Q63 – 111: Acute Graft vs. Host Disease (GVHD)

*Autologous Transplants
If this was an autologous infusion, continue with the Infection Prophylaxis section. The graft-versus-host disease sections should only be completed if an allogeneic donor was used.

!Acute GVHD Prophylaxis
Acute GVHD prophylaxis questions can only be completed on the 100-day follow-up form. These questions will be skipped for all subsequent reporting periods.

*Combined Follow Up and Acute GVHD
In scenarios where an HCT was given after a cellular therapy and this form is now being completed based on the subsequent HCT date, acute GVHD will always be reported on the Post-Infusion Follow-Up (2100) Form and is disabled on the Cellular Therapy Essential Data Follow-Up (4100) Form.

*Ex Vivo Manipulation for GVHD Prophylaxis
Ex vivo manipulation performed for GVHD prophylaxis should not be reported in the GVHD prophylaxis section of this form.

Questions 63 – 71: Select specific therapy used after the start of the preparative regimen to prevent acute GVHD. (Check all that apply) (Note: do not include growth factors reported in questions 15 – 23, or ex vivo T-cell depletion reported on the Product Insert. Do not include drugs given as part of the preparative regimen)

Following an allogeneic HCT, specific immunosuppressive therapy may be administered to prevent GVHD or to immunosuppress the host marrow. Most transplant centers have specific GVHD prophylaxis protocols and graft rejection protocols. Any agent a recipient receives as a result of these protocols should be included in this section. The type of acute GVHD prophylaxis is included in almost every analysis of allogeneic transplantation.

The prophylactic drug options listed on the form are intended to be systemic (IV or oral administration).

The Post-Infusion Follow-Up (2100) Form lists the generic immune suppression drug names. The following website provides the trade names under which generic drugs are manufactured: http://www.rxlist.com/drugs/alpha_a.htm.

If GVHD prophylaxis is used for a syngeneic (monozygotic or identical twin) or autologous HCT, upload documentation in FormsNet3 using the attachment feature. Contact CIBMTR Center Support with questions.

Specify the therapy given after the start of the preparative regimen to prevent acute GVHD or graft rejection. Check all that apply. If acute GVHD prophylaxis was not given, report None.

• Abatacept (Orencia): Immunomodulator that works to block the activity of T-cells.
• Alemtuzumab (Campath): Monoclonal antibody that targets common antigens found on B-cells and T-cells (part of the body’s immune system). If this drug was given as acute GVHD prophylaxis and report the total ordered dose administered in milligrams.
• ALG (Anti-Lymphocyte Globulin), ALS (Anti-Lymphocyte Serum), ATG (Anti-Thymocyte Globulin) ATS (Anti-Thymocyte Serum): Serum or gamma globulin preparations containing polyclonal immunoglobulins directed against lymphocytes. These drugs are usually prepared from horse or rabbits immunized against human lymphocytes. Also report the animal source. If Other is selected, specify the source.
• Blinded randomized trial: If the recipient is on a blinded randomized trial, specify agent being studied in the trial. Additionally, update the Post-Infusion Follow-Up (2100) once the trial is over to specify whether the recipient received the trial drug or placebo.
• Corticosteroids (systemic) (e.g., prednisone, dexamethasone): Usually combined with cyclosporine when used for prophylaxis. Only report systemic steroids in this section.
• Cyclophosphamide (Cytoxan): Given in high doses near the date of infusion as prophylaxis. Report the total administered dose in milligrams.
• Cyclosporine (CSA, Neoral, Sandimmune, Gengraf): Calcineurin inhibitor which decreases cytokine production by T-cells. Usually given for ≥ 3 months.
• In vivo immunotoxin: Antibody preparations linked to a toxin that is infused in the recipient following HCT. Specify the in vivo immunotoxin.
• Methotrexate (MTX) (Amethopterin): Inhibits the metabolism of folic acid. It is most often used with calcineurin inhibitors and is usually for a short duration of time.
• Mycophenolate mofetil (MMF) (CellCept, Myfortic): Inhibits the de novo pathway used for lymphocyte proliferation and activation.
• Sirolimus (Rapamycin, Rapamune): Inhibits the response to interleukin-2, blocking the activation of T-cells.
• Tacrolimus (Prograf): Inhibits the production of interleukin-2 by T-cells.
• Other in vivo monoclonal antibody: Antibody preparations that are infused for GVHD prophylaxis. Specify if an in vivo monoclonal antibody other than Alemtuzumab (Campath) or an in vivo immunotoxin was used.
• Other agent: If the drug is not listed on the form, select this option and specify the other agent being given as GVHD prophylaxis.

