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Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.

Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P.001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.

Purpose: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. Experimental design: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m2 i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. Results: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%–43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%–44%) randomized to rituximab. Six (17%; 95% CI, 7%–34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%–29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27+) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. Conclusions: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab. Clin Cancer Res; 22(2); 319–27. ©2015 AACR.

To examine safety and efficacy of bandage soft contact lenses (BSCLs) for ocular chronic graft-versus host disease (GVHD), we conducted a phase II clinical trial. Extended-wear BSCLs were applied under daily topical antibiotic prophylaxis. Patients completed standardized symptom questionnaires at enrollment and at 2 weeks, 4 weeks, and 3 months afterward. Ophthalmologic assessment was performed at enrollment, at 2 weeks, and afterward as medically needed. Assessments at follow-up were compared with baseline by paired t-test. Nineteen patients with ocular GVHD who remained symptomatic despite conventional treatments were studied. The mean Lee eye subscale score was 75.4 at enrollment and improved significantly to 63.2 at 2 weeks (P = .01), to 61.8 at 4 weeks (P = .005), and to 56.3 at 3 months (P = .02). The ocular surface disease index score and 11-point eye symptom ratings also improved significantly. According to the Lee eye subscale, clinically meaningful improvement was observed in 9 patients (47%) at 2 weeks, in 11 patients (58%) at 4 weeks, and in 9 patients (47%) at 3 months. Visual acuity improved significantly at 2 weeks compared with enrollment values. Based on slit lamp exam at 2 weeks, punctate epithelial erosions improved in 58% of the patients, showed stability in 16%, and worsened in 5%. No corneal ulceration or ocular infection occurred. BSCLs are a widely available, safe, and effective treatment option that improves manifestations of ocular GVHD in approximately 50% of patients. This study was registered at www.clinicaltrials.gov as NCT01616056.

Ocular involvement can be quite symptomatic in patients with chronic graft-versus-host disease (GVHD). The prevalence of and risk factors for ocular GVHD and its impact on quality of life (QOL) in patients with chronic GVHD were studied in a prospective, multicenter, longitudinal, observational study. This study enrolled 342 patients with 1483 follow-up visits after allogeneic hematopoietic cell transplantation. All patients in this analysis were diagnosed with chronic GVHD requiring systemic treatment and enrolled within 3 months of chronic GVHD diagnosis. The symptom burden of ocular GVHD was based on the degree of dry eye symptoms, frequency of artificial tear usage, and impact on activities of daily living. Patients' QOL was measured by self-administered questionnaires. Variables associated with ocular GVHD at enrollment and subsequent new-onset ocular GVHD and the associations with QOL were studied. Of the 284 chronic GVHD patients, 116 (41%) had ocular GVHD within 3 months of chronic GVHD diagnosis (“early ocular GVHD”). Late ocular GVHD (new onset > 3 months after chronic GVHD diagnosis) occurred in 64 patients. Overall cumulative incidence at 2 years was 57%. Female gender (P = .005), higher acute GVHD grade (P = .04), and higher prednisone dose at study entry (P = .04) were associated with early ocular GVHD. For patients who did not have ocular GVHD within 3 months of chronic GVHD diagnosis, presence of prior grades I to IV acute GVHD (HR 1.78, P = .04) was associated with shorter time to late ocular GVHD, whereas female donor–male recipient (HR .53, P = .05) was associated with longer time to late ocular GVHD onset. Using all visit data, patients with ocular GVHD had worse QOL, as measured by Functional Assessment of Cancer Therapy Bone Marrow Transplantation (P = .002), and greater chronic GVHD symptom burden, as measured by the Lee symptom overall score excluding the eye component (P < .001), compared with patients without ocular GVHD. In conclusion, this large, multicenter, prospective study shows that ocular GVHD affects 57% of patients within 2 years of chronic GVHD diagnosis. Women, patients on higher doses of prednisone at study entry, and those with a history of acute GVHD were at higher risk for ocular GVHD. Strong evidence suggests that ocular GVHD is associated with worse overall health-related QOL.

Although older patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) may experience higher morbidity, the impact of chronic graft-versus-host disease (GVHD) on quality of life (QOL) and survival outcomes for older compared with younger patients is currently unknown. We utilized data of patients with moderate or severe chronic GVHD (N = 522, 1661 follow-up visits, a total of 2183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. We examined the relationship between age group (adolescent and young adult, “AYA,” 18 to 40 years; “middle-aged,” 41 to 59 years; and “older,” ≥ 60 years) and QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]), physical functioning (Human Activity Profile [HAP]), functional status (2-minute walk test [2MWT]), nonrelapse mortality, and overall survival. Because of multiple testing, P values < .01 were considered significant. This study included 115 (22%) AYA, 279 (53%) middle-aged, and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD. Despite more physical limitations in older patients as measured by worse functional status (shorter 2MWT [P

Objective To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. Methods In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Results Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician- and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Conclusion Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases.

There are no validated biomarkers for chronic GVHD (cGVHD). We used a protein microarray and subsequent sequential enzyme-linked immunosorbent assay to compare 17 patients with treatment-refractory de novo-onset cGVHD and 18 time-matched control patients without acute or chronic GVHD to identify 5 candidate proteins that distinguished cGVHD from no cGVHD: CXCL9, IL2Rα, elafin, CD13, and BAFF. We then assessed the discriminatory value of each protein individually and in composite panels in a validation cohort (n = 109). CXCL9 was found to have the highest discriminatory value with an area under the receiver operating characteristic curve of 0.83 (95% confidence interval, 0.74-0.91). CXCL9 plasma concentrations above the median were associated with a higher frequency of cGVHD even after adjustment for other factors related to developing cGVHD including age, diagnosis, donor source, and degree of HLA matching (71% vs 20%; P < .001). A separate validation cohort from a different transplant center (n = 211) confirmed that CXCL9 plasma concentrations above the median were associated with more frequent newly diagnosed cGVHD after adjusting for the aforementioned factors (84% vs 60%; P = .001). Our results confirm that CXCL9 is elevated in patients with newly diagnosed cGVHD.

