Report any chronic graft-versus-host disease occurring in this reporting period in response to allogeneic HCT or cellular therapy. Chronic GVHD affects 25-50% of long-term survivors of allogeneic transplants and usually develops after day 100. However, it has been documented as occurring as early as day 60. Chronic GVHD may result in response to transplant or donor cellular infusion. The mechanism of tissue damage differs from acute GVHD and a greater variety of organs may be affected. For further information on acute GVHD, refer to the Acute GVHD section of the manual.

Question 234: Did chronic GVHD develop since the date of the last report?

Indicate whether a new clinical diagnosis of chronic GVHD was documented during the reporting period. If chronic GVHD was diagnosed during the reporting period, report “yes” and continue with question 235.

If the recipient had a flare of chronic GVHD occurring after at least a 30 day period of symptom quiescence, report “yes” and continue with question 235. Report “no” if symptoms resolve or become quiescent prior to the date of last report and then flare within 30 days. This should be reported as persistent chronic GVHD which is captured in question 236.
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Report “no” if chronic GVHD was not clinically diagnosed – initially or as a flare – in the reporting period; this includes instances where chronic GVHD persists from a prior reporting period.

Indicate “unknown” if there is no information about the recipient’s GVHD status for the reporting period. This option should be used sparingly and only when no judgment can be made about the presence or absence of GVHD in the reporting period.

Question 235: Date of chronic GVHD diagnosis

Report the date of clinical diagnosis of chronic GVHD. The clinical diagnosis date may not necessarily be the date the symptoms began (example: the recipient developed shortness of breath one month prior to the clinical diagnosis of pulmonary chronic GVHD). If the clinical diagnosis is documented, but the diagnosis date is unclear, obtain documentation from the primary physician confirming the clinical diagnosis date.

If the recipient developed more than one episode of chronic GVHD in the same reporting period, report the date of onset of the first episode of chronic GVHD.

For more information regarding reporting partial or unknown dates, see General Instructions, General Guidelines for Completing Forms.

Question 236: Did chronic GVHD persist since the date of last report?

Indicate whether chronic GVHD was clinically diagnosed during a previous reporting period and persisted, with active symptoms, into the present reporting period. Do not report quiescent or inactive chronic GVHD, or a prior history of GVHD. If “yes,” continue with question 302; questions concerning chronic GVHD at the time of diagnosis will be skipped. See question 234 for instructions on reporting a chronic GVHD flare.

If the recipient has no active symptoms during the reporting period, report “no” continue with question 400.

Indicate “unknown” if there is no information about the recipient’s GVHD status for the reporting period. This option should be used sparingly and only when no judgment can be made about the presence or absence of GVHD in the reporting period.

Question 237: Onset of chronic GVHD was:

Indicate whether the onset of chronic GVHD was:

  • Progressive – acute GVHD present within 2 weeks prior to onset of chronic GVHD
  • Interrupted – acute GVHD resolved for greater than 2 weeks, then chronic GVHD developed
  • De novo – acute GVHD never developed

Question 238: Were signs of acute GVHD present at the time of chronic GVHD diagnosis (overlap syndrome)?

Chronic GVHD can be separated into two different categories; classical chronic GVHD and overlap syndrome. Overlap syndrome is a condition where there are features of both acute and chronic GVHD at the time of diagnosis. Indicate whether signs of acute GVHD were present at the time of diagnosis of chronic GVHD (overlap syndrome). Refer to question 157 for instructions on how to complete the acute and chronic GVHD sections for recipients with overlap syndrome.

Question 239-241: Karnofsky/Lansky score at time of chronic GVHD diagnosis

The Karnofsky Scale is designed for recipients aged 16 years and older, and is not appropriate for children under the age of 16. The Lansky Scale is designed for recipients one year old to less than 16 years old. If the recipient is less than one year old, leave questions 239-241 blank.

Indicate the score (10-100) that best represents the recipient’s activity status at diagnosis of chronic GVHD. The only valid scores are 10-100, zero is not a valid response for this scale, nor are values not ending in zero, such as “85.” The Karnofsky/Lansky scale can be found in Appendix L, Karnofsky/Lansky Performance Staus.

For further information on reporting Karnofsky / Lansky Scores refer to the instructions for Questions 651-653 below.

Question 242: Platelets (at diagnosis of chronic GVHD):

Report the lowest platelet count recorded within 14 days (+ / -) of the diagnosis of chronic GVHD whether or not the recipient has received a platelet transfusion. Indicate the units.

Question 243: Total serum bilirubin (at diagnosis of GVHD):

Report the highest total serum bilirubin value (and units) within 14 days (+ / -) of the diagnosis of chronic GVHD. Indicate the units.

Question 244: Was chronic GVHD evaluated by biopsy (histology)? (at diagnosis)

Histological tests may be performed to confirm the clinical diagnosis of GVHD; however, the scoring of GVHD should be based on clinical evidence, not histological results.

