Abstract: Refractory chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic cell transplantation remains a leading cause of late morbidity and mortality among transplant survivors. Therapeutic targeting of the Janus kinase (JAK)–STAT pathway has proved to be an effective approach for cGVHD; however, toxicities and short response durability have limited the use of available agents. The safety and efficacy of the JAK 1/2 inhibitor baricitinib were investigated in patients with severe cGVHD refractory to at least 2 lines of therapy. This single-center phase 1/2 study enrolled 24 adult patients who received 2 dose levels (DLs) of baricitinib, 2 and 4 mg daily, in an intrapatient dose escalation study design. No dose-limiting toxicities were observed at either DL. Overall response rate at 6 months was 76.2% (95% confidence interval [CI], 52.8-91.8), with responses observed across all involved organs, including sclerotic skin and pulmonary. Median failure-free survival was 19 months (95% CI, 11-26), with no deaths or malignancy relapse on treatment. Clinically meaningful improvements in patient-reported and functional outcomes were seen in this highly morbid cohort. Immune correlative studies showed that baricitinib induced significant reductions in cytokine-induced signaling (STAT phosphorylation) in both CD4+ and CD8+ T cells and in proinflammatory cytokine secretion. Baricitinib was well tolerated and exhibited a high rate of durable responses in a cohort of patients with severe cGVHD, warranting further evaluation in earlier-line and larger-scale studies. This trial was registered at www.clinicaltrials.gov as NCT02759731.

Deficits in motor performance and functional abilities represent a severe complication for individuals with steroid refractory chronic graft versus host disease (cGVHD) and is associated with decreased survival and high morbidity. The objective of this study was to characterize the impact of pomalidomide on motor and functional outcomes in patients with cGVHD. Thirty-four adult patients with cGVHD were enrolled in a randomized and unblinded trial. Pomalidomide was administered orally at two dose levels: low (0.5 mg/d) or high (initial 0.5 mg/d, escalating 0.5 mg/d every 2 weeks to a maximum 2 mg/d). Efficacy was assessed primarily by the Activity Card Sort (ACS), 2 Minute Walk Test (2MWT), Medical Outcomes Study Short Form 36 (SF-36), Active Range of Motion (AROM), Disabilities of the Arm, Shoulder, and Hand (DASH), and Manual Abilities Measure 36 (MAM). Compared to baseline, the pooled sample of study participants at 6 months showed improvement in hand skills (MAM, P = .01), upper extremity (UE) function (DASH, P = .01), and health related quality of life (SF-36 Physical Component Summary score (PCS), P = .02). Though no statistically meaningful differences between the two dose groups were found, the low-dose group had greater improvements in AROM, walk distance, UE and hand function, and in the high-demand physical leisure and social subdomains of the ACS as compared to the high-dose group. Responders to pomalidomide performed better than nonresponders on most measures at the 6-month endpoint. The study suggests pomalidomide, at both dose levels, may improve several aspects of motor and functional abilities. However, further study is warranted to determine if the trends found in this study, are sustained over time in larger, and in more diverse cGVHD populations. The findings highlight the potential utility of administering functional and motor tests, such as the ACS, DASH, and MAM, to patients with cGVHD, to fully elucidate the efficacy of treatment options for persons with steroid refractory cGVHD.

