International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium

Abstract

Acute graft-versus-host disease (GVHD) remains a leading cause of morbidity and non-relapse mortality following allogeneic hematopoietic cell transplantation. The clinical staging of GVHD varies greatly between transplant centers and is frequently not agreed upon by independent reviewers. The lack of standardized approaches to handle common sources of discrepancy in GVHD grading likely contributes to why promising GVHD treatments reported from single centers have failed to show benefit in randomized multi-center clinical trials. We developed guidelines through international expert consensus opinion to standardize the diagnosis and clinical staging of GVHD for use in a large international GVHD research consortium. During the first year of use, the guidance was following discussion of complex clinical phenotypes by experienced transplant physicians and data managers. These guidelines increase the uniformity of GVHD symptom capture which may improve the reproducibility of GVHD clinical trials after further prospective validation.

Higher tacrolimus concentrations early after transplant reduce the risk of acute GvHD in reduced-intensity allogeneic stem cell transplantation

“…Acute GVHD was graded according to the modified Glucksberg criteria and guidelines for data collection recently published by the MAGIC Consortium. 15,16 Chronic GVHD was graded according to the National Institutes of Health Consensus Criteria. 17 Disease relapse was defined as morphological, cytogenetic, or radiological evidence of disease demonstrating pre-transplant characteristics.…”

Therapeutic targets and emerging treatment options in gastrointestinal acute graft-versus-host disease

“…The average volume per episode of diarrhea in an adult has been estimated to be ~200 ml, allowing for staging and grading of GI GVHD when only the number of diarrhea episodes is known. [9]…”

“…Next, recently published uniform GVHD staging guidelines that reduce grading variability among centers will facilitate comparisons of treatment responses across studies. [9] In addition, biomarker-defined GVHD scoring allows for early identification of high-risk patients. We hypothesize that earlier treatment of high-risk patients will improve TRM and overall survival before damage becomes firmly established.…”

“… * When stool volume is not quantified, a 200-ml/episode can be used as an estimate for adults [9]. Overall clinical grade (based on most severe target organ involvement):…”

Ruxolitinib for the Treatment of Patients with Steroid-Refractory GVHD: An Introduction to the REACH Trials

“…development of GVHD in a new organ after ≥1 mg/kg methylprednisolone or equivalent for skin GVHD or patients who progress during tapering before a 50% decrease in corticosteroids is achieved. GVHD stage will be evaluated from screening through the end of treatment using the Mount Sinai Acute GVHD International Consortium guidelines [46]. Patients are excluded if they have had >1 allogeneic HSCT, >1 systemic treatment in addition to corticosteroids for aGVHD, cGVHD including overlap syndrome, splenectomy, active uncontrolled infection, severe organ failure, relapse of primary disease, corticosteroid treatment for indications other than GVHD within 7 days of enrollment, JAK inhibitor treatment after allogeneic HSCT or treatment with any other investigational agent, device or procedure within 21 days or five half-lives (whichever is longer) of enrollment.…”