Do not report the following:

• Ex vivo T-cell depletion
  • Report ex vivo T-cell depletion on the HCT Infusion Form (Form 2006).
• Agents used to prevent infection
  • Report infection prophylaxis agents in the Infection section
• Topical corticosteroids or ursodeoxycholic acid (ursodiol, actigal).
  

*GVHD Reporting Instruction Overview
Review the GVHD Reporting Instruction Overview for detailed GVHD reporting instructions and various GVHD reporting scenarios.

*Acute / Chronic GVHD
If acute GVHD is diagnosed prior to chronic GVHD, report the diagnosis information, maximum severity of any symptoms, and treatment administered up to the date of diagnosis of chronic GVHD in the acute GVHD section of the form. Do not include any signs, symptoms, or treatment occurring on or after the onset of chronic GVHD when completing the acute GVHD section.
Report any new or persistent acute GVHD symptoms occurring on or after the onset of chronic GVHD only in the chronic GVHD section. If chronic GVHD was diagnosed in a prior reporting period, report No when asked if acute GVHD developed or persisted in each subsequent reporting period. See the reporting scenarios included in the GVHD Reporting Instruction Overview.

Question 72: Did acute GVHD develop?

Indicate whether acute GVHD developed in the reporting period.

The Unknown option should only be used when there is no information about the recipient’s GVHD status for the entire reporting period. This option should be used sparingly and only when no judgement can be made about the presence or absence of GVHD in the reporting period.

For detailed instructions regarding whether a new development of acute GVHD should be captured, review the GVHD Reporting Instruction Overview.

Question 73: Date of acute GVHD diagnosis

Report the date of clinical diagnosis of acute GVHD. The clinical diagnosis date may not necessarily be the date the symptoms began (example: the recipient developed a rash one week prior to the physician clinically diagnosing acute skin 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 acute GVHD in the same reporting period, report the date of onset of the first episode of acute GVHD.

If the exact clinical diagnosis date is unknown, but the treatment start date is known, report the date treatment started as the date of acute GVHD diagnosis.

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

!Persistent GVHD and Day 100 Reporting Period
Previously, reporting Yes for Did acute GVHD persist since the date of last report was not an applicable option for the Day 100 reporting period. However, if there was a prior infusion, the recipient developed acute GVHD in the last reporting period of the previous infusion and acute GVHD persisted into the Day 100 reporting period of the current infusion, report Yes, acute GVHD persisted since the date of last report.

Question 74: Did acute GVHD persist?

Indicate if acute GVHD was clinically diagnosed in the previous reporting period and persisted, with active symptoms, into the current reporting period. For detailed instructions on how to report a flare of acute GVHD, review the GVHD Reporting Instruction Overview.

The Unknown option should only be used when there is no information about the recipient’s GVHD status for the entire reporting period. This option should be used sparingly and only when no judgement can be made about the presence or absence of GVHD in the reporting period.

Review the GVHD Reporting Instruction Overview for various GVHD reporting examples.

Question 75: Was acute GVHD evaluated by biopsy (histology)? (at diagnosis)

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

Indicate Yes or No if a biopsy was used to diagnose acute GVHD. If biopsy was not performed or unknown if performed at diagnosis, report No.

Questions 99 – 105: Specify result(s)

For each organ listed, indicate the test result documented on the pathology report as either Positive, Suggestive, Negative, Inconclusive / equivocal, or Not done.

Suggestive or Inconclusive / equivocal should be reported if in the final diagnosis or comments section of the pathology report, those words are used.

Biopsy report may use the term “consistent with GVHD” which could be interpreted as either Positive or Suggestive, depending on the comments listed in the report.

If the biopsy was performed on an “other site,” specify the site biopsied.

Additionally, indicate whether documentation was submitted to the CIBMTR (e.g., pathology report). For further instructions on how to attach documents in FormsNet3, refer to the FormsNet3 Training Guide.

Question 83 – 89: Overall grade of acute GVHD at diagnosis

These questions are intended to capture each organ stage and the overall grade at the time of acute GVHD diagnosis. For reporting purposes, “at diagnosis” is defined as the period between onset of signs / symptoms and the initiation of therapy to treat GVHD (topical or systemic). The acute GVHD grading scale is based on clinical evidence (physician observation), not histology. Pathology reports sometimes list a histologic grade of GVHD. Do not report the histologic grade. Biopsy of affected organs allows for more precise diagnosis as to the presence or absence of GVHD, not its severity. However, overall grading remains clinical and is based on the criteria published by Przepiorka et al., Bone Marrow Transplant 1995; 15(6):825-8, see the GVHD Grading and Staging table below.

Report the overall grade and organ staging at the diagnosis of acute GVHD. Review the GVHD Reporting Instruction Overview for additional information and on the criteria for each organ staging and grading.