Kidney complications have been studied in allogeneic hematopoietic stem cell transplant patients but not specifically among chronic graft-versus-host disease (cGVHD) patients. Participants (n = 365) enrolled in the cross-sectional cGVHD natural history study (NCT00092235) were assessed for kidney dysfunction and overall survival. Kidney dysfunction was analyzed for associations in univariate and multivariable analyses. Kidney dysfunction (eGFR < 60) was found in 64 patients, and 29 patients had moderate-severe kidney dysfunction (eGFR < 45). Patients with kidney dysfunction were more likely treated with cyclosporine at evaluation or to have received it for GVHD prophylaxis, or prior treatment of GVHD. Patients with kidney dysfunction were less severely affected by cGVHD of skin, mouth, and joints/fascia. In multivariable modeling, history of cyclosporine use (OR = 2.19, 95% CI 1.13–4.25), angiotensin receptor blocker use (OR = 5.57, 95% CI 1.49–20.84), proteinuria (OR = 2.39, 95% CI 1.19–4.79), lower CRP (OR = 0.95, 95% CI 0.91–0.99), lower C3 (OR = 0.98, 95% CI 0.97–0.99), and lower hemoglobin (OR = 0.70, 95% CI 0.58–0.84) were jointly associated with kidney dysfunction. Overall survival was lower in those with moderate-severe kidney dysfunction (p = 0.015), demonstrating the importance of addressing kidney dysfunction in this population. The association of kidney dysfunction with less severe cGVHD suggests an etiology unrelated to cGVHD but potentially a consequence of drug-related toxicities.

Patients with chronic graft-versus-host disease (cGVHD) are at heightened risk for components of metabolic syndrome (MetS), yet the prevalence and impact of MetS in the cGVHD patient population remain unknown. Adult patients (n = 229) with cGVHD enrolled in the cross-sectional NIH cGVHD Natural History Study (NCT00092235) were evaluated for MetS at enrollment and for variables associated with MetS. A majority (54.1%, 124/229) of the cohort met the diagnostic criteria for MetS. Patients with higher body mass index and lower performance status scores were more likely to have MetS (P < 0.0001; P = 0.026; respectively). Higher circulating erythrocyte sedimentation rate, C-reactive protein, and creatinine concentrations, along with lower estimated glomerular filtration rate, were associated with MetS (P < 0.001; P < 0.004; P = 0.02; P = 0.002; respectively). Patients with MetS compared to patients without MetS had no statistical differences in survival or NRM (5-year OS: 64% [95% CI: 54.8–71.8%] vs. 75.1% [95% CI: 65.6–82.3%]; respectively; overall P = 0.20; 5-year NRM: 21.7% [95% CI: 13.6–30.9%] vs. 10.1% [95% CI: 4.4–18.7%]; respectively; overall P = 0.12). Additionally, there was no difference in cGVHD severity between the two groups. Given the high prevalence of MetS in this cohort, clinicians should screen for its presence before it develops into comorbidities that complicate the course of cGVHD treatment.

Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of chronic graft-versus-host disease (cGVHD) following hematopoietic cell transplantation (HCT). Montelukast interrupts cysteinyl leukotriene (CysLT) activity and may diminish the activation and homing of cells to bronchioles and subsequent fibrosis. We performed a prospective phase II trial to test whether montelukast altered lung decline for patients with BOS after HCT. In this single-arm, open-label, multi-institutional study, the primary endpoints were stability or improvement (<15% decline) in forced expiratory volume in 1 second (FEV1) and a <1-point decline in the slope of FEV1 after 6 months of treatment. Secondary endpoints included symptom and functional responses and immune correlates investigating the role of leukotrienes in BOS progression. The study enrolled 25 patients with moderate to severe lung disease after 3 months of stable cGVHD therapy. Montelukast was well tolerated, and no patient required escalation of BOS-directed therapy. At the primary endpoint, all 23 evaluable patients met the criteria for treatment success using FEV1% predicted, and all but 1 patient had stable or improved FEV1 slope. In those with a >5% improvement in FEV1, clinically meaningful improvements were seen in the Lee scores of breathing, energy, and mood. Improvements in the Human Activity Profile and 6-minute-walk test were observed in those with a <5% decline in FEV1. Overall survival was 87% at 2 years. Immune correlates showed elevated leukotriene receptor levels on blood eosinophils and monocytes versus healthy controls, elevated urine leukotrienes in 45% of the cohort, and CysLT receptors in bronchoalveolar lavage subsets and a predominance of Th2 cells, all pretreatment. These data suggest that montelukast may safely halt the progression of BOS after HCT, and that leukotrienes may play a role in the biology of BOS.