Indicate whether a biopsy was used to diagnose chronic GVHD. If “yes,” specify the site(s) / result(s) in questions 245-251. If “no,” continue with question 252.

Question 245-251: Specify result(s):

For each organ listed, indicate the result documented on the laboratory report as either “positive,” “suggestive,” “negative,” or “inconclusive / equivocal.” If a biopsy was not completed for a specific organ, select “not done” and continue with the next organ. If “other site” is selected, specify the site biopsied in question 251.

Question 252-301: Organ involvement and NIH scoring at diagnosis of chronic GVHD

Report the organ involvement and NIH score of chronic GVHD for each organ / system listed at the time of diagnosis. For each involved organ, specify any features present at time of diagnosis. Refer to the Organ Scoring of Chronic GVHD Table below for the NIH Consensus Criteria, 2014 for organ scoring of chronic GVHD.

Signs or symptoms occurring at the time of diagnosis may be partially or entirely attributed to GVHD. Alternatively, reportable features may be observed at diagnosis, but attributed entirely to non-GVHD causes. In any case, report “yes” for organ involvement if any reportable signs / symptoms are documented during the reporting period regardless of whether those features are attributed to GVHD. Features entirely explained by non-GVHD causes will be excluded when determining the overall severity of chronic GVHD, but are still collected on the form. Spaces have been provided to document non-GVHD causes.

Specify all features observed at the time of diagnosis and report the score for each organ using the criteria from the Organ Scoring of Chronic GHVD Table below. If any reported features are attributed entirely to non-GVHD causes, specify the non-GVHD cause(s) in the appropriate field. If a sign or symptom is caused by a combination of chronic GVHD and other causes, then the section on “non-GVHD causes” does not need to be completed. Further instruction has been provided under each organ below.

If a recipient has signs / symptoms of both acute and chronic GVHD during the reporting period, refer to question 157 for additional instructions. Scenarios C and D below have also been provided for further clarification.

GVHD Reporting Scenarios:

A. A recipient developed a maculopapular rash covering 25% BSA as well as deep sclerotic features. Both features are attributed to chronic GVHD. In this case, report “yes” and “score 3” for skin involvement (based on findings of deep sclerotic features).

B. A recipient developed a maculopapular rash covering 25% BSA as well as diarrhea without significant weight loss. Both findings were identified and diagnosed at the same time. The skin rash was attributed to acute GVHD while diarrhea was entirely attributed to chronic GVHD. In this case, report “yes” and “Score 2” for skin involvement. Report “yes” and “score 1” for GI involvement. Any acute findings identified on or after the date of chronic GVHD diagnosis must be reported in the chronic GVHD section. The skin rash would not be reported in the acute GVHD section of the form unless identified and diagnosed prior to any findings of chronic GVHD.

C. A recipient developed a maculopapular rash covering 25% BSA. This was diagnosed as acute GVHD, treated, and completely resolved during the 100 day reporting period. During the six month reporting period, the recipient developed mild dry eyes which was diagnosed as chronic GVHD. Shortly thereafter, the recipient was also diagnosed with an acute flare of skin GVHD.

100 Day Post-HCT Data Form: Report the acute GVHD findings (maculopapular rash) in the acute GVHD section of the form. Report “no” for questions 234 and 235 to indicate chronic GVHD was not diagnosed during the 100 day reporting period.

6 Month Post-HCT Data Form: Report acute and chronic GVHD findings in the chronic GVHD section of the form. Report “no” for questions 157 and 159 to indicate no acute GVHD symptoms were identified during the reporting period. Even though acute skin GVHD was diagnosed, it is not necessary to report these symptoms in both acute and chronic sections of the form. Once a chronic GVHD diagnosis is made, report all signs / symptoms of GVHD (acute and chronic) in the chronic GVHD section of the form.

D. A recipient is diagnosed with acute skin GVHD early in the reporting period. This is treated and quickly resolves. During the same reporting period, the recipient later develops chronic GVHD of the gut. Shortly after the diagnosis of chronic GVHD, the recipient has a flare of their skin GVHD.

Acute GVHD data fields: Report any signs or symptoms of acute GVHD documented prior to the diagnosis of chronic GVHD in the acute GVHD section of the form (Questions 157-183). In this case, the initial diagnosis of skin GVHD as well as any treatments initiated prior to the diagnosis of chronic GVHD will be reported in acute GVHD data fields.

Chronic GVHD data fields: Report any signs or symptoms of GVHD (acute or chronic) documented on or after the diagnosis of chronic GVHD in the chronic GVHD section of the form (Questions 234-323). In this case, the initial diagnosis of gut GVHD as well as the subsequent flare of skin GVHD will be reported in chronic GVHD data fields. Any treatments continued or initiated on or after the date of diagnosis of chronic GVHD will be reported in chronic GVHD data fields.