Chronic graft-versus-host disease (cGVHD) is associated with mortality, disability and impaired quality of life. Understanding the role of comorbidity in patients with cGVHD is important both for prognostication and potentially for tailoring treatments based on mortality risks. In a prospective cohort study of patients with cGVHD (n=239), we examined the performance of two comorbidity scales, the Functional Comorbidity Index (FCI) and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Both scales detected a higher number of comorbidities at cGVHD cohort enrollment than pre-HCT (p

Although data support adverse prognosis of overlap subtype of chronic grant-versus-host disease (GVHD), the importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Using data from the Chronic GVHD Consortium observational cohort study (N = 567, total of 2115 visits), we examined whether the site of GI (esophageal, upper GI, or lower GI) and type of hepatic (bilirubin, alkaline phosphatase, alanine aminotransferase) involvement are associated with overall survival (OS) and nonrelapse mortality (NRM), symptoms, quality of life (QOL) and functional status measures. In multivariate analysis utilizing data from enrollment visits only, lower GI involvement (HR, 1.67; P = .05) and elevated bilirubin (HR, 2.46; P = .001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR, 1.69; P = .02) and elevated bilirubin (HR, 3.73; P

Oral chronic graft-versus-host disease (cGVHD) is a serious complication of allogeneic stem cell transplantation. Scales and instruments to measure oral cGVHD activity and severity have not been prospectively validated. The objective of this study was to describe the characteristics of oral cGVHD and determine the measures most sensitive to change. Patients enrolled in the cGVHD Consortium with oral involvement were included. Clinicians scored oral changes according to the NIH criteria, and patients completed symptom and quality of life measures at each visit. Both rated change on an 8-point scale. Of 458 participants, 72% (n=331) had objective oral involvement at enrollment. Lichenoid change was the most common feature (n=293; 89%). At visits where oral change could be assessed, 50% of clinicians and 56% of patients reported improvement, with worsening reported in 4–5% for both groups (weighted kappa = 0.41). Multivariable regression modeling suggested that the measurement changes most predictive of perceived change by clinicians and patients were erythema and lichenoid, NIH severity and symptom scores. Oral cGVHD is common and associated with a range of signs and symptoms. Measurement of erythema and lichenoid changes and symptoms may adequately capture the activity of oral cGVHD in clinical trials but require prospective validation.

Purpose To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes. Design Prospective follow-up study. Participants Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort. Methods Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation. Main Outcome Measures An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits. Results In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa=0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients. Conclusions Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

lips. He did not have diarrhea or pancytopenia. Biopsy of the rash showed lymphocytic interface dermatitis and formation of multiple necrotic keratinocytes with resultant separation at the dermal epidermal junction; findings consistent with GVHD of the skin. When the rash started, the patient was concomitantly on Sulfamethoxazole/ Trimethoprim for pneumocystis jirovecii prophylaxis and was on broad spectrum antibiotics for suspected sepsis; the rash however continued to progress despite stopping these antibiotics two days after the rash appeared. A repeat biopsy was performed to confirm that GVHD is more likely than a drug reaction and this again showed features of GVHD. Short tandem repeat testing to evaluate for chimerism failed to show that in the blood but showed 11% donor cells in the skin biopsy. A diagnosis of GVHD was made, IV steroids were starteddfive days after the rash developeddwith a methylprednisolone bolus followed by 1mg/kg; this achieved mild improvement. Etanercept was added after four days of steroids (25 mg subcutaneously twice weekly for 8 doses) with further improvement. Conclusions: GVHD post solid organ transplant as a diagnosis is often missed, because the presenting signs and symptoms are nonspecific and the condition is rare. Prognosis is in general poor and complications of pancytopenia usually lead to the high mortality associated with this disease. There are no guidelines as to how to treat this condition but careful intensification (or withdrawal) of immunosupression can potentially lead to successful control of this disease process. We treated this patient with parenteral steroids and added etanercept with a favorable outcome.

The 2005 National Institutes of Health (NIH) Consensus Conference recommended assessment of lung function in patients with chronic graft-versus-host disease (GVHD) by both pulmonary function tests (PFTs) and assessment of pulmonary symptoms. We tested whether pulmonary measures were associated with nonrelapse mortality (NRM), overall survival (OS), and patient-reported outcomes (PRO). Clinician and patient-reported data were collected serially in a prospective, multicenter, observational study. Available PFT data were abstracted. Cox regression models were fit for outcomes using a time-varying covariate model for lung function measures and adjusting for patient and transplantation characteristics and nonlung chronic GVHD severity. A total of 1591 visits (496 patients) were used in this analysis. The NIH symptom-based lung score was associated with NRM (P = .02), OS (P = .02), patient-reported symptoms (P < .001) and functional status (P < .001). Worsening of NIH symptom-based lung score over time was associated with higher NRM and lower survival. All other measures were not associated with OS or NRM; although, some were associated with patient-reported lung symptoms. In conclusion, the NIH symptom-based lung symptom score of 0 to 3 is associated with NRM, OS, and PRO measures in patients with chronic GVHD. Worsening of the NIH symptom-based lung score was associated with increased mortality.