Grip myotonia and weakness are attractive treatment response biomarkers in clinical trials of myotonic dystrophy type 1 (DM1). There is a need to develop simple, patient-friendly and reproducible methods of quantifying grip myotonia in multisite trial settings. We designed a HandClench Relaxometer (HCR) that measures grip myotonia and strength. In contrast with the existing quantitative myometry (QMA) setup, the HCR is portable, economical, can be used with any laptop and generates automated command prompts. We demonstrate the feasibility and reliability of HCR device in twenty DM1 individuals and ten age-matched controls; patients returned for follow up within two months. The device showed excellent day to day reproducibility (ICC >0.80) in patients. The HCR device detected myotonia in milder muscle disease and measured longer myotonia duration than QMA indicating enhanced sensitivity for quantifying myotonia in DM1. The reaction time to the relax but not squeeze command was delayed and showed warm up similar to myotonia in DM1. HCR outcomes were correlated with key pinch strength, hand dexterity test, and fat replacement in the MRI of the long finger flexor muscles. Use of the HCR is warranted for grip myotonia and strength measurements in longitudinal observational and interventional studies of DM1.

Musculoskeletal symptoms in chronic graft-versus-host disease (cGVHD) are rare manifestations contributing to disease burden. This study assesses the frequency of muscle cramps, joint and muscle aches, and muscle weakness in a cohort of patients severely affected by cGVHD. Three hundred thirty-four patients participated in the NCI natural history study of cGVHD (NCT00092235) from October 2004 to March 2017. Five-point Lee cGVHD Symptom Scale was dichotomized (less symptom bother-0, 1, 2; severe symptom bother-3, 4) and tested for associations with: Short Form 36 (SF36), 2-minute walk test, grip strength, joint range of motion, and human activity profile, clinical and laboratory data. Seventy-five point four percent of patients reported joint and muscle aches (36.8% severe, Lee Symptom Scale score 3-4), 74.3% muscle cramps (33.5% severe), and 82.34% muscle weakness (45.51% severe), which were associated with reduced functional capacity (SF36 Physical Component Scale, P < 0.0001). Muscle cramps were associated with limited joint movement (P < 0.0001) and skin manifestations (skin thickening, P = 0.0008; itchy skin, P = 0.0003). Muscle cramps did not show association with potential causative agents, such as concomitant calcineurin inhibitors therapy, statins, or use of antidiabetic drugs. Joint and muscle aches showed associations with multiple variables (including strong associations with mood symptoms and fatigue, P < 0.0001). Muscle weakness was not associated with steroid dose, but was significantly associated with depression (P < 0.0001) and anxiety (P = 0.0009). This study documents a high frequency of musculoskeletal symptoms in a cohort of adult patients with cGVHD. The multivariable logistic regression models showed that a joint set of factors were moderately well associated with musculoskeletal symptoms in this study.