Questions 90 – 91: Maximum overall grade of acute GVHD

These questions are intended to capture the maximum overall grade of acute GVHD within the reporting period.

Report the maximum acute GVHD grade in the reporting period and the first date of the maximum acute GVHD grade based on clinical judgement. If the recipient had multiple instances in which the GVHD reached the same maximum grade, report the earliest date, regardless of any variation in the organ staging.

If chronic GVHD was diagnosed during the reporting period, report the maximum overall grade of acute GVHD prior to the onset of chronic GVHD.

For detailed reporting instructions about reporting the maximum grade and organ staging of acute GVHD, review the GVHD Reporting Instruction Overview.

!Maximum Organ Staging
Due to further clarification provided, the instructions for reporting the maximum organ staging were updated with the Fall 2023 Quarterly Release. The intent of the maximum organ staging questions is to capture the maximum stage of each organ involved with acute GVHD in the reporting period; not at the time of the maximum overall grade, despite what the question text states. The question text will be revised with the next revision of the Post-Infusion Follow-Up (2100) Form.

Questions 92 – 97: Specify organ involvement at time of maximum grade

These questions are intended to capture the maximum organ staging within the reporting period.

Report the maximum acute GVHD stage of each organ involved, consistent with the reported maximum overall grade, in the reporting period. The maximum staging does not need to be at the time when the maximum overall grade occurred.

If chronic GVHD was diagnosed during the reporting period, report the maximum organ staging of acute GVHD prior to the onset of chronic GVHD.

For detailed reporting instructions about reporting the maximum grade and organ staging of acute GVHD, review the GVHD Reporting Instruction Overview.

Question 121: Corticosteroids (topical GI) (check all that apply)

Select all topical corticosteroids (beclomethasone and / or budesonide) used to treat GI GVHD. If topical corticosteroids to treat GI GVHD were not given, select None.

Topical therapies used for skin or lung GVHD are not captured in this question. Also, do not report systemic corticosteroids such as prednisone or dexamethasone. Systemic therapies are captured below

*Corticosteroids
Corticosteroids are captured differently depending on whether they are used topically or systemically. Use the following guidelines when determining how to report corticosteroids used to treat acute GVHD:
Topical Creams for Skin: Do not report topical ointments or creams used to treat skin GVHD including corticosteroid creams such as Triamcinolone or Hydrocortisone.
Other Topical Treatments: Certain corticosteroid treatments are not absorbed and are therefore considered topical. Examples include beclomethasone and budesonide. If these treatments are given for acute GI GVHD during the reporting period, report Yes for Corticosteroids. If these treatments were given for other organ involvement of GVHD, contact the CIBMTR Customer Service Center to determine the best option for reporting this therapy.
Systemic Treatments: Systemic administration of corticosteroids, including use of prednisone and dexamethasone, should be reported in Select systemic treatment used to treat acute GVHD).

*Reporting Multiple Systemic Therapies
Complete the GVHD specific therapy questions for each reported systemic therapy by adding an additional instance in the FormsNet3^SM application.

Questions 99 – 111: Was specific therapy given for acute GVHD?

Specify the systemic therapy used to treat acute GVHD during the reporting period. Report any prophylactic drugs as therapy for acute GVHD if they were continued after the date of diagnosis.

If systemic therapy was given to treat acute GVHD during the reporting period, specify the drugs given and indicate if the treatment was continued from prophylaxis. If the drug was continued from prophylaxis, select Yes and continue with Specify if the treatment was continued from prophylaxis. If the drug was started in a prior reporting period and continued into the current reporting period, select Previously reported. The Previously reported option is not applicable for the Day 100 reporting period.

If the drug was not continued from prophylaxis and was not started in the prior reporting period and continued into the current reporting period, select No and report the therapy start date. When reporting the date started, report the first day the drug was given on or after the GVHD diagnosis date (reported in Date of acute GVHD diagnosis).

If Alemtuzumab (Campath) is selected, report the total administered dose in milligrams during the reporting period. Do not report the prescribed or daily doses.

If ALG, ALS, ATG, ATS is selected, report the total administered dose in milligrams during the reporting period. Do not report the prescribed or daily doses. In addition, specify the animal (horse or rabbit) source. If Other is selected, specify the source.

If Anti CD25 (Zenapax, Daclizumab, AntiTAC), Blinded randomized trial, In vivo immunotoxin, Other in vivo monoclonal antibody, or Other JAK2 inhibitor is selected, specify the agent.

If the therapy is not listed on the form, select Other agent and specify the therapy.

If no therapy was given, indicate None.

Section Updates:

Question Number	Date of Change	Add/Remove/Modify	Description	Reasoning (If applicable)
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