E. A recipient developed a maculopapular rash covering 25% BSA as well as diarrhea without significant weight loss. The skin rash was entirely attributed to a drug reaction while the diarrhea was attributed to chronic GVHD and an ongoing CMV infection. In this case, report “yes” and “score 2” for skin involvement. The center should also specify the observed rash was entirely attributed to a drug reaction in questions 259-260. Report “yes” and “score 1” for GI involvement. Do not specify CMV as a non-GVHD cause in questions 273-274 because the observed symptoms were not entirely explained by this diagnosis.

F. A recipient developed maculopapular rash covering 55% BSA as well as superficial sclerotic features of the skin. The rash is attributed to a drug reaction and the sclerotic findings are entirely attributed to chronic GVHD. In this case, report “yes” and “score 3” as well as “superficial sclerotic features” for skin involvement. The center should also specify the observed rash was entirely attributed to a drug reaction in questions 259-260.

Organ Scoring of Chronic GVHD

Organ Score 0 Score 1 Score 2 Score 3
Skin % BSA1 No BSA involved 1-18% BSA 19-50% BSA >50% BSA
Skin Features No sclerotic features N/A Superficial sclerotic features, but not “hidebound” Deep sclerotic features; “hidebound;” impaired mobility; ulceration
Mouth No symptoms Mild symptoms with disease signs but not limiting oral intake significantly Moderate symptoms with disease signs with partial limitation of oral intake Severe symptoms with disease signs with major limitation of oral intake
Eyes No symptoms Mild dry eye symptoms not affecting ADL (requirement of lubricant drops ≤ 3x/day) Moderate dry eye symptoms partially affecting ADL (requiring lubricant drops > 3x/day or punctal plugs) WITHOUT new vision impairment due to keratoconjunctivitis sicca (KCS) Severe dry eye symptoms significantly affecting ADL (special eyewear to relieve pain) OR unable to work because of ocular symptoms OR loss of vision due to keratoconjunctivitis sicca (KCS)
GI Tract No symptoms Symptoms without significant weight loss (< 5%) Symptoms associated with mild to moderate weight loss (5-15%) within 3 months OR moderate diarrhea without significant interference with daily living Symptoms associated with significant weight loss (> 15%) within 3 months, requires nutritional supplement for most calorie needs OR esophageal dilation OR severe diarrhea with significant interference with daily living.
Liver Normal total bilirubin and ALT or AP < 3 x ULN Normal total bilirubin with ALT ≥ 3 to 5 x ULN or AP ≥ 3 x ULN Elevated total bilirubin but ≤ 3 mg / dL or ALT > 5 x ULN Elevated total bilirubin > 3 mg / dL
Lungs Symptom Score: No symptoms Mild symptoms (SOB after climbing one flight of steps) Moderate symptoms (SOB after walking on flat ground) Severe symptoms (SOB at rests; requires O2)
Lungs Lung Score: FEV1 ≥ 80% FEV1 60-79% FEV1 40-59% FEV1 ≤ 39%
Joints and Fascia No symptoms Mild tightness of arms or legs, normal or mild decreased range of motion AND not affecting ADL Tightness of arms or legs OR joint contractures, erythema thought to be due to fasciitis, moderate decrease of range of motion AND mild to moderate limitation of ADL Contractures WITH significant decrease of range of motion AND significant limitation of ADL (unable to tie shoes, button shirts, dress self, etc.)
Genital Tract2 No signs Mild signs and females with or without discomfort on exam Moderate signs and may have signs of discomfort on exam Severe signs with or without symptoms
Other Features3 No GVHD Mild Moderate Severe

NIH Consensus Criteria, 2014

1 Features to be scored by BSA: Maculopapular rash, lichen planus-like features, sclerotic features, papulosquamous lesions or ichthyosis, keratosis pilaris-like GVHD.

2 Scoring is based on severity of the signs instead of symptoms, based on limited available data and the opinions of experts. Female or male genital GVHD is not scored if a practitioner is unable to examine the patient.

3 May include ascites, pericardial effusion, pleural effusion(s), nephrotic syndrome, myasthenia gravis, peripheral neuropathy, polymyositis, weight loss without GI symptoms, eosinophilia > 500/μL, platelets < 100,000/μL, others.

Skin: Ranges from skin discoloration to severe scarring and tightness. Includes, but is not limited to:

  • Sclerosis: thickening of the skin, which may cause loss of suppleness
  • Maculopapular rash / erythema: reddish skin with small confluent bumps / redness
  • Lichen planus-like features: erythematous / violaceous flat-topped papules or plaques with or without surface reticulations or a silvery or shiny appearance.
  • Papulosquamous lesions or ichthyosis: dry, scaly, or thickened skin
  • Keratosis pilaris: small acne-like bumps and rough patches
  • Poikiloderma: atrophy, pigmentary changes, and telangiectasia

If any skin abnormalities were present, but explained entirely by non-GVHD causes, specify any documented causes in question 260.

