Below a short survey- the survey cannot be anonymous to potentially allow to clarify and seek amendments if needed; thank you to ensure a senior member with previous experience of filling in the survey and to get the approval of the Director of Transplant Program.

General Information

GITMO CENTRE______CIC CODE______

HEAD OF TRANSPLANT UNIT

Name______Email______

TRASPLANT MD

Name______Email______

NURSE

Name______Email______

DATA MANAGER

Name______Email______

The survey has been designed to include, mostly, yes or no/close ended questions. Additional comments, if any, should be short and relevant. Attachments, when requested, can be included and must be named in a relevant manner (ex: Rome Center, CIC code, Attachment, second-line treatment, etc.)

Preliminary inquiry:

  1. Are you aware of potential published guidelines for systematic first line treatment of cGVHD?

YES (please specify the references)

NO

  1. Do you consider them adequate?

YES

NO

YES, partially (please specify______

  1. In the GITMO context, do you believe that it is possible to conduct a randomized trial for cGVHD treatment?

YES, in the setting of first line treatment

YES, in the setting of second line treatment

NO, I do not believe it is possible

  1. What would you suggest as an alternative?

Observational, prospective Trial

Retrospective study

Phase 1 and phase 2 trials

International studies

Part One - First Line Treatment

  1. Do you have a specific policy for the first line systemic treatment of cGVHD?

YES

NO

  1. Which patient need a systemic treatment for cGVHD? (select more than one if needed)

All patients suffering from cGVHD regardless the disease severity and/or negative prognostic factors

Any cGVHD degree of severity with the following negative prognostic factors:

  • progressive cGVHD (aGVHD followed by cGVHD)
  • overlap Syndrome (acute and cronic)
  • thrombocytopenia
  • other prognostic factor (Please specify:______)

cGVHD only with the following severity characteristics:

  • moderate/severe in the NIH scale
  • extensive cGVHD (Shulman, Am J Med 1980)
  • other severity evaluations (Please specify:______)
  1. Use of corticosteroid in first line treatment:

Yes, as monotherapy

Yes, in association with other drug/treatment (including ECP)

  1. Starting dose of corticosteroid ( in mg/kg/die of Prednisone or equivalent dose)

______

  1. What is the minimum duration of the treatment for an initial response to be expected (steroid + potential additional drug)?

MIN______weeks

MAX______weeks

  1. Alternative added treatment:

ECP [Please specify treatment schedule______]

Drug:______dose:______duration:______

Drug:______dose:______duration:______

  1. In case of complete response, how do you modify the treatment?

slow tapering of steroid (% reduction per week______)

fast steroid-tapering with the addition of a steroid-sparing drug (specify______)

other (please specify drug______, dose______, duration______)

  1. In case of a partial response, how do you modify the treatment?

I do not make a distinction between full and partial response

slow tapering of steroid (% reduction per week______)

fast steroid-tapering with the addition of a steroid-sparing drug (specify______)

  1. In NIH scoring system, “steroid dependency” is defined as the need of doses of steriod > 0.4 mg/kg/die for >8-12 weeks in order to maintain the obtained benefits. Do you consider this specific definition when modifying the patient treatment (for example when adding a steroid-sparing drug) if no other clinical events are detected?

YES, considering the same criteria as suggested by NIH (doses and timing)

YES, but with different criteria (reduction of _____ mg/kg/die of prednisone after ____weeks from the beginning of first line treatment)

NO

  1. Do you use defined criteria to evaluate the response to a first line treatment?

YES (please specify),

.i.2005 NIH criteria (Pavletic SZ, BBMT 2006)

.ii.Simplified NIH criteria (GITMO Nilo-GVHD protocol)

.iii.Couriel criteria (Couriel, BJH 2005)

.iv.Criteria as defined internally by your own department

.v.Others criteria (______)

NO

  1. Regardless of the criteria chosen, what elements do you consider as critical when defining the response to the treatment (Select criteria with values from “0: not important” to “5: essential”):