INTRODUCTION:Melorheostosis is a rare bone disorder with limited literature that describes the effect of this disease on functional and motor abilities. As part of a natural history study, four outcome measures were administered to better understand the burden this disease has on a person's ability to engage in basic and instrumental activities of daily living.OBJECTIVE:To investigate the relationship between functional engagement, fatigue, and motor ability in patients with melorheostosis.DESIGN:Cross-sectional data gathered from a longitudinal natural history observational study.SETTING:Rehabilitation department within a single institution.PARTICIPANTS:Forty-seven adult volunteers with melorheostosis were enrolled. Two participants were removed for failure to meet diagnosis eligibility. Thirty patients had lower extremity (LE) osteosclerotic bone lesions, 14 had upper extremity (UE) lesions, and one had lesions in both UEs and LEs.INTERVENTIONS:Not applicable.MAIN OUTCOME MEASURES:Activity Card Sort, Second Edition (ACS); Multi-Dimensional Fatigue Inventory; Lower Extremity Functional Scale; Upper Extremity Functional Index.RESULTS:On the ACS, high-demand leisure (HDL) activities were the least retained (p < .001). Of the activities rated most important, HDL activities were the most likely to have been given up (27%). General fatigue (μ = 11.8) and physical fatigue (μ = 11.0) were the two most limiting fatigue constructs. There were moderate negative correlations with HDL activities compared to physical fatigue (r = -0.524, p < .001) and reduced activity fatigue (r = -0.58, p = .001). LE lesions had a large effect on completing LE tasks (d = 0.95) and UE lesions had a medium effect on completing tasks involving the UE (d = 0.69).CONCLUSIONS:Patients with melorheostosis experience fatigue and low engagement in HDL activities. The results of this study underscore the importance of acknowledging activity domain, fatigue constructs, and lesion location to support and provide targeted evidence-based rehabilitative therapy.CLINICAL TRIAL REGISTRATION NUMBER:NCT02504879.

Abstract Date Presented 04/6/21 Melorheostosis is a rare skeletal disorder with symptoms that include loss of range of motion and pain. Four measures were used to understand the burden of these symptoms on activity engagement. Results revealed decreased participation in high-demand leisure and lower extremity tasks. There was a correlation between physical and reduced activity fatigue constructs and activity engagement. Further study will provide insight on disease burden across the life cycle within this population. Primary Author and Speaker: Kathleen Farrell Additional Authors and Speakers: Danielle Cawley, Rebecca Irwin, Paige Pachuilo, and Kaitlin Wheeler

Steroid-refractory chronic graft-versus-host disease (cGVHD) is a therapeutic challenge. Sclerotic skin manifestations are especially difficult to treat. We conducted a randomized phase 2 clinical trial (#NCT01688466) to determine the safety, efficacy, and preferred dose of pomalidomide in persons with moderate to severe cGVHD unresponsive to corticosteroids and/or subsequent lines of therapy. Thirty-four subjects were randomized to receive pomalidomide 0.5 mg per day orally (n = 17; low-dose cohort) or 2 mg per day at a starting dose of 0.5mg per day increasing to 2mg per day over 6 weeks (n = 17; high-dose cohort). The primary endpoint was overall response rate (ORR) at 6 months according to the 2005 National Institutes of Health cGVHD Response Criteria. Thirty-two patients had severe sclerotic skin and received a median of 5 (range, 2-10) previous systemic therapies. ORR was 47% (95% confidence interval, 30-65) in the intention-to-treat analyses. All were partial responses, with no difference in ORR between the cohorts. ORR was 67% (45%-84%) in the 24 evaluable subjects at 6 months. Nine had improvement inNational Institutes of Health joint/fascia scores (P = .018). Median change from the baseline in body surface area involvement of skin cGVHD was -7.5% (-10% to 35%; P = .002). The most frequent adverse events were lymphopenia, infection, and fatigue. Eight subjects in the high-dose cohort had dose decreases because of adverse events. There was 1 death in the low-dose cohort from bacterial pneumonia. Our data indicate antifibrotic effects of pomalidomide and possible association with increases in concentrations of blood regulatory T-cell and interleukin-2. Pomalidomide 0.5mg per day is a safe and effective therapy for advanced corticosteroid-refractory cGVHD.

Adult-onset histiocytoses (AOH), primarily Rosai-Dorfman disease (RDD), Erdheim-Chester Disease (ECD), and adult Langerhans cell histiocytosis (ALCH), are a group of related histiocytic neoplastic disorders featuring multisystemic manifestations. The disorders are largely incurable, and are essentially chronic neoplastic diseases with a variable prognosis. Prompt diagnosis and treatment is important to prevent debilitating and even life-threatening complications. Survivorship issues abound in AOH, due to their multisystemic manifestations and the sometimes recalcitrant chronic inflammation, which can lead to other debilitating complications such as fatigue, weakness, and pain. Because these disorders are rare, few healthcare professionals are proficient in their management; therefore the aim of these guidelines is to offer guidance on how to manage patients, and how to create survivorship care plans through the efforts of an interdisciplinary team.

