Lee cGVHD Symptom Scale Research Articles

Burden of Illness in Chronic Graft vs. Host Disease - A Prospective Cohort Study.

BACKGROUND: Chronic Graft vs. Host Disease (cGVHD) is a complex and prevalent complication in long term survivors after allogeneic stem cell transplant. The scope and severity of abnormalities in cGVHD have never been systematically described and are essential for health care delivery planning or testing new therapies.METHODS: Patients with cGVHD were studied in a cross-sectional prospective natural history protocol. They were systematically assessed by a multidisciplinary team specialized in cGVHD clinical research. A detailed history, organ-specific evaluations, functional performance and laboratory parameters were obtained using standardized measures. Questionnaires administered in strictly controlled conditions included clinician-administered NIH scoring (Filipovich et al, BMT 11:945, 2005) and measures of quality of life (FACT-BMT, SF-36, Lee cGVHD symptom scale). An exploratory statistical analysis was performed by grouping parameters into “predictors” (patient and transplant characteristics, laboratory data) and “outcomes” (cGVHD severity, functional performance, QOL) using descriptive statistics and correlation analysis (p<0.01 or correlation coefficient >0.70 as indicators of strong association).RESULTS: Cohort included 52 patients (29 male, median age 48) with cGVHD. Median time post-transplant was 27 mo and time from diagnosis of cGVHD 14 mo, 42 patients had a sibling donor, 47 received peripheral blood stem cells, 26 had progressive onset of cGVHD, 51 had extensive disease, 38 were on systemic immunosuppression (31 on two or more drugs). Median number of organ systems involved was 5, range from 2 to 9 (max possible 9 for women, 8 for men); median total NIH score was 7.5, range from 2 to 15 (max 27 for women, 24 for men); 22 patients had at least one organ with NIH score of 3 indicating seriously disabling manifestations. Unrelated donor transplant recipients had more organ systems involved (p=0.009) and higher total score (p=0.036). Male recipients with female donors had higher NIH scores (p<0.043). Myeloablative regimens were associated with higher scores for eye (p=0.004). Patients with longstanding cGVHD had higher scores for skin sclerosis (p<0.003), eye (p<0.005) and joint (p<0.0001) while those with early onset of cGVHD had higher mouth scores (p=0.005). Total white count and absolute lymphocyte count were associated with eye involvement (p=0.01 and 0.007 respectively), total cholesterol and LDL with mouth involvement (p=0.0004 and 0.003 respectively), complement C3 and IL-6 with skin sclerosis (p= 0.003 and 0.006 respectively). 26 patients had at least one auto-antibody present and 9 had two or more. Presence of anti-cardiolipin antibodies IgG type was associated with higher skin score (p=0.0008) and IgM with lower eye score (p=0.009). B-cell activating factor (BAFF) was higher in patients who were 9 mo or less from their transplant (p=0.024). BAFF was negatively associated with eye disease (p<0.05) and positively with beta-2-microglobulin (p=0.0001). There were no significant correlations between any predictor and QOL outcomes.CONCLUSION: Patients with cGVHD manifest wide range of clinical and laboratory abnormalities. Some abnormalities occur together and are time related suggesting heterogeneous and dynamic disease biology. Patient reported QOL measures may not be good correlates of cGVHD pathophysiology. A substantial number of associations are worthy of further exploration to better understand the mechanisms which generate the diverse clinical spectrum of cGVHD.

Feasibility and Reproducibility of the New NIH Consensus Criteria To Evaluate Response in Chronic GvHD - A Pilot Study.

Background- The lack of standardized response criteria has been identified as one of the major obstacles in the development of new therapeutic agents for chronic graft-versus host disease (cGvHD). In 2004, the National Institutes of Health initiated a multidisciplinary consensus project, one aim of which was to develop criteria for measuring response in therapeutic trials for cGvHD (http://palladianpartners.com/GvHD/docs/ ). This report presents the results of the first pilot study evaluating the feasibility and reproducibility of these new response criteria.Methods- Eight raters (Oncology Fellows and Oncology Nurse Practitioners with limited experience with cGvHD) participated in a 2 ½ hour training session designed to provide an overview of comprehensive response evaluation in cGvHD and an opportunity to practice conducting functional and organ-specific evaluations. Each participant received a syllabus and a photo atlas illustrating common oral, ocular, and dermatologic manifestations of cGvHD. Feasibility and inter-rater agreement between experts in cGvHD (transplantation, dermatology, oral medicine, and rehabilitation medicine) and the panel of 8 novice raters were evaluated using four adult patients with varying manifestations of cGvHD. Percent Agreement was calculated using the following formula: %Agreement = #Agreements/(#Agreements + #Disagreements) x 100ResultsResponse CriterionExtent of Agreement Between Experts(Es)-Novices (Ns) AgreementErythematous and/or Papular Skin Rash62% agreement between Es and NsSuperficial Sclerosis62% agreement between Es and NsDeep Sclerosis83% agreement between Es and NsSkin Ulcers97% agreement between Es and NsOral CavityPearson correlations ranged from 0.43–0.92Gastrointestinal SystemUpper GI: 100% agreement; Esophageal: 83% agreement; Lower GI: 86% agreementFunctional Performance Measures2 Minute Walk: 66% of Ns within 95% CI of Es;Grip Strength: 75% of Ns within 95% CI of EsKarnofsky PSAll Ns within ± 20% of EscGvHD Mild, Moderate, Severe?All Ns rated consistently one severity category lower than EsSeverity of cGvHD Symptoms (0–10 scale)All Ns scored symptom severity within ± 2 points of EscGvHD Improving, Stable, Worse? (7-point scale)50% of Ns in absolute accord with Es; 50% of Ns direction of change consistent with EsClinical evaluation of a patient with cGVHD by the novice raters lasted a median of 36 minutes (range 19–60). Completion of the five patient self report measures (SF-36, Lee cGVHD Symptom Scale, Human Activity Profile, FACT-BMT, and cGvHD Activity Assessment Patient Self-Report) required a median total of 14 minutes (range 18–22).Conclusions- We are currently improving the clarity of the skin and oral definitions, and refining the photo atlas and training syllabus. Pediatric modifications of these criteria will undergo testing in Fall of 2005. Although limited by small sample size, this pilot study offers preliminary evidence of the reliability and feasibility of these cGvHD response criteria, and supports their use for prospective validation in larger patient cohorts and clinical trials.