Hand grip strength (HGS) and the 2-minute walk test (2MWT) have been proposed as elements of chronic graft-versus-host disease (GVHD) assessment in clinical trials. Using all available data (n = 584 enrollment visits, 1689 follow-up visits, total of 2273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, MOS 36-Item Short-Form Health Survey [SF-36], and Functional Assessment of Cancer Therapy [FACT]-Bone Marrow Transplantation quality of life instruments and Human Activity Profile [HAP]), chronic GVHD global severity (National Institutes of Health global score, clinician global score, and patient-reported global score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival, nonrelapse mortality, and failure-free survival) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all P < .001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with overall survival, nonrelapse mortality, and failure-free survival, whereas no association was found for HGS. 2MWT and HGS were not sensitive to National Institutes of Health or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials.

Hand grip strength (HGS) and 2 minute walk test (2MWT) have been proposed as elements of chronic graft-vs-host disease (GVHD) assessment in clinical trials. Using all available data (n=584 enrollment visits, 1,689 follow-up visits, total of 2,273 visits) from a prospective observational cohort study, we explored the relationship between HGS and 2MWT and patient-reported measures (Lee symptom scale, SF-36 and FACT-BMT quality of life instruments, and Human Activity Profile, or HAP), chronic GVHD global severity (NIH global 0–3 score, clinician global 0–3 score, and patient-reported global 0–3 score), calculated and clinician-reported chronic GVHD response, and mortality (overall survival (OS), non-relapse mortality (NRM), and failure-free survival (FFS)) in multivariable analyses adjusted for significant covariates. 2MWT was significantly associated with intuitive domains of the Lee Symptom Scale (overall, skin, lung, energy), SF-36 domain and summary scores, FACT summary and domain scores, and HAP scores (all p < 0.001). Fewer associations were detected with the HGS. The 2MWT and HGS both had significant association with global chronic GVHD severity. In multivariable analysis, 2MWT was significantly associated with OS, NRM, and FFS, while no association was found for HGS. 2MWT and HGS were not sensitive to NIH or clinician-reported response. Based on independent association with mortality, these data support the importance of the 2MWT for identification of high-risk chronic GVHD patients. However, change in 2MWT is not sensitive to chronic GVHD response, limiting its usefulness in clinical trials.

To determine whether changes in objective response measures proposed by the National Institutes of Health correlate with clinical benefit, such as symptom burden, quality of life, and survival outcomes, we analyzed data from a multicenter prospective cohort of 283 patients with chronic graft-versus-host disease requiring systemic treatment. The median follow-up time of survivors was 25.1 months (range, 5.4-47.7 months) after enrollment. Symptom measures included the Lee symptom scale and 10-point patient-reported symptoms. Quality-of-life measures included the Short Form-36, Functional Assessment of Cancer Therapy–Bone Marrow Transplantation, and Human Activities Profile. Overall and organ-specific responses were calculated by comparing manifestations at the 6-month visit and those at the enrollment visit using a provisional algorithm. Complete or partial responses were considered "response," and stable or progressive disease was considered "no response." Overall response rate at 6 months was 32%. Organ-specific response rates were 45% for skin, 23% for eyes, 32% for mouth, and 51% for gastrointestinal tract. Response at 6 months, as calculated according to the provisional response algorithm, was correlated with changes in symptom burden in patients with newly diagnosed chronic graft-versus-host disease, but not with changes in quality of life or survival outcomes. Modification of the algorithm or validation of other more meaningful clinical endpoints is warranted for future clinical trials of treatment for chronic graft-versus-host disease.

Background The National Institutes of Health Consensus Conference proposed the term “overlap” graft- versus -host disease to describe the situation when both acute and chronic graft- versus -host disease are present. Design and Methods We examined whether the overlap subtype of graft- versus -host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to “classic” chronic graft- versus -host disease without any acute features. Results Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft- versus -host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment ( P =0.01), were more likely to be incident cases ( P

In 2005, the National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic GVHD proposed a new scoring system for individual organs and an algorithm for calculating global severity (mild, moderate, severe). The Chronic GVHD Consortium was established to test these new criteria. This report includes the first 298 adult patients enrolled at 5 centers of the Consortium. Patients were assessed every 3-6 months using standardized forms recommended by the Consensus Conference. At the time of study enrollment, global chronic GVHD severity was mild in 10% (n = 32), moderate in 59% (n = 175), and severe in 31% (n = 91). Skin, lung, or eye scores determined the global severity score in the majority of cases, with the other 5 organs determining 16% of the global severity scores. Conventional risk factors predictive for onset of chronic GVHD and nonrelapse mortality in people with chronic GVHD were not associated with NIH global severity scores. Global severity scores at enrollment were associated with nonrelapse mortality (P < .0001) and survival (P < .0001); 2-year overall survival was 62% (severe), 86% (moderate), and 97% (mild). Patients with mild chronic GVHD have a good prognosis, while patients with severe chronic GVHD have a poor prognosis. This study was registered at www.clinicaltrials.gov as no. NCT00637689.