Subsequent cancer (SC) is a significant cause of morbidity and mortality in long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Chronic graft-versus-host disease (cGVHD) and treatment-related immunosuppression have been recognized as risk factors for SC. This study sought to investigate the incidence and risk factors for SC in patients with established cGVHD, assessed separately for onset of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)-categorized into nonmelanoma skin cancer (NMSC)-and all cancers other than NMSC. Two hundred and four patients were enrolled in the prospective cross-sectional cGVHD Natural History Study and underwent comprehensive clinical evaluation. Patients were followed-up with an annual survey. The cumulative incidences of NMSC and cancers other than NMSC with competing risks were estimated separately, and transplantation- and cGVHD-related factors were assessed for association with outcomes using Gray's test and multivariable Cox models. The time period for all analyses began at 2 years postevaluation to restrict analyses to patients presumed to not have had SC present at evaluation. Nineteen patients were diagnosed with NMSC and 19 were diagnosed with cancers other than NMSC, with 10-year cumulative incidences of 15.5% (95% confidence interval, 9.0% to 27.6%) and 13.8% (95% CI, 8.2% to 20.8%), respectively. Age at transplantation (hazard ratio [HR], 1.94; 95% CI, 1.23 to 3.06) and higher C-reactive protein level at evaluation (HR, 9.49; 95% CI, 1.26 to 71.58) were jointly associated with NMSC, and gastrointestinal cGVHD at evaluation (HR, 0.26; 95% CI, 0.09 to 0.78) was associated with reduced risk of NMSC. T cell depletion at transplantation (HR, 3.09; 95% CI, 1.17 to 8.20), lymphoma as an indication for transplantation (HR, 3.96; 95% CI, 1.56 to 10.05), and oral cGVHD severity at evaluation (HR, 4.36; 95% CI, 1.52 to 12.46) were jointly associated with cancers other than NMSC. This study estimates the incidence of SC in a population of allo-HSCT recipients with severe cGVHD and identifies correlations with the subsequent development of SC. These factors seem to differ between NMSC and cancers other than NMSC. Further longitudinal investigations accounting for dynamic and cumulative processes are needed to improve our understanding and management of SC.

Graft-versus-host disease (GVHD) is a multisystemic disorder that affects 30%-80% of patients who undergo allogeneic hematopoietic stem cell transplantation 10%-15% of GVHD patients develop sclerotic features affecting the skin or deeper tissues, leading to functional limitations and poor quality of life. There is limited literature regarding the indications and efficacy of specific rehabilitative interventions in sclerotic GVHD (sclGVHD). In this article, we summarize the current evidence supporting rehabilitation intervention in sclGVHD and offer our approach to the multidisciplinary management of this disease. In addition, we review techniques that have been employed in other sclerotic skin diseases (eg, iontophoresis, extracorporeal shock waves, botulinum toxin A, adipose derived stromal vascular fraction), but that require further validation in the sclGVHD setting. Ultimately, optimal care for this complex disease requires a multidisciplinary approach that includes a rehabilitation and adaptive program tailored to each patient's needs.

Date Presented 03/28/20 This study used the Activity Card Sort (ACS) and the Medical Outcome Short Form 36 (SF-36) to evaluate activity participation and QoL in patients with cGVHD. The positive correlation between the ACS global score and the SF-36 physical component score (PCS) suggests that activity participation is related to physical QoL. OT consultation may improve the QoL of patients with cGVHD by facilitating meaningful activity engagement. Primary Author and Speaker: Jessica Thornton Contributing Authors: Rafael Jiménez-Silva, Pei-Shu Ho, Galen Joe, Tiara Dunigan, Leora Comis

To explore improvement in motor ability, function, health-related quality of life (HRQOL), and symptom severity in patients with sclerotic chronic graft-versus-host disease (ScGVHD) in response to treatment as well as the relationship among changes on such measures.

