial | What is the reference time point used for calculation of weight loss? (Q45) | GI |
| Controversial | If a patient doesn’t have PFTs results, how should we determine the NIH lung score? (Q63) | Lung |
| Controversial | Can the NIH genital score be completed without gynecological exam? (Q66) | Genital |
*
Questions that asked specifically whether the current NIH recommendations should be revised. (R) = Revision recommended by respondents. (NR) = Respondents recommended against revision.