Quality of life (QOL) after hematopoietic cell transplantation (HCT) is compromised by chronic GVHD. In a prospectively assembled multicenter cohort of adults with chronic GVHD (n = 298), we examined the relationship between chronic GVHD severity defined by National Institutes of Health (NIH) criteria and QOL as measured by the SF-36 and FACT-BMT instruments at time of enrollment. Chronic GVHD severity was independently associated with QOL, adjusting for age. Compared with population normative data, SF-36 scores were more than a SD (10 points) lower on average for the summary physical component score (PCS) and role-physical subscale, and significantly lower (with magnitude 4-10 points) for several other subscales. Patients with moderate and severe cGVHD had PCS scores comparable with scores reported for systemic sclerosis, systemic lupus erythematosus, and multiple sclerosis, and greater impairment compared with common chronic conditions including diabetes, hypertension, and chronic lung disease. Moderate to severe cGVHD as defined by NIH criteria is associated with significant compromise in multiple QOL domains, with PCS scores in the range of other systemic autoimmune diseases. Compromised QOL provides a functional assessment of the effects of chronic GVHD, and may be measured in cGVHD clinical studies using either the SF-36 or the FACT-BMT.

The global severity score (GS) was devised by experts during the 2005 NIH Consensus for chronic graft-versus-host disease (GVHD) to reflect the overall severity of chronic GVHD at any time point. According to this scale, overall involvement is categorized as mild, moderate or severe. Several studies demonstrated that the NIH GS was associated with subsequent mortality in patients with chronic GVHD. We used multivariate time-varying analysis accounting for longitudinal changes of severity in individual organs over time to try to develop a better global mortality score than the NIH GS. Methods Data were derived from the Chronic GVHD Consortium, a prospective, multicenter, longitudinal, observational study. A total of 2202 visits from 574 adult patients with systemically treated chronic GVHD through January 2013 were used for analysis. At follow-up visits every 3-6 months, clinicians reported standardized information including NIH organ severity scores. Objective medical data including laboratory and pulmonary function test results were abstracted through standardized chart review after each visit. Time-varying Cox models accounting for varied times of entry into the study and longitudinal changes in organ severity over time were used to correlate severity in individual sites with overall mortality. All models were adjusted for time after transplantation, study site and known chronic GVHD mortality risk factors. 424 randomly selected patients with 1602 visit ratings were used to develop a new global mortality score, and the remaining 150 patients with 600 visit ratings were used to validate the model. Risk stratification was compared between the final model and the NIH GS model. Results In the training phase, multivariate models showed that organ severity scores in skin, gastrointestinal tract, liver and lung were independently associated with overall mortality (Table 1), while scores in mouth, eyes, joint or fascia and genital tract were not. Mortality scores were assigned based on observed hazard ratios, and 3 risk groups were identified based on the total mortality score (Table 2). In the validation cohort (n=150), the intermediate (329 visit ratings, HR 3.7, p=0.05) and high-risk categories (89 visit ratings, HR 10.8, p=0.001) were associated with higher risk of overall mortality compared with the low-risk category (185 visit ratings). Using the NIH GS instead, the severe category (196 visit ratings, HR 3.1, p=0.01) was associated with higher risk of overall mortality compared with the mild or moderate category (22 plus 382 visit ratings). Although agreement in risk categories was slight (weighted kappa = 0.32), the two models did not differ statistically based on log likelihood ratios, showing that they performed equally well in identifying groups with different mortality risks. Conclusion The influence of organ scores on mortality differs according to individual sites, with the largest influence from lung followed by liver, skin and gastrointestinal tract. The model fitness did not differ statistically between the 2 models, suggesting that the NIH GS is an adequate model for risk stratification based on mortality in patients with chronic GVHD. Disclosures: No relevant conflicts of interest to declare.

Introduction Older patients undergoing allogeneic stem cell transplantation may experience a higher degree of morbidity and limitations from transplant related complications. Chronic graft-versus –host disease (GVHD) causes a significant reduction in patients’ quality of life (QOL), physical functioning, and functional status. However, it is not known if moderate to severe chronic GVHD has a worse impact on QOL, or survival outcomes for older patients. Methods We analyzed data of patients with moderate or severe chronic GVHD (N=522, 1661 follow-up visits, a total of 2,183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. Moderate or severe chronic GVHD was defined by the National Institutes of Health global severity score at the time of enrollment. We examined the relationship between age group (adolescent and young adult “AYA” 18-40, “middle-aged” 41-59, and “older” ≥ 60 years) and clinical manifestations of chronic GVHD, patient-reported outcomes, functional status, non-relapse mortality and overall survival. Clinical manifestations of chronic GVHD were determined by the clinician-reported individual organ scores. Patient-reported outcomes included (1) QOL as measured by Functional Assessment of Cancer Therapy Bone Marrow Transplantation (FACT-BMT) and the Medical Outcome Short-Form Health Survey (SF-36) (2) chronic GVHD symptom burden as measured by the Lee Symptom Scale; and (3) physical fitness as measured by the Human Activity Profile (HAP). Functional status was assessed using the 2-minute walk test (2MWT). Because of multiple testing, p-values Results There were 115 (22%) AYA, 279 (53%) middle-aged and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD included. At study enrollment, older patients (≥60) were similar to younger patients in sex, time from transplant (median 12 months), prior acute GVHD, percentage of severe chronic GVHD, and current co-morbidity scores but differed in disease distribution and conditioning regimen intensity. At enrollment, in unadjusted analyses using all available data, older patients had similar rates and severity of global and organ-specific manifestations of chronic GVHD compared to younger patients, except for genital involvement, which was more prevalent and severe in AYA patients. Although older patients reported worse physical functioning [SF-36 Physical Functioning (p=0.01)], shorter 2MWT (p=0.002), and lower HAP scores (p=0.001) than AYA and middle-aged patients suggesting they have more physical limitations, older patients had better QOL [FACT-BMT (p=0.01)] scores compared to middle-aged patients and similar to AYA patients. Older patients had better psychological [Lee Psychological Scale (p70 (n=16) age groups, except for more moderate-severe skin involvement in the 65-70 year olds. Conclusion Despite higher physical and functional limitations, older patients with moderate or severe chronic GVHD have preserved QOL, comparable disease manifestations and symptom burden, and similar overall survival and non-relapse mortality when compared to younger patients. Therefore we did not find evidence that older age itself is associated with worse QOL or survival in patients with moderate or severe chronic GVHD. Disclosures: No relevant conflicts of interest to declare.