Mouth: Refers to white plaques, scarring, and ulcers occurring in the mouth and throat.

  • Lichen planus-like features: whitish lacy patches that usually appear first on inner cheeks, but can involve roof of mouth, gums, and / or tongue

If any mouth abnormalities were present, but explained entirely by non-GVHD causes, specify any documented causes in question 265.

Eyes: Recipients may have dry eyes and corneal ulcers due to keratoconjunctivits sicca.

  • Keratoconjuctivitis sicca (KCS): dry eye syndrome

If any eye abnormalities were present, but explained entirely by non-GVHD causes, specify documented causes in question 270.

Gastrointestinal tract (GI):

  • Esophageal web / proximal stricture or ring: extension of esophageal tissue
  • Dysphagia: difficulty swallowing
  • Anorexia
  • Nausea
  • Vomiting
  • Diarrhea
  • Weight loss: weight loss ≥ 5%
  • Failure to thrive

If any GI abnormalities were present, but explained entirely by non-GVHD causes, specify documented causes in question 274.

Liver: Record all types of liver abnormalities either clinical or histological.

  • Liver involvement may be manifested by elevation of any of the liver function tests (bilirubin, particularly the direct component: alkaline phosphatase; GGT; SGOT [AST]; SGPT [ALT]).

If any liver abnormalities were present, but explained entirely by non-GVHD causes, specify documented causes in question 286.

Lung: This ranges from mild impairment on pulmonary function tests to severe disorders.

If pulmonary function tests were performed, specify FEV1 percent in question 290.

If any lung abnormalities were present, but explained entirely by non-GVHD documented causes, specify causes in question 292.

Joints and fascia:

  • Contractures: loss of joint mobility due to skin or fascia changes

If any joint or fascia abnormalities were present, but explained entirely by non-GVHD causes, specify causes in question 296.

Genital tract:

  • Female: Vaginitis / stricture: pain, ulceration, inflammation, eventually scarring / narrowing of the vaginal opening.
  • Male: Pain, burning sensation, lichen planus or lichen sclerosis features, scarring, stenosis.

If any genital tract abnormalities were present, but explained entirely by non-GVHD causes, specify documented causes in question 301.

Question 302: Maximum grade of chronic GVHD: (according to best clinical judgment)

Report the maximum chronic GVHD involvement since the date of last report, based on clinical grade, as documented by the recipient’s primary care provider. The intent of this question is to capture the maximum grade based on the best clinical judgment. If the maximum clinical grade is not documented, request documentation from the recipient’s primary care provider. Guidelines on how to report the maximum grade of chronic GVHD are outlined below:

  • Mild: Signs and symptoms of chronic GVHD do not interfere substantially with function and do not progress once appropriately treated with local therapy or standard systemic therapy (e.g. corticosteroids and/or cyclosporine or FK 506)
  • Moderate: Signs and symptoms of chronic GVHD interfere somewhat with function despite appropriate therapy or are progressive through first line systemic therapy (e.g. corticosteroids and/or cyclosporine or FK 506)
  • Severe: Signs and symptoms of chronic GVHD limit function substantially despite appropriate therapy or are progressive through second line therapy.

Indicate “unknown” if there is no information about the recipient’s GVHD status for the reporting period. This option should be used sparingly and only when no judgment can be made about the presence or absence of GVHD in the reporting period. Please note, questions 303 and 304 must still be answered if question 302 is reported as “unknown.”

Question 303: Specify if chronic GVHD was limited or extensive:

The grading system for chronic GVHD is divided into two categories: limited and extensive. Definitions are based on Sullivan KM, Blood 1981; 57:267.

Report the extent of chronic GVHD since the date of last report. Report “limited” if chronic GVHD includes only localized skin involvement and/or liver dysfunction. Report “extensive” if any of the following symptoms are attributed to chronic GVHD:

  • Generalized skin involvement and / or liver dysfunction
  • Liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis
  • Involvement of the eye: Schirmer’s test with < 5 mm wetting, or
  • Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy (labial biopsy not required), or
  • Involvement of any other target organ

The intent of this question is to capture if chronic GVHD was limited or extensive throughout the entire reporting period and is not dependent on the maximum grade and date of chronic GVHD (Q302 and Q304). If the criteria to report extensive was met at any time in the reporting period, report “extensive”.

Question 304: Date of maximum grade of chronic GVHD:

Report the date of maximum chronic GVHD involvement since the date of last report, based on clinical grade. If the recipient had multiple instances in which their GVHD reached the same maximum grade, report the earliest date.

For more information regarding reporting partial or unknown dates, see General Instructions, General Guidelines for Completing Forms.

Question 305-323: Indicate whether there was organ specific manifestations with chronic GVHD since the date of last report:

Report if there were any organ specific manifestations associated with chronic GVHD. If “yes,” answer any additional questions. If “no,” continue with the next option.

