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Multicenter Study
. 2023 Apr 1;159(4):393-402.
doi: 10.1001/jamadermatol.2022.6624.

Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease

Emily Baumrin  1 , Laura X Baker  2 , Michael Byrne  3 , Paul J Martin  4   5 , Mary E Flowers  4   5 , Lynn Onstad  4 , Najla El Jurdi  6 , Heidi Chen  7 , Alicia Beeghly-Fadiel  3 , Stephanie J Lee  4   5 , Eric R Tkaczyk  8   9
Affiliations
Multicenter Study

Prognostic Value of Cutaneous Disease Severity Estimates on Survival Outcomes in Patients With Chronic Graft-vs-Host Disease

Emily Baumrin et al. JAMA Dermatol. .

Abstract

Importance: Prior studies have demonstrated an association between cutaneous chronic graft-vs-host disease (cGVHD) and mortality. Assessment of the prognostic value of different measures of disease severity would assist in risk stratification.

Objective: To compare the prognostic value of body surface area (BSA) and National Institutes of Health (NIH) Skin Score on survival outcomes stratified by erythema and sclerosis subtypes of cGVHD.

Design, setting, and participants: Multicenter prospective cohort study from the Chronic Graft-vs-Host Disease Consortium including 9 medical centers in the US, enrolled from 2007 through 2012 and followed until 2018. Participants were adults and children with a diagnosis of cGVHD requiring systemic immunosuppression and with skin involvement during the study period, who had longitudinal follow-up. Data analysis was performed from April 2019 to April 2022.

Exposures: Patients underwent continuous BSA estimation and categorical NIH Skin Score grading of cutaneous cGVHD at enrollment and every 3 to 6 months thereafter.

Main outcomes and measures: Nonrelapse mortality (NRM) and overall survival (OS), compared between BSA and NIH Skin Score longitudinal prognostic models, adjusted for age, race, conditioning intensity, patient sex, and donor sex.

Results: Of 469 patients with cGVHD, 267 (57%) (105 female [39%]; mean [SD] age, 51 [12] years) had cutaneous cGVHD at enrollment, and 89 (19%) developed skin involvement subsequently. Erythema-type disease had earlier onset and was more responsive to treatment compared with sclerosis-type disease. Most cases (77 of 112 [69%]) of sclerotic disease occurred without prior erythema. Erythema-type cGVHD at first follow-up visit was associated with NRM (hazard ratio, 1.33 per 10% BSA increase; 95% CI, 1.19-1.48; P < .001) and OS (hazard ratio, 1.28 per 10% BSA increase; 95% CI, 1.14-1.44; P < .001), while sclerosis-type cGVHD had no significant association with mortality. The model with erythema BSA collected at baseline and first follow-up visits retained 75% of the total prognostic information (from all covariates including BSA and NIH Skin Score) for NRM and 73% for OS, with no statistical difference between prognostic models (likelihood ratio test χ2, 5.9; P = .05). Conversely, NIH Skin Score collected at the same intervals lost significant prognostic information (likelihood ratio test χ2, 14.7; P < .001). The model incorporating NIH Skin Score instead of erythema BSA accounted for only 38% of the total information for NRM and 58% for OS.

Conclusions and relevance: In this prospective cohort study, erythema-type cutaneous cGVHD was associated with increased risk of mortality. Erythema BSA collected at baseline and follow-up predicted survival more accurately than the NIH Skin Score in patients requiring immunosuppression. Accurate assessment of erythema BSA may assist in identifying patients with cutaneous cGVHD at high risk for mortality.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Martin reported receiving grants from AltruBio and personal fees from Mesoblast, Rigel, Janssen, Therakos, and Mallinckrodt outside the submitted work. Dr Beeghly-Fadiel reported receiving grants from NIH: Precision Medicine and Health Disparities Collaborative (pilot study) and NIH: Meharry Medical College/Vanderbilt-Ingram Cancer Center/Tennessee State University Cancer Partnership (funded study) outside the submitted work; and employment by CorEvitas, LLC. Dr Lee reported receiving grants from NIH/National Cancer Institute during the conduct of the study; and grants from Amgen, Kadmon, AstraZeneca, Incyte, Pfizer, and Syndax; personal fees (advisory board) from Mallinckrodt, Equillium, and Kadmon; and nonfinancial support from Novartis (steering committee for a clinical trial) outside the submitted work. Dr Tkaczyk reported receiving grants from the US Department of Veterans Affairs and NIH during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Onset and Response to Treatment of Erythema and Sclerosis
Among 225 incident patients who enrolled with skin involvement or developed skin involvement during the study, erythema occurred earlier compared with sclerosis. A, Onset from transplant. B, From study enrollment. Skin chronic graft-vs-host disease (cGVHD) in incident and prevalent patients with skin involvement at the time of enrollment (n = 267) was more responsive for erythema compared with sclerosis. Spaghetti plot of body surface area (BSA) over time for erythema-type (n = 206) (C) and sclerosis-type (n = 103) cGVHD (D) (n = 42 patients with combination disease are included in both plots). A locally estimated scatterplot smoothed (LOESS) curve (orange) demonstrates the overall trend fitting the reported data, censored at n = 20 observations. Lines ending with a filled circle represent patients who died; lines without a filled circle represent patients lost to follow-up. Wilcoxon test compared continuous variables.
Figure 2.
Figure 2.. NRM According to BSA and 2005 NIH Skin Score for Patients With Erythema at First Follow-up Visit
Cumulative incidence of nonrelapse mortality (NRM) in patients with erythema is higher for (A) body surface area (BSA) greater than 10% vs 10% or less at first follow-up visit and (B) 2005 National Institutes of Health (NIH) Skin Score of 2 or 3 vs NIH Skin Score of 0 or 1 at first follow-up visit. A χ2 test compared variables.
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