Abstract 1940 Background: Chronic graft-versus-host disease (GVHD) is a significant source of morbidity, mortality, impaired patient-reported quality of life (QOL), greater symptom burden, and prolonged duration of immune suppressive therapy following allogeneic hematopoietic cell transplantation (HCT). While available data support the adverse prognosis of overlap subtype of chronic GVHD, the relative importance of site of gastrointestinal (GI) and type of hepatic involvement is not known. Methods: We analyzed prospectively acquired observational cohort data to examine whether the site of GI involvement (esophageal, upper GI, lower GI) and type of hepatic laboratory test abnormality (bilirubin, alkaline phosphatase (AP), alanine aminotransferase (ALT) elevation over the upper limit of normal based on study site-specific laboratory reference ranges) among chronic GVHD-affected patients are associated with overall survival (OS) and non-relapse mortality (NRM), symptoms (Lee Symptom Scale), and quality of life (QOL) per SF-36 and FACT-BMT instruments. Results: This analysis included 567 individual subjects with baseline and 1548 follow up visits. The majority were incident cases (59%), adults (98%), and predominantly White/Non-Hispanic. Median time from HCT to cohort enrollment was 11.9 months (range 3–294 months). Overall NIH chronic GVHD severity was mild in 10%, moderate in 52%, and severe in 38% at enrollment. Prior acute GVHD was noted in 66%, KPS < 80% in 17%, and platelet count at chronic GVHD onset of < 100 K/uL in 23%. At enrollment, GI involvement was seen in 40% (upper GI 20%, esophagus 16%, lower GI 13%), and liver involvement was seen in 52% (AP 38%, ALT 38%, bilirubin 10%). Time from transplant to cGVHD onset was not different for patients with or without GI involvement or hepatic involvement. In multivariate analysis utilizing data from enrollment visits only and adjusting for patient and transplant variables, lower GI involvement (HR 1.7, p=0.03) and elevated bilirubin (HR 2.36, p=0.001) were associated with OS; both were also associated with NRM. In multivariable analysis using all visits (time-dependent covariates), GI score greater than zero (HR 1.7, p=0.01) and elevated bilirubin (HR 3.7, p Conclusion: These data support important differences in patient-reported outcomes according to GI and hepatic involvement among chronic GVHD affected patients, and identify those with elevated bilirubin or higher GI score at any time, or lower GI involvement at cohort enrollment, as patients at greater risk for mortality under current treatment approaches. Disclosures: No relevant conflicts of interest to declare.

Abstract 1988 Background: In 2005, the National Institutes of Health (NIH) Consensus Conference recommended measurement tools to capture clinician or patient-assessed chronic GVHD manifestations. The NIH Conference also proposed a set of provisional definitions to calculate response using these measures. The correlation of the calculated NIH responses with patient-reported quality of life (QOL) or symptoms has not been examined. Ideally, improvement according to NIH response criteria would be associated with better QOL and fewer symptoms compared to patients who have stable disease or progress. Patients and methods: We studied 274 patients with chronic GVHD requiring systemic treatment who were enrolled in a multi-center, prospective, longitudinal, observational cohort. Treatment of chronic GVHD was not uniform for this study. 256 patients had follow-up visits at 6 months after enrollment. The 6 month time point was chosen to be consistent with many earlier phase II studies. Responses were classified according to the calculated NIH response algorithm (BBMT 2006;12:491) as complete, partial, stable or progression, separately in skin, eye, mouth, lung, liver and gastrointestinal (GI) tract as well as overall by comparing organ manifestations reported at the follow-up visit to the enrollment visit. Complete or partial response was considered “response”, and stable disease or progression as “no response”. QOL measures included the SF-36, FACT-BMT and Human Activities Profile (HAP) score. Symptom measures included the Lee symptom scale and 10-point global rating of symptoms. Linear regression models were used to estimate the change in measures associated with response vs. no response, adjusting for case type (incident vs. prevalent), donor/patient gender and NIH global severity at enrollment. Results: Patients with a median age of 52 years were enrolled at a median of 13 months from transplant. Of 274 patients, 247 (90%) had mobilized blood cell transplant, 132 (48%) had HLA-matched related donors, 138 (50%) had unrelated donors, and 153 (56%) had myeloablative conditioning. At 6 months, overall response rates were 10 (4%) CR, 72 (28%) PR, 14(6%) SD, and 157(62%) PD, for a CR+PR rate of 32%. Organ-specific CR+PR response rates were 31% for skin, 16% for eye, 26% for mouth, 23% for GI, and 31% for liver. Compared with no response, overall response was associated with improved overall symptom burden measures, but not with changes in QOL measures. For example, the Lee overall score was estimated to be 4.6 points lower in responders than in non-responders ( Table 1 ). Organ-specific analyses showed that organ response was associated with improved symptom burden in skin, eye, mouth and GI except for mouth dryness ( Table 2 ). Conclusion: The calculated organ-specific and overall NIH responses by the provisional algorithm correlated with corresponding organ-specific and overall changes in patient-reported symptom burden, but calculated overall response did not correlate with changes in patient-reported QOL. Our results suggest that the calculated NIH response is a surrogate measure for patient symptom burden in clinical trials. Table 1 . Estimated change in QOL and symptom measures associated with overall response Outcome Clinically meaningful change 1 R vs. NR Estimated change (95% CI) P SF-36 PCS 4.8 0.8 (−1.9–3.5) .57 SF-36 MCS 5.2 0.1 (−2.7–2.9) .93 FACT-BMT 10 2.7 (−1.8–7.1) .24 HAP MAS 6.2 0.7 (−3.2–4.6) .73 HAP AAS 8.4 1.6 (−2.6–5.8) .45 Lee symptom overall score 6.2 −4.6 (−7.3–−1.9) .001 Patient-rated overall symptoms 2 −0.9 (−1.6–−0.3) .003 R, response; NR, no response; PCS, physical component score; MCS, mental component score; MAS, maximum activity score; AAS, adjusted activity score. 1 Half-standard deviation of baseline score or 2-point change on a 10-point scale. Table 2 . Estimated change in symptom measures for each organ associated with organ response Organ Clinically meaningful change R vs. NR Estimated change (95% CI) P Lee symptom scale Skin 10.4 −7.3 (−14–−0.8) .03 Eye 14.8 −16 (−27–−4.7) .005 Mouth 13.8 −16 (−24–−7.6) GI (nutrition) 6.2 −7.1 (−13–−1.1) .02 Patient-rated symptoms Skin itching 2 −1.0 (−1.8–−0.1) .03 Eye problem 2 −1.3 (−2.4–−0.2) .03 Mouth dryness 2 −0.1 (−1.1–0.8) .81 Mouth pain 2 −1.1 (−1.9–−0.2) .02 Mouth sensitivity 2 −1.0 (−1.9–−0.1) .03 R, response; NR, no response. Disclosures: No relevant conflicts of interest to declare.