Sclerosis of skin:

  • Scleroderma: thickening of the skin, which may cause loss of suppleness
  • Fasciitis: inflammation of the fascia of a muscle or organ
  • Morphea: thickening or hardening patches of the skin which are discolored

Erythematous skin rash: skin rash characterized by redness.

Join contractures: loss of joint mobility due to skin or fascia changes.

Other skin or hair involvement: other skin or hair involvement, includes, but is not limited to:

  • Ulcers
  • Pruritus: itching of the skin
  • Dyspigmentation: change in color of the skin. Usually erythema (redness) or vitiligo (loss of skin color)
  • Alopecia: scalp hair loss
  • Lichenoid skin changes: purplish rash

Eyes: Dry eyes and corneal ulcers due to keratoconjunctivitis sicca.

  • Xerophthalmia: dry eyes
  • Abnormal Schirmer’s test: a measure of tear production, decreased wetting <5 mm
  • Abnormal slit lamp: The binocular slit lamp examination provides stereoscopic magnified view of the eye structures in detail
  • Corneal erosion / conjunctivitis: ulcers on the cornea, usually quite painful, or inflammation of thin membrane covering the eye and inner lids

Mouth: Refers to white plaques, red inflammation, scarring, and ulcers occurring in the mouth and throat.

  • Lichenoid changes: whitish lacy patches that usually appear first on inner cheeks, but can involve roof of mouth, gums, and/or tongue
  • Mucositis / ulcers: similar to cold sores but they can involve any part of the mouth, important not to confuse with herpes simplex infections
  • Erythema: redness

Bronchiolitis obliterans: scarring of the small airways. Usually diagnosed by lung biopsy or pulmonary function tests (showing obstruction of airflow). Symptoms include shortness of breath (dyspnea), dry cough, and wheezing. If bronchiolitis obliterans was a manifestation of chronic GVHD, also complete the Pulmonary Function section, questions 441-489.

Other lung involvement: includes related pulmonary disorders here. Do not report interstitial pneumonitis (IPn). Report IPn in the Pulmonary Function section, questions 441-489.

Upper gastrointestinal tract:

  • Esophageal: may have difficulty swallowing (dysphagia), pain when swallowing (odynophagia), narrowing of esophagus (esophageal web), poor motility (food does not move down esophagus normally).
  • Chronic nausea / vomiting: either nausea or vomiting that occurs on at least 25% of days (1 out of 4 days) or occurs frequently enough to interfere with functioning and lifestyle.

Lower gastrointestinal tract:

  • Chronic diarrhea: occurs on at least 25% of days (1 out of 4 days) or occurs frequently enough to interfere with functioning and lifestyle. This may occur due to thickening of the intestinal wall.
  • Malabsorption: inability to digest or absorb the nutrients from food. Diagnosed with specific tests measuring fecal fat, xylose uptake, or vitamin level.
  • Abdominal pain or cramping.

Liver: Record all types of liver abnormalities either clinical or histological.

  • Liver involvement may be manifested by elevation of any of the liver function tests (bilirubin, particularly the direct component; alkaline phosphatase; GGT; SGOT [AST]; SGPT [ALT]).
  • A liver biopsy may show obliteration of bile ducts (canaliculi) or cirrhosis.

Genitourinary tract: Includes, but is not limited to:

  • Vaginitis / stricture: pain, ulceration, inflammation, eventually scarring/narrowing of the vaginal opening

Musculoskeletal: Refers to pain, contractures, and / or joint deformities.

  • Arthritis: inflammation of joints
  • Myositis: inflammation of muscles
  • Myasthenia: weakness of muscles

Thrombocytopenia: Decreased platelet count (<100,000).

Eosinophilia: Elevation in eosinophils in the peripheral blood (> 500 cells / µL)

Serositis: Inflammation of a serous membrane, includes but is not limited to:

  • Pleural effusion: Buildup of fluid between the chest and the tissues which line the lungs
  • Ascites: Accumulation of fluid in the peritoneal cavity
  • Pericardial effusion: Accumulation of fluid in the pericardial cavity

Other:

  • Weight loss
  • Other organ involvement from chronic GVHD: specify the additional site

Question 324: Were corticosteroids (topical GI) given for chronic GVHD?

Report if corticosteroids (topical GI) were given for chronic GVHD. Examples include beclomethasone and budesonide. Do not report corticosteroids (topical GI) given as a GVHD prophylaxis.

Question 325: Was systemic therapy given to treat chronic GVHD?

Indicate whether systemic therapy was given to treat chronic GVHD during the reporting period. If systemic therapy was given as treatment for chronic GVHD, report “yes” and continue with question 326. If systemic therapy was not given for treatment of chronic GVHD, report “no” and continue with question 399. See questions 328-399 for Chronic GVHD Treatment Reporting Scenarios.

Question 326: Was the date therapy was first started previously reported?