Background: The cognitive profile of Turner syndrome, a genetic disorder resulting from partial or complete X-chromosome deletion, presents characteristic deficits. Despite this, studies have yet to evaluate how deficits translate into and are compensated for in academic settings. This study seeks to explore cognitive functioning, as well as the accessibility and development of academic accommodations in females with Turner syndrome from adolescence to adulthood. Materials and Methods: This cross-sectional study took place at the National Institutes of Health. Females with Turner syndrome (age range: 10-68; n=142) were evaluated on need for and procurement of academic accommodations. Cognitive functioning was evaluated in participants aged 20 years and older (n=101), as per the age validation of the Repeatable Battery for the Assessment of Neuropsychological Status. Data were analyzed using descriptive statistics, one-sample comparisons, and analyses of variance. Results: Females with Turner syndrome scored significantly lower than the normative population on visuospatial (p<0.001), delayed memory (p<0.001), and overall (p<0.001) functioning. About 25.9% of participants reported that accommodations were not needed, despite displaying one or more cognitive deficits. Approximately 12.7% reported needing but not receiving accommodations, however, this is only reported by females 30 years and older; no females aged 10-29 years indicated this discrepancy. Conclusions: Findings suggest that procurement of academic accommodations has increased within recent decades. Still, there is a discrepancy between those displaying cognitive deficits and those receiving academic accommodations. We highlight frequently received accommodations so that students and professionals can target deficits with appropriate accommodations.

Date Presented 04/05/19 This study explored the relationship between participation and quality of life (QOL) in transplant survivors with cGVHD. Participants lost nearly 30% of their global participation following the onset of cGVHD. Losses were especially notable in high-demand leisure activities. Retained global activity was associated with better physical and mental QOL. OTs can play a key role in promoting participation and well-being among persons with cGVHD. Primary Author and Speaker: Emily Rosenthal Contributing Authors: Sandra Mitchell, Steven Pavletic, Leora Comis

Introduction In allogeneic hematopoietic stem cell transplant survivors, sclerotic chronic graft-versus-host disease (ScGVHD) is associated with poor quality of life (QOL) and range of motion restrictions. The latter can limit patients’ ability to perform important activities of daily living (ADLs). The NIH Consensus Development Project established a standard set of measures to monitor chronic GVHD (cGVHD) progression. This includes indicators of patient-reported QOL and symptom burden, which is defined as the subjective severity and impact of physiological symptoms. Adding measures of functional performance may allow clinicians to more fully characterize the impact of ScGVHD on daily life. Objective To determine whether change in functional capacity and QOL relate to changes in symptom burden and clinician-rated cGVHD severity. Methods Between December 2008 and February 2011, patients with ScGVHD enrolled in a single-arm prospective clinical trial assessing the efficacy of imatinib mesylate. At baseline and 6 months, patients completed measures of functioning [Disabilities of the Arm, Shoulder, and Hand (DASH); Human Activity Profile (HAP); Manual Ability Measure (MAM-36)] and QOL [Short Form 36 version 2 (SF 36); Lee Symptom Scale (Lee)]. Clinicians rated patients’ ADL ability [Assessment of Motor and Process Skills version 7 (AMPS)] and cGVHD symptom severity [Provider Global Score (PGS)]. Spearman's rank correlation tests evaluated the association among measures. The alpha level was set to 0.01. Results Twenty patients with ScGVHD enrolled in the trial; 13 patients were assessable for primary endpoint analysis. At study entry, patients were a median of 53 years old, a median of 53 months post-transplant, and had a median of 5 cGVHD-affected organs. Change in PGS was not correlated with change of any measures. Reduced symptom burden (Lee) correlated with improved SF 36 physical component scores (r = -0.72, p = 0.008), AMPS ADL motor skill scores (r = -0.84, p < 0.001), and DASH scores (r = 0.71, p = 0.010). No measures showed evidence of ceiling or floor effects. Conclusion Our results suggest the value of supplementing the Lee scale and the SF 36 with functional measures to assess clinical response to ScGVHD treatment. The association between changes in symptom burden and changes in ADL ability (AMPS and DASH scores) indicate the potential utility of these measures in this clinical population. Such scales may allow for a better understanding of patients’ functional limitations, thereby promoting individualized clinical care and rehabilitative efforts. Clinician-reported cGVHD severity may not have been related to functional changes due to insufficient sensitivity of the measure or the small size of this sample. Our findings highlight the potential relevance of the AMPS and DASH in patients with cGVHD, though further exploration in larger and more diverse samples is necessary.

