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assessment of chronic gvhd will

| SCORE 0                                                                              | SCORE I               | SCORE 2                | SCORE 3                   |                        |
|--------------------------------------------------------------------------------------|-----------------------|------------------------|---------------------------|------------------------|
| PERFORMANCE                                                                          | ❏ Asymptomatic and    | - Symptomatic,         | - Symptomatic,            | □ Symptomatic,         |
| SCORE:                                                                               | fully active (ECOG    | fully ambulatory,      | ambulatory, capable       | limited self-care,     |
| 0; KPS or LPS                                                                        | restricted only in    | of self-care, >50%     | > 50% of waking           |                        |
| 100%)                                                                                | physically            | of waking hours ou     | hours in bed (ECOG        |                        |
| KPS ECOG LPS                                                                         | strenuous activity    | of bed (ECOG 2,        | 3-4. KPS or LPS           |                        |
| (COG 1, KPS                                                                          | KPS or LPS 60-        | <60%)                  |                           |                        |
| or LPS 80-90%)                                                                       | 70%)                  |                        |                           |                        |
| SKIN†                                                                                |                       |                        |                           |                        |
| SCORE % BSA                                                                          |                       |                        |                           |                        |
| GVHD features to be scored                                                           | 0 No BSA              | 0 1-18% BSA            | 1 19-50% BSA              | ❏ >50% BSA             |
| by BSA:                                                                              | involved              |                        |                           |                        |
| Check all that apply:                                                                |                       |                        |                           |                        |
| □ Maculopapular rash/erythema                                                        |                       |                        |                           |                        |
| ❏ Lichen planus-like features                                                        |                       |                        |                           |                        |
| □ Sclerotic features                                                                 |                       |                        |                           |                        |
| ❏ Papulosquamous lesions on                                                          |                       |                        |                           |                        |
| ichthyosis                                                                           |                       |                        |                           |                        |
| □ Keratosis pilaris-like GVHD                                                        |                       |                        |                           |                        |
| SKIN FEATURES                                                                        | Check all that apply: |                        |                           |                        |
| SCORE:                                                                               | □ No sclerotic        | □ Superficial          | ❏ Deep sclerotic          |                        |
| features                                                                             | sclerotic features    | features               |                           |                        |
| □ "Hidebound"                                                                        |                       |                        |                           |                        |
| "not hidebound"                                                                      |                       |                        |                           |                        |
| (able to pinch)                                                                      | (unable to pinch)     |                        |                           |                        |
| ❏ Impaired mobility                                                                  |                       |                        |                           |                        |
| 0 Ulceration                                                                         |                       |                        |                           |                        |
| Other skin GVHD features (NOT scored by BSA)                                         |                       |                        |                           |                        |
| Check all that apply:                                                                |                       |                        |                           |                        |
| □ Hyperpigmentation                                                                  |                       |                        |                           |                        |
| □ Hypopigmentation                                                                   |                       |                        |                           |                        |
| ❏ Poikiloderma                                                                       |                       |                        |                           |                        |
| □ Severe or generalized pruritus                                                     |                       |                        |                           |                        |
| ❏ Hair involvement                                                                   |                       |                        |                           |                        |
| □ Nail involvement                                                                   |                       |                        |                           |                        |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                       |                        |                           |                        |
| MOUTH                                                                                | ❏ No symptoms         | 0 Mild symptoms        | D Moderate                | □ Severe symptoms with |
| Lichen planus-like                                                                   | with disease signs    | symptoms with          | disease signs on          |                        |
| but not limiting                                                                     |                       |                        |                           |                        |
| features present:                                                                    | disease signs with    | examination with major |                           |                        |
| □ Yes                                                                                | oral intake           | partial limitation     | limitation of oral intake |                        |
| □ No                                                                                 | significantly         | of oral intake         |                           |                        |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                       |                        |                           |                        |  