Indicate whether the date therapy was first started for chronic GVHD was previously reported. If the therapy start date was previously reported, select “yes” and continue with question 328. If the therapy start date for chronic GVHD has not been reported, select “no” and report the start date in question 327.

If treatment is started for a flare of chronic GVHD (see question 234 for definition of flare), report “no” for question 326 and report the date treatment was started for the flare in question 327.

Question 327: Date therapy was first started:

Report the first date when therapy was started for chronic GVHD if the date has not been previously reported. If the recipient continued GVHD prophylaxis drugs after the onset of chronic GVHD, report the date of diagnosis of chronic GVHD as the treatment start date. If the recipient starts treatment multiple times during the same reporting period, report the earliest treatment start date.

For more information regarding reporting partial or unknown dates, see General Instructions, General Guidelines for Completing Forms.

Question 328-399: Specify systemic therapy started or escalated for chronic GVHD since the date of last report:

If a therapy was started or escalated for chronic GVHD, report “yes” and answer any additional questions (if applicable). If a dose is required, report the total ordered dose planned to be given at the time treatment was initiated. This may include doses which are planned to be given after the date of contact. Report “yes” for prophylactic drugs if they were continued after the onset of chronic GVHD. Report the date of diagnosis of chronic GVHD as the treatment start date for any prophylactic medications which were continued. See Chronic GVHD Treatment Reporting Scenarios below.

If treatment is started and subsequently escalated during the same reporting period, report the earliest date treatment was actually given during the reporting period. If a dose is required, contact your center’s liaison to determine how to complete the data field. Additionally, report the earliest start date if a drug is started multiple times during the same reporting period.

Refer to questions 132-156 for a description of most agents listed. Agents not described under acute GVHD are described below under Additional Agents. “Systemic” refers to drugs given by mouth, intramuscularly (IM), or intravenously (IV). “Topical” refers to drugs applied to the skin, eye drops, or inhalation therapy. An exception to this would be the drug budesonide; it is a drug given by mouth for treatment of gut GVHD, but it is considered a “topical” drug since it is not absorbed.

Chronic GVHD Treatment Reporting Scenarios:

A. During the one year reporting period, a recipient on cyclosporine for GVHD prophylaxis was diagnosed with chronic skin GVHD (5/1/2016). This was initially treated with topical steroids in addition to continuing their cyclosporine at the current dose. The chronic skin GVHD worsened shortly thereafter. On 5/15/2016, prednisone was started and the dose of cyclosporine was increased. Symptoms persisted into the two year reporting period, but improved shortly thereafter. Upon resolution of symptoms, prednisone and cyclosporine doses were tapered.

One Year Post-HCT Data Form

Question 324: Report “no” to indicate no topical GI corticosteroids were given. Topical steroids applied to the skin should not be reported here.
Question 325: Report “yes” to indicate systemic therapy was given to treat chronic GVHD.
Question 326: Report “no” to indicate the therapy start date was not previously reported.
Question 327: Report 5/1/2016 as the treatment start date. This is the date cyclosporine was started as treatment for chronic GVHD. Note, topical steroids should not be considered when completing questions 325-399.
Question 328-399: Corticosteroids will be reported as “yes” with a start date of 5/15/2016. Cyclosporine will be reported as “yes” with a start date of 5/1/2016. All other medications will be reported as “no.”

Two Year Post-HCT Data Form

Question 324: Report “no” to indicate no topical GI corticosteroids were given. Topical steroids applied to the skin should not be reported here.
Question 325: Report “yes” to indicate systemic therapy was given to treat chronic GVHD.
Question 326: Report “yes” to indicate the therapy start date was previously reported.
Question 327: Leave blank. This question will be skipped when question 326 has been answered “yes.”
Question 328-399: All medications will be reported as “no.” Prednisone and cyclosporine would only be reported on this form if a dose increase was given to treat chronic GVHD during the reporting period.

B. During the one year reporting period, a recipient on sirolimus for GVHD prophylaxis was diagnosed with chronic gut GVHD (7/1/2016). This was initially treated with topical steroids (oral budesonide) in addition to continuing sirolimus at the current dose. Prednisone was started 7/30/2016 due to minimal improvement. The chronic gut GVHD resolved and budesonide as well as prednisone were discontinued. Sirolimus was continued as prophylaxis. Later in the one year reporting period, a severe flare chronic gut GVHD occurred (10/15/2016). This was first treated by restarting prednisone on the date of diagnosis; however, no response was observed. Equine ATG was started on 10/20/2016 with a plan to give 6 total doses of 30 mg / kg. Symptoms resolved following administration of ATG.