Patients (pts) with chronic graft-versus-host-disease (cGvHD) prospectively enrolled in a natural history study (NCT00092235) from 10/2004 - 11/2016 were evaluated according to 2005 NIH cGvHD Staging Criteria (SC) and followed for survival. Supervised by a physician experienced in cGvHD, two selected team members rescored pts retrospectively using 2014 SC based on the original 2005 NIH cGvHD scoring forms and concurrently obtained medical records. 284 pts were analyzed. Distributions of Organ Scores (OS) and Global Severity Scores (GSS) of 2005 and 2014 NIH cGvHD SC were compared, and their associations to functional and quality of life (QOL) outcome measures were tested: Lee symptom scale (LSS), Short Form 36 (SF36), 2-minute walk test (2MW), grip strength (GS), joint range of motion (ROM), Human Activity Profile (HAP), and Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT). Pts had median age of 46 yrs (range 19-71); 37% received moderate and 40% high levels of systemic immunosuppression. Pts scored by 2014 NIH SC had slightly lower GSS in comparison to 2005 NIH SC (72% vs 75% pts with severe cGvHD, P = .0009). cGvHD Liver Score was significantly worse using 2005 NIH SC (score of 0: 89% vs 55%, P < .0001). cGvHD Lung Score, scored exclusively using pulmonary function tests, were significantly lower when scored by 2014 vs 2015 SC (P < .0001). NIH scores for Skin, Mouth, Eye, Gastrointestinal tract, Joints &Fascia, and Genital did not show statistically significant difference. 2005 and 2014 NIH Skin Scores were associated with reduced GS and ROM (both P < .0001) and higher LSS (P = .0001). 2005 and 2014 NIH Lung Scores were associated with impairments in gait speed (2MW), and physical function (SF36 and HAP Maximum Activity Scale (MAS)), (all P < .0001) and a trend towards association with reduced GS (P = .002). Both 2005 and 2014 NIH Global Scores were significantly associated with ROM and GS. Compared to 2005 NIH GSS, weaker associations were seen between the 2014 NIH GSS and patient self-report of symptoms, functional status and quality of life (SF36, HAP MAS, and FACT-BMT) P < .001 and P < .05 respectively. Five-year overall survival in this cohort was 70.9% (95% CI: 64.8-76.1%) with median potential follow-up of 79 months. The final Cox survival model included 2014 NIH Lung Score (3 vs 0-2, HR = 2.67, 95% CI: 1.47-4.84; P = .0012), time from cGvHD diagnosis to consent (≥4 yrs vs <4 yrs, HR = .53, 95% CI: .31-0.94, P = .028), and Karnofsky performance status (80-100% vs <80%, HR = .48, 95% CI: .30-0.77; P = .0020). In conclusion, this cross-sectional cohort of patients severely affected by cGvHD shows the 2014 NIH cGvHD SC OS and GSS being significantly associated with functional and QOL measures. Refinements in grading criteria for lung and liver cGvHD resulted in lower scores for these organs. Implications of these findings need to be elucidated in prospective, large-cohort studies.