Abstract 1978 In 2005, a NIH consensus conference was held to better define methods for research in chronic GVHD (cGVHD). Provisional definitions of response categories for individual organs and overall cGVHD disease activity were proposed: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). These response criteria were designed to improve consistency in documentation of disease activity across different centers, to allow less biased response assessments by comparison of enrollment and follow-up measures, rather than relying on clinician perceptions of change in the setting of clinical trials. In this study, we compared the proposed response criteria with clinician-reported changes in organ specific and overall responses. Good agreement would suggest that the proposed response criteria mirror clinician judgments of whether patients are responding to treatment or not. Methods: Patients ≥ 2 years of age diagnosed with cGVHD requiring systemic treatment ≤ 3 years after transplantation were eligible and assessed every 3–6 months. At each visit, clinicians reported the following: organ specific measures (used to calculate the NIH organ response for skin, mouth, eye and overall), perception of change in organ and overall involvement (completely gone = CR; very much or moderately improved = PR; a little better, stable, or a little worse = SD; or moderately or very much worse = PD), and overall aggregate response (CR, PR, SD, PD). Kappa statistics were used to compare agreement between these measures, with 0.21–0.4 considered fair agreement. Results: As of September 2010, 290 patients who had at least one follow-up visit 3 or 6 months beyond enrollment were included, with median age of 51 years (2–79). Based on NIH overall response criteria, 24 (8%) had CR, 83 (29%) had PR, 25 (9%) had SD, and 158 (54%) had PD for an overall CR+PR of 37%. In contrast, clinicians reported that 31 (11%) had CR, 171 (59%) had PR, 30 (10%) had SD and 56 (19%) had PD for an overall CR+PR of 70%. For organ specific comparisons, agreement rates between NIH proposed response measures and clinician reported changes in skin, mouth and eye were fair. For overall response, agreement rates between the calculated NIH response and clinician-reported overall change and clinician-reported response status were also fair. (Table) Conclusions: For both organ-specific and overall comparisons, the proposed NIH response criteria do not agree well with responses determined by clinicians. These data suggest that conclusions from prior literature reporting high overall CR+PR rates based on clinician judgment would not be supported if the current NIH response criteria had been used to measure response. Additional studies are needed to validate candidate response criteria through correlation with a robust, objective and informative gold standard.Table.Calculated NIH and clinician reported response rates in specific organs and overallOrganResponse measureNNICRPRSDPDKappa with NIH responseSkinCalculated NIH skin response28635%22%7%15%21%Clinician reported skin change28629%17%17%32%5%0.39*/0.43**MouthCalculated NIH mouth response28720%15%7%45%13%Clinician reported mouth change28720%15%29%33%4%0.28*/0.35**EyeCalculated NIH eye response16840%10%4%26%19%Clinician reported eye change16844%2%10%39%5%0.29*/0.26**OverallCalculated NIH overall response288—8%29%9%54%Clinician reported overall change285—7%41%45%8%0.24**Clinician reported response status288—11%59%10%19%0.20**NI, not involved; CR, complete response/completely resolved; PR, partial response/moderately better, very much better; SD, stable disease/a little better/stable/a little worse; PD, progressive disease/moderately worse, very much worse*simple kappa, including all patients**weighted kappa, limited to patients with involvement by both measures at enrollment Disclosures: No relevant conflicts of interest to declare.