A Phase 2 Study of Ibrutinib Maintenance After Reduced-Intensity Conditioning and Allogeneic  
| SCORE 0                                                                              | SCORE 1                  | SCORE 2                | SCORE 3                    |                       |
|--------------------------------------------------------------------------------------|--------------------------|------------------------|----------------------------|-----------------------|
| E YES                                                                                | ❏ No symptoms            | ❏ Mild dry eye         | ❏ Moderate dry eye         | ❏ Severe dry eye      |
| symptoms not                                                                         | symptoms partially       | symptoms significantly |                            |                       |
| Keratoconjunctivitis                                                                 | affecting ADL            | affecting ADL          | affecting ADL (special     |                       |
| sicca (KCS) confirmed                                                                | (requirement of          | (requiring lubricant   | eyeware to relieve pain)   |                       |
| by ophthalmologist:                                                                  | lubricant eye            | eye drops > 3 x per    | O unable to work           |                       |
|                                                                                      | drops < 3 x per          | dy or punctal          | because of ocular          |                       |
|                                                                                      | symptoms OR loss of      |                        |                            |                       |
| day)                                                                                 | plugs),                  |                        |                            |                       |
| ❏ Not examined                                                                       | WITHOUT new              | vision due to KCS      |                            |                       |
| vision impairment                                                                    |                          |                        |                            |                       |
| due to KCS                                                                           |                          |                        |                            |                       |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                          |                        |                            |                       |
| GI Tract                                                                             | ❏ No symptoms            | □ Symptoms             | 0 Symptoms                 | □ Symptoms associated |
| associated with                                                                      | with significant weight  |                        |                            |                       |
| Check all that apply:                                                                | without                  |                        |                            |                       |
| significant weight                                                                   | mild to moderate         | loss* > 15%, requires  |                            |                       |
| ❏ Esophageal web/                                                                    | loss* (<5%)              | weight loss®           | nutritional supplement for |                       |
| proximal stricture                                                                   | (5-15%) OR               | most calorie needs OR  |                            |                       |
| or ring                                                                              | moderate diarrhea        |                        |                            |                       |
| ❏ Dysphagia                                                                          | esophageal dilation OR   |                        |                            |                       |
| 0 Anorexia                                                                           | without                  | severe diarrhea with   |                            |                       |
| significant                                                                          | significant interference |                        |                            |                       |
| ❏ Nausea                                                                             | interference with        | with daily living.     |                            |                       |
| □ Vomiting                                                                           | dily living              |                        |                            |                       |
| □ Diarrhea                                                                           |                          |                        |                            |                       |
|                                                                                      |                          |                        |                            |                       |
| □ Failure to thrive                                                                  |                          |                        |                            |                       |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                          |                        |                            |                       |
| LIVER                                                                                | 0 Normal total           | □ Normal total         | 0 Elevated total           | 0 Elevated total      |
| bilirubin and                                                                        | bilirubin with ALT       | bilirubin but          | bilirubin > 3 mg/dL        |                       |
| ALT or AP                                                                            | >3 to 5 x ULN or         | < 3 mg/dL or           |                            |                       |
| AP ≥ 3 x ULN                                                                         | ALT > 5 ULN              |                        |                            |                       |
| < 3 x ULN                                                                            |                          |                        |                            |                       |
| □ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                          |                        |                            |                       |
| LUNGS®®                                                                              | □ No symptoms            | ❏ Mild symptoms        | 0 Moderate                 | ❏ Severe symptoms     |
| Symptom score:                                                                       | (shortness of            | symptoms               | (shortness of breath  at   |                       |
| breath after                                                                         | (shortness of breath     | rest; requiring 0 2 )  |                            |                       |
| climbing one flight                                                                  | after walking on         |                        |                            |                       |
| of steps)                                                                            | flat ground)             |                        |                            |                       |
| Lung score:                                                                          | 0 FEV1>80%               | 0 FEV1 60-79%          | 0 FEV1 40-59%              | ❏ FEV1 <39%           |
| % FEV1                                                                               |                          |                        |                            |                       |