One Year Post-HCT Data Form

Question 324: Report “yes” to indicate topical GI corticosteroids were given. Budesonide should be reported here.
Question 325: Report “yes” to indicate systemic therapy was given to treat chronic GVHD.
Question 326: Report “no” to indicate the therapy start date was not previously reported.
Question 327: Report 7/1/2016 as the treatment start date. This is the date sirolimus was started as treatment for chronic GVHD. Note, topical steroids, including budesonide, should not be considered when completing questions 325-399.
Question 328-399:

  • ATG will be reported as “yes” with a start date of 10/20/2016 . The total dose will be reported as 180 mg / kg to reflect the total planned dose at the time treatment was initiated (6 * 30 mg / kg).
  • Corticosteroids will be reported as “yes” with a start date of 7/30/2016. Report the earliest start date if a medication is started multiple times during the reporting period.
  • Sirolimus will be reported as “yes” with a start date of 7/1/2016.
  • All other medications will be reported as “no.”

C. During the six month reporting period, a recipient off all immunosuppression was diagnosed with chronic gut GVHD (9/15/2016). This was initially treated with topical steroids (oral budesonide). Cyclosporine was started on 9/20/2016 due to minimal response. Symptoms resolved by the one year date of contact (10/1/2016) at which time budesonide was discontinued. The recipient remained on cyclosporine. During the one year reporting period, a flare of chronic gut GVHD occurred on 11/15/2016 while attempting to taper cyclosporine. This was treated by increasing the dose of cyclosporine on the date of diagnosis of the flare.

Six Month Post-HCT Data Form

Question 325: Report “yes” to indicate systemic therapy was given to treat chronic GVHD.
Question 326: Report “no” to indicate the therapy start date was not previously reported.
Question 327: Report 9/20/2016 as the treatment start date. This is the date cyclosporine was started as treatment for chronic GVHD. Note, topical steroids, including budesonide, should not be considered when completing questions 325-399.
Question 328-399: Cyclosporine will be reported as “yes” with a start date of 9/20/2016. All other medications will be reported as “no.”

One Year Post-HCT Data Form

Question 325: Report “yes” to indicate systemic therapy was given to treat chronic GVHD.
Question 326: Report “no” to indicate the therapy start date was not previously reported. See question 326 for further instructions.
Question 327: Report 11/15/2016 as the treatment start date.
Question 328-399: Cyclosporine will be reported as “yes” with a start date of 11/15/2016. All other medications will be reported as “no.”

Additional Agents:

Aldesleukin (Proleukin): Increases production of several white blood cells including regulatory T-cells. This drug is also known as interleukin-2.

Azathioprine (Imuran):. Azathioprine inhibits purine synthesis. Usually it is used at low doses in combination with other treatments.

Hydroxychloroquine (Plaquenil): Hydroxychloroquine inhibits transcription of DNA to RNA and is commonly used as an anti-malarial drug.

Interleukin Inhibitor: Interleukin inhibitors suppress production of white blood cells and are grouped according to their target. Examples of IL-2 inhibitors include daclizumab (Zynbryta) and basiliximab (Simulect). Examples of IL-6 inhibitors include tocilizumab (Actemra) and siltuximab (Sylvant).

Janus Kinase 2 Inhibitors: Suppress function of T-effector cells. Examples: ruxoloitinib (Jakafi, Jakavi) and tofacitinib (Xeljanz, Jakvinus).

Pentostatin (Nipent): Inhibits adenosine deaminase, which blocks DNA (and some RNA) synthesis.

Tyrosine Kinase Inhibitor (TKI): Suppress function of tyrosine kinases thereby downregulating the function of many other cellular proteins / processes including fibrosis and inflammation. Examples: imatinib (Gleevec, Glivec), nilotinib (Tasigna), and dasatinib (Sprycel).

UV Therapy: UVA or UVB radiation administered to affected areas of the skin in order to suppress proliferation of cells responsible for GVHD.

PUVA (Psoralen and UVA): Psoralen is applied or taken orally to sensitize the skin, and then the skin is exposed to UVA radiation.

UVB: Broadband- or Narrowband-UVB radiation is applied to the affected areas of the skin.

Alternative treatments may be used in combination with drug therapy (example: low dose cyclophosphamide). If alternative treatments were used, report in “other agent” (questions 397-399).

Question 400: Are symptoms of GVHD still present on the date of actual contact (or present at the time of death)?

Questions 400-406 refer to any symptoms of GVHD (acute and / or chronic) observed during the reporting period. This section of the form must be completed if the center reported yes for question 157, 159, 234, or 236.

Indicate whether the recipient has active clinical signs / symptoms of acute and/or chronic GVHD on the date of contact (question 1). If the recipient has died, indicate whether GVHD symptoms were present at the time of death.

Question 401: Is the recipient still taking systemic steroids? (Do not report steroids for adrenal insufficiency, ≤ 10 mg/day for adults, < 0.1 mg/kg/day for children)

Indicate whether the recipient is still taking systemic steroids to treat or prevent GVHD on the date of contact. If the recipient is no longer taking systemic steroids for GVHD, report “no” and continue with question 402. If the recipient is still receiving systemic steroids during the reporting period to treat or prevent GVHD, report “yes” and continue with question 404. Refer to the guidelines included in the question text if the recipient is taking low dose steroids or steroids for adrenal insufficiency.