Abstract 220 The classification of chronic graft-versus-host disease (cGVHD) proposed by the 2005 National Institutes of Health (NIH) Consensus Criteria established a new scoring system for individual organs (0-3) and a global severity scale (mild, moderate, and severe) according to the number and severity of organs involved. The Chronic GVHD Consortium was established to validate these criteria, since the scoring system was based on consensus opinion not yet supported by empiric data. This report includes results from the first 298 adult patients (pts) enrolled at 5 centers of this Consortium. Pts were assessed using standardized clinical data collection forms every 3–6 months (741 total visits). At the time of study enrollment, global cGVHD severity according to NIH consensus criteria was calculated from reported data as mild in 10% (n=31, no more than 2 organs with score 1), moderate in 59% (n=175, 3 or more organs with score 1, lung score 1 or any other organ score 2) and severe in 31% (n=92, lung score=2 or any organ score=3). Severity distribution was similar across incident (54%, cGVHD diagnosis within 3 months of enrollment) vs. prevalent (46%) cases (p=0.35), and between pts with overlap acute and chronic GVHD (40%) vs. classic chronic (60%) cGVHD (p=0.61). Skin, mouth, eye and liver were most commonly involved. (Figure) Score 3 skin (> 50% BSA, or deep sclerotic features, or impaired mobility) and score 2 lung involvement (FEV1 40–59% or lung function score 6–9 or shortness of breath after walking on flat ground) accounted for most of the cases in the severe category, while scores of 3 in the mouth, eye, GI tract, joints, genital tract (females only) occurred in only 3–11% of patients in this category. Higher global severity scores (n=741) were attributable to skin (32%), lung (21%), eye (18%), mouth (9%), liver (6%), joint (6%), GI tract (4%) and genital involvement (3%). Previously reported risk factors associated with onset of cGVHD or treatment-related mortality in pts with cGVHD were analyzed for their association with severity of cGVHD using generalized estimating equations (GEE) to adjust for baseline characteristics, repeated observations per pt, variable time to study enrollment and center effect (n=296 adults, 731 assessments). Global severity of cGVHD was not associated with age, gender-match, donor type, conditioning intensity, stem cell source, prior CMV infection, underlying disease, disease status, prior acute GVHD, time intervals from transplant to onset of cGVHD and enrollment, or platelet count at onset of cGVHD (< or ≥ 100 × 109/L). Moderate or severe cGVHD at onset was associated with Karnofsky performance status ≤ 70 (odds ratio [OR] 2.41, 95% CI (1.5-4.0), p=0.0004). In conclusion, skin, lung and eye involvement accounted for 71% of the global severity score, although all organs contributed and should be scored. Conventional risk factors for development of cGVHD were not associated with NIH cGVHD global severity categories. Most pts fit into the moderate category, suggesting that additional refinements to the global severity scoring may be able to distinguish prognostically different subgroups within this category. Funded by NCI CA118953. Registered as NCT00637689. Disclosures: Miklos: Novartis: Honoraria, Research Funding.

2256 Poster Board II-233 Correlation of the NIH and Vienna Skin scores with provider and patient-reported skin changes in chronic graft-versus-host disease (GVHD) In 2007 we began a multi-center, prospective, observational study of patients diagnosed with chronic GVHD (cGVHD) by National Institute of Health (NIH) Consensus Conference criteria. A major objective is to develop sensitive and valid organ-specific criteria for cGVHD activity to document clinically meaningful changes in clinical trials. This preliminary analysis evaluated the NIH skin tool and the Vienna Skin scale (VS) for their ability to quantify the type and extent of skin involvement, and for their correlation with provider and patient perceptions of change in the skin. Methods: Patients ≥ age 2 diagnosed with cGVHD within 3 years after allogeneic hematopoietic cell transplantation requiring systemic treatment were eligible. Providers and patients complete multiple cGVHD assessment tools at study entry and every 3-6 months. The NIH scale grades 8 body regions according to the percent of body surface area (BSA) involvement by 3 manifestations: 1) erythematous rash, 2) moveable sclerosis, and 3) non-moveable sclerosis, with possible values of 0-100% total BSA for each manifestation. The VS scores each of 10 body regions with percentage involvement of 4 types of skin manifestations: 1 = hypo/hyperpigmentation, erythematous rash, 2 = lichenoid plaque, thickening, able to move, 3 = thickened, limited motion, pinchable, 4 = hidebound, unable to move or pinch. For areas scored as 3 or 4, concurrent fraction involved with erythema is also recorded. Regional scores are summed for a Vienna Skin Total (VST) score of 0-50. At follow-up visits patients and providers rated change in skin involvement as improved, stable, or worse . Proportional odds regression was used to predict improved, stable and worse rates using the difference in NIH subscales or VST since the last visit (change scores). Predictive ability for each scale was summarized using the c index of concordance. Results: Of the 229 participants as of 4/30/09, 61% were males, the median age was 52 years (2-79) and median time from transplant to study entry was 393 days (91-1233). [Table 1][1] shows the scores on the two scales for patients with any skin involvement at baseline (n=161, 70%). At 168 follow-up visits with NIH and VS data, skin GVHD was rated by the providers as improved, stable, or worse in 43%, 48%, and 9%, respectively. Both tools appeared to predict subjective change with the c index of concordance of 0.76 for NIH and 0.71 for VS. Compared to providers, patients were more likely to rate the skin as improved (56%), and less likely to report stable (38%) or worse (6%). The same differences (VST, and NIH erythema and non-moveable sclerosis) were still significant predictors of patients' subjective change. Concordance (c index) and parameter estimates (odds ratios) were attenuated compared to models of provider ratings. Results of the 4 models are summarized in [Table 2][2]. Conclusions: Skin involvement is frequent in cGVHD. Both NIH and VS scores are associated with provider- and patient-reported changes in skin severity. These results suggest that the NIH and VS tools are quantitative measures that are sensitive to provider and patient-perceived skin changes over time. Data from additional patients with a broader range of skin severity and longer follow up are needed to better define the roles of these scales as endpoints in clinical trials. | | N=161 | Median | Range | Mean | STD | |:------------------------- | --------- | ------ | ---------- | ----- | ----- | | NIH Erythema | 99 (61%) | 10.4% | 0.01-98.2% | 24.8% | 27.3% | | NIH movable sclerosis | 47 (29%) | 7.2% | 0.7-50.4% | 10.2% | 12.6% | | NIH non-movable sclerosis | 20 (12%) | 4.8% | 0.1-44.1% | 10.9% | 13.3% | | VST | 157 (98%) | 1.8 | 0.01-19.1 | 3.4 | 3.6 | Table 1 Baseline skin involvement | | Provider assessment (N = 168) | Patient assessment (N = 129) | |:----------------------------- | ----------------------------- | ---------------------------- | | NIH Model: c index | 0.76 | 0.65 | | Erythema[*][3] | 1.9 (< 0.001) | 1.4 (0.02) | | Moveable sclerosis[*][3] | 1.2 (0.22) | 1.1 (0.54) | | Non-moveable sclerosis[*][3] | 1.7 (0.02) | 1.7 (0.09) | | VS Model: c index | 0.71 | 0.61 | | VST[*][3] | 1.9 (< 0.001) | 1.5 (0.003) | * [↵][4]* Odds ratio (p-value in parentheses) for differences of the standard deviation reported in Table 1 for each measure. Table 2. Proportional odds regression models with NIH or VS predicting improved, stable, worse skin involvement compared to 3-6 months ago, as assessed by providers or patients. Disclosures: Jagasia: Genzyme: Research Funding. [1]: #T1 [2]: #T2 [3]: #fn-1 [4]: #xref-fn-1-1