| Pulmonary function tests                                                             |                          |                        |                            |                       |
| □ Not performed                                                                      |                          |                        |                            |                       |
| □ Abnormality present but explained entirely by non-GVHD documented cause (specify): |                          |                        |                            |                       |  
| SCORE 0                                                                                                         | SCORE 1                               | SCORE 2                                      | SCORE 3                   |          |
|-----------------------------------------------------------------------------------------------------------------|---------------------------------------|----------------------------------------------|---------------------------|----------|
| JOINTS AND FASCIA                                                                                               |                                       | ❏ Mild tightness of                          | ❏ Tightness of arms or    |          |
| symptoms                                                                                                        | arms or legs,                         | legs OR joint                                | significant decrease of   |          |
| P-ROM score                                                                                                     | normal or mild                        | contractures,                                | ROM AND significant       |          |
| decreased range of                                                                                              | erythema thought                      | limitation of ADL                            |                           |          |
| (see below)                                                                                                     |                                       |                                              |                           |          |
| Shoulder (1-7):                                                                                                 | motion (ROM)                          | due to fasciitis,                            | (unable to tie shoes,     |          |
| Elbow (1-7):                                                                                                    | AND not affecting                     | moderate decrease                            | button shirts, dress self |          |
| Wrist/finger (1-7):                                                                                             | ROM AND mild to                       |                                              |                           |          |
| ADL                                                                                                             | etc.)                                 |                                              |                           |          |
| Ankle (1-4):                                                                                                    | moderate limitation                   |                                              |                           |          |
| of ADL                                                                                                          |                                       |                                              |                           |          |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify):                            |                                       |                                              |                           |          |
| GENITAL TRACT                                                                                                   | ❏ No signs N Mild signs 2 and         | □ Moderate signs 3 and S Severe signs 3 with |                           |          |
| (See Supplemental figure*)                                                                                      | females with or                       | may have                                     | or without                |          |
| ❏ Not examined                                                                                                  | without discomfort                    | symptoms with                                | symptoms                  |          |
| Currently sexually active                                                                                       | on exam                               | discomfort on exam                           |                           |          |
| 0 Yes                                                                                                           |                                       |                                              |                           |          |
|                                                                                                                 |                                       |                                              |                           |          |
| ❏ Abnormality present but explained entirely by non-GVHD documented cause (specify):                            |                                       |                                              |                           |          |
| Other indicators, clinical features or complications related to chronic GVHD (check all that apply and assign a |                                       |                                              |                           |          |
| score to severity (0-3) based on functional impact where applicable none - 0,mild –1, moderate –2, severe - 3)  |                                       |                                              |                           |          |
| ❏ Ascites (serositis)                                                                                           | ❏ Myasthenia Gravis                   |                                              |                           |          |
| □ Pericardial Effusion                                                                                          | ❏ Peripheral Neuropathy               | ❏ Eosinophilia > 500/ul                      |                           |          |
| □ Pleural Effusion(s)_                                                                                          | 0 Polymyositis                        | □ Platelets <100,000/pl                      |                           |          |
| ❏ Nephrotic syndrome                                                                                            | ❏ Weight loss>5%* without GI symptoms | ❏ Others (specify):                          |                           |          |
| Overall GVHD Severity                                                                                           | ❏ No GVHD                             | ❏ Mild                                       | ❏ Moderate                | ❏ Severe |
| (Opinion of the evaluator)                                                                                      |                                       |                                              |                           |          |
| Photographic Range of Motion (P-ROM)                                                                            |                                       |                                              |                           |          |  
  
Mild chronic GVHD
1 or 2 Organs involved with no more than score 1 plus Lung score 0 Moderate chronic GVHD
3 or More organs involved with no more than score 1 OR
At least 1 organ (not lung) with a score of 2 O
Lung score 1 Severe chronic GVHD
At least 1 organ with a score of 3 O
Lung score of 2 or 3 Key points:
In skin: higher of the 2 scores to be used for calculating global severity. In lung: FEV1 is used instead of clinical score for calculating global severity.  