If the recipient did not receive systemic steroids for acute and / or chronic GVHD during the reporting period, report “Not applicable” and continue with question 404.

Indicate “Not applicable” in any of the following scenarios:

  • The recipient has never received systemic steroids (> 10 mg / day for adults or ≥ 0.1 mg / kg / day for children) to treat or prevent GVHD.
  • This form is being completed for a subsequent HCT and the recipient has never received systemic steroids (> 10 mg / day for adults or ≥ 0.1 mg / kg / day for children) to treat or prevent GVHD since the start of the preparative regimen for the most recent infusion (or since the date of the most recent infusion if no preparative regimen is given).
  • The recipient stopped taking systemic steroids (> 10 mg / day for adults or ≥ 0.1 mg / kg / day for children) to treat or prevent GVHD in a previous reporting period and did not restart systemic steroids (> 10 mg / day for adults or ≥ 0.1 mg / kg / day for children) during the current reporting period.

Indicate “unknown” if there is no information to determine if the recipient is still taking systemic steroids and continue with question 404. This option should be used sparingly and only when no judgment can be made about the recipient still receiving treatment for GVHD on the date of contact.

If the recipient has died prior to the discontinuation of systemic steroids used to treat or prevent acute and / or chronic GVHD, select “yes.”

Review the examples below for more information:

Example 1: In the 100-day reporting period, a recipient is on Prednisone at 7 mg per day for the entire reporting period. Question 401 should be answered as “Not applicable” since the dose of systemic steroids were never > 10 mg / day.

Example 2: At the beginning of the 6-month reporting period, a recipient is on 20 mg of Prednisone per day. After three months, the dose is decreased to 10 mg per day and is maintained at that level until the end of the reporting period. In this scenario, question 401 should be answered as “No” since the recipient received greater than 10 mg of systemic steroids within the reporting period but on the date of contact, the dose was ≤ 10 mg / day.

Example 3: Throughout the 100-day reporting period, a recipient is on 30 mg Methylprednisolone given every other day. In this scenario the average daily dose is approximately 15 mg / day. Hence, question 401 should be captured as “Yes,” as the dose of systemic steroids is > 10 mg / day.

Question 402-403: Date final treatment administered

Indicate whether the date when systemic steroids were discontinued is “known” or “unknown.” If the final treatment date is “known,” continue with question 403. If the date is “unknown,” continue with question 404.

For question 403, report the date when the final dose of systemic steroids was administered. For more information regarding reporting partial or unknown dates, see General Instructions, General Guidelines for Completing Forms.

Question 404: Is the recipient still taking (non-steroid) immunosuppressive agents (including PUVA) for GVHD?

Indicate whether the recipient is still taking non-steroidal immunosuppressive agents (including PUVA) to treat or prevent acute and / or chronic GVHD on the date of contact. If the recipient is still taking non-steroid immunosuppressive agents, report “yes” and continue with question 407. If the recipient is no longer receiving non-steroid agents for GVHD, report “no” and continue with question 405.

If the recipient did not receive non-steroidal immunosuppressive agents to treat or prevent acute and / or chronic GVHD during the reporting period, report “Not applicable” and continue with question 407.

Indicate “Not applicable” in any of the following scenarios:

  • The recipient has never received non-steroidal immunosuppressive agents (including PUVA) to treat or prevent GVHD.
  • This form is being completed for a subsequent HCT and the recipient has never received non-steroidal immunosuppressive agents (including PUVA) to treat or prevent GVHD since the start of the preparative regimen for the most recent infusion (or since the date of the most recent infusion if no preparative regimen was given).
  • The recipient stopped taking non-steroidal immunosuppressive agents (including PUVA) to treat or prevent GVHD in a previous reporting period and did not restart non-steroidal immunosuppressive agents (including PUVA) during the current reporting period.

Indicate “unknown” if there is no information to determine if the recipient is still taking non-steroidal immunosuppressive agents and continue with question 407. This option should be used sparingly and only when no judgment can be made about the recipient still receiving treatment for GVHD in the reporting period.

If the recipient has died prior to discontinuation of non-steroidal immunosuppressive agents used to treat or prevent acute and/or chronic GVHD, select “yes.”

Question 405-406: Date final treatment administered

Indicate whether the final administration date of non-steroidal immunosuppressive agents (including PUVA) is “known” or “unknown.” If the final treatment date is “known,” continue with question 406. If the date is “unknown,” continue with question 407.

For question 405, report the date when the final treatment or prophylaxis dose of non-steroidal immunosuppressive agents was administered.

For more information regarding reporting partial or unknown dates, see General Instructions, General Guidelines for Completing Forms.

Last modified: Aug 19, 2020

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