In 2005, a National Institutes of Health consensus conference was held to refine methods for research in patients with chronic graft-versus-host disease, including proposed objective response measures and a provisional algorithm for calculating organ-specific and overall response. In this study, we used weighted kappa statistics to evaluate the level of agreement between clinician response ratings and calculated response categories in patients with chronic graft-versus-host disease. The study included 290 patients who had paired enrollment and follow-up visits. Based on a set of objective measures, 37% of the patients had an overall complete or partial response, whereas clinicians reported an overall complete or partial response rate of 71% (slight to fair agreement, weighted kappa 0.20). Agreement rates between calculated organ-specific responses and clinician-reported changes in skin, mouth, and eyes were fair to moderate (weighted kappa, 0.28-0.54). We conclude that for both overall and organ-specific comparisons, clinician response ratings did not agree well with calculated response categories. Possible reasons for this discrepancy include a high clinical sensitivity for detecting response, a clinical predisposition to recognize selective improvements as overall response, the large change in objective measures proposed to define response, and the high incidence of progressive disease based on new manifestations. Conclusions from prior literature reporting high overall response rates based on clinician judgment would not be supported if the provisional algorithm had been applied to calculate response. Our analysis also highlights the need to define an overall response measure that incorporates both patient-reported and objective measures and accurately reflects the outcome in patients with a mixed response in which one organ or site improves, whereas another shows new involvement.

response rates following second-line therapy for SR-aGVHD in this modern era. Methods: We retrospectively analyzed day 28 response rates and clinical outcomes of 113 HCT patients (median age 39 years, range 1-75) who received second-line therapy for SR-aGVHD from 1998-2012 at the University of Minnesota. Results: Patients received grafts from 43 related (38 matched, 5 mismatched), 31 unrelated (23 HLA 6-8/8, 8 HLA 25/8) and 39 cord blood donors (23 HLA 6-8/8, 16 HLA 25/8); 76 patients (67.3%) received myeloablative regimens. Second-line therapy consisted of ATG (44.2%), MMF (24.8%), steroid boost (22.1%) or other (8.8%). Patients receiving ATG had higher-risk GVHD Risk Scores (MacMillan et al, Br J Haem, 2012) at second-line initiation compared with patients receiving MMF or steroids. At day 28, overall response (complete response [CR]/partial response [PR]) was observed in 32 patients (28%). All therapies had similar responses. In multivariate analysis, factors associated with day 28 CR/PR included GVHD Risk Score and days from onset of aGVHD to second-line therapy (Table); Six-month non-relapse mortality (NRM) was lower among patients receiving steroid boosts (24% [7-41%, 95% CI]) vs. ATG (64% [48-90%, 95% CI]) with no differences vs. MMF or other therapies (P1⁄40.01, Figure 1).

Ocular Gvhd: Epidemiology, Risk Factors and Impact on Quality of Life-a Chronic Gvhd Consortium Study Madan H. Jagasia , Xiaoyu Chai , Joseph Pidala , Yoshihiro Inamoto , Mukta Arora , Corey S. Cutler , Mary E.D. Flowers , Laura Johnston , Steven Z. Pavletic , Stephanie J. Lee . 1 Vanderbilt University Medical Center, Nashville, TN; 2 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; 4 Fred Hutchinson Cancer Research Center, Seattle, WA; Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN; Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA; 7 Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA; Division of Blood and Marrow Transplantation, Stanford University Medical Center, Stanford, CA; 9 Experimental Transplantation and Immunology Branch, National Cancer Institute, Bethesda, MD