If the entire abnormality in an organ is noted to be unequivocally explained by a non-GVHD documented cause, that organ is not included for calculation of the global severity.  
If the abnormality in an organ is attributed to multifactorial causes
(GVHD plus other causes) the scored organ will be used for calculation of the global severity regardless of the contributing causes (no downgrading of organ severity score).
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appendix e inhibitors and inducers

Inhibitors of CYP3A are defined as follows. A comprehensive list of inhibitors can be found at the following website: http://medicine.iupui.edu/clinpharm/ddis/table.aspx. The general categorization into strong, moderate, and weak inhibitors according to the website is displayed below. Refer to Section 6 on instructions for concomitant use of CYP3A inhibitors and inducers with ibrutinib.  
| Inhibitors of CYP3A                                                                                                                                                                                                                                                                      | Inducers of CYP3A   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|
| Strong inhibitors:                                                                                                                                                                                                                                                                       | carbamazepine       |
| indinavir                                                                                                                                                                                                                                                                                | efavirenz           |
| nelfinavir                                                                                                                                                                                                                                                                               | nevirapine          |
| ritonavir                                                                                                                                                                                                                                                                                | barbiturates        |
| clarithromycin                                                                                                                                                                                                                                                                           | glucocorticoids     |
| itraconazole                                                                                                                                                                                                                                                                             | modafinil           |
| ketoconazole                                                                                                                                                                                                                                                                             | oxcarbarzepine      |
| nefazodone                                                                                                                                                                                                                                                                               | phenobarbital       |
| saquinavir                                                                                                                                                                                                                                                                               | phenytoin           |
| suboxone                                                                                                                                                                                                                                                                                 | pioglitazone        |
| telithromycin                                                                                                                                                                                                                                                                            | rifabutin           |
| cobicistat                                                                                                                                                                                                                                                                               | rifampin            |
| boceprevir                                                                                                                                                                                                                                                                               | St John's Wort      |
| mibefradil                                                                                                                                                                                                                                                                               | troglitazone        |
| telaprevir troleandomycin posaconazole Moderate inhibitors: aprepitant amprenavir amiodarone atazanavir ciprofloxacin crizotinib darunavir/ritonavir dronedarone erythromycin diltiazem  fluconazole fosamprenavir grapefruit juice Seville orange juice verapamil voriconazole imatinib |                     |  
| Weak inhibitors: cimetidine fluvoxamine All other inhibitors: chloramphenicol delaviridine diethyl-dithiocarbamate gestodene mifepristone norfloxacin norfluoxetine star fruit   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
| Measure                         | 1 point   | 2 points                                        | 3 points                         |
|---------------------------------|-----------|-------------------------------------------------|----------------------------------|
| Total bilirubin, μmol/L (mg/dL) | <34 (<2)  | 34 to 50 (2 to 3)                               | > 50 (> 3)                       |
| Serum albumin, g/L (g/dL)       | > 35      | 28 to 35 (2.8 to 3.5)                           | < 28 (< 2.8)                     |
| (> 3.5)                         |           |                                                 |                                  |
| PT INR                          | <1.7      | 1.71 to 2.30                                    | > 2.30                           |
| Ascites                         | None      | Mild                                            | Moderate to Severe               |
| Hepatic encephalopathy          | None      | Grade I or II (or  suppressed with  medication) | Grade III or IV  (or refractory) |
| Points                          | Class     |                                                 |                                  |
| 5-6                             | A         |                                                 |                                  |
| 7-9                             | B         |                                                 |                                  |
| 10-15                           | C         |                                                 |                                  |
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appendix f. child-pugh score

Source:
1. Child CG, Turcotte JG. "Surgery and portal hypertension". In Child CG. The liver and portal hypertension. Philadelphia:Saunders. 1964. pp. 50-64.  
2. Pugh RN, Murray-Lyon IM, Dawson L, Pietroni MC, Williams R. "Transection of the oesophagus for bleeding oesophageal varices". *The British journal of* surgery, 1973;60:646-649.