____Instrumental/laboratory evaluation (for example: FEV1, transaminase, etc.)

____Clinical scale (for example: Schubert scale for oral lesions, BSA or Rodnan for skin damages etc.)

____Improvement as reported by the physician (based on the same scales)

____Improvement of the symptoms as reported by the patient (based on Lee scale)

____Sustained reduction or suspension of the steroid/ immunosuppressive treatment

  1. Based on of the mentioned criteria, what is the minimum improvement needed to define a response to the treatment?

Any improvement, even a minimal one, as long as measurable

An improvement greater than the variability of the measurement method

An improvement greater than 50% compared to the scale used

  1. Do you consider including the trajectory of the disease (fast/slow onset/stability of symptoms) within the evaluation of the response, feasible?

NO

YES, on serial instrumental evaluations (e.g. FEV1)

YES, based on the physician subjective evaluation

YES,based on the evolution of the patient symptoms

YES, based on the global evaluation of all above mentioned factors

  1. Timing of the response: it is preferable to choose a criteria based on:

Fixed time point (measuring the response on a predefined time point, for example 3 months after the beginning of the treatment)

Best response (registered at any point without verifying the minimum duration)

Best sustained response (at least 2 consecutive measurements - at least 6/8 weeks between- during which the improvement is to be stable, in absence of any modification to the immunosuppressive treatment)

Other (please specify______)

  1. Which of the following definition of the endpoint :"sustained reduction/suspension of the steroid/immunosuppressive therapy", do you consider the most appropriate for a clinical study:

Ability to reduce it by at least 25% for at least 5-8 weeks

Abilityto reduce it by at least 50% for at least 5-8 weeks

Sustained reduction (6-8 weeks minimum) of the steroid dose at <0.3 mg/kg/die

Ability to stop the steroid for at least 6-8 weeks

Ability to interrupt the entire immunosuppressive therapy for at least 6-8 weeks

Other (please specify______)

  1. In the case of a mixed response (improvement in an organ associated with worsening or new spotting in other organs), do you prefer the prevalence criterion? (e.g.: a significant improvement/worsening in an important organ/district exceed a potential worsening/clinically irrelevant improvement and/or in non relevant districts)?

YES

No

I don’t know

  1. What are the criteria to define the flare of a previously successfully treated cGVHD?

A clinically significant worsening that requires to resume steroid treatment (if already stopped) or to increase by 50% the dose of the steroid for more than one week

A significant worsening of relevant laboratorial/instrumental/clinical parameter (for example bilirubin/transaminase, FEV1, lung TC)

Other criteria (please specify______)

  1. Which ones of the following criteria determine the treatment failure with the need to suspend/substitute the treatment itself?

cGVHD progression

Relapse of the hematological disease

Absence of an objective response (evaluated through instruments/ scales/ hematological-chemical tests) within predefine timing

Increase of the immunosuppressive therapy or addition of immunosuppressive drugs due to the insufficient response (as by physician observation)

Frequent disease flares (see next question for a definition)

Grade III-IV toxicity drug-related

Other criteria (please specify______)

  1. Among the following, which criterion (among the following) define a steroid-intolerance during cGVHD treatment?

Diabetes which is hardly controlled by drugs

Hypertension which is hardly controlled by drugs

Glaucoma

Heart failure

Frequent CMV reactivations

Frequent bacterial infections

Frequent viral infections

Cushing-like syndrome

Osteoporosis

Osteoporosis with pathological fractures

Psychosis

Gastrointestinal bleedings

Other (please specify______)

  1. What is the number of flares during a period of 3 months after which you declare the first line treatment failure?

1

2

3

>3

  1. After the treatment failure due to frequent flares, do you use the same first-line treatment or do you switch to a second-line treatment?

Yes, often I use the same first-line treatment

No, I always change the treatment

  1. Which one of the following criteria define the treatment failure, followed by the need to stop /change the treatment?

cGVHD progression

Relapse of the hematological disease

Absence of an objective response (evaluated through instruments/ scales/ hematological-chemical tests) within predefine timing

Increase of the immunosuppressive therapy or addition of immunosuppressive drugs due to the insufficient response (as by physician observation)

Frequent disease flares (see question 20 for a definition)

Grade III-IV toxicity drug-related

Other criteria (please specify______)

  1. What motivates you switch to a second line treatment?

Steroid-dependency (see question 9)

Steroid-intolerance (see question 19)

Steroid-refractoriness (absence of response: see question 12)

Treatment failure (see question 22)

Other (please specify______)

  1. What is your ideal time-point to evaluate patient response after the beginning of the first line treatment?

<4 weeks

5-8 weeks

9-12 weeks

>12 weeks

Part Two - cGVHD steroid-refractory management

  1. Do you have a specific policy for the treatment of steroid-refractory cGVHD (SECOND line treatment)?

YES (please attach the file with treatment schedule or specify the references______)

NO (in the following questions, please indicate the behavior most frequent choice)

  1. Regardless of your department policy, how do you treat a steroid-refractory cGVHD patient (second line treatment)?

I treat every patient differently (it is not possible to establish a pattern)

I have various preferences based on the severity of the disease

.i.If MODERATE I prefer______

.ii.If SEVERE I prefer______

I have various preferences based on which organs are involved

.i.Skin:______

.ii.Lung:______

.iii.Liver:______

.iv.Gut:______

.v.Other (please specify):______

I tend to use the same treatment for all patients (please specify): ______

  1. Do you have a specific policy for the treatment of steroid-refractory cGVHD (THIRD line treatment)?

YES (please attach the file with treatment schedule or specify the references______)

NO (in the following questions, please indicate the the most frequent choice)

  1. Regardless of your department policy, how do you treat a steroid-refractory cGVHD patient (second line treatment)?

I treat every patient differently (it is not possible to establish a pattern)

I have various preferences based on the severity of the disease

.i.If MODERATE I prefer______

.ii.If SEVERE I prefer______

I have various preferences based on which organs are involved

.i.Skin:______

.ii.Lung:______

.iii.Liver:______

.iv.Gut:______

.v.Other (please specify):______

I tend to use the same treatment for all patients (please specify): ______

  1. How many patient do you actually treat with systemic therapy for cGVHD?

<5

5-10

10-20

20-30

>30

  1. How many of those patients do you treat with:

Rituximab: ____patients

Mycophenolate mofetil: ____patients

TKI (imatinib, nilotinib) : ____patients

Pentostatine: ____patients

IL-2: ____patients

cyclosporine/tacrolimus/others calcineurin inhibitors: ____patients

methotrexate: ____patients

other drug (specify______): ____patients

other drug (specify______): ____patients

  1. Do you have any ECP treatment system available?

YES (please specify: model______and open/closed system______)

NO

  1. Do you have any ongoing trial for the tratment of steroid-refractory cGVHD?

YES (please specify EUDRACT or NCT code______)

NO

Part Three – Participating in a GITMO study

  1. Are you interested in standardizing cGVHD first line treatment in the context of a GITMO study? Are you interested in sharing unified and uniformed criteria to define treatment failure and the potential second line treatment?

YES

NO

  1. Are you interested in participating to a prospective non interventional GITMO study to evaluate cGVHD second line treatment?

YES

NO

  1. Are you interested in sharing unique criteria to define treatment response in a standardized and immediate manner?

YES

NO

  1. Are you interested in using a free of charge software to centralize all new cases of cGVHD, to register treatments and calculate the response using the new NIH criteria?

YES

NO

  1. Are you available to be contacted for potential queries on the survey?

YES

NO

The filled-in form is to be saved with the following name: "Survey_GITMO_nameofyourcentre" and is to be send to the following addresses: