Establishing a standardized system for review and adjudication of chronic graft‐vs‐host disease data in accordance with the National Institutes Consensus criteria

Dierov, Djamilia; Webb, Nicholas J.A.; Fatmi, Samira; Nwanne, Chamberlain; Ciolino, Cristi; Mosesso, Kara; Nieves, Jimmy; Perales, Miguel-Ángel; Prockop, Susan E.; Ponce, Doris M.

doi:10.1002/acg2.62

Cited by 7 publications

(4 citation statements)

References 43 publications

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“…Acute GVHD (aGVHD) was graded using the International Bone Marrow Transplant Registry (IBMTR) grading system, except grades A–D were labelled as grades I–IV 16 . Grading was reviewed by a transplant clinician panel 17 …”

Section: Methodsmentioning

confidence: 99%

The Simplified Comorbidity Index predicts non‐relapse mortality in reduced‐intensity conditioning allogeneic haematopoietic cell transplantation

Elias,

Brown,

Devlin

et al. 2023

Br J Haematol

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SummaryComorbidity assessment before allogeneic haematopoietic cell transplantation (allo‐HCT) is essential for estimating non‐relapse mortality (NRM) risk. We previously developed the Simplified Comorbidity Index (SCI), which captures a small number of ‘high‐yield’ comorbidities and older age. The SCI was predictive of NRM in myeloablative CD34‐selected allo‐HCT. Here, we evaluated the SCI in a single‐centre cohort of 327 patients receiving reduced‐intensity conditioning followed by unmanipulated allografts from HLA‐matched donors. Among the SCI factors, age above 60, mild renal impairment, moderate pulmonary disease and cardiac disease were most frequent. SCI scores ranged from 0 to 8, with 39%, 20%, 20% and 21% having scores of 0–1, 2, 3 and ≥4 respectively. Corresponding cumulative incidences of 3‐year NRM were 11%, 16%, 22% and 27%; p = 0.03. In multivariable models, higher SCI scores were associated with incremental risks of all‐cause mortality and NRM. The SCI had an area under the receiver operating characteristic curve of 65.9%, 64.1% and 62.9% for predicting 1‐, 2‐ and 3‐year NRM versus 58.4%, 60.4% and 59.3% with the haematopoietic cell transplantation comorbidity index. These results demonstrate for the first time that the SCI is predictive of NRM in patients receiving allo‐HCT from HLA‐matched donors after reduced‐intensity conditioning.

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Section: Methodsmentioning

confidence: 99%

The Simplified Comorbidity Index predicts non‐relapse mortality in reduced‐intensity conditioning allogeneic haematopoietic cell transplantation

Elias,

Brown,

Devlin

et al. 2023

Br J Haematol

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Section: Discussionmentioning

confidence: 99%

“…These findings support the utility of real-time adjudication in improving data quality and the implementation of this system in both interventional and observational studies, which is already routine practice in the Mount Sinai Acute GVHD International Consortium and other institutions. 11,13 GVHD remains a clinical diagnosis. Pathologic findings have limited utility because of lack of specificity and sampling error, in particular, in intestinal biopsies.…”

Section: Discussionmentioning

confidence: 99%

Acute GVHD Diagnosis and Adjudication in a Multicenter Trial: A Report From the BMT CTN 1202 Biorepository Study

Reshef

Saber

Bolaños-Meade

et al. 2021

JCO

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PURPOSE Accurate and reproducible methods to diagnose, grade, and report acute graft-versus-host disease (GVHD) are critical for the evaluation of therapies and biomarkers. PATIENTS AND METHODS The Blood and Marrow Transplant Clinical Trials Network 1202 study is an observational study of 1,709 allogeneic hematopoietic cell transplantation recipients that implemented weekly data reporting and near real-time data adjudication by an end point review committee (ERC), assigning a confidence level (confirmed, probable, possible, or negative) to the diagnosis of acute GVHD at onset. RESULTS During the first 100 days, symptoms consistent with GVHD developed in 90% of cases but were often determined by centers to be due to causes other than GVHD. Indeed, GVHD was under consideration in only 23% of cases at symptom onset. Diagnostic biopsies were obtained in 40% of cases, but treatment often was incongruous with biopsy findings and 10.5% of biopsies were equivocal. Importantly, more than 40% of steroid courses were started for reasons other than GVHD. The ERC modified the determination of GVHD diagnosis and/or grade in 12.3% of onset cases. The cumulative incidence of acute GVHD as reported by the centers was 62%. When the ERC adjudicated GVHD onset to be present only if the confidence level was probable or confirmed, the incidence of GVHD declined to 49%. CONCLUSION This study demonstrates that the incidence of GVHD may be overestimated at symptom onset, establishes a contemporary benchmark for acute GVHD, and suggests a structured framework for reporting and adjudication of GVHD that could be used in prospective trials.

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“…The patients with GVHD underwent allo-HCT at Memorial Sloan Kettering Cancer Center (MSKCC) between 2014 and 2018. Structured retrospective assessments for GVHD through HCT days 100, 180, and 365 were conducted by an institutional consensus committee (tables S2 and S3) ( 66 ). In the cases where death occurred after day 365, GVHD symptoms in the 8 weeks before death were assessed following the same structured format.…”

Section: Methodsmentioning

confidence: 99%

Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse

DeWolf,

Elhanati,

Nichols

et al. 2023

Sci. Transl. Med.

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T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.

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Establishing a standardized system for review and adjudication of chronic graft‐vs‐host disease data in accordance with the National Institutes Consensus criteria

Cited by 7 publications

References 43 publications

The Simplified Comorbidity Index predicts non‐relapse mortality in reduced‐intensity conditioning allogeneic haematopoietic cell transplantation

The Simplified Comorbidity Index predicts non‐relapse mortality in reduced‐intensity conditioning allogeneic haematopoietic cell transplantation

Acute GVHD Diagnosis and Adjudication in a Multicenter Trial: A Report From the BMT CTN 1202 Biorepository Study

Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse

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