Skin response using NIH consensus criteria vs Hopkins scale in a phase II study for steroid-refractory chronic GVHD

Jacobsohn, David A.; Rademaker, Alfred; Kaup, Michele; Vogelsang, Georgia B.

doi:10.1038/bmt.2009.84

Cited by 16 publications

(10 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The population standard deviations were based on data from an ongoing cGVHD natural history study at the National Cancer Institute (N=155) (clinicaltrials.gov#NCT00331968). These means and standard deviations (erythema 8.5% ± 15.1% BSA; movable sclerosis 6.9% ± 15% BSA; nonmovable sclerosis 9.6% ± 17.8% BSA; oral 1.96 ± 2.0) are comparable to those recently reported in another series 13 .…”

Section: Discussionsupporting

confidence: 89%

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

Mitchell

Jacobsohn

Powers

et al. 2011

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

The lack of standardized criteria for measuring therapeutic response is a major obstacle to the development of new therapeutic agents for chronic graft-versus-host disease (cGVHD). National Institutes of Health (NIH) consensus criteria for evaluating therapeutic response were published in 2006. We report the results of four consecutive pilot trials evaluating the feasibility and estimating the inter-rater reliability and minimum detectable change of these response criteria. Hematology-oncology clinicians with limited experience in applying the NIH cGVHD response criteria (n=34), participated in a 2.5 hour training session on response evaluation in cGVHD. Feasibility and inter-rater reliability between subspecialty cGVHD experts and this panel of clinician raters were examined in a sample of 25 children and adults with cGVHD. The minimum detectable change was calculated using the standard error of measurement. Clinicians’ impressions of the brief training session, the photo atlas, and the response criteria documentation tools were generally favorable. Performing and documenting the full set of response evaluations required a median of 21 minutes (range 12 to 60 minutes) per rater. The Schirmer tear test required the greatest time of any single test (median 9 minutes). Overall, inter-rater agreement for skin and oral manifestations was modest, however, in the third and fourth trials, the agreement between clinicians and experts for all dimensions except movable sclerosis approached satisfactory values. In the final two trials, the threshold for defining change exceeding measurement error was 19–22% body surface area (BSA) for erythema, 18–26% BSA for movable sclerosis, 17–21% BSA for nonmovable sclerosis, and 2.1–2.6 points on the 15 point NIH Oral cGHVD scale. Agreement between clinician-expert pairs was moderate to substantial for the measures of functional capacity and for the gastrointestinal and global cGVHD rating scales. These results suggest that the NIH response criteria are feasible for use, and these reliability estimates are encouraging, because they were observed following a single 2.5 hour training session given at multiple transplant centers, with no opportunity for iterative training and calibration. Research is needed to evaluate inter- and intra-rater reliability in larger samples, and to evaluate these response criteria as predictors of outcomes in clinical trials.

show abstract

Section: Discussionsupporting

confidence: 89%

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

Mitchell

Jacobsohn

Powers

et al. 2011

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

show abstract

“…Two methods were used in our study to grade responses with the Hopkins scale yielding higher response rates than the National Institutes of Health consensus cGVHD criteria (data not shown). This may be because of greater sensitivity to sclerotic changes (the predominant feature in this trial's population) as recently reported by Jacobsohn et al 35 Because 5 of 6 criteria for the Hopkins score are based on physical examination or reported symptoms, assessments of response to imatinib are limited by an element of subjectivity. Assessing treatment response in cGVHD is complicated: the best tool for assessing cGVHD is being actively investigated, and the great variability in response evaluation makes appropriate comparisons between studies difficult.…”

Section: Discussionmentioning

confidence: 99%

A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies

Chen

Arai

Flowers

et al. 2011

Blood

View full text Add to dashboard Cite

Stimulatory antiplatelet derived growth factor receptor ␣ (PDGFRA) antibodies have been associated with extensive chronic graft-versus-host disease (cGVHD). We performed a phase 1 dose escalation trial of imatinib in corticosteroid-dependent/ refractory cGVHD to assess the safety of imatinib and test the hypothesis that abrogation of PDGFRA signaling can ameliorate the manifestations of cGVHD. Fifteen patients were enrolled. Mean follow-up time was 56.6 weeks (range, 18-82.4 weeks).Imatinib 400 mg daily was associated with more frequent moderate to life-threatening adverse events than 200 mg daily. The main adverse events were nausea, edema, confusion, diarrhea, liver function test elevation, fatigue, and myalgia. The overall response rate was 40% (6 of 15). The treatment failure rate was 40% (6 of 15). Twenty percent (3 of 15) of subjects had stable disease. Of 4 subjects with phospho-PDGFRA and phospho-PDGFRB immunohistochemistry studies before and after treatment, inhibition of phosphorylation was observed in 3 but correlated with response in one. Anti-PDGFRA antibodies were observed in 7 of 11 evaluable subjects but correlated with clinical activity in 4. We conclude that cGVHD responds to imatinib through multiple pathways that may include PDGFRA signal transduction. This study is registered at www.clinicaltrials.gov as #NCT00760981. (Blood. 2011;118(15):4070-4078)

show abstract

“…The assessment of overall response is further complicated when an organ can have multiple manifestations. For example, a change from 10% non-movable sclerosis at baseline to 8% non-moveable and 2% moveable sclerosis at the follow-up assessment could reflect inter-observer variability [18], softening of preexisting sclerosis (i.e., improvement) or extension of sclerosis into previously unaffected areas (i.e., worsening). In the current analysis, the provisional algorithm would have assigned this patient to the PD category.…”

Section: Discussionmentioning

confidence: 99%

Poor Agreement between Clinician Response Ratings and Calculated Response Measures in Patients with Chronic Graft-versus-Host Disease

Palmer

Lee

Chai

et al. 2012

Biology of Blood and Marrow Transplantation

View full text Add to dashboard Cite

In 2005, a NIH consensus conference was held to refine methods for research in chronic graft-versus-host disease (GVHD), 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 GVHD. 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 eye 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 where one organ or site improves, while another shows new involvement.

show abstract

Skin response using NIH consensus criteria vs Hopkins scale in a phase II study for steroid-refractory chronic GVHD

Cited by 16 publications

References 11 publications

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA antibodies

Poor Agreement between Clinician Response Ratings and Calculated Response Measures in Patients with Chronic Graft-versus-Host Disease

Contact Info